Immunology Exam 3

Most vaccines currently administered are delivered by intramuscular injection. Yet the pathogenic organisms these vaccines aim to protect against usually enter the body by a different route. For instance, many viruses infect us via the respiratory tract, and many bacterial pathogens infect via the gastrointestinal tract. One major advantage of delivering vaccines against these organisms via their normal route of infection would be: A. That the vaccines would no longer require the incorporation of an adjuvant in their composition B. That the vaccines would elicit IgA antibodies in addition to IgG antibodies C. That the vaccines would no longer require several boosters to elicit protective responses D. That the vaccines would be more stable and not require refrigeration E. That the vaccines would be safer and have fewer side effects than injected vaccines

B. That the vaccines would elicit IgA antibodies in addition to IgG antibodies

The mucosal immune system provides protection for a vast area of the body and contains three-quarters of all the lymphocytes in the body. A key feature of the mucosal immune system is its: A. Ability to respond to thousands of different bacterial species B. Inability to provide adequate protection, leading to millions of deaths per year due to mucosal infections C. Ability to avoid responding to the large numbers and differing species of commensal microbes D. Use of the identical mechanisms and response features compared to the systemic immune system E. Inability to produce antibodies that cross epithelial barriers

C. Ability to avoid responding to the large numbers and differing species of commensal microbes

The vaccine to Haemophilus influenzae type b is called a conjugate vaccine. It is composed of the tetanus toxoid protein conjugated to the capsular polysaccharide of the H. influenzae type b bacteria. When used to vaccinate infants, the antibody response generated by this vaccine would include: A. Antibodies to the bacterial polysaccharide and the tetanus toxoid B. Antibodies to the tetanus toxoid only C. Antibodies to the bacterial polysaccharide only D. Antibodies that only bind to the protein-polysaccharide conjugate in the vaccine E. Antibodies that recognize the polysaccharide capsule when shed by the bacteria

A. Antibodies to the bacterial polysaccharide and the tetanus toxoid

Secretory IgA produced in the epithelium of mucosal surfaces has several functions in protective immunity. Among these are neutralization of pathogens or toxins in the gastrointestinal tract lumen or in epithelial cell endosomes, neutralization of pathogens or toxins that cross the epithelial barrier, and transport of pathogens or toxins across M cells for delivery to lamina propria dendritic cells. All of these functions share the common feature that they: A. Fail to induce local inflammation in the gastrointestinal epithelium B. Are efficient at inducing opsonization of pathogens for uptake by phagocytes C. Are efficient at inducing complement activation D. Fail to completely protect the epithelium from cytotoxic effects of pathogens E. Induce IgA-secreting plasma cells to produce increased amounts of secretory IgA

A. Fail to induce local inflammation in the gastrointestinal epithelium

The pre-B-cell receptor provides an important signal that induces transition of pro-B cells to pre-B cells. An important characteristic of this receptor is that: A. It signals without binding to an extracellular ligand. B. It is composed of immunoglobulin heavy chains and the VJ region of a rearranged gamma light chain. C. It is expressed at very high levels on the surface of the pro-B cell. D. It signals without requiring association with B-cell receptor signaling subunits, Ig-alpha and Ig-beta E. It signals without requiring the B cell receptor signaling kinase, BTK.

A. It signals without binding to an extracellular ligand.

Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by: A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes B. Blocking the binding of anti-microbial antibodies to the pathogen surface C. Cleaving the antibody into fragments that separate the antigen-binding region from the effector function D. Inducing aggregation of the anti-microbial antibodies by multivalent binding to the pathogen-derived protein E. Preventing the antibody from neutralizing the pathogen

A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes

Salmonella typhimurium is the causative agent of typhoid fever, and infects the host by translocating across the intestinal epithelium. Recent studies have shown that S. typhimurium produces an effector protein called SopB that induces intestinal enterocytes to differentiate into M cells. This is beneficial to the bacteria because: A. S. typhimurium gains access to the host by crossing the intestinal epithelium inside M cells. B. M cells are unable to secrete antimicrobial peptides as do the enterocytes. C. M cells are unable to secrete mucus as do the enterocytes. D. S. typhimurium utilizes the M cell metabolic machinery for its proliferation. E. M cells lack the pattern recognition receptors that induce innate responses to pathogens.

A. S. typhimurium gains access to the host by crossing the intestinal epithelium inside M cells.

Mice lacking the poly Ig receptor (pIgR) have an immunodeficiency disease characterized by increased susceptibility to mucosal infections and an increase in the penetration of commensal microbes into the body's tissues. Yet, a genetic deficiency in the production of IgA antibodies is the most common form of human immunodeficiency, and is generally a mild disease and often even asymptomatic. This dichotomy can be explained by: A. The difference in the immune system between mice and humans B. The different types of commensal microbes found in mice and humans C. The ability of pIgR to transport IgM across the gut epithelium D. The reduced exposure of humans compared to mice to pathogens that infect via the gastrointestinal epithelium E. The development of improved human hygiene, including pasteurization

C. The ability of pIgR to transport IgM across the gut epithelium

CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell ones (i.e., lymphoid follicles) of secondary lymphoid organs. A conditional knockout mouse in which CXCR5 was specifically deleted only in T cells would have: A) no defects in any type of antibody response B) defects in the initial activation of all B cells C) A lack of discrete B cell and T cell zones in the lymphoid organ D) A defect in T cell-dependent antibody responses E) An increased number and size of germinal centers

D) A defect in T cell-dependent antibody responses

IgM is the first antibody isotype secreted following activation of a naive B cell. IgM is found at high concentrations in the serum, and is found as a very high molecular weight complex. This high molecular weight complex is composed of: A. A single IgM monomer plus monomers of IgA and IgG B. A single IgM monomer bound to several non-immunoglobulin serum proteins C. A single IgM monomer bound to serum complement components D. A pentamer of IgM monomers E. Two dimers of IgM plus IgD forming a tetrameric complex

D. A pentamer of IgM monomers

It is well documented that antibody affinities for an immunizing antigen continue to increase upon successive rounds of immunization (i.e., secondary, tertiary, etc.). This is due to the fact that: A. At each round of immunization, new naive B cells are recruited into the response. B. At each round of immunization, the expression of AID increases, leading to higher rates of somatic hypermutation. C. Memory B cells express higher levels of AID than naive B cells, leading to higher rates of somatic hypermutation. D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation. E. At each round of immunization, germinal centers become larger and have increased numbers of B cells in them.

D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation.

Vibrio cholerae causes an acute diarrheal illness that can be fatal if not treated. Several vaccines have been developed in an effort to prevent this disease. The oral cholera vaccine is a mixture of killed Vibrio cholerae bacteria plus additional inactivated cholera toxin protein. Efficacy studies of this vaccine indicate that it prevents 50-60% of the cases of cholera infection observed in non-vaccinated individuals. In contrast, injectable vaccines made from killed bacteria or purified bacterial subunits are substantially less effective at preventing infections. This is likely due to the fact that: A. The injectable vaccine fails to elicit gut-homing immune responses. B. The oral vaccine lasts substantially longer in the body than the injectable vaccine. C. The oral vaccine has a higher concentration of bacterial antigens than the injectable vaccine. D. The oral vaccine contains the inactivated cholera toxin. E. The injectable vaccine does not contain protein epitopes to elicit CD4 helper T cells.

A. The injectable vaccine fails to elicit gut-homing immune responses.

In germinal centers, proliferating B cells undergo a process called somatic hypermutation, in which mutations are introduced into the V regions of the antibody heavy and light chain genes. When this process is complete after several weeks, the overall affinities of the antibodies produced are greatly increased compared to those present early in the primary response. The somatic hypermutation process leads to increased antibody affinity because: A) mutations that decrease the antibody affinity lead to an arrest of B cell proliferation B) B cells making higher affinity antibodies receive more help from T FH cells C) somatic hypermutations only take place in the sequences encoding the CDR1, CDR2, and CDR3 regions D) mutations that increase antibody affinity lead to an increased rate of B cell proliferation E) the majority of nucleotide changes introduced by AID don't change the aa coding sequence

B) B cells making higher affinity antibodies receive more help from T FH cells

Neutralizing antibodies are effective at preventing infection or toxicity mediated by pathogens or their toxic products. In fact, nearly all vaccines currently in use function by eliciting neutralizing antibodies. One example is the tetanus vaccine, in which neutralizing antibodies are generated against an inactivated form of the tetanus toxin (i.e., the tetanus toxoid). The most important feature of a neutralizing antibody is: A. Having a high degree of multi-valency, such as being a pentamer or hexamer of immunoglobulin monomers B. Having high affinity for the antigen C. Being present at a high concentration in the circulation D. Being efficient at activating the complement cascade E. Having a long half-life in the body

B. Having high affinity for the antigen

True/False: Oral tolerance to food antigens and immune tolerance to gut microbiota share the property that foreign antigens encountered in the gastrointestinal (GI) tract—food and commensal microbes, respectively—do not elicit immune effector responses. Yet, these processes differ in that commensal microbes will still elicit protective adaptive immune responses if they cross the GI epithelium and enter the body.

True

True/False: When a B cell differentiates into a plasma cell, it goes from expressing membrane-bound IgM to making mostly the secreted form of IgM. A deletion of the first polyadenylation site in the μ heavy chain gene would prevent activated B cells from making the secreted form of IgM

True

10.15 Multiple choice: In humans, IgA is produced in copious amounts, estimated to be a rate of 3 g/day. Nearly all of the IgA secreting plasma cells are found in the gastrointestinal(GI) tract where the secreted IgA is transported across the GI epithelium into the lumen of the gut. There, this antibody protects the GI epithelium against intestinal pathogens. In contrast, none of the GI resident long-lived antibody secreting cells produce antibodies of the IgG class. The differential localization of long-lived antibody secreting cells producing IgA compared to those producing IgG is likely due to: A. Their interactions with TFH cells specific for pathogens that infect the gut B. The lack of germinal centers in the mucosal lymphoid organs C. The absence of S1PR1 expression on IgA-secreting plasma cells D. Their priming and differentiation in mucosal lymphoid organs E. Their inability to access the bone marrow compartment

D. Their priming and differentiation in mucosal lymphoid organs

which close up view of these two V domains has the amino acid sequences most important for antigen-binding highlighted correctly in red?

a) all of them

A mouse is immunized with the tetanus toxoid protein (inactivated toxin) in adjuvant. One week later, the entire population of splenic B cells are isolated from the mouse and mixed with tetanus toxoid-specific CD4 T FH cells plus the purified tetanus toxoid protein. Four days later, the total number of B cells in the culture and the number of tetanus toxoid-specific B-cells are determined and compared to the starting population on the day of isolation. The tetanus-specific B cells preferentially survive and proliferate because: A. They are the only B cells that express CD40. B. They are the only B cells that express the receptor for IL-21. C. They are the only B cells that proliferate in response to their antigen. D. They are the only B cells presenting the tetanus peptide to the T FH cells. E. They are the only B cells that received a TLR stimulus during priming.

D. They are the only B cells presenting the tetanus peptide to the T FH cells.

Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of T EM cells provides an important component of protective immunity to re- infection by the same pathogen because: A. They are the only memory cell subset that can produce effector cytokines within a few hours of antigen re-encounter. B. They are able to respond to S1PR1 and enter the blood circulation rapidly upon re-infection. C. They express the integrin alpha-E beta-7 that binds to integrin ligands expressed on epithelial cells. D. They can protect against re-infection that occurs in a different site in the body than the primary infection. E. They can simultaneously express cytokines associated with all three effector T cell lineages.

D. They can protect against re-infection that occurs in a different site in the body than the primary infection.

Individuals that overexpress the cytokine BAFF show increased susceptibility to autoimmune diseases such as Sjögren's syndrome, a disease that targets the exocrine glands that produce saliva, tears, and other bodily secretions. If one examined the circulating antibodies in these patients, one would expect to find: A. Increased development of B cells in the bone marrow B. A failure of receptor editing of immunoglobulin light chain genes in the bone marrow C. An increased rate of immature B cell export from the bone marrow D. Reduced B-cell receptor signaling following strong cross-linking of the receptor E. An increased number of circulating mature autoreactive B cells

E. An increased number of circulating mature autoreactive B cells

Virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by: A.Lysis from the virus infection B. Engulfment and destruction by phagocytes in the body C. Destruction by cytotoxic T cells D. Natural killer cell lysis E. Fas-induced death or cytokine withdrawal

E. Fas-induced death or cytokine withdrawal

Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VHCDR3 loops of >30 amino acids are readily detected in the repertoire. These antibody heavy chains with CDR3 lengths of >30 amino acids would likely be missing in individuals lacking: A.RAG-1 and RAG-2 B. DNA-dependent protein kinase (DNA PK) C. The nuclease, Artemis D. The Ku70:Ku80 complex E. Terminal deoxynucleotidyl transferase (TdT)

E. Terminal deoxynucleotidyl transferase (TdT)

10.22 Multiple choice: IgM antibodies are much more efficient than IgG at activating the complement cascade. However, under certain circumstances, IgG antibodies will activate the complement pathway. One example of a situation in which IgG binding to its antigen will not trigger the complement cascade is when: A. The IgG antibodies bind to a multivalent soluble antigen in solution, such as a polysaccharide structure shed from a bacterial pathogen. B. The IgG antibodies bind to a viral capsid protein that is present in more than 100 copies on the viral particle surface. C. The IgG antibodies bind to a bacterial surface by recognizing a repetitive polysaccharide component of the bacterial capsule. D. The IgG antibodies are binding self-antigens such as chromatin released from dead cells. E. The IgG antibodies are neutralizing a bacterial toxin protein by blocking the receptor-attachment site on the toxin.

E. The IgG antibodies are neutralizing a bacterial toxin protein by blocking the receptor-attachment site on the toxin.

T/F: the different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has four distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.

F

T/F: Like innate sensors of infections (TLRs, NLRs, RLRs), antibodies frequently recognize nucleic acids of pathogenic organisms

False

T/F: Once B cells begin secreting antibodies, they cease dividing and have a life-span of only a few days.

False

Analysis of human milk from lactating mothers shows that it contains IgA antibodies against infections that were recent (<3 weeks earlier) and those from the distant past (>1 year). These antibodies are directed against a host of organisms, including viruses, such as enteroviruses, herpes simplex viruses, respiratory syncytial virus, rubella, reovirus, and rotavirus. In addition, IgA antibodies against many bacteria are found in human milk, including those reactive to E. coli, Shigella, Salmonella,Campylobacter, Vibrio cholerae, H. influenzae, S. pneumoniae, Clostridium difficile, C. botulinum, and Klebsiella pneumoniae. IgA antibodies to the parasite Giardia and the fungus, Candida albicans, are also seen in human milk. Since most of these infections were localized in the gastrointestinal tract of the mother, these IgA antibodies ended up in breast milk by: A. Being transported from the lymph fluid in the breast tissue into across the breast epithelium into the secretory glands. B. The trafficking of germinal center B cells from the mother's mesenteric lymph nodes to the breast epithelium. C. The trafficking of gut-primed activated B cells from the mother's circulation into the lactating milk gland. D. The ability of gut-primed activated B cells to traffic to all secondary lymphoid tissues in the mother. E. The ability of activated B cells primed in the spleen to switch to IgA secretion after entering the mother's lactating milk gland.

C. The trafficking of gut-primed activated B cells from the mother's circulation into the lactating milk gland.

The US Department of Health and Human Services has a stated goal for the seasonal influenza vaccine of vaccinating 80% of healthy (i.e., low-risk) individuals. This vaccine is formulated each year from the serotypes of influenza likely to be circulating in the population during the coming flu season. The reason this goal is not 100% of individuals is because: A) it is not feasible to expect 100% of healthy individuals to get the flu vaccine every year B) Individuals who had the flu vaccine the year before will already be protected C) individuals who are healthy need not be too concerned about getting infected with the flu. D) healthy individuals are unlikely to spread the virus to others E) Unvaccinated individuals are protected when 80% of people around them are vaccinated.

E) Unvaccinated individuals are protected when 80% of people around them are vaccinated.