Context: Consultant pharmacy practice focuses more on medication regimen review (i.e. "cognitive services") than on actual dispensing of drugs. Consultant pharmacists most typically work in nursing homes, but are increasingly branching into other institutions and non-institutional settings. Traditionally consultant pharmacists were usually independent business owners, though in the United States many now work for several large pharmacy management companies (primarily Omnicare, Kindred Healthcare and PharMerica). This trend may be gradually reversing as consultant pharmacists begin to work directly with patients, primarily because many elderly people are now taking numerous medications but continue to live outside of institutional settings. Some community pharmacies employ consultant pharmacists and/or provide consulting services.

Question: What is consultant pharmacy mainly concerned with?

Question: Where do a majority of consultant pharmacists tend to work?

Question: What are some large pharmacy management companies?

Question: What is the main reason consulting pharmacists are increasingly working directly with patients?

Question: What do some community pharmacies do?


Context: Since about the year 2000, a growing number of Internet pharmacies have been established worldwide. Many of these pharmacies are similar to community pharmacies, and in fact, many of them are actually operated by brick-and-mortar community pharmacies that serve consumers online and those that walk in their door. The primary difference is the method by which the medications are requested and received. Some customers consider this to be more convenient and private method rather than traveling to a community drugstore where another customer might overhear about the drugs that they take. Internet pharmacies (also known as online pharmacies) are also recommended to some patients by their physicians if they are homebound.

Question: When did internet pharmacies begin to come into being?

Question: Who often operates internet pharmacies?

Question: What are internet pharmacies also called?

Question: What is one reason a patient might choose an internet pharmacy?

Question: What is the main difference between online pharmacies and community pharmacies?


Context: While most Internet pharmacies sell prescription drugs and require a valid prescription, some Internet pharmacies sell prescription drugs without requiring a prescription. Many customers order drugs from such pharmacies to avoid the "inconvenience" of visiting a doctor or to obtain medications which their doctors were unwilling to prescribe. However, this practice has been criticized as potentially dangerous, especially by those who feel that only doctors can reliably assess contraindications, risk/benefit ratios, and an individual's overall suitability for use of a medication. There also have been reports of such pharmacies dispensing substandard products.

Question: Why might customers order from internet pharmacies?

Question: Who has criticized ordering from online pharmacies that don't require prescriptions?

Question: What is a criticism of online pharmacies that issue drugs without a prescription?

Question: What practice do some internet pharmacies engage in?

Question: What do most online pharmacies do?


Context: In the United States, there has been a push to legalize importation of medications from Canada and other countries, in order to reduce consumer costs. While in most cases importation of prescription medications violates Food and Drug Administration (FDA) regulations and federal laws, enforcement is generally targeted at international drug suppliers, rather than consumers. There is no known case of any U.S. citizens buying Canadian drugs for personal use with a prescription, who has ever been charged by authorities.

Question: What is a reason for the movement to legalize importing medicines from other countries?

Question: What is one country that has been suggested for importation of medicines?

Question: Who are FDA laws against importing medications aimed at?

Question: Has there ever been anyone charged with importing drugs from Canada for personal medicinal use?

Question: What is there a push for in the U.S. to reduce consumer drug costs?


Context: Pharmacy informatics is the combination of pharmacy practice science and applied information science. Pharmacy informaticists work in many practice areas of pharmacy, however, they may also work in information technology departments or for healthcare information technology vendor companies. As a practice area and specialist domain, pharmacy informatics is growing quickly to meet the needs of major national and international patient information projects and health system interoperability goals. Pharmacists in this area are trained to participate in medication management system development, deployment and optimization.

Question: What two things does pharmacy informatics bring together?

Question: What fields may pharmacy informatics also work in?

Question: Whose needs will the growth in pharmacy informatics meet?

Question: What areas are pharmacy informatics prepared to work in?

Question: How fast is pharmacy informatics growing?


Context: Specialty pharmacies supply high cost injectable, oral, infused, or inhaled medications that are used for chronic and complex disease states such as cancer, hepatitis, and rheumatoid arthritis. Unlike a traditional community pharmacy where prescriptions for any common medication can be brought in and filled, specialty pharmacies carry novel medications that need to be properly stored, administered, carefully monitored, and clinically managed. In addition to supplying these drugs, specialty pharmacies also provide lab monitoring, adherence counseling, and assist patients with cost-containment strategies needed to obtain their expensive specialty drugs. It is currently the fastest growing sector of the pharmaceutical industry with 19 of 28 newly FDA approved medications in 2013 being specialty drugs.

Question: What is the fastest growing area in the pharmaceutical industry?

Question: How many drugs approved by the FDA in 2013 were specialty drugs?

Question: What types of diseases are specialty drugs often used against?

Question: What types of medications do specialty pharmacies stock?

Question: Besides drugs, what else do specialty pharmacies provide?


Context: In most jurisdictions (such as the United States), pharmacists are regulated separately from physicians. These jurisdictions also usually specify that only pharmacists may supply scheduled pharmaceuticals to the public, and that pharmacists cannot form business partnerships with physicians or give them "kickback" payments. However, the American Medical Association (AMA) Code of Ethics provides that physicians may dispense drugs within their office practices as long as there is no patient exploitation and patients have the right to a written prescription that can be filled elsewhere. 7 to 10 percent of American physicians practices reportedly dispense drugs on their own.

Question: How are pharmacists regulated in most jurisdictions?

Question: Who do most jurisdictions say can give scheduled drugs to the public?

Question: What body has stated that physicians can also dispense drugs under specific conditions?

Question: What is the estimate of how many physicians give out drugs on their own?

Question: What are pharmacists forbidden to do?


Context: In some rural areas in the United Kingdom, there are dispensing physicians who are allowed to both prescribe and dispense prescription-only medicines to their patients from within their practices. The law requires that the GP practice be located in a designated rural area and that there is also a specified, minimum distance (currently 1.6 kilometres) between a patient's home and the nearest retail pharmacy. This law also exists in Austria for general physicians if the nearest pharmacy is more than 4 kilometers away, or where none is registered in the city.

Question: What is another country that permits physicians to give out drugs from within their practice?

Question: Where are some physicians permitted to prescribe and give out medications within their practices?

Question: What is the minimum distance between a patient's home and the nearest pharmacy that allows a physician to give out medication?

Question: What is the minimum distance between a patient's home and the nearest pharmacy that allows a physician in Austria to give out medicine?


Context: The reason for the majority rule is the high risk of a conflict of interest and/or the avoidance of absolute powers. Otherwise, the physician has a financial self-interest in "diagnosing" as many conditions as possible, and in exaggerating their seriousness, because he or she can then sell more medications to the patient. Such self-interest directly conflicts with the patient's interest in obtaining cost-effective medication and avoiding the unnecessary use of medication that may have side-effects. This system reflects much similarity to the checks and balances system of the U.S. and many other governments.[citation needed]

Question: Why is majority rule used?

Question: Why might a physician diagnose a large number of conditions?

Question: What do rules about conflict of interest involving doctors diagnosing patients resemble?

Question: How else might a physician take advantage of self-interest?

Question: Where might the doctor's self-interest be at odds with the patient's self-interest?


Context: In the coming decades, pharmacists are expected to become more integral within the health care system. Rather than simply dispensing medication, pharmacists are increasingly expected to be compensated for their patient care skills. In particular, Medication Therapy Management (MTM) includes the clinical services that pharmacists can provide for their patients. Such services include the thorough analysis of all medication (prescription, non-prescription, and herbals) currently being taken by an individual. The result is a reconciliation of medication and patient education resulting in increased patient health outcomes and decreased costs to the health care system.

Question: What will be the importance of the pharmacist in coming decades?

Question: What responsibilities are pharmacists believed to be taking on more in the future?

Question: What is included in Medication Therapy Management?

Question: What are examples of clinical services that pharmacists can provide?

Question: What are outcomes expected with Medication Therapy Management?


Context: This shift has already commenced in some countries; for instance, pharmacists in Australia receive remuneration from the Australian Government for conducting comprehensive Home Medicines Reviews. In Canada, pharmacists in certain provinces have limited prescribing rights (as in Alberta and British Columbia) or are remunerated by their provincial government for expanded services such as medications reviews (Medschecks in Ontario). In the United Kingdom, pharmacists who undertake additional training are obtaining prescribing rights and this is because of pharmacy education. They are also being paid for by the government for medicine use reviews. In Scotland the pharmacist can write prescriptions for Scottish registered patients of their regular medications, for the majority of drugs, except for controlled drugs, when the patient is unable to see their doctor, as could happen if they are away from home or the doctor is unavailable. In the United States, pharmaceutical care or clinical pharmacy has had an evolving influence on the practice of pharmacy. Moreover, the Doctor of Pharmacy (Pharm. D.) degree is now required before entering practice and some pharmacists now complete one or two years of residency or fellowship training following graduation. In addition, consultant pharmacists, who traditionally operated primarily in nursing homes are now expanding into direct consultation with patients, under the banner of "senior care pharmacy."

Question: Which provinces in Canada limit the rights of pharmacists in prescribing?

Question: Who pays Australian pharmacists for doing Home Medicines Reviews?

Question: What are pharmacists in the United Kingdom being increasingly paid for?

Question: What fields have increased in influence on pharmacy in the United States?

Question: What degree is now mandatory in the U.S. in order to be a licensed pharmacist?


Context: The two symbols most commonly associated with pharmacy in English-speaking countries are the mortar and pestle and the ℞ (recipere) character, which is often written as "Rx" in typed text. The show globe was also used until the early 20th century. Pharmacy organizations often use other symbols, such as the Bowl of Hygieia which is often used in the Netherlands, conical measures, and caduceuses in their logos. Other symbols are common in different countries: the green Greek cross in France, Argentina, the United Kingdom, Belgium, Ireland, Italy, Spain, and India, the increasingly rare Gaper in the Netherlands, and a red stylized letter A in Germany and Austria (from Apotheke, the German word for pharmacy, from the same Greek root as the English word 'apothecary').

Question: What are the two symbols that signify pharmacy in English-speaking countries?

Question: What symbol was employed until early in the 20th century?

Question: What country uses the Bowl of Hygieia as a symbol of pharmacy?

Question: What countries use a red stylized A to signify pharmacy?

Question: Which countries use the green Greek cross as a symbol of pharmacy?


Context: Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self molecules. In immunology, self molecules are those components of an organism's body that can be distinguished from foreign substances by the immune system. Conversely, non-self molecules are those recognized as foreign molecules. One class of non-self molecules are called antigens (short for antibody generators) and are defined as substances that bind to specific immune receptors and elicit an immune response.

Question: The adaptive immune system must distinguish between what types of molecules?

Question: What molecules are parts of the body of an organism in immunology?

Question: What molecules are recognized as foreign by the immune system?

Question: What term is shorthand for antibody generators?

Question: Antigens bind to what in order to elicit a response of the immune system?


Context: Microorganisms or toxins that successfully enter an organism encounter the cells and mechanisms of the innate immune system. The innate response is usually triggered when microbes are identified by pattern recognition receptors, which recognize components that are conserved among broad groups of microorganisms, or when damaged, injured or stressed cells send out alarm signals, many of which (but not all) are recognized by the same receptors as those that recognize pathogens. Innate immune defenses are non-specific, meaning these systems respond to pathogens in a generic way. This system does not confer long-lasting immunity against a pathogen. The innate immune system is the dominant system of host defense in most organisms.

Question: What part of the innate immune system identifies microbes and triggers immune response?

Question: For most organisms, what is the dominant system of defense?

Question: Pattern recognition receptors recognize components present in broad groups of what?

Question: The innate immune system responds in a generic way, meaning it is what?


Context: Several barriers protect organisms from infection, including mechanical, chemical, and biological barriers. The waxy cuticle of many leaves, the exoskeleton of insects, the shells and membranes of externally deposited eggs, and skin are examples of mechanical barriers that are the first line of defense against infection. However, as organisms cannot be completely sealed from their environments, other systems act to protect body openings such as the lungs, intestines, and the genitourinary tract. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the respiratory tract. The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.

Question: What is a mechanical barrier in insects that protects the insect?

Question: What is an example of a mechanical barrier on leaves?

Question: What responses protect the lungs by mechanically ejecting pathogens from the respiratory system?

Question: What is secreted by the respiratory tract to trap microorganisms?

Question: The flushing action of what expels pathogens from the eyes?


Context: Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β-defensins. Enzymes such as lysozyme and phospholipase A2 in saliva, tears, and breast milk are also antibacterials. Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains defensins and zinc to kill pathogens. In the stomach, gastric acid and proteases serve as powerful chemical defenses against ingested pathogens.

Question: What are the anitmicrobial peptides secreted by the skin called?

Question: What enzymes in saliva are antibacterial in nature?

Question: Semen contains what in order to kill pathogens?

Question: What compounds in the stomach protect against ingested pathogens?

Question: Vaginal secretions serve as a chemical protective barrier following what?


Context: Within the genitourinary and gastrointestinal tracts, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, by changing the conditions in their environment, such as pH or available iron. This reduces the probability that pathogens will reach sufficient numbers to cause illness. However, since most antibiotics non-specifically target bacteria and do not affect fungi, oral antibiotics can lead to an "overgrowth" of fungi and cause conditions such as a vaginal candidiasis (a yeast infection). There is good evidence that re-introduction of probiotic flora, such as pure cultures of the lactobacilli normally found in unpasteurized yogurt, helps restore a healthy balance of microbial populations in intestinal infections in children and encouraging preliminary data in studies on bacterial gastroenteritis, inflammatory bowel diseases, urinary tract infection and post-surgical infections.

Question: What serves as a biological barrier by competing for space and food in the GI tract?

Question: Most antibiotics target bacteria and don't affect what class of organisms?

Question: What probiotic flora is found in unpasteurized yogurt?

Question: Commensal flora can change what specific conditions of their environment in the gastrointestinal tract?


Context: Inflammation is one of the first responses of the immune system to infection. The symptoms of inflammation are redness, swelling, heat, and pain, which are caused by increased blood flow into tissue. Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes). Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell. Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.

Question: What is one of the first responses the immune system has to infection?

Question: What causes the symptoms of inflammation?

Question: What compounds are released by injured or infected cells, triggering inflammation?

Question: Eicosanoids include what compounds that result in fever and blood vessel dilation?

Question: What cytokines are responsible for communication between white blood cells?


Context: Phagocytosis is an important feature of cellular innate immunity performed by cells called 'phagocytes' that engulf, or eat, pathogens or particles. Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines. Once a pathogen has been engulfed by a phagocyte, it becomes trapped in an intracellular vesicle called a phagosome, which subsequently fuses with another vesicle called a lysosome to form a phagolysosome. The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome. Phagocytosis evolved as a means of acquiring nutrients, but this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism. Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals.

Question: What type of cells engulf or eat pathogens and foreign particles?

Question: Phagocytes can be called to a specific location by what?

Question: When a pathogen has been eaten by a phagocyte it becomes trapped in what vesicle?

Question: What is formed when a phagosome fuses with a lysosome?

Question: Phagocytosis first evolved as means of doing what?


Context: Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading pathogens. Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, normally representing 50% to 60% of the total circulating leukocytes. During the acute phase of inflammation, particularly as a result of bacterial infection, neutrophils migrate toward the site of inflammation in a process called chemotaxis, and are usually the first cells to arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and produce a wide array of chemicals including enzymes, complement proteins, and regulatory factors such as interleukin 1. Macrophages also act as scavengers, ridding the body of worn-out cells and other debris, and as antigen-presenting cells that activate the adaptive immune system.

Question: What are two types of phagocytes that travel through the body to find invading pathogens?

Question: What are the most abundant kind of phagocyte?

Question: What percentage of leukocytes do neutrophils represent?

Question: What is the process in which neutrophils move towards the site of inflammation called?

Question: What is a regulatory factor produced by macrophages?


Context: Leukocytes (white blood cells) act like independent, single-celled organisms and are the second arm of the innate immune system. The innate leukocytes include the phagocytes (macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells. These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms. Innate cells are also important mediators in the activation of the adaptive immune system.

Question: What are white blood cells known as?

Question: What cells are the second arm of the innate immune system?

Question: Innate cells can act as mediators in the activation of what branch of the immune system?

Question: What are three kinds of phagocytes?


Context: Dendritic cells (DC) are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines. They are named for their resemblance to neuronal dendrites, as both have many spine-like projections, but dendritic cells are in no way connected to the nervous system. Dendritic cells serve as a link between the bodily tissues and the innate and adaptive immune systems, as they present antigens to T cells, one of the key cell types of the adaptive immune system.

Question: What are the phagocytes that are located in tissues in contact with the external environment called?

Question: Dendritic cells are named that because they resemble what?

Question: What are one of the key cell types of the adaptive immune system?

Question: Dendritic cells present antigens to what cells of the adaptive nervous system?


Context: Natural killer cells, or NK cells, are a component of the innate immune system which does not directly attack invading microbes. Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by a condition known as "missing self." This term describes cells with low levels of a cell-surface marker called MHC I (major histocompatibility complex) – a situation that can arise in viral infections of host cells. They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self." For many years it was unclear how NK cells recognize tumor cells and infected cells. It is now known that the MHC makeup on the surface of those cells is altered and the NK cells become activated through recognition of "missing self". Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens are recognized by killer cell immunoglobulin receptors (KIR) which essentially put the brakes on NK cells.

Question: Natural killer cells recognize cells that should be targeted by a condition known as what?

Question: What is one part of the innate immune system that doesn't attack microbes directly?

Question: Missing self desribes cells that only have small amounts of what cell-surface marker?

Question: MHC antigens on normal body cells are recognized by what receptor on NK cells?


Context: The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by a signature antigen. The adaptive immune response is antigen-specific and requires the recognition of specific "non-self" antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.

Question: In what types of organisms did the adaptive immune system first evolve?

Question: The adaptive immune system recognizes non-self antigens during a process called what?

Question: Antigen specificity  allows responses that are specific to certain types of what?


Context: Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a "non-self" target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a "self" receptor called a major histocompatibility complex (MHC) molecule. There are two major subtypes of T cells: the killer T cell and the helper T cell. In addition there are regulatory T cells which have a role in modulating immune response. Killer T cells only recognize antigens coupled to Class I MHC molecules, while helper T cells and regulatory T cells only recognize antigens coupled to Class II MHC molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC receptors.

Question: What are the two major subtypes of T cells?

Question: What kind of T cells have the purpose of modulating the immune response?

Question: Killer T cells can only recognize antigens coupled to what kind of molecules?

Question: Helper and regulatory T cells can only recognize antigens coupled to what kind of molecules?

Question: What class of T cells recognizes intact antigens that are not associated with MHC receptors?


Context: Killer T cells are a sub-group of T cells that kill cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. As with B cells, each type of T cell recognizes a different antigen. Killer T cells are activated when their T cell receptor (TCR) binds to this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a co-receptor on the T cell, called CD8. The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such cells, it releases cytotoxins, such as perforin, which form pores in the target cell's plasma membrane, allowing ions, water and toxins to enter. The entry of another toxin called granulysin (a protease) induces the target cell to undergo apoptosis. T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T cells (see below).

Question: What kind of T cells kill cells that are infected with pathogens?

Question: What co-receptor on the T cell helps in recognizing the MHC-antigen complex?

Question: What is the receptor that killer T cells use to bind to specific antigens that are complexed with the MHC Class 1 receptor of another cell?

Question: What toxin induces apoptosis in the target cell?

Question: When an activated killer T cell finds cells where the MHC 1 receptor has specific antigens, it releases cytotoxins such as what?


Context: Helper T cells express T cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex is also recognized by the helper cell's CD4 co-receptor, which recruits molecules inside the T cell (e.g., Lck) that are responsible for the T cell's activation. Helper T cells have a weaker association with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200–300) on the helper T cell must be bound by an MHC:antigen in order to activate the helper cell, while killer T cells can be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell. The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell's surface, such as CD40 ligand (also called CD154), which provide extra stimulatory signals typically required to activate antibody-producing B cells.

Question: What co-receptor recruits molecules inside the T cell that are responsible for cell activation?

Question: How many receptors on a helper T cell must be bound to a MHC:antigen complex in order for the cell to be activated?

Question: The receptors on a killer T cell must bind to how many MHC: antigen complexes in order to activate the cell?

Question: Activation of a helper T cell causes it to release what chemicals that influence cell activity?

Question: What is a ligand on the cell surface that is upregulated after helper T cell activation?


Context: Gamma delta T cells (γδ T cells) possess an alternative T cell receptor (TCR) as opposed to CD4+ and CD8+ (αβ) T cells and share the characteristics of helper T cells, cytotoxic T cells and NK cells. The conditions that produce responses from γδ T cells are not fully understood. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted Natural Killer T cells, γδ T cells straddle the border between innate and adaptive immunity. On one hand, γδ T cells are a component of adaptive immunity as they rearrange TCR genes to produce receptor diversity and can also develop a memory phenotype. On the other hand, the various subsets are also part of the innate immune system, as restricted TCR or NK receptors may be used as pattern recognition receptors. For example, large numbers of human Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted Vδ1+ T cells in epithelia respond to stressed epithelial cells.

Question: Gamma delta T cells share the characteristics of what other types of T cells?

Question: Gamma delta T cells have a different version of what receptor?

Question: What type of T cells help with both innnate and adaptive immunity?

Question: Gamma delta T cells rearrange TCR genes to produce what?

Question: What kind of human T cells respond to common molecules produced by microbes?


Context: A B cell identifies pathogens when antibodies on its surface bind to a specific foreign antigen. This antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides. The B cell then displays these antigenic peptides on its surface MHC class II molecules. This combination of MHC and antigen attracts a matching helper T cell, which releases lymphokines and activates the B cell. As the activated B cell then begins to divide, its offspring (plasma cells) secrete millions of copies of the antibody that recognizes this antigen. These antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen and mark them for destruction by complement activation or for uptake and destruction by phagocytes. Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells.

Question: What kind of cell identifies pathogens when the antibodies on its surface complex with a specific foreign antigen?

Question: What is the process by which the antigen/antibody complex is processed in to peptides?

Question: What does the matching helper T cell release when it binds with the MHC:antigen complex of the B cell?


Context: When B cells and T cells are activated and begin to replicate, some of their offspring become long-lived memory cells. Throughout the lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again. This is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges. Immunological memory can be in the form of either passive short-term memory or active long-term memory.

Question: When B cells and T cells begin to replicate, what do some of their offspring cells become?

Question: The function of long-lived memory cells is an example of what kind of immune response?

Question: Immunological memory can take what two forms?

Question: Long-lived memory cells can remember previous encounters with what?


Context: Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. During pregnancy, a particular type of antibody, called IgG, is transported from mother to baby directly across the placenta, so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother. Breast milk or colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies. This is passive immunity because the fetus does not actually make any memory cells or antibodies—it only borrows them. This passive immunity is usually short-term, lasting from a few days up to several months. In medicine, protective passive immunity can also be transferred artificially from one individual to another via antibody-rich serum.

Question: Newborns are vulnerable to infection because they have no previous exposure to what?

Question: What antibody is transported from the mother to baby across the placenta?

Question: Antibodies are transferred to the gut of the infant through what means?

Question: Antibodies transported from the mother to an infant via the placenta is an example of what type of short-lived immunity?


Context: Hormones can act as immunomodulators, altering the sensitivity of the immune system. For example, female sex hormones are known immunostimulators of both adaptive and innate immune responses. Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their onset often coincides with puberty. By contrast, male sex hormones such as testosterone seem to be immunosuppressive. Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D.

Question: Hormones can alter the sensitivity of the immune system, so they can be referred to as what?

Question: Female sex hormones are immunostimulators of which immune responses?

Question: What is an autoimmune disease that affects women preferentially?

Question: What is the effect of testosterone on the male immune system?


Context: When suffering from sleep deprivation, active immunizations may have a diminished effect and may result in lower antibody production, and a lower immune response, than would be noted in a well-rested individual. Additionally, proteins such as NFIL3, which have been shown to be closely intertwined with both T-cell differentiation and our circadian rhythms, can be affected through the disturbance of natural light and dark cycles through instances of sleep deprivation, shift work, etc. As a result, these disruptions can lead to an increase in chronic conditions such as heart disease, chronic pain, and asthma.

Question: What is a protein that is closely intertwined with circadian rhythms?

Question: Disruptions in sleep can lead to increase in what chronic conditions?

Question: What kind of deprivation results in diminished immune response and lower antibody production?


Context: It is conjectured that a progressive decline in hormone levels with age is partially responsible for weakened immune responses in aging individuals. Conversely, some hormones are regulated by the immune system, notably thyroid hormone activity. The age-related decline in immune function is also related to decreasing vitamin D levels in the elderly. As people age, two things happen that negatively affect their vitamin D levels. First, they stay indoors more due to decreased activity levels. This means that they get less sun and therefore produce less cholecalciferol via UVB radiation. Second, as a person ages the skin becomes less adept at producing vitamin D.

Question: What is partially responsible for weakened immune response in older individuals?

Question: As a person gets older, what does the skin produce less of?

Question: The production of what signalling molecules is regulated by the immune system?

Question: Older people get less sun and produce less of what chemical via UVB radiation?


Context: The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells. Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to recognize the tumor cell as abnormal. NK cells also kill tumorous cells in a similar way, especially if the tumor cells have fewer MHC class I molecules on their surface than normal; this is a common phenomenon with tumors. Sometimes antibodies are generated against tumor cells allowing for their destruction by the complement system.

Question: What type of immune cells help to destroy abnormal cells in tumors?

Question: Lots of tumor cells have fewer of what type of molecule on their surface?

Question: Tumor antigens are complexed with MHC class I molecules in the same way as what antigens?

Question: The immune system also produces what molecules in order to allow for tumor destruction by the complement system?


Context: Unlike animals, plants lack phagocytic cells, but many plant immune responses involve systemic chemical signals that are sent through a plant. Individual plant cells respond to molecules associated with pathogens known as Pathogen-associated molecular patterns or PAMPs. When a part of a plant becomes infected, the plant produces a localized hypersensitive response, whereby cells at the site of infection undergo rapid apoptosis to prevent the spread of the disease to other parts of the plant. Systemic acquired resistance (SAR) is a type of defensive response used by plants that renders the entire plant resistant to a particular infectious agent. RNA silencing mechanisms are particularly important in this systemic response as they can block virus replication.

Question: Plants lack what kind of immune cells?

Question: Plant cells respond to the molecules associated with pathogens known as what?

Question: Cells of the site of an infection in a plant undergo what process to prevent spread of the disease?

Question: What is a kind of defense response that makes the entire plant resistant to a particular agent?

Question: What is a mechanism that can help plants block virus replication?


Context: Overactive immune responses comprise the other end of immune dysfunction, particularly the autoimmune disorders. Here, the immune system fails to properly distinguish between self and non-self, and attacks part of the body. Under normal circumstances, many T cells and antibodies react with "self" peptides. One of the functions of specialized cells (located in the thymus and bone marrow) is to present young lymphocytes with self antigens produced throughout the body and to eliminate those cells that recognize self-antigens, preventing autoimmunity.

Question: What kind of disorders are the result of an overactive immune response?

Question: In autoimmune disorders, the immune system doesn't distinguish between what types of cells?

Question: Where are the specialized cells that eliminate cells that recognize self-antigens located?

Question: Under normal conditions, T cells and antibodies produce what kind of peptides?


Context: Immunodeficiencies occur when one or more of the components of the immune system are inactive. The ability of the immune system to respond to pathogens is diminished in both the young and the elderly, with immune responses beginning to decline at around 50 years of age due to immunosenescence. In developed countries, obesity, alcoholism, and drug use are common causes of poor immune function. However, malnutrition is the most common cause of immunodeficiency in developing countries. Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, IgA antibody concentrations, and cytokine production. Additionally, the loss of the thymus at an early age through genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection.

Question: What kind of disorders occur when part of the immune system isn't active?

Question: In what two age groups is the strength of the immune system reduced?

Question: At what age do immune responses typically begin to decline?

Question: What are some causes of reduced immune function in developed countries?

Question: What is the most common cause of immunodeficiency in developing nations?


Context: Long-term active memory is acquired following infection by activation of B and T cells. Active immunity can also be generated artificially, through vaccination. The principle behind vaccination (also called immunization) is to introduce an antigen from a pathogen in order to stimulate the immune system and develop specific immunity against that particular pathogen without causing disease associated with that organism. This deliberate induction of an immune response is successful because it exploits the natural specificity of the immune system, as well as its inducibility. With infectious disease remaining one of the leading causes of death in the human population, vaccination represents the most effective manipulation of the immune system mankind has developed.

Question: By what process can active immunity be generated in an artificial manner?

Question: What is the process of vaccination also known as?

Question: In the process of vaccination, what is introduced in order to develop a specific immunity?

Question: Vaccination exploits what feature of the human immune system in order to be successful?


Context: The success of any pathogen depends on its ability to elude host immune responses. Therefore, pathogens evolved several methods that allow them to successfully infect a host, while evading detection or destruction by the immune system. Bacteria often overcome physical barriers by secreting enzymes that digest the barrier, for example, by using a type II secretion system. Alternatively, using a type III secretion system, they may insert a hollow tube into the host cell, providing a direct route for proteins to move from the pathogen to the host. These proteins are often used to shut down host defenses.

Question: Bacteria often secrete what kind of proteins to ingest a physical barrier?

Question: What kind of system of infection involves inserting a hollow tube into a host cell?

Question: In a type III secretion system, proteins are transported to the host cell in order to do what?

Question: The success of pathogens is predicated on their ability to do what?


Context: In the mid-1950s, Frank Burnet, inspired by a suggestion made by Niels Jerne, formulated the clonal selection theory (CST) of immunity. On the basis of CST, Burnet developed a theory of how an immune response is triggered according to the self/nonself distinction: "self" constituents (constituents of the body) do not trigger destructive immune responses, while "nonself" entities (pathogens, an allograft) trigger a destructive immune response. The theory was later modified to reflect new discoveries regarding histocompatibility or the complex "two-signal" activation of T cells. The self/nonself theory of immunity and the self/nonself vocabulary have been criticized, but remain very influential.

Question: Who formulated the idea of clonal selection theory of immunity?

Question: What are two examples of nonself entities in accordance with Frank Burnet's theory?

Question: What is the complex "two-signal" activation of T cells referred to?

Question: What other scientist influence Frank Burnet when he was formulating his theory of immunity?


Context: Anti-inflammatory drugs are often used to control the effects of inflammation. Glucocorticoids are the most powerful of these drugs; however, these drugs can have many undesirable side effects, such as central obesity, hyperglycemia, osteoporosis, and their use must be tightly controlled. Lower doses of anti-inflammatory drugs are often used in conjunction with cytotoxic or immunosuppressive drugs such as methotrexate or azathioprine. Cytotoxic drugs inhibit the immune response by killing dividing cells such as activated T cells. However, the killing is indiscriminate and other constantly dividing cells and their organs are affected, which causes toxic side effects. Immunosuppressive drugs such as cyclosporin prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.

Question: What are the most powerful class of anti-inflammatory drugs?

Question: Low doses of anti-inflammatories are sometimes used with what classes of drugs?

Question: What are two examples of cytotoxic or immunosuppressive drugs?

Question: What is an example of an immunosuppressive drug that prevents T cell activity by altering signal transduction pathways?


Context: In contrast, during wake periods differentiated effector cells, such as cytotoxic natural killer cells and CTLs (cytotoxic T lymphocytes), peak in order to elicit an effective response against any intruding pathogens. As well during awake active times, anti-inflammatory molecules, such as cortisol and catecholamines, peak. There are two theories as to why the pro-inflammatory state is reserved for sleep time. First, inflammation would cause serious cognitive and physical impairments if it were to occur during wake times. Second, inflammation may occur during sleep times due to the presence of melatonin. Inflammation causes a great deal of oxidative stress and the presence of melatonin during sleep times could actively counteract free radical production during this time.

Question: What are examples of differentiated effector cells that peak during wake periods?

Question: What are two anti-inflammatory molecules that peak during awake hours?

Question: Inflammation occurs during sleep times because of the presence of what molecule?

Question: Melatonin during sleep can actively counteract the production of what?


Context: When a T-cell encounters a foreign pathogen, it extends a vitamin D receptor. This is essentially a signaling device that allows the T-cell to bind to the active form of vitamin D, the steroid hormone calcitriol. T-cells have a symbiotic relationship with vitamin D. Not only does the T-cell extend a vitamin D receptor, in essence asking to bind to the steroid hormone version of vitamin D, calcitriol, but the T-cell expresses the gene CYP27B1, which is the gene responsible for converting the pre-hormone version of vitamin D, calcidiol into the steroid hormone version, calcitriol. Only after binding to calcitriol can T-cells perform their intended function. Other immune system cells that are known to express CYP27B1 and thus activate vitamin D calcidiol, are dendritic cells, keratinocytes and macrophages.

Question: What does a T cell extend when it encounters a foreign pathogen?

Question: What is the active form of vitamin D known as?

Question: What is the nature of the relationship between T-cells and vitamin D?

Question: What gene is responsible for converting calcidiol into calcitriol?

Question: Other than T cells, what other immune cells express CYP27B1?


Context: Pattern recognition receptors are proteins used by nearly all organisms to identify molecules associated with pathogens. Antimicrobial peptides called defensins are an evolutionarily conserved component of the innate immune response found in all animals and plants, and represent the main form of invertebrate systemic immunity. The complement system and phagocytic cells are also used by most forms of invertebrate life. Ribonucleases and the RNA interference pathway are conserved across all eukaryotes, and are thought to play a role in the immune response to viruses.

Question: What are the proteins that organisms use to identify molecules associated with pathogens?

Question: What are the antimicrobial peptides that are the main form of invertebrate systemic immunity called?

Question: What cell type is also used for immune response in most types of invertebrate life?

Question: What pathway that plays a role in immune response to viruses is present in all eukaryotes?


Context: Evolution of the adaptive immune system occurred in an ancestor of the jawed vertebrates. Many of the classical molecules of the adaptive immune system (e.g., immunoglobulins and T cell receptors) exist only in jawed vertebrates. However, a distinct lymphocyte-derived molecule has been discovered in primitive jawless vertebrates, such as the lamprey and hagfish. These animals possess a large array of molecules called Variable lymphocyte receptors (VLRs) that, like the antigen receptors of jawed vertebrates, are produced from only a small number (one or two) of genes. These molecules are believed to bind pathogenic antigens in a similar way to antibodies, and with the same degree of specificity.

Question: What molecules of the adaptive immune system only exist in jawed vertebrates?

Question: What are two examples of primitive jawless vertebrates?

Question: Primitive jawless vertebrates possess an array of receptors referred to as what?

Question: Evolution of what part of the immune system occurred in the evolutionary ancestor of jawed vertebrates?


Context: It is likely that a multicomponent, adaptive immune system arose with the first vertebrates, as invertebrates do not generate lymphocytes or an antibody-based humoral response. Many species, however, utilize mechanisms that appear to be precursors of these aspects of vertebrate immunity. Immune systems appear even in the structurally most simple forms of life, with bacteria using a unique defense mechanism, called the restriction modification system to protect themselves from viral pathogens, called bacteriophages. Prokaryotes also possess acquired immunity, through a system that uses CRISPR sequences to retain fragments of the genomes of phage that they have come into contact with in the past, which allows them to block virus replication through a form of RNA interference. Offensive elements of the immune systems are also present in unicellular eukaryotes, but studies of their roles in defense are few.

Question: Invertebrates do not generate what type of cells that are a part of the vertebrate adaptive immune system?

Question: What is the main defense mechanism of bacteria known as?

Question: The restriction modification system is used by bacteria for protection from what pathogens?

Question: What is the system by which prokaryotes retain phage gene fragments that they have previously come in contact with?


Context: Immunology is strongly experimental in everyday practice but is also characterized by an ongoing theoretical attitude. Many theories have been suggested in immunology from the end of the nineteenth century up to the present time. The end of the 19th century and the beginning of the 20th century saw a battle between "cellular" and "humoral" theories of immunity. According to the cellular theory of immunity, represented in particular by Elie Metchnikoff, it was cells – more precisely, phagocytes – that were responsible for immune responses. In contrast, the humoral theory of immunity, held, among others, by Robert Koch and Emil von Behring, stated that the active immune agents were soluble components (molecules) found in the organism’s “humors” rather than its cells.

Question: What were the two main theories of immunity at the end of the 19th century?

Question: Who was the main proponent of the cellular theory of immunity?

Question: Under Elie Metchnikoff's cellular theory, what cells were responsible for immune response?

Question: What two scientists were proponents of the humoral theory of immunity?

Question: According to the humoral theory of immunity, what were the bodies immune agents?


Context: Clearly, some tumors evade the immune system and go on to become cancers. Tumor cells often have a reduced number of MHC class I molecules on their surface, thus avoiding detection by killer T cells. Some tumor cells also release products that inhibit the immune response; for example by secreting the cytokine TGF-β, which suppresses the activity of macrophages and lymphocytes. In addition, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells.

Question: Tumors that are able to evade the body's immune response can become what?

Question: What receptors do tumor cells often have reduced concentrations of?

Question: What is a chemical secreted by tumors that suppresses the immune response?

Question: Cytokine TBF-B suppresses the activity of what cell types?


Context: Hypersensitivity is an immune response that damages the body's own tissues. They are divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction. Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by IgE, which triggers degranulation of mast cells and basophils when cross-linked by antigen. Type II hypersensitivity occurs when antibodies bind to antigens on the patient's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies. Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis (poison ivy). These reactions are mediated by T cells, monocytes, and macrophages.

Question: What is the name for a response of the immune system that damages the body's native tissues?

Question: How many classes of immune hypersensitivity are there?

Question: What type of hypersensitivity is associated with allergies?

Question: What is the chemical that mediates Type 1 hypersensitivity?

Question: Antibody-dependent hypersensitivity belongs to what class of hypersensitivity?


Context: An evasion strategy used by several pathogens to avoid the innate immune system is to hide within the cells of their host (also called intracellular pathogenesis). Here, a pathogen spends most of its life-cycle inside host cells, where it is shielded from direct contact with immune cells, antibodies and complement. Some examples of intracellular pathogens include viruses, the food poisoning bacterium Salmonella and the eukaryotic parasites that cause malaria (Plasmodium falciparum) and leishmaniasis (Leishmania spp.). Other bacteria, such as Mycobacterium tuberculosis, live inside a protective capsule that prevents lysis by complement. Many pathogens secrete compounds that diminish or misdirect the host's immune response. Some bacteria form biofilms to protect themselves from the cells and proteins of the immune system. Such biofilms are present in many successful infections, e.g., the chronic Pseudomonas aeruginosa and Burkholderia cenocepacia infections characteristic of cystic fibrosis. Other bacteria generate surface proteins that bind to antibodies, rendering them ineffective; examples include Streptococcus (protein G), Staphylococcus aureus (protein A), and Peptostreptococcus magnus (protein L).

Question: What is the process by which pathogens evade the immune system by hiding inside the host cells called?

Question: What food bacteria is an example of intracellular pathogenesis?

Question: What is the eukaryotic parasite responsible for malaria known as?

Question: What bacteria lives inside a protective capsule that serves to prevent cell lysis?

Question: What protein does Staphylococcus aureus produce to make antibodies ineffective?


Context: The mechanisms used to evade the adaptive immune system are more complicated. The simplest approach is to rapidly change non-essential epitopes (amino acids and/or sugars) on the surface of the pathogen, while keeping essential epitopes concealed. This is called antigenic variation. An example is HIV, which mutates rapidly, so the proteins on its viral envelope that are essential for entry into its host target cell are constantly changing. These frequent changes in antigens may explain the failures of vaccines directed at this virus. The parasite Trypanosoma brucei uses a similar strategy, constantly switching one type of surface protein for another, allowing it to stay one step ahead of the antibody response. Masking antigens with host molecules is another common strategy for avoiding detection by the immune system. In HIV, the envelope that covers the virion is formed from the outermost membrane of the host cell; such "self-cloaked" viruses make it difficult for the immune system to identify them as "non-self" structures.

Question: What is the process by which the adaptive immune system is evaded by the chainging of non-essential epitopes called?

Question: What is an example of a virus that uses antigenic variation?

Question: What is an example of a parasite that used the antigenic variation strategy to evade destruction?

Question: What compounds can be masked with the molecules of the host cell in order for a virus to evade detection?


Context: Another important role of the immune system is to identify and eliminate tumors. This is called immune surveillance. The transformed cells of tumors express antigens that are not found on normal cells. To the immune system, these antigens appear foreign, and their presence causes immune cells to attack the transformed tumor cells. The antigens expressed by tumors have several sources; some are derived from oncogenic viruses like human papillomavirus, which causes cervical cancer, while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells. One example is an enzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells (e.g. melanocytes) into tumors called melanomas. A third possible source of tumor antigens are proteins normally important for regulating cell growth and survival, that commonly mutate into cancer inducing molecules called oncogenes.

Question: What is the process by which the immune system identifies tumors called?

Question: What is the virus in humans that causes cervical cancer?

Question: What is an example of an enzyme that can transform skin cells into tumors when expressed at high levels?

Question: What are cancerous tumors of the skin known as?

Question: What are the skin cells that can be transformed into tumors known as?


Context: Larger drugs (>500 Da) can provoke a neutralizing immune response, particularly if the drugs are administered repeatedly, or in larger doses. This limits the effectiveness of drugs based on larger peptides and proteins (which are typically larger than 6000 Da). In some cases, the drug itself is not immunogenic, but may be co-administered with an immunogenic compound, as is sometimes the case for Taxol. Computational methods have been developed to predict the immunogenicity of peptides and proteins, which are particularly useful in designing therapeutic antibodies, assessing likely virulence of mutations in viral coat particles, and validation of proposed peptide-based drug treatments. Early techniques relied mainly on the observation that hydrophilic amino acids are overrepresented in epitope regions than hydrophobic amino acids; however, more recent developments rely on machine learning techniques using databases of existing known epitopes, usually on well-studied virus proteins, as a training set. A publicly accessible database has been established for the cataloguing of epitopes from pathogens known to be recognizable by B cells. The emerging field of bioinformatics-based studies of immunogenicity is referred to as immunoinformatics. Immunoproteomics is the study of large sets of proteins (proteomics) involved in the immune response.

Question: At what size and larger can drugs elicit a neutralizing immune response?

Question: What kind of amino acids are overrepresented in epitope regions?

Question: What is the study of proteins involved in immune response known as?

Question: There is a public database of epitopes for pathogens known to be recognizable by what cells?

Question: What is the field of studying immunogenicity through bioinformatics known as?


Context: In addition to the negative consequences of sleep deprivation, sleep and the intertwined circadian system have been shown to have strong regulatory effects on immunological functions affecting both the innate and the adaptive immunity. First, during the early slow-wave-sleep stage, a sudden drop in blood levels of cortisol, epinephrine, and norepinephrine induce increased blood levels of the hormones leptin, pituitary growth hormone, and prolactin. These signals induce a pro-inflammatory state through the production of the pro-inflammatory cytokines interleukin-1, interleukin-12, TNF-alpha and IFN-gamma. These cytokines then stimulate immune functions such as immune cells activation, proliferation, and differentiation. It is during this time that undifferentiated, or less differentiated, like naïve and central memory T cells, peak (i.e. during a time of a slowly evolving adaptive immune response). In addition to these effects, the milieu of hormones produced at this time (leptin, pituitary growth hormone, and prolactin) support the interactions between APCs and T-cells, a shift of the Th1/Th2 cytokine balance towards one that supports Th1, an increase in overall Th cell proliferation, and naïve T cell migration to lymph nodes. This milieu is also thought to support the formation of long-lasting immune memory through the initiation of Th1 immune responses.

Question: Drop in the blood levels of cortisol and epinephrine results in increase levels of what hormones?

Question: Hormones released during sleep support the interaction of T-cells and what species?

Question: Sleep hormones shift the cytokine balance to which cytokine?

Question: Sleep hormone release supports formation of immune memory by initiating what immune response?


Context: In humans, this response is activated by complement binding to antibodies that have attached to these microbes or the binding of complement proteins to carbohydrates on the surfaces of microbes. This recognition signal triggers a rapid killing response. The speed of the response is a result of signal amplification that occurs following sequential proteolytic activation of complement molecules, which are also proteases. After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other complement proteases, and so on. This produces a catalytic cascade that amplifies the initial signal by controlled positive feedback. The cascade results in the production of peptides that attract immune cells, increase vascular permeability, and opsonize (coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their plasma membrane.

Question: Complement proteins bind to what kind of molecules on the surface of microbes in order to elicit an immune response?

Question: How can the deposition of compliment kill invader cells directly?

Question: The speed of the killing response of the human immune system is a product of what process?

Question: What type of cascade results when complement proteins bind to microbes and activate their protease activity?


Context: Many of the same decisions and principles that apply in other criminal investigations and arrests arise also in civil disobedience cases. For example, the suspect may need to decide whether or not to grant a consent search of his property, and whether or not to talk to police officers. It is generally agreed within the legal community, and is often believed within the activist community, that a suspect's talking to criminal investigators can serve no useful purpose, and may be harmful. However, some civil disobedients have nonetheless found it hard to resist responding to investigators' questions, sometimes due to a lack of understanding of the legal ramifications, or due to a fear of seeming rude. Also, some civil disobedients seek to use the arrest as an opportunity to make an impression on the officers. Thoreau wrote, "My civil neighbor, the tax-gatherer, is the very man I have to deal with--for it is, after all, with men and not with parchment that I quarrel--and he has voluntarily chosen to be an agent of the government. How shall he ever know well that he is and does as an officer of the government, or as a man, until he is obliged to consider whether he will treat me, his neighbor, for whom he has respect, as a neighbor and well-disposed man, or as a maniac and disturber of the peace, and see if he can get over this obstruction to his neighborliness without a ruder and more impetuous thought or speech corresponding with his action."

Question: What type of government investigations apply to civil disobedience?

Question: What is a way you can show police officers civil disobedience ?

Question: What should be avoided when talking to authorities?

Question: What reasons cause failure of the disobedience with authorities?

Question: Why do some people purposely resist officers of the law?


Context: Some civil disobedients feel it is incumbent upon them to accept punishment because of their belief in the validity of the social contract, which is held to bind all to obey the laws that a government meeting certain standards of legitimacy has established, or else suffer the penalties set out in the law. Other civil disobedients who favor the existence of government still don't believe in the legitimacy of their particular government, or don't believe in the legitimacy of a particular law it has enacted. And still other civil disobedients, being anarchists, don't believe in the legitimacy of any government, and therefore see no need to accept punishment for a violation of criminal law that does not infringe the rights of others.

Question: What do some civil disobedient people feel the need to acknowledge.

Question: Why is the need for acceptance of punishment needed?

Question: What do some people protest against?

Question: What is the group called that does not agree with government at all?

Question: Anarchists do not want to accept punishment for what reason?


Context: An important decision for civil disobedients is whether or not to plead guilty. There is much debate on this point, as some believe that it is a civil disobedient's duty to submit to the punishment prescribed by law, while others believe that defending oneself in court will increase the possibility of changing the unjust law. It has also been argued that either choice is compatible with the spirit of civil disobedience. ACT-UP's Civil Disobedience Training handbook states that a civil disobedient who pleads guilty is essentially stating, "Yes, I committed the act of which you accuse me. I don't deny it; in fact, I am proud of it. I feel I did the right thing by violating this particular law; I am guilty as charged," but that pleading not guilty sends a message of, "Guilt implies wrong-doing. I feel I have done no wrong. I may have violated some specific laws, but I am guilty of doing no wrong. I therefore plead not guilty." A plea of no contest is sometimes regarded as a compromise between the two. One defendant accused of illegally protesting nuclear power, when asked to enter his plea, stated, "I plead for the beauty that surrounds us"; this is known as a "creative plea," and will usually be interpreted as a plea of not guilty.

Question: What is an important personal decision for civil disobedients?

Question: Which duty do some people believe civil disobedients have?

Question: Why would one plead guilty to a crime involving civil disobedience?

Question: Which reason is given sometimes to plead not guilty involving these matters?

Question: What third type of plea uses creative words?


Context: When the Committee for Non-Violent Action sponsored a protest in August 1957, at the Camp Mercury nuclear test site near Las Vegas, Nevada, 13 of the protesters attempted to enter the test site knowing that they faced arrest. At a pre-arranged announced time, one at a time they stepped across the "line" and were immediately arrested. They were put on a bus and taken to the Nye County seat of Tonopah, Nevada, and arraigned for trial before the local Justice of the Peace, that afternoon. A well known civil rights attorney, Francis Heisler, had volunteered to defend the arrested persons, advising them to plead "nolo contendere", as an alternative to pleading either guilty or not-guilty. The arrested persons were found "guilty," nevertheless, and given suspended sentences, conditional on their not reentering the test site grounds.[citation needed]

Question: Where in Las Vegas did a famous protest take place?

Question: What was the civil disobedience performed at the test site?

Question: What was the result of the disobedience protesting the nuclear site?

Question: How did their lawyer suggest they would plea?

Question: What type of sentences were the protesters given?


Context: Howard Zinn writes, "There may be many times when protesters choose to go to jail, as a way of continuing their protest, as a way of reminding their countrymen of injustice. But that is different than the notion that they must go to jail as part of a rule connected with civil disobedience. The key point is that the spirit of protest should be maintained all the way, whether it is done by remaining in jail, or by evading it. To accept jail penitently as an accession to 'the rules' is to switch suddenly to a spirit of subservience, to demean the seriousness of the protest...In particular, the neo-conservative insistence on a guilty plea should be eliminated."

Question: Why do some people chose to go to jail for their disobedience?

Question: Going to jail accomplished what goal of civil disobedience?

Question: What is the most important item for civil disobedience to follow through?

Question: Why should one not go to jail?


Context: Sometimes the prosecution proposes a plea bargain to civil disobedients, as in the case of the Camden 28, in which the defendants were offered an opportunity to plead guilty to one misdemeanor count and receive no jail time. In some mass arrest situations, the activists decide to use solidarity tactics to secure the same plea bargain for everyone. But some activists have opted to enter a blind plea, pleading guilty without any plea agreement in place. Mohandas Gandhi pleaded guilty and told the court, "I am here to . . . submit cheerfully to the highest penalty that can be inflicted upon me for what in law is a deliberate crime and what appears to me to be the highest duty of a citizen."

Question: What type of punishment is sometimes offered to civil disobedients?

Question: What is usually the goal of taking a plea bargain?

Question: When many people are arrested, what is a common tactic negotiating?

Question: What type of plea is sometimes taken as an act of disobedience?

Question: Which famous Indian took a plea and put himself at the mercy of the courts?


Context: Some civil disobedience defendants choose to make a defiant speech, or a speech explaining their actions, in allocution. In U.S. v. Burgos-Andujar, a defendant who was involved in a movement to stop military exercises by trespassing on U.S. Navy property argued to the court in allocution that "the ones who are violating the greater law are the members of the Navy". As a result, the judge increased her sentence from 40 to 60 days. This action was upheld because, according to the U.S. Court of Appeals for the First Circuit, her statement suggested a lack of remorse, an attempt to avoid responsibility for her actions, and even a likelihood of repeating her illegal actions. Some of the other allocution speeches given by the protesters complained about mistreatment from government officials.

Question: What way do some people perform civil disobedience in a constructive way?

Question: Why would one want to give a speech?

Question: Why is giving a defiant speech sometimes more harmful for the individual?

Question: Why would one want to give more punishment?

Question: What type of treatment do civil disobedients usually receive?


Context: Steven Barkan writes that if defendants plead not guilty, "they must decide whether their primary goal will be to win an acquittal and avoid imprisonment or a fine, or to use the proceedings as a forum to inform the jury and the public of the political circumstances surrounding the case and their reasons for breaking the law via civil disobedience." A technical defense may enhance the chances for acquittal but make for more boring proceedings and reduced press coverage. During the Vietnam War era, the Chicago Eight used a political defense, while Benjamin Spock used a technical defense. In countries such as the United States whose laws guarantee the right to a jury trial but do not excuse lawbreaking for political purposes, some civil disobedients seek jury nullification. Over the years, this has been made more difficult by court decisions such as Sparf v. United States, which held that the judge need not inform jurors of their nullification prerogative, and United States v. Dougherty, which held that the judge need not allow defendants to openly seek jury nullification.

Question: What is the primary goal of pleading not guilty when arrested for Civil Disobedience?

Question: What is a secondary goal of pleading not guilty?

Question: What would someone who is civilly disobedient do in court?

Question: What US war has a large amount of Civil Disobedients?

Question: What can sympathetic Jurors in cases with civil disobedients?


Context: One theory is that, while disobedience may be helpful, any great amount of it would undermine the law by encouraging general disobedience which is neither conscientious nor of social benefit. Therefore, conscientious lawbreakers must be punished. Michael Bayles argues that if a person violates a law in order to create a test case as to the constitutionality of a law, and then wins his case, then that act did not constitute civil disobedience. It has also been argued that breaking the law for self-gratification, as in the case of a homosexual or cannabis user who does not direct his act at securing the repeal of amendment of the law, is not civil disobedience. Likewise, a protestor who attempts to escape punishment by committing the crime covertly and avoiding attribution, or by denying having committed the crime, or by fleeing the jurisdiction, is generally viewed as not being a civil disobedient.

Question: What needs to be avoided with civil disobedience?

Question: Why should disobedience by the general public be avoided?

Question: What is one main reason that civil disobedience is not recognized?

Question: Why should someone not commit a crime when they are protesting?

Question: For what reason would someone avoid crimes while protesting?


Context: Courts have distinguished between two types of civil disobedience: "Indirect civil disobedience involves violating a law which is not, itself, the object of protest, whereas direct civil disobedience involves protesting the existence of a particular law by breaking that law." During the Vietnam War, courts typically refused to excuse the perpetrators of illegal protests from punishment on the basis of their challenging the legality of the Vietnam War; the courts ruled it was a political question. The necessity defense has sometimes been used as a shadow defense by civil disobedients to deny guilt without denouncing their politically motivated acts, and to present their political beliefs in the courtroom. However, court cases such as U.S. v. Schoon have greatly curtailed the availability of the political necessity defense. Likewise, when Carter Wentworth was charged for his role in the Clamshell Alliance's 1977 illegal occupation of the Seabrook Station Nuclear Power Plant, the judge instructed the jury to disregard his competing harms defense, and he was found guilty. Fully Informed Jury Association activists have sometimes handed out educational leaflets inside courthouses despite admonitions not to; according to FIJA, many of them have escaped prosecution because "prosecutors have reasoned (correctly) that if they arrest fully informed jury leafleters, the leaflets will have to be given to the leafleter's own jury as evidence."

Question: What is violating a law which is not the goal of the protest called?

Question: When the law is a direct target of the protest, what is this called?

Question: What US war caused a high amount of civil disobedience?

Question: What type of defense is sometimes used in court by protestors?

Question: Why are people who distribute leaflets inside courthouses not been arrested?


Context: Along with giving the offender his "just deserts", achieving crime control via incapacitation and deterrence is a major goal of criminal punishment. Brownlee argues, "Bringing in deterrence at the level of justification detracts from the law’s engagement in a moral dialogue with the offender as a rational person because it focuses attention on the threat of punishment and not the moral reasons to follow this law." Leonard Hubert Hoffmann writes, "In deciding whether or not to impose punishment, the most important consideration would be whether it would do more harm than good. This means that the objector has no right not to be punished. It is a matter for the state (including the judges) to decide on utilitarian grounds whether to do so or not."

Question: What is the main goal of criminal punishment of civil disobedients?

Question: What should be the main goal of not using punishment in a just system?

Question: Who decides the fate of protesters most of the time?

Question: What should the punishment rely on instead in a just society?


Context: Construction is the process of constructing a building or infrastructure. Construction differs from manufacturing in that manufacturing typically involves mass production of similar items without a designated purchaser, while construction typically takes place on location for a known client. Construction as an industry comprises six to nine percent of the gross domestic product of developed countries. Construction starts with planning,[citation needed] design, and financing and continues until the project is built and ready for use.

Question: What is the process of constructing a building or infrastructure?

Question: What typically involves mass production of similar items without a designated purchaser?

Question: What percentile of gross domestic product is construction comprised of?

Question: What three things are needed for construction to take place?

Question: Construction takes place on location for who?


Context: Large-scale construction requires collaboration across multiple disciplines. An architect normally manages the job, and a construction manager, design engineer, construction engineer or project manager supervises it. For the successful execution of a project, effective planning is essential. Those involved with the design and execution of the infrastructure in question must consider zoning requirements, the environmental impact of the job, the successful scheduling, budgeting, construction-site safety, availability and transportation of building materials, logistics, inconvenience to the public caused by construction delays and bidding, etc. The largest construction projects are referred to as megaprojects.

Question: Who normally manages a construction job?

Question: Who normally supervises a construction job?

Question: What is essential for the successful execution of a project?

Question: The largest construction projects are known as what?

Question: Zoning requirements, environmental impact, budgeting, and logistics are things who should consider?


Context: In general, there are three sectors of construction: buildings, infrastructure and industrial. Building construction is usually further divided into residential and non-residential (commercial/institutional). Infrastructure is often called heavy/highway, heavy civil or heavy engineering. It includes large public works, dams, bridges, highways, water/wastewater and utility distribution. Industrial includes refineries, process chemical, power generation, mills and manufacturing plants. There are other ways to break the industry into sectors or markets.

Question: What are the three sectors of construction?

Question: Building construction is usually further divided into what categories?

Question: Infrastructure is often called what?

Question: Large public works, dams, bridges, highways, water/wastewater and utility distribution are under what construction sector?

Question: Refineries, process chemical, power generation, mills and manufacturing plants are under what sector of construction?


Context: Engineering News-Record (ENR) is a trade magazine for the construction industry. Each year, ENR compiles and reports on data about the size of design and construction companies. They publish a list of the largest companies in the United States (Top-40) and also a list the largest global firms (Top-250, by amount of work they are doing outside their home country). In 2014, ENR compiled the data in nine market segments. It was divided as transportation, petroleum, buildings, power, industrial, water, manufacturing, sewer/waste, telecom, hazardous waste plus a tenth category for other projects. In their reporting on the Top 400, they used data on transportation, sewer, hazardous waste and water to rank firms as heavy contractors.

Question: What is Engineering News-Record?

Question: What compiles and reports on data about the size of design and construction companies?

Question: In what year did ENR compile data in nine market segments?

Question: ENR used data on what to rank Top 400 firms as heavy contractors?


Context: The Standard Industrial Classification and the newer North American Industry Classification System have a classification system for companies that perform or otherwise engage in construction. To recognize the differences of companies in this sector, it is divided into three subsectors: building construction, heavy and civil engineering construction, and specialty trade contractors. There are also categories for construction service firms (e.g., engineering, architecture) and construction managers (firms engaged in managing construction projects without assuming direct financial responsibility for completion of the construction project).

Question: What are the three construction subsectors?

Question: There are other categories for what?

Question: What has a classification system for construction companies?

Question: What are construction managers?


Context: Building construction is the process of adding structure to real property or construction of buildings. The majority of building construction jobs are small renovations, such as addition of a room, or renovation of a bathroom. Often, the owner of the property acts as laborer, paymaster, and design team for the entire project. Although building construction projects typically include various common elements, such as design, financial, estimating and legal considerations, many projects of varying sizes reach undesirable end results, such as structural collapse, cost overruns, and/or litigation. For this reason, those with experience in the field make detailed plans and maintain careful oversight during the project to ensure a positive outcome.

Question: What is the process of adding structure to real property or construction of buildings?

Question: The majority of building construction jobs are what?

Question: Who acts as laborer, paymaster, and design team for a renovation project?

Question: What are some examples of undesirable end results of a project?

Question: What do those in the field do to ensure a positive outcome?


Context: Residential construction practices, technologies, and resources must conform to local building authority regulations and codes of practice. Materials readily available in the area generally dictate the construction materials used (e.g. brick versus stone, versus timber). Cost of construction on a per square meter (or per square foot) basis for houses can vary dramatically based on site conditions, local regulations, economies of scale (custom designed homes are often more expensive to build) and the availability of skilled tradespeople. As residential construction (as well as all other types of construction) can generate a lot of waste, careful planning again is needed here.

Question: Residential construction practices, technologies, and resources must conform to what?

Question: What generally dictates the construction materials used?

Question: Residential construction can generate what is not carefully planned?

Question: Site conditions, local regulations, economies of scale and the availability of skilled tradespeople all affect what?


Context: New techniques of building construction are being researched, made possible by advances in 3D printing technology. In a form of additive building construction, similar to the additive manufacturing techniques for manufactured parts, building printing is making it possible to flexibly construct small commercial buildings and private habitations in around 20 hours, with built-in plumbing and electrical facilities, in one continuous build, using large 3D printers. Working versions of 3D-printing building technology are already printing 2 metres (6 ft 7 in) of building material per hour as of January 2013[update], with the next-generation printers capable of 3.5 metres (11 ft) per hour, sufficient to complete a building in a week. Dutch architect Janjaap Ruijssenaars's performative architecture 3D-printed building is scheduled to be built in 2014.

Question: New techniques of building construction are being researched, made possible by advances in what?

Question: Building printing is making it possible to flexibly construct small commercial buildings and private habitations in what amount of time?

Question: Dutch architect Janjaap Ruijssenaars's performative architecture 3D-printed building is scheduled to be built when?

Question: Working versions of 3D-printing building technology are already printing how much building material per hour?


Context: In the modern industrialized world, construction usually involves the translation of designs into reality. A formal design team may be assembled to plan the physical proceedings, and to integrate those proceedings with the other parts. The design usually consists of drawings and specifications, usually prepared by a design team including Architect, civil engineers, mechanical engineers, electrical engineers, structural engineers, fire protection engineers, planning consultants, architectural consultants, and archaeological consultants. The design team is most commonly employed by (i.e. in contract with) the property owner. Under this system, once the design is completed by the design team, a number of construction companies or construction management companies may then be asked to make a bid for the work, either based directly on the design, or on the basis of drawings and a bill of quantities provided by a quantity surveyor. Following evaluation of bids, the owner typically awards a contract to the most cost efficient bidder.

Question: A formal design team may be assembled to do what?

Question: Construction involves the translation of what?

Question: The design team is most commonly employed by who?

Question: Who provides the bill of quantities?

Question: The owner typically awards a contract to who?


Context: The modern trend in design is toward integration of previously separated specialties, especially among large firms. In the past, architects, interior designers, engineers, developers, construction managers, and general contractors were more likely to be entirely separate companies, even in the larger firms. Presently, a firm that is nominally an "architecture" or "construction management" firm may have experts from all related fields as employees, or to have an associated company that provides each necessary skill. Thus, each such firm may offer itself as "one-stop shopping" for a construction project, from beginning to end. This is designated as a "design build" contract where the contractor is given a performance specification and must undertake the project from design to construction, while adhering to the performance specifications.

Question: The modern trend in design is toward integration of what?

Question: Even in large firms, architects, interior designers, engineers, developers, construction managers, and general contractors were more likely to be what?

Question: In modern times, firms may offer themselves as what for a construction project?

Question: What kind of contract is given when the contractor is given a performance specification and must undertake the project from design to construction, while adhering to the performance specifications?


Context: Several project structures can assist the owner in this integration, including design-build, partnering and construction management. In general, each of these project structures allows the owner to integrate the services of architects, interior designers, engineers and constructors throughout design and construction. In response, many companies are growing beyond traditional offerings of design or construction services alone and are placing more emphasis on establishing relationships with other necessary participants through the design-build process.

Question: What project structures assist the owner in integration?

Question: These project structures allow the owner to integrate the services of who throughout the design and construction?

Question: Many construction companies are now placing more emphasis on what?


Context: Construction projects can suffer from preventable financial problems. Underbids happen when builders ask for too little money to complete the project. Cash flow problems exist when the present amount of funding cannot cover the current costs for labour and materials, and because they are a matter of having sufficient funds at a specific time, can arise even when the overall total is enough. Fraud is a problem in many fields, but is notoriously prevalent in the construction field. Financial planning for the project is intended to ensure that a solid plan with adequate safeguards and contingency plans are in place before the project is started and is required to ensure that the plan is properly executed over the life of the project.

Question: What can construction projects suffer from?

Question: What is an underbid?

Question: When do cash flow problems exist?

Question: What financial issue is notoriously prevalent in the construction field?


Context: Mortgage bankers, accountants, and cost engineers are likely participants in creating an overall plan for the financial management of the building construction project. The presence of the mortgage banker is highly likely, even in relatively small projects since the owner's equity in the property is the most obvious source of funding for a building project. Accountants act to study the expected monetary flow over the life of the project and to monitor the payouts throughout the process. Cost engineers and estimators apply expertise to relate the work and materials involved to a proper valuation. Cost overruns with government projects have occurred when the contractor identified change orders or project changes that increased costs, which are not subject to competition from other firms as they have already been eliminated from consideration after the initial bid.

Question: Who are likely participants in creating an overall plan for the financial management of the building construction project?

Question: The presence of who is highly likely even in small projects?

Question: Who studies the expected monetary flow over the life of the project and to monitor the payouts throughout the process?

Question: Cost overruns with government projects have occurred when the contractor did what?

Question: Who applies expertise to relate the work and materials involved to a proper valuation?


Context: The project must adhere to zoning and building code requirements. Constructing a project that fails to adhere to codes does not benefit the owner. Some legal requirements come from malum in se considerations, or the desire to prevent things that are indisputably bad – bridge collapses or explosions. Other legal requirements come from malum prohibitum considerations, or things that are a matter of custom or expectation, such as isolating businesses to a business district and residences to a residential district. An attorney may seek changes or exemptions in the law that governs the land where the building will be built, either by arguing that a rule is inapplicable (the bridge design will not cause a collapse), or that the custom is no longer needed (acceptance of live-work spaces has grown in the community).

Question: What must a project adhere to?

Question: Constructing a project that fails to adhere to codes does not benefit whom?

Question: What is malum in se considerations?

Question: What are malum prohibitum considerations?

Question: Who may seek changes or exemptions in the law that governs the land where the building will be built?


Context: A construction project is a complex net of contracts and other legal obligations, each of which all parties must carefully consider. A contract is the exchange of a set of obligations between two or more parties, but it is not so simple a matter as trying to get the other side to agree to as much as possible in exchange for as little as possible. The time element in construction means that a delay costs money, and in cases of bottlenecks, the delay can be extremely expensive. Thus, the contracts must be designed to ensure that each side is capable of performing the obligations set out. Contracts that set out clear expectations and clear paths to accomplishing those expectations are far more likely to result in the project flowing smoothly, whereas poorly drafted contracts lead to confusion and collapse.

Question: What is a complex net of contracts and other legal obligations?

Question: What is the exchange of a set of obligations between two or more parties?

Question: What does the time element in construction mean?

Question: Contracts must be designed to ensure what?

Question: What leads to confusion and collapse?


Context: There is also a growing number of new forms of procurement that involve relationship contracting where the emphasis is on a co-operative relationship between the principal and contractor and other stakeholders within a construction project. New forms include partnering such as Public-Private Partnering (PPPs) aka private finance initiatives (PFIs) and alliances such as "pure" or "project" alliances and "impure" or "strategic" alliances. The focus on co-operation is to ameliorate the many problems that arise from the often highly competitive and adversarial practices within the construction industry.

Question: A growing number of new forms of procurement involves what?

Question: What is PPP?

Question: What is a PPP also known as?

Question: Focus on what is to ameliorate the many problems that arise from the often highly competitive and adversarial practices within the construction industry.