Exam 24: The Innate and Adaptive Immune Systems

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."

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?

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.

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?

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.

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

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

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?

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.

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

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, …

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.

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.

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.

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.

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

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.

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

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.

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