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Infection and
Immunity Part 2
Adaptive Immunity to Infection
Mucosal Immunity
Immune Memory
Regulation of Immune Responses
For convenience sake in explaining how the immune system works, we divide immune responses into innate and adaptive, cellular and humoral. However, all components of the immune system must work together to eliminate pathogen and provide protective immunity against future infection.
Infection begins with pathogen attachment to epithelial surfaces of the body and penetration through those surfaces. (see Infectious Disease). Species and tissue-specificity of many pathogens is due in some measure to the availability of adherence molecules for the pathogen on host tissues. Some microbes never enter the body but damage it by secretion of exotoxins. Once microbes have entered, they create a local infection to which the innate immune system responds. Local infection may cause few or minimal symptoms and may be eliminated by innate immunity before the adaptive system is involved. Interaction of macrophages and NK cells with pathogen results in secretion of inflammatory chemokines and cytokines and in complement activation.
If these measures do not eliminate pathogen, it is carried by lymph, macrophages and dendritic cells through lymphatic vessels into local (draining) lymph nodes to activate lymphocytes and initiate adaptive immunity. Effector Th2 cells activate specific B cells in the local lymphoid tissue to proliferate and secrete antibody. Antibody and effector Th1 and CTL migrate to the infection site to eliminate antigen there. Antibody neutralizes toxins and opsonizes antigen to promote phagocytosis. Th2 cells activate macrophages to more efficiently kill phagocytosed pathogen, especially those that naturally resist destruction in the phagolysosome. CTL eliminate cytoplasmic antigen by killing infected host cells. Note that along with adaptive immunity, phagocytes, complement and NK cells continue to participate in pathogen elimination. Macrophages also function in healing damaged tissues once the infection has been eliminated. Memory cells have been generated in the process that can respond more quickly and in greater numbers to a repeat infection by the same pathogen.
Some pathogens are not completely eliminated even though disease symptoms disappear. Mycobacteria can persist in macrophages and Herpes viruses in nerve ganglia, kept in check by cellular immunity but able to cause disease if that immunity weakens. Some pathogens target the immune system directly; HIV eliminates CD4 T cells at such a rate that the body eventually cannot maintain sufficient numbers to protect even against normally nonpathogenic organisms (see Microbe Evasion of Immune Responses).
Adaptive Immunity to Infection
Innate immune responses not only precede adaptive responses, they must do so to initiate adaptive immunity. Pathogen activation of macrophage chemokine and cytokine secretion activates vascular endothelial cells, attracts other leukocytes to the infection site to contain the infection, and stimulates acute phase protein synthesis by the liver. Acute phase LPS-binding protein (LPB) binds LPS and cell surface CD14 to activate tissue dendritic cell migration to draining lymph nodes and differentiation into mature antigen-presenting DC.
Circulating T and B cells use L-selectin to adhere loosely to lymph node HEV addressins and LFA-1 to bind vascular ICAM-1. Once tightly bound, lymphocytes crawl between endothelial cells and penetrate the basement membrane with proteases to enter the lymph nodes. T cells sample peptides on dendritic cell MHC; if they bind their specific peptide, they adhere tightly to the APC while they receive co-stimulatory signals and proliferate. Experiments have shown that within 48 hours of antigen stimulation, all T cells specific for that antigen are retained in the draining lymph node. By day five following antigen stimulation, effector T cells leave the lymph nodes in large numbers and travel to the infection site.
Early cytokine contact and the nature of the antigen signal influence differentiation of Th0 cells into either Th1 or Th2 effectors. Viruses and some bacteria induce dendritic cells to secrete IL-12, which activates NK cells to secrete IFNg. IFNg signals Th0 cells to become Th1 cells and secrete IL-2, TNFb, and more IFNg and to activate macrophages. IFNg also inhibits proliferation of Th2 cells. Cytotoxic T cells can secrete Th1 or Th2 cytokines to influence the immune response (these cells are sometimes called Tc1 or Tc2 cells).
Other pathogens, including helminths, do not activate dendritic cells to make IL-12 but instead activate a special subset of T cells, NK1.1+ T cells (so named because they bear a membrane marker usually restricted to NK cells). NK1.1+ T cells have very non-diverse ab TCR which bind CD1, Class I-like MHC molecules. Some CD1 molecules present glycolipids; the nature of the antigen bound by NK1.1+ T cells is unknown. CD1 expression is induced on professional APC and intestinal epithelial cells by infection. NK1.1+ T cells secrete large amounts of IL-4, which signals Th0 cells to become Th2 cells and secrete IL-4, IL-5, IL-6, IL-10, and IL-13 to activate B cells. IL-10 inhibits Th1 cell activation and proliferation.
The avidity of the antigen signal also appears to influence Th0 differentiation. Peptides presented at high density on APC surfaces generate Th1 responses, while peptides at low density generate Th2 responses. This may be especially important for allergens, which usually enter the body in low concentrations through mucus membranes and induce IL-4 production and isotype switching to IgE (see Too Much of a Good Thing: Allergy and Hypersensitivity).
Armed effector Th1 cells and CTL leave the secondary lymphoid organs for the infection site. Membrane L-selectin has been replaced by VLA-4, which allows the effectors to enter the tissues. Not all pathogens trigger inflammation and vascular endothelium activation; however, effector T cells appear able to enter all tissues to some extent. If they bind specific antigen there, effector T cells activate the vascular endothelium themselves with TNFa and secrete the chemokine RANTES to activate T cell adhesion molecules. Upregulation of vascular adhesion molecules increases recruitment of more effector T cells to the infection site.
B cells are activated by Th2 cells in the T cell areas of the lymph nodes. By five days following antigen contact, small primary foci of dividing B cells can be seen. Some of these B cells migrate to the medullary cords, where they divide for 2-3 days, differentiate into plasma cells, and secrete antibody for an additional 2-3 days before undergoing apoptosis. About 10% of these early plasma cells live longer. This early antibody synthesis allows for antigen capture on follicular dendritic cells.
Most of the activated B cells, with their specific Th2 cells, migrate to the follicles and form germinal centers of rapidly proliferating B cells. Here B cells undergo somatic mutation and must successfully bind antigen on FDC to survive. B cells also switch antibody isotypes in response to T cell cytokines. B cells leave the germinal centers as plasmablasts (pre-plasma cells). B cells from the lymph nodes and spleen go to the bone marrow to become plasma cells, while B cells from the MALT migrate to epithelial surfaces to secrete antibody. Most of these plasma cells live for months to years, secreting antibody that can protect from repeat infection. Studies with non-replicating antigen indicate that germinal centers last for 3-4 weeks following antigen injection, but a small number of proliferating B cells remain in the germinal centers for months.
As antigen is eliminated, most effector cells die and are removed by macrophages. Protective immunity depends on both long-lived antibody and effector cells and on memory cells that can be activated to become effector cells. Immunity is protective if it prevents or lessens symptoms on re-infection. What kind of immunity is protective depends on the pathogen. Neutralizing IgA can block pathogen adherence to mucosal membranes, while neutralizing IgG blocks toxin action and virus infection of internal host cells. Opsonizing IgG (with complement) promotes phagocytosis of extracellular pathogens. Memory Tc or Th1 cells can be rapidly activated to deal with intracellular pathogens.
The immune system is distributed throughout the body but is divided into four distinct compartments: tissues and blood, mucosal tissues, body cavities, and the skin. An immune response made to pathogens in one of these compartments tends to be confined to that compartment, and lymphocytes within a compartment recirculate into that compartment because of their homing molecules and compartment-specific vascular addressins. Because it is easiest to study experimentally, most is known about the tissue and blood compartment and its lymphoid tissues the spleen and peripheral lymph nodes. More research is increasing our knowledge of the largest compartment, the MALT.
Mucosal surfaces are designed for exchange of gasses (lungs), nutrients (digestive tract), sensory functions (eyes, nose, mouth and throat), and reproductive signals (vagina and uterus), so they are more vulnerable to infection than other body surfaces. The digestive tract in particular is home to about 1014 commensal organisms and regularly encounters pathogens. An additional challenge for the gut-associated lymphoid system is that ideally food antigens should be ignored while pathogen antigens should induce vigorous immune responses.
Gut-associated lymphoid tissues include the tonsils and adenoids at the back of the throat, the Peyers Patches of the small intestine, the appendix, isolated lymphoid follicles of the large intestine and rectum, and small foci of lymphocytes and plasma cells in the lamina propria of the gut wall. Consider the anatomy of the small intestine as a model for mucosal immune tissue. The lumen of the intestine ("outside" or food side) is lined with epithelial cells (enterocytes) whose luminal surface is folded into microvilli to maximize surface area for nutrient absorption. Enterocytes are interrupted by smoother M cells which overlay the Peyers Patches, large B cell follicles with adjacent T cell areas surrounding a germinal center. M cells take up antigen by endocytosis or phagocytosis and transport it in vesicles across their cytoplasm (transcytosis) to release it to the underlying lymphocytes and APC in the Peyers Patches. Mucus-secreting cells and ducts delivering digestive enzymes are also present between enterocytes. The whole epithelial layer is folded into villi separated by crypts. Under the epithelial layer is a thin basement membrane, connective tissue (lamina propria) and submucosal layers containing blood vessels, and a muscular layer for peristalsis.
Naïve lymphocytes from the bone marrow migrate to the MALT and recirculate between the MALT and blood circulation, using the vascular addressin MAdCAM-1 to reenter mucosal lymphoid tissue. Antigen from the intestine activates B and T cells in the Peyers Patches in the same way those cells are activated in the peripheral lymph nodes. Effector T cells and plasma cells then migrate through the lymphatics draining the intestines via the mesenteric lymph nodes and the thoracic duct into the blood circulation. Once in the blood, effector cells can reenter the MALT using MAdCAM-1 in lymphoid tissues of the intestinal lamina propria, respiratory and reproductive mucosa, and lactating breast tissue. This means that an immune response at any point in the MALT is spread throughout the MALT for more widespread protection.
In addition to the many conventional CD4 or CD8 ab TCR+ T cells in the MALT, the intestinal epithelium is also home to relatively high numbers of gd T cells. gd T cells are not educated in the thymus and have little diversity in their TCR V regions. A subset of T cells expressing the Vd1 gene segment has the C type lectin NK cell receptor NKG2D, which binds MHC-like molecules MIC-A and MIC-B. MIC-A and MIC-B are expressed on infected or otherwise damaged enterocytes, which can then be killed by the NKG2D+ gd T cells.
Some Vd1 T cells bind Class I MHC-like molecule CD1c, present on activated monocytes and dendritic cells, that presents endogenous lipid and glycolipid antigens. Antigen binding stimulates the T cells to secrete IFNg, which may stimulate Th1 responses from mucosal ab T cells.
MALT plasma cells secrete primarily dimeric IgA in an IgA1:IgA2 ratio of 3:2. (IgA secreted in the tissue and blood compartment is primarily monomeric IgA in an IgA1:IgA2 ratio of 4:1). IgA2 is more resistant to proteolysis by pathogens than IgA1. IgA from the plasma cells binds the poly Ig receptor on epithelial cells at the base of the intestinal crypts, is transported across the cells by transcytosis, and is secreted into the intestinal lumen with the secretory piece attached. Secretory IgA attaches to the mucus overlying the enterocytes, where it can neutralize pathogens or their toxins.
Food antigens usually induce immune tolerance. Although lymphocytes are not negatively selected for binding food antigens in the primary lymphoid organs, no high affinity antibodies to food antigens are detected. Oral feeding can induce oral tolerance to antigens that are immunogenic if injected. For example, ovalbumin (egg albumin) is quite immunogenic if injected into mice. If mice are first fed ovalbumin and then injected, no response to ovalbumin can be detected.
Each of us has over 400 species of normal intestinal microorganisms, totaling over a kilogram in weight. These organisms compete with pathogens for attachment space and nutrients; they also supply us with vitamins K and B12. Elimination of normal flora by prolonged antibiotic treatment allows pathogens such as Clostridium difficile to colonize intestinal surfaces and damage the intestine with its toxins, resulting in bloody diarrhea. Although usually not pathogenic, normal flora cause disease if they get past the intestinal epithelium or in immunodeficient people, indicating that normal immune function is important in controlling normal flora without eliminating them. Germ free (gnotobiotic) mice have greatly reduced secondary lymphoid tissues and serum antibody levels.
Common intestinal pathogens include bacteria (Listeria, Salmonella, Shigella, Yersinia), viruses (polio, Norwalk, and adenovirus), and parasites (Entamoeba histolytica, Cryptosporidium and Giardia). Some pathogens infect enterocytes, which secrete chemokines to attract monocytes, eosinophils and T cells. Infected enterocytes also express MIC-A and MIC-B, allowing them to be recognized and killed by gd T cells. Some pathogens infect M cells, using them as a direct path into the Peyers Patches. There many of them are eliminated, but if some escape they spread to other tissues. Polio virus uses M cells as a path into mucosal nervous tissue and from there to the central nervous system. HIV may use M cells to infect macrophages in the rectum.
Helicobacter pylori infects the stomach, living protected from stomach acid under the mucus layer. In about 5% of infected people, H. pylori-induced inflammation either stimulates acid production to induce peptic ulcers or suppresses acid production and leads to stomach carcinoma (cancer).
Both food antigens and pathogen antigens are presented to T cells. The difference between responses to pathogen antigen and tolerance to food antigen is due to the inflammation stimulated by the former. T cells are believed to respond in three ways to intestinal antigen. High doses of oral antigen induce clonal deletion (apoptosis) of specific T cells; this probably does not occur to any great extent with physiological doses of food antigens. If food antigens are presented on APC which do not have co-stimulatory molecules, T cell anergy may result. Finally, food antigens may stimulate regulatory T cells which suppress immune responses. Regulatory T cells which produce IL-4, IL-10, and TGFb (Th3 cells) have been described that are associated with low levels of antibody production and inhibition of Th1 responses.
Immune memory refers to the ability of the immune system to respond more quickly and effectively to a second antigen exposure. Memory responses are what provide protective immunity following vaccination.
The kinetics of primary and secondary immune responses are different. The primary antibody response to a protein antigen is largely IgM, becoming detectable in serum 5-7 days after injection of antigen and dropping off after about 2 weeks. IgG may be produced late in the primary response. Primary and secondary responses may be merged when the antigen is a replicating pathogen that persists in the body. More antibody is produced during a secondary response, it is produced faster (peak at 7 days instead of 12-14), and after the first few days almost all the antibody produced is IgG, IgA, or IgE.
Early in a secondary immune response, antibody from a previous response may be present and can bind antigen. Immune complexes enter the secondary lymphoid tissues containing memory T and B cells. FDC bind immune complexes with their FcR and complement receptors; B cells seeing antigen on FDC membranes are activated more quickly. T cells near the germinal centers are activated by and provide help to nearby antigen-presenting B cells. Because of their increased frequency and antigen-presenting specificity, B cells are very efficient APC in secondary responses.
The study of memory B and T cells is an area of active research. Studies of isolated populations indicate that memory persists in the absence of repeated antigen exposure. A single dose of protein antigen given to a mouse, followed by adoptive transfer (see Designer Mice) of cells from that mouse to naïve animals and immunization with the same antigen, demonstrate that memory helper T cells are present in the immunized animal by 5 days following original antigen exposure. Memory B cells appear a few days later and reach their peak by about 30 days. Both memory B and T cells persist for the lifetime of the mouse. Frequencies of both antigen-specific B and T cells increase by 100-1,000 fold following immunization. Memory cells are more sensitive to antigen than are naïve cells.
The presence of memory T and B cells appears to suppress activation of naïve T and B cells. This is illustrated by the observation of original antigenic sin in responses to influenza virus. Influenza virus continually undergoes antigenic drift that results in different hemagglutinin (HA) and neuraminidase (N) serotypes from year to year. A small child responding for the first time to influenza virus makes antibodies specific for all immunodominant epitopes on HA and N of that virus. When exposed to another influenza virus in the future, that child now responds only to the HA and N epitopes shared between the new serotype and the original serotype; new unshared epitopes are ignored by the immune system. This phenomenon continues for the person's lifetime. Only when encountering an influenza virus having no shared epitopes with the original virus will naïve cells be stimulated to respond to HA and N.
One of the challenges in studying memory cells has been differentiating between naïve, effector, and memory cells. It has been easier with B cells because memory cells have switched Ig isotype and undergone somatic mutation and affinity maturation, while naïve cells have not. Effector B cells are plasma cells which are quite distinct from naïve or memory cells even under the light microscope.
T cells do not undergo isotype switching or somatic mutation. Effector and memory cells have similar membrane marker phenotypes: less L-selectin and CD45RA that naïve cells, more VLA-4, LFA-1, LFA-3, CD2, and CD45RO. CD45 is a transmembrane tyrosine phosphatase that is present on all hematopoietic cells and is also called Leukocyte Common Antigen (LCA), B220, and T200. It is important for signal transduction. The gene for CD45 is composed of seven exons which can be translated into different isoforms of the protein. Naïve cells express CD45RA, translated from all seven exons with exons A, B, and C encoding a domain external to the plasma membrane. CD45RA does not associate with the TCR-CD3 complex or with CD4. CD45RA, expressed by effector and memory cells, is a smaller isoform translated from alternatively spliced mRNA which does not have exons A, B and C. CD45RA associates well with the TCR and co-receptor complexes and provides more efficient signal transduction.
Effector CTL can be distinguished from resting Tc cells by their cytoplasmic granules and ability to rapidly (within 5 minutes) program target cells for apoptosis. However, effector CD4 cells can only be distinguished by their ability to secrete cytokine or divide in response to presented antigen, and assays for these functions take several days for both effectors and resting memory cells. New flow cytometry assays for intracellular cytokines are improving our ability to differentiate between effector and resting CD4 T cells.
Regulation of Immune Responses
The basis of a functional immune system is genetic: the ability to make mature lymphocytes and accessory cells bearing the required antigen-specific receptors, co-receptors, MHC, and co-stimulatory molecules. Functional genes for complement, inflammatory mediators, and cytokines are also required. Environment is important: nutrition, the presence of chronic disease, and life style all affect immune responsiveness. As we age, our immune systems work less efficiently: thymus atrophy results in fewer circulating and functional T cells, primary (but not memory) immune responses become weaker, and older people suffer from more infections, cancer, hypersensitivity, and autoimmunity.
Immune responses are regulated by antigen, antibody, cytokines, and hormones. Some common bacterial antigens activate complement and stimulate macrophages to express co-stimulatory molecules. Antigen stimulates adaptive immune responsiveness by activating lymphocytes, which in turn make antibody to activate complement and cytokines to increase antigen elimination and recruit additional leukocytes. As antigen is eliminated, activation ceases; high affinity B cells are selected by low antigen concentrations. Antigen is also a negative regulator of immune responsiveness: when antigen binds immature cells or binds without co-stimulatory signal, the lymphocytes are killed (clonal deletion) or inactivated (clonal anergy).
Secreted antibodies compete with B cells for antigen and block B cell activation. Immune complexes bind FcR on B cells; at low levels they increase the sensitivity of B cells to antigen and increase responsiveness, while at high levels they give negative signals to B cells to reduce humoral responses. Anti-idiotype antibodies bind secreted and membrane antibodies to inhibit the humoral immune response. Th1 and Th2 cytokines inhibit one another's production and function: Th1 cells stimulate cellular immunity and suppress humoral immunity, while Th2 cytokines have the opposite effect.
The new area of psychoneuroimmunology is devoted to understanding the interactions between the immune system, central nervous system, and endocrine system. For example, IL-1 induces sleep and fever, and stimulates release of pituitary hormones (ACTH, TSH, GH). Thymic and many steroid and peptide hormones also influence our ability to make immune responses.
Practice Quiz
Pick the one BEST answer for each question by clicking on the letter of the correct choice.
1. Innate immune responses are important in the initiation of adaptive responses because
a. antigen cannot bind B cells until it has first bound complement.
b. inflammatory chemokines attract naïve B and T cells to the infection site to be activated.
c. inflammatory cytokines and acute phase proteins stimulate the expression of co-stimulatory molecules on dendritic cells.
d. lymphocytes cannot enter the secondary lymphoid organs until inflammatory cytokines upregulate CAM expression on HEV.
e. T cells are stimulated to express co-stimulatory molecules by acute phase proteins.
2. Th0 differentiation into Th1 or Th2 cells is influences by all of the following EXCEPT
a. antigen density on the APC MHC.
b. avidity of peptide binding to TCR.
c. cytokines being produced by nearby dendritic cells.
d. cytokines being secreted by nearby T cells.
e. whether the T0 cell has already begun to make IL-2.
3. Armed effector CTL find and kill their target cells in
a. draining lymph nodes.
b. the site of pathogen entry into the body.
c. the spleen.
d. whatever tissues have APC to provide co-stimulatory signals.
e. whatever tissues are infected.
4. Naïve lymphocytes enter the lymph nodes
a. any time they pass by the lymph node HEV.
b. any time inflammatory chemokines signal them to go to the lymph nodes.
c. only during infection.
d. only when their specific antigen is NOT present in the tissues.
e. only when their specific antigen is present.
5. Effector B cells (plasma cells) secrete antibody in the
a. bone marrow.
b. germinal centers.
c. primary follicles.
d. secondary follicles.
e. T cell follicles.
6. Immune memory is provided by persisting
a. antibody molecules.
b. effector CTL.
c. memory cells that can be activated by antigen to become effectors.
d. plasma cells
e. All of the above contribute to immune memory.
7. Lymphocytes which are part of the MALT do not generally recirculate through the peripheral lymph nodes because
a. MALT lymphocytes do not recirculate.
b. the antigens for which they are specific cannot go to the lymph nodes.
c. the APC that activate them are found only in the MALT.
d. they are negatively selected against MALT self antigens in the bone marrow and must stay in the MALT to avoid inducing autoimmunity
e. they bind better to MAdCAM on the mucosal vascular endothelium than they do to CD34 on the lymph node HEV.
8. All of the following are part of the gut-associated lymphoid tissue EXCEPT the
a. adenoids.
b. appendix.
c. enterocytes.
d. M cells.
e. Peyer's Patches.
9. The function of the M cells is to
a. induce apoptosis in food antigens.
b. kill infected enterocytes.
c. migrate to the Peyer's Patches and present antigen to T cells.
d. phagocytose or endocytose antigen.
e. secrete neutralizing IgA.
10. The mucosal equivalent of the lymph node, where naïve T and B cells are activated, is the
a. appendix.
b. crypt.
c. MAdCAM-1 vesicle.
d. Peyer's Patches.
e. submucosal lymphoid tissue.
11. Plasma cells activated in the gut-associated lymphoid tissue secrete IgA in the
a. bone marrow.
b. lamina propria lymphoid tissues.
c. mucosa of gut, lungs, and genital tracts.
d. Peyer's Patches.
e. spleen
12. Specialized gd T cells in the mucosal epithelium
a. are educated in the thymus to be tolerant to food antigens.
b. become ab T cells when stimulated by Th1 cytokines.
c. kill infected enterocytes expressing MIC-1 and MIC-2.
d. recognize peptides presented on Class I MHC.
e. remove food antigens before they can be phagocytosed by M cells.
13.
The principal effector function that eliminates intestinal pathogens is
a. CTL in the Peyer's Patches.
b. macrophages in the intestinal lumen.
c. neutralizing secretory IgA in the mucus.
d. opsonizing secretory IgA on M cells.
e. tolerance.
14. Normal flora in the intestine
a. are neither harmful nor beneficial.
b. block adherence of pathogens by secreting toxins that kill them.
c. cannot cause disease.
d. induce no immune response unless they damage the intestinal epithelium.
e. None of the above is true.
15.
Intestinal pathogens
a. cannot survive in the stomach because of the low pH there.
b. mimic food antigens to avoid the immune response.
c. must enter the body to cause disease.
d. stimulate inflammatory cytokine secretion to suppress immune responses.
e. use M cells as an entry way into the body.
16. Food antigens induce tolerance by
a. activating regulatory cells that suppress immune responses.
b. entering the body through enterocytes instead of M cells.
c. failing to induce inflammatory cytokine production.
d. inducing clonal proliferation in specific T cells.
e. Both a and c are correct.
17.
A secondary humoral response
a. becomes detectable in serum overnight following antigen stimulation.
b. is T cell independent.
c. produces antibody of lower average affinity than a primary response
d. requires the presence of antibody from the primary response to initiate activation of memory cells.
e. results in high serum levels of IgG.
18.
Primary and secondary humoral immune responses do NOT differ in their
a. antibody affinities.
b. effector mechanisms.
c. kinetics.
d. peak antibody titers
e. ratio of IgM:IgG.
19.
An Elvis impersonator comes to you with a sore throat. You run some tests and
learn that his C3 levels are low, IgM levels are moderate, and IgG levels are
very high. This laboratory data tells you that your patient
a. does not have an infection, because complement levels rise during an infection.
b. has not previously been exposed to the infectious organism.
c. is probably undergoing a secondary immune response.
d. must have a bacterial infection, since viruses cannot induce an IgG response.
e. must be the King himself.
20.
Original antigenic sin
a. activates memory cells more quickly than naïve cells.
b. indicates that memory responses suppress the activation of naïve cells.
c. occurs in response to eating apples.
d. occurs when an autoimmune response is produced.
e. only occurs during responses to influenza virus.
Problem
1. You have developed an oral vaccine that you hope will induce immunity to a new serotype of E. coli. You are testing it in mice which respond to E. coli infection by developing diarrhea. Design an experiment to assess the memory response to your vaccine. Think about both in vivo and in vitro measurements of immunity.
