Deck 24: The Innate and Adaptive Immune Systems

Question 1

Gout patients have high uric acid levels in their blood and suffer from arthritis in their joints as a result of formation of intracellular and extracellular uric acid crystals. Would you expect treatment with glucocorticoids (G), which inhibit prostaglandin synthesis, or with tumor necrosis factor (TNF) to be normally used to treat such patients?

Answer 1

G

Question 2

If mice are injected with antibodies against selectin homing receptors or against the integrin ligand I-CAM1 (which is expressed on the surface of endothelial cells), they show immune defects, such as higher susceptibility to bacterial infections. Which of the following properties of lymphocytes at endothelial cells would you expect to observe after injection with both antibodies?

A) Normal lymphocyte rolling and normal lymphocyte adhesion
B) Impaired lymphocyte rolling but normal lymphocyte adhesion
C) Normal lymphocyte rolling but impaired lymphocyte adhesion
D) Impaired lymphocyte rolling and impaired lymphocyte adhesion

Answer 2

D
Explanation: Selectins have a key role in the rolling step, which is followed by the integrin-dependent adhesion.

Question 3

Mice whose immune systems had previously rejected a tissue transplant from a certain strain of donor mouse received another transplant shortly afterward, either from the same donor strain or a new one. All of the recipient mice eventually rejected the transplant. However, one group did so more quickly than the other group. Do you think this group received the graft from the original mouse strain (O) or the new strain (N)? Write down O or N as your answer.

Answer 3

O

Question 4

Which of the following groups of proteins are pattern recognition receptors?

A) NOD-like receptors
B) Toll-like receptors
C) RIG-like receptors
D) C-type lectin receptors
E) All of the above

Question 5

Indicate whether each of the following descriptions is shared (S) or not shared (N) between macrophages and neutrophils in destroying invading pathogens in vertebrates. Your answer would be a four-letter string composed of letters S and N only, e.g. SSSS.
( ) They use a respiratory burst and create toxic reactive oxygen species to kill engulfed pathogens.
( ) They are normally found in most tissues even before pathogen invasion.
( ) They are long-lived and normally survive long after activation.
( ) They secrete pro-inflammatory cytokines upon encountering invading pathogens.

Question 6

Indicate true (T) and false (F) statements below regarding lymphocytes in the adaptive immune system. Your answer would be a four-letter string composed of letters T and F only, e.g. TTFF.
( ) To induce an adaptive immune response, an invading pathogen must invade a peripheral lymphoid organ.
( ) Lymphocytes continuously circulate between central and peripheral lymphoid organs.
( ) Upon encountering its specific antigen in a peripheral lymphoid organ, a lymphocyte remains there to proliferate and differentiate into effector and memory cells.
( ) Memory B and T cells do not recirculate, but rather remain in the peripheral lymphoid organ in which they develop.

Question 7

Blood-group compatibility is an important consideration in red blood cell transfusions that are administered in millions of liters worldwide every year. In the ABO blood-group system, individuals with AB blood type are the universal recipient (can accept blood from any donor), while those with O type are universal donors. If an incompatible transfusion is made between an A-type (donor) and a B-type (recipient) individual, for example, the anti-A antibodies present in the recipient's plasma would rapidly destroy the transfused blood cells with the help of the complement system, with potentially serious consequences. But why do we produce antibodies against other blood-group antigens even without having been exposed to those foreign blood cells before? It has been suggested that these antibodies are generated in response to minor infections (in early life) with microbes of the normal flora of our bodies, and that, in addition to binding to the microbial antigens, these antibodies can cross-react with the similar A- and B-type carbohydrate antigens of the ABO blood-group system. If this is indeed the case, blood plasma from a "germ-free" individual would react with …

A) blood of any ABO type.
B) blood of no other ABO type.
C) blood from O-type individuals only.
D) blood from non-O-type individuals only.
E) blood from AB-type individuals only.

Question 8

Fill in the blank in the following paragraph regarding the innate and adaptive immune systems. Do not use abbreviations.
"As key components of the innate immune response, … cells provide the link between the innate and adaptive immune responses. Upon exposure to pathogens in tissues, they engulf the microbe, become activated, and travel to nearby lymphoid organs where they present the processed antigens to the lymphocytes of the adaptive immune system."

Question 9

Indicate true (T) and false (F) statements below regarding the complement system. Your answer would be a four-letter string composed of letters T and F only, e.g. TTFT.
( ) The early complement components form the membrane attack complex, whereas the late complement components cleave and activate C3.
( ) The classical pathway of complement activation is triggered by binding of a secreted PRR to mannose-containing glycoproteins or glycolipids on the surface of pathogens.
( ) Some pathogens such as Neisseria gonorrhoeae hide from the complement reaction via sialic acid camouflage.
( ) Once a membrane attack complex is formed, it can attack multiple pathogens before becoming inactivated.

Question 10

A cell has been infected with an RNA virus. As a consequence, it may …

A) reduce the expression of its surface class I MHC molecules.
B) secrete type I interferons such as interferon-α.
C) shut down most protein translation and destroy most of its RNA.
D) be induced to die by apoptosis.
E) All of the above.

Question 11

Which of the following are recognized by pattern recognition receptors as pathogen-associated molecular patterns?

A) Double-stranded viral RNAs
B) Formylmethionine-containing proteins
C) Unmethylated CpG motifs
D) Bacterial flagella components
E) All of the above

Question 12

Which of the following cell types is NOT phagocytic?

A) Macrophage
B) Monocyte
C) Neutrophil
D) Lymphocyte
E) Dendritic cell

Question 13

If heart surgery is necessary in a newborn, the thymus is sometimes removed to gain better access to the heart. If a lymph node of such a patient is later studied in a microscope, one particular area of the node is found to have an unusually low number of cells. Looking at the drawing below, what is the name of this area?

Question 14

Mammals produce five major classes of immunoglobulins. Indicate whether each of the following descriptions better applies to the immunoglobulin A, D, E, G, or M class. Your answer would be a five-letter string composed of letters A, D, E, G, and M only, e.g. GMADE.
( ) It binds to cells that secrete histamine.
( ) It is the major antibody in secretions such as saliva.
( ) It is the major antibody circulating in the blood.
( ) It is found on the surface of naïve B cells along with IgM.
( ) It forms wheel-like pentamers involved in the primary immune response.

Question 15

Indicate whether each of the following descriptions better applies to an adaptive (A) or innate (I) immune response. Your answer would be a four-letter string composed of letters A and I only, e.g. AAAA.
( ) It is found in invertebrate and vertebrate animals as well as in plants.
( ) It has a long-lasting memory.
( ) It is highly specific to the particular invading pathogen.
( ) It employs natural killer (NK) cells to induce apoptosis in infected host cells.

Question 16

Indicate whether each of the following descriptions better applies to the clonal anergy (A), clonal deletion (D), receptor editing (E), or clonal suppression (S) mechanism of immunological self-tolerance. Your answer would be a five-letter string composed of letters A, D, E, and S only, e.g. SADSS.
( ) It involves apoptosis of self-reactive cells.
( ) It is mostly limited to B cells.
( ) It involves regulatory T (T??g) cells.
( ) It involves DNA recombination.
( ) It is limited to central tolerance processes.

Question 17

In contrast to a primary immune response, a secondary immune response generally …

A) has a longer lag period.
B) is stronger.
C) involves induction of effector cells to become memory cells.
D) takes longer to develop.
E) All of the above.

Question 18

How are natural killer (NK) cells different from cytotoxic T (TC) cells?

A) NK cells induce apoptosis in their target cells, whereas TC cells are professional phagocytes.
B) NK cells kill virus-infected cells, whereas TC cells kill cancerous cells.
C) NK cells kill cells with a high level of class I MHC protein expression, whereas killing by TC cells requires low expression levels.
D) NK cells respond quickly to a virus infection, whereas the activation of TC cells to become cytotoxic is a slow process.
E) NK cells are normally abundant in the tissue even before infection, whereas TC cells are mostly in the bloodstream.

Question 19

Consider two receptors, one inhibitory and one activating, on the surface of natural killer (NK) cells: KIR receptors that interact with certain class I MHC proteins, and special Fc receptors that recognize the tail region of IgG antibodies. When NK cells are incubated with an immortalized B cell line derived by infection of human B cells with Epstein-Barr Virus, the B cells are killed by NK cells. Normal B cells, in contrast, are not efficiently killed by NK cells. In each of the following scenarios, indicate whether the described changes are expected to enhance (E) or suppress (S) the cytotoxicity (killing activity) of the NK cells in this system. Your answer would be a four-letter string composed of letters E and S only, e.g. SEEE.
( ) The cell line is transformed with human class I MHC genes, and the genes are expressed.
( ) An anti-CD23 IgG antibody is added to the cells. (CD23 is a known marker on the surface of the immortalized B cells.)
( ) The cells are treated with stibogluconate, an inhibitor of KIR receptor signaling.
( ) Type I interferons are added to the cells.

Question 20

Polyclonal antibodies can be generated against almost any protein of interest by repeatedly injecting the purified protein into an animal (such as a rabbit) and collecting blood serum once the animal's immune system has produced antibodies against the protein. In this process, the antigen is not injected alone; it is co-injected with a so-called adjuvant to "trick" the immune system. Additionally, the adjuvant used in the first injection is often different from that used in later "booster" injections. Freund's complete adjuvant (C) contains a water-oil emulsion plus heat-killed Mycobacteria. In contrast, Freund's incomplete adjuvant (I) lacks the Mycobacteria component. Which adjuvant (C or I) do you think is used in the booster injections? Which immune response-primary (P) or secondary (S)-is triggered after the first purified protein injection? Activation of which antigen-specific immune cells-memory (M) or effector (E)-is chiefly responsible for the "boosting" effect of the later injections? Write down your answer as a three-letter string, e.g. ISM.

Question 21

Indicate whether each of the following statements is true (T) or false (F) regarding all the cell-surface immunoglobulin molecules produced by a single, mature, naïve B cell.
( ) They all have the same heavy chain.
( ) They all have the same light chain.
( ) They all have the same antigen-binding site.

Question 22

Indicate whether each of the following descriptions better applies to B cells (B) or T cells (T) of the adaptive immune system. Your answer would be a four-letter string composed of letters B and T only, e.g. BTTT.
( ) Their effector cells act mainly at short range.
( ) Their receptors recognize protein fragments that have been processed in antigen-presenting cells.
( ) They do NOT normally express CD8 protein on their surface.
( ) They can become "killer" cells.

Question 23

Antigens and antibodies can form large, insoluble, cross-linked aggregates that precipitate from solution. The maximal amount of precipitant is observed at a certain antigen/antibody ratio; adding either excess antigen or excess antibody can prevent (or even reverse) the precipitation. Consider an antigen with multiple identical antigenic determinants that can be recognized by either bivalent or decavalent (i.e. pentameric) antibodies with binding sites that recognize the determinants. The amount of precipitation in the presence of a constant antigen concentration is plotted as a function of antibody concentration in the following qualitative graph. Which curve (1 or 2) in the graph do you think corresponds to the bivalent antibody? Would you expect to see such a bell-shaped curve if the antibodies were monovalent?

A) Curve 1; yes
B) Curve 2; yes
C) Curve 1; no
D) Curve 2; no
E) Curve 2; only if the antigen was also monovalent

Question 24

The transcription regulator AIRE (autoimmune regulator) plays a key role in developing immunological self-tolerance by promoting the production of various cellular proteins that are mainly expressed outside the thymus. Which of the following cells have the highest level of AIRE?

A) Double-negative thymocytes
B) Double-positive thymocytes
C) Lymphoid follicle cells in lymph nodes
D) Thymus epithelial cells
E) Peyer's patch cells

Question 25

In antigen presentation to helper T cells (TH cells), both the TCR and co-receptor proteins…

A) are expressed on the dendritic cell.
B) bind to the class II MHC protein.
C) bind to the presented peptide antigen.
D) All of the above.

Question 26

Which of the following better describes cross-presentation of protein antigens by professional antigen-presenting cells to naïve TC cells?

A) Presentation of intracellular antigens by class I MHC proteins
B) Presentation of intracellular antigens by class II MHC proteins
C) Presentation of extracellular antigens by class I MHC proteins
D) Presentation of extracellular antigens by class II MHC proteins

Question 27

Consider the following three diseases associated with activation-induced deaminase (AID) and indicate whether you think each of them is accompanied by a higher (H) or lower (L) AID activity in the affected cells compared to normal cells. Your answer would be a three-letter string composed of letters H and L only, e.g. LLL.
( ) Burkitt's lymphoma is a cancer of B lymphocytes originating from the germinal center. In this cancer, chromosomal translocations are observed between the immunoglobulin heavy-chain genes and proto-oncogenes (genes whose overexpression can promote cancer), resulting in aberrant expression of the latter.
( ) Diffuse large B cell lymphoma is a cancer of B lymphocytes in which, in addition to chromosomal translocations, high mutation rates are observed in many genes including proto-oncogenes.
( ) Hyper IgM syndrome is a genetic immunodeficiency syndrome in which IgM antibodies are produced by B cells at high levels and for extended periods, while levels of IgA, IgE, and IgG antibodies are abnormally reduced.

Question 28

After having cereal and nut mix for breakfast, your friend realizes that the mix contains a nut to which she is allergic. Soon afterward, symptoms of an allergic reaction start to appear, and she is going to take an antihistamine pill to alleviate them. During the allergic reaction in her body, …

A) mast cells synthesize and secrete IgE antibodies into the blood.
B) the allergen molecules bind to IgE antibodies that are bound to Fc receptors on the surface of basophils and mast cells.
C) histamine and other amines are recognized by IgE antibodies.
D) histamine binds to mast cells and induces IgE production.
E) All of the above.

Question 29

Normally, naïve cytotoxic and helper T cells interact for the first time with foreign antigens presented by dendritic cells in …

A) the thymus.
B) the bloodstream.
C) peripheral lymphoid organs.
D) the bone marrow.
E) inflamed tissues.

Question 30

You have prepared glass beads coated with rabbit anti-Ig antibodies that were isolated from rabbits that were immunized with mouse immunoglobulin (Ig). If you incubate a sample of mononucleated cells from mouse spleen with these beads, which of the following cell types do you think would stick to the beads?

A) Only macrophages
B) Only B cells
C) Only cytotoxic T cells
D) B cells and cytotoxic T cells
E) B cells and macrophages

Question 31

In the schematic drawing of an antibody molecule below, indicate which letter (A to E) corresponds to each of the following features. Your answer would be a five-letter string composed of letters A to E only, e.g. DAECB.

( ) N-terminus
( ) C-terminus
( ) Light chain
( ) Antigen-binding site
( ) Disulfide bond

Question 32

T cell receptors that do not interact at all with self-peptide-MHC complexes during T cell development in the thymus normally undergo …

A) positive selection.
B) negative selection.
C) receptor editing.
D) clonal suppression.
E) "death by neglect."

Question 33

Indicate whether each of the following descriptions better applies to class switching (C), somatic hypermutation (S), or both (B). Your answer would be a four-letter string composed of letters B, C, and S only, e.g. SSSB.
( ) It is dependent on activation-induced cytidine deaminase.
( ) It involves sequence changes in the CH domains only.
( ) It increases the affinity of antibody-antigen binding.
( ) It takes place in germinal centers after antigen stimulation.

Question 34

Indicate whether each of the following normally occurs before (B) or after (A) antigen stimulation of B cells. Your answer would be a four-letter string composed of letters A and B only, e.g. AAAA.
( ) V(D)J recombination
( ) Class switch recombination
( ) Somatic hypermutation
( ) Junctional diversification

Question 35

Indicate whether each of the following descriptions better applies to B cell receptors (B) or T cell receptors (T). Your answer would be a four-letter string composed of letters B and T only, e.g. BTTT.
( ) They can also be produced as secreted antibodies with the same antigen specificity.
( ) They diversify by class switching and somatic hypermutation.
( ) They often exist as heterodimers.
( ) They have a relatively low antigen-binding affinity.

Question 36

Indicate whether each of the following descriptions better applies to class I (1) or class II (2) MHC proteins of vertebrates. Your answer would be a four-digit number composed of digits 1 and 2 only, e.g. 2221.
( ) They mainly present intracellular peptide fragments.
( ) They are found on most nucleated cells.
( ) They present antigens mainly to helper or regulatory T cells.
( ) They are recognized by CD4 co-receptors on helper and regulatory T cells.

Question 37

Indicate true (T) and false (F) statements below regarding the proteins of our adaptive immune system. Your answer would be a four-letter string composed of letters T and F only, e.g. TTFT.
( ) Both B cell receptors and T cell receptors have domains with an immunoglobulin fold, which consists of a ?-sandwich and an intrachain disulfide bond.
( ) MHC proteins are the most polymorphic among human proteins.
( ) MHC proteins and CD4 and CD8 co-receptors are all members of the Ig superfamily.
( ) Both B cell receptors and T cell receptors are stably associated with invariant transmembrane protein chains that are required for activating intracellular signaling pathways.

Question 38

How many hypervariable loops are there in a bivalent IgG antibody? Write down your answer in digits, e.g. 5.

Question 39

Where are the hypervariable regions located in a typical antibody molecule?

A) Only in the N-terminal region of the light chain
B) Only in the C-terminal region of the light chain
C) Only in the N-terminal region of the heavy chain
D) Only in the C-terminal region of the heavy chain
E) In the N-terminal region of both the light and the heavy chain

Question 40

Consider two solution chambers of equal volume divided by a dialysis membrane that is impermeable to antibody molecules but permeable to small antigens. Starting with an antigen concentration of 4.8 nM in both chambers, you add its specific IgG antibody to one of the chambers at 1 nM concentration. You then measure the concentration of the antigen in the other chamber after equilibrium is reached, which turns out to be about 4 nM. What is the association constant (K_a) for the binding of the antigen to each antigen-binding site of IgG? Assume independent antigen-binding sites in each antibody molecule. Write down your answer in liters per mole, in scientific notation with one decimal place, e.g. 5.0 × 10² liters/mole).

Question 41

Indicate whether each of the following cell-surface proteins is expressed mainly by B cells (B), dendritic cells (D), or T cells (T). Your answer would be a four-letter string composed of letters B, D, and T only, e.g. DBBB.
( ) Co-stimulatory protein B7, which is recognized by CD28
( ) Invariant CD3 complex
( ) Inhibitory CTLA4 protein
( ) CD40 receptor, which recognizes the co-stimulatory protein CD40 ligand on a helper T cell

Question 42

The schematic drawing below summarizes the differentiation of naïve helper T cells (TH cells) into various effector T cells, which occurs in a peripheral lymphoid organ. Indicate which effector cell (A to E) in the drawing is better described by each of the following descriptions. Your answer would be a four-letter string composed of letters A to E only, e.g. DEAE.

( ) It can also develop from thymocytes in the thymus, as well as from naïve TH cells.
( ) It suppresses the development, activation, or function of most other immune cells.
( ) It produces IFN? and activates macrophages.
( ) They reside in lymphoid follicles close to developing B cells.

Question 43

Sort the following events to reflect the order in which they occur in the presentation of viral peptides to cytotoxic T cells by a virus-infected cell. Your answer would be a four-letter string composed of letters A to D only, e.g. BDCA.
(A) Peptide transport into the ER lumen
(B) Partial proteasomal degradation of the viral protein into peptide fragments
(C) Peptide binding to class I MHC protein in the ER lumen
(D) The appearance of viral protein in the cytosol

Question 44

Different mice have different allelic variants of class I MHC genes. Therefore, cytotoxic T cell (TC cell) clones can be generated by culturing lymphocytes harboring MHC allele A in the presence of nondividing nucleated cells harboring MHC allele B (and vice versa). These T cells can normally kill cells harboring allele B by inducing them to undergo apoptosis. Imagine two strains of mice with MHC allele A that are either wild type (WT) for the gene encoding perforin (A1) or are mutant and lack the gene (A2). Also imagine two strains of mice with MHC allele B that are either WT for the gene encoding Fas (B1) or are mutant and lack the gene (B2). Cytotoxic T cells derived from the A1 strain can induce apoptosis in both B1 and B2 cells. However, those derived from the A2 strain are only able to induce apoptosis in B1 cells and not B2 cells. Indicate whether each of the following statements is (Y) or is not (N) consistent with these observations. Your answer would be a four-letter string composed of letters Y and N only, e.g. NYNY.
( ) The perforin-granzyme pathway is the only way through which TC cells induce apoptosis in mouse target cells.
( ) The activation of the Fas-FasL pathway is sufficient to induce apoptosis by TC cells.
( ) There are other major pathways (not dependent on perforin or Fas) through which TC cells induce apoptosis in mouse target cells.
( ) Both pathways (Fas-FasL and perforin-granzyme) are required simultaneously for the induction of apoptosis by TC cells in mouse target cells.

Question 45

In the following schematic diagram, which curve (A to D) do you think better shows the qualitative relationship between the affinity of a developing T cell's TCR for self-peptide-MHC complexes in the thymus and the survival chance of the cell?

Question 46

From an evolutionary perspective, which mating pattern confers a higher fitness to a mammalian population: preferred mating between pairs whose MHC genes are most similar (S) or between those whose MHC genes are most dissimilar (D)? Write down D or S as your answer.

Question 47

A patient with persisting larger-than-normal lymph nodes is suspected to have a T cell lymphoma, a cancer of T lymphocytes. Abnormally enlarged lymph nodes are also found in local infections, when lymphocytes are activated to proliferate there. In order to distinguish between cancer and infection, you take tissue samples from the patient, as well as from a healthy individual, and perform a so-called clonality test. You extract DNA from the tissues and amplify a small chromosomal region that includes the T-cell-receptor ? chain D-J junctions. Amplification is done by PCR, using primers that hybridize to specific DNA sequences flanking the junctions. You then analyze the size distributions of the PCR products by capillary electrophoresis, which makes it possible to distinguish between DNA molecules with small differences in size. Based on the results, presented in the following schematic graphs, you conclude that, unfortunately, it is likely that the patient has developed a T cell lymphoma. Which graph (1 or 2) represents the patient's test results? Write down 1 or 2 as your answer.