Question 1

Several effector T cell functions are mediated by cell surface molecules on the effector cell interacting with binding partners on the target cells. In the case of the CD40-CD40 ligand interaction, effector CD4 T cells express CD40 ligand, which binds to CD40 target cells. Individuals with a genetic deficiency in CD40 ligand expression show greatly reduced antibody responses, particularly to protein antigens which require CD4 T_FH cell interactions with B cells. Another expected defect in these individuals would be: A) Reduced recruitment of eosinophils by T_H2 cells B) Reduced recruitment of neutrophils by T_H17 cells C) Reduced production of anti-microbial peptides induced by T_H17 cells D) Reduced suppression of dendritic cells by T_reg cells E) Reduced activation of macrophages by T_H1 cells

Accepted Answer

The CD40-CD40 ligand interaction is crucial for the activation of macrophages by CD4 T cells. A deficiency in CD40 ligand expression would impair this interaction, leading to reduced activation of macrophages.

Question 2

In a lymph node, nT_reg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nT_reg cell and the naive T cell must share the same antigen specificity.

Accepted Answer

The term "nT_reg cells" does not correspond to any known cell type in immunology. Regulatory T cells (Tregs), however, are known to inhibit the responses of other T cells, but this description does not accurately represent any specific cell type or mechanism.

Question 3

Cytotoxic granules released from cytotoxic T cells contain proteins that enter target cells and induce apoptosis. Do any of the mechanisms of apoptosis induction by cytotoxic effector T cells rely on the protein APAF-1? If so, which pathway?

Accepted Answer

The answer of Cytotoxic granules released from cytotoxic T cells...

Question 4

Eosinophils are a subset of granulocytes that normally reside in the circulation. When activated, these cells secrete toxic compounds that are a key component in the eradication of helminthic parasite infections. Eosinophils are recruited to sites of parasite infections by: A) Interferon-$\gamma$ produced by T_H1 cells B) CCL11 produced by T_H2 cells C) Interferon-$\gamma$ produced by CD8 cytotoxic T cells D) CCL20 produced by T_H17 cells E) GM-CSF produced by T_H1, T_H2, and T_H17 cells

Accepted Answer

Eosinophils are recruited to sites of parasite infections by CCL11 (also known as eotaxin), which is produced by T_H2 cells. Interferon-F1F1F1S1γF1F1F10 (IFN-γ) produced by CD8 cytotoxic T cells and GM-CSF produced by various immune cells can also activate eosinophils, but they do not directly recruit them to sites of infection. CCL20 is a chemokine that primarily recruits other immune cells, such as dendritic cells and T cells, and is not involved in eosinophil recruitment to parasite infections.

Question 5

Each subset of effector T cells produces a distinct array of secreted factors known as cytokines. One common feature of nearly all effector T cell responses is the rapid production of increased numbers of macrophages, granulocytes, and dendritic cells from the bone marrow. This response occurs due to:
A) Effector T cell trafficking to the bone marrow to activate hematopoietic progenitor cells
B) Depletion of peripheral myeloid cells after leaving the blood, leading to increased bone marrow production
C) Inflammation-induced blood vessel dilation causing transient reductions in circulating myeloid cells
D) Pathogen-induced migration of tissue-resident dendritic cells to lymph nodes inducing new dendritic cell production
E) Effector T cell production of GM-CSF that traffics to the bone marrow

Accepted Answer

Effector T cells can produce granulocyte-macrophage colony-stimulating factor (GM-CSF), which can stimulate bone marrow to produce more myeloid cells. Therefore, effector T cells can indirectly induce an increase in the number of macrophages, granulocytes, and dendritic cells through their production of GM-CSF.

Question 6

Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in Figure will the T_H1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific T_H1 cells. A) B) C) D) E) An immunological synapse forms between effector T cells and their targets to regulate signaling and to direct the release of effector molecules

Accepted Answer

The answer of Most effector T cells migrate out of...

Question 7

Cytotoxic T cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes.

Accepted Answer

Perforin is essential for delivering granzymes into target cells to induce apoptosis. Without perforin, granzymes cannot enter the target cells effectively, making the cytotoxic T cells less effective in killing.

Question 8

The compound LE135 is an inhibitor of the retinoic acid receptor, and blocks signaling through this receptor. In a mouse model of inflammatory bowel disease (IBD), inflammation in the gastrointestinal (GI) epithelium is significantly exacerbated if animals are treated with LE135. Analysis of the CD4 T cell subsets found in the GI epithelium of LE135-treated mice compared to controls with IBD would likely show: A) Reduced numbers of CD4 T cells of all subsets in the LE135-treated mice B) Increased numbers of TGF-$\beta$ and IL-10-producing CD4 cells in the LE135-treated mice C) Reduced numbers of IL-17 and IL-22-producing CD4 cells in the LE135-treated mice D) Reduced numbers of iT_regs in the LE135-treated mice E) Increased numbers of naive CD4 T cells in the LE135-treated mice

Accepted Answer

Retinoic acid signaling is important for the differentiation and function of regulatory T cells (Tregs). Inhibiting this pathway with LE135 would likely reduce the numbers of Tregs in the GI epithelium, exacerbating inflammation.

Question 9

The Bcl-2 protein was first identified based on its overexpression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Subcellular localization experiments would show that Bcl-2 is present:
A) In the nucleus, where it blocks DNA fragmentation
B) In the cytotoxic granules where it inactivates granzymes
C) In the mitochondria where it blocks cytochrome c release
D) In the cytosol where it blocks caspase activation
E) In the plasma membrane where it blocks death receptor signaling

Accepted Answer

Subcellular localization experiments have shown that Bcl-2 is present in the mitochondria, where it blocks the release of cytochrome c and thus inhibits the initiation of the apoptotic cascade.

Question 10

Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:
A) The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter
B) The extremely rapid production of granzymes and perforin by cytotoxic effector cells upon encountering a target cell
C) The extremely potent activity of perforins in poking holes in target cell membranes allowing entry of granzymes
D) The efficient activity of granzymes in cleaving effector caspases leading to direct activation of apoptosis
E) The large number of cytotoxic granules made and secreted by a single effector cytotoxic T cell

Accepted Answer

Cytotoxic T cells store perforin and granzymes in cytotoxic granules before encountering a target cell. The interaction with the target cell stimulates the release of these cytotoxic granules containing perforin and granzymes, leading to the initiation of apoptosis in the target cell within minutes.

Question 11

Wiskott-Aldrich syndrome is an immunodeficiency disease that causes a defect in antibody responses. The most severe defects are in antibody responses to protein antigens, which are dependent on CD4 effector T_FH cells providing cytokines to the B cell. The protein defective in individuals with the disease, known as WASp, functions in cytoskeletal reorganization and polarization through its role in promoting actin polymerization. This immune defect could be fixed by a gene therapy approach that restored WASp expression in: A) Antigen-presenting cells such as dendritic cells B) B cells C) B cells and T cells D) T cells E) T cells and antigen-presenting cells

Accepted Answer

Restoring WASp expression in T cells would address the defect in CD4 effector T_FH cells, which are crucial for providing the necessary help to B cells for antibody responses to protein antigens.

Question 12

Cytotoxic effector T cells also produce inflammatory cytokines such as IFN-$\gamma$ and TNF-$\alpha$ when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is due to:
A) The increased production of perforin and granzymes by CD8 cells
B) The up-regulation of MHC class I protein expression by IFN-$\gamma$
C) The ability of TNF-$\alpha$ to induce vascular leakage
D) The effect of cytokines on promoting target cell apoptosis
E) The effect of IFN-$\gamma$ to enhance viral replication leading to increased viral antigen presentation

Accepted Answer

IFN-γ up-regulates MHC class I expression, enhancing the ability of CD8 T cells to recognize and kill infected cells.

Question 13

A mouse line (called 'Wm') is discovered that has an unexpected immunodeficiency. Genetic studies indicate that the immunodeficiency is due to a single gene defect. The Wm mice have normal numbers of all immune cell lineages, including T cell, B cells, macrophages, dendritic cells, NK cells, and granulocytes. When infected with viruses or intracellular bacteria and protozoa, the Wm mice mount normal protective T cell responses and clear the infections. However, given a helminthic parasite infection, the Wm mice cannot clear the infection and succumb to the disease. A set of wild-type (WT) and Wm mice were infected with the helminthic parasite, Nippostrongylus brasiliensis, and cytokine production by the CD4 T cells was analyzed. For this experiment, CD4 T cells were isolated from mice at day 8 post-infection, stimulated in vitro for 24 hr stimulation with anti-CD3 antibody to elicit cytokine secretion, and then cytokine levels in the culture supernatants were examined by ELISA. The results are shown in Figure.

a) What process is likely defective in the Wm mice?
b) Which molecules are the best candidates for the defective gene in Wm mice? Note that the transcription factor GATA-3 is not a likely candidate gene, as GATA-3-deficient mice have an early block in T cell development in the thymus, and completely lack all T cells.and Wm mice and were stimulated in vitro with anti-CD3 plus anti-CD28 antibodies, in the presence of additional cytokines and blocking antibodies as indicated. After three days of stimulation, the T cells are isolated, washed, and restimulated with anti-CD3 antibody in medium lacking any cytokines or antibodies. After 24 hr, the cytokines present in the supernatants of these restimulated CD4 T cells are examined by ELISA. These data are show in Figure. 
 
c) Do these results change your answers to parts (a) or (b) above?
To continue to identify the molecule or pathway defective in Wm T cells, CD4 T cells are isolated from Wm mice and stimulated in vitro with anti-CD3 + anti-CD28 antibodies in the presence of IL-4 and anti-IFN-$\gamma$ antibody, as above. One day later, the cells are transduced with a vector expressing the transcription factor GATA3. From this vector, GATA3 will be expressed constitutively and at high levels, in all of the T cells. As a control, an 'empty' vector (not containing GATA-3) is also transduced into Wm CD4 T cells. Three days later, the cells are washed and restimulated for cytokine secretion analysis by ELISA, as above. Additionally, flow cytometry analysis of naive wild-type and Wm CD4 T cells stained with an antibody to the IL-4 receptor was performed, and the results are shown.and Wm CD4 T cells was then performed to examine the expression of the four Jak-family tyrosine kinases required for downstream signaling induced by the cytokine receptors expressed on T cells. The results from these experiments are shown in Figure. 
 
d) With the new information provided by the data shown above, name the most likely candidate molecule for the defect in Wm T cells, and explain your reasoning.

Accepted Answer

The answer of A mouse line (called 'Wm') is discovered...

Question 14

At early timepoints following an infection, examination of lymph node CD4 T cells responding to the pathogen would show a heterogeneous population of cells representing several different effector lineages. Likewise, the cytokines produced by these cells would include IFN$\gamma$, IL-4, and possibly others. However, approximately one week later at the peak of the T cell response, the pathogen-specific CD4 T cell population would be largely homogeneous in their production of a single effector subset cytokine profile. This change comes about due to:
A) Death of the CD4 T cells making the non-protective cytokines
B) Increased proliferation of CD4 T cells making protective cytokines
C) Enhanced differentiation of newly activated CD4 T cells into one effector subset
D) Inhibition of antigen-presenting cells by CD4 T cell-derived cytokines
E) Impaired proliferation of effector CD4 T cells by IFN$\gamma$

Accepted Answer

As the T cell response progresses, newly activated CD4 T cells differentiate into one effector subset, allowing for a more focused and effective immune response to the pathogen. This is driven by the T cell receptor signaling pathways and cytokine signals received by the T cells.

Question 15

Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to:
A) Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site
B) Express a mutant form the caspase that lacked the pro-domain
C) Express a constitutively active form of the initiator caspase
D) Generate a knockout mutation that prevented expression of the Fas receptor
E) Generate a mutation in the proteins required for autophagy

Accepted Answer

Mutating the initiator caspase cleavage site on the pro-caspase would prevent its activation, thereby eliminating the activity of the effector caspase.

Question 16

Following their activation, naive CD4 T cells differentiate into one of several subsets of effector T cells. This developmental choice is determined by which specific cytokines the T cells are exposed to during their activation; in turn, the cytokines that are produced will reflect the nature of the infecting pathogen. In order for this system to be flexible enough to produce all five effector CD4 subsets (T_H1, T_H2, T_H17, T_FH, and iT_reg): A) Each naive CD4 T cell must already express one of the lineage-specific transcription factors (i.e., T-bet, GATA-3, etc.). B) Each naive CD4 T cell must express all of the STAT proteins. C) Each naive CD4 T cell must express only a single STAT protein (i.e., STAT1 or STAT6 or STAT3, etc.). D) Each naive CD4 T cell must already express low levels of the subset specific cytokines (i.e., IFN$\gamma$, IL-4, IL-17, etc.). E) Each naive CD4 T cell must express all of the lineage-specific transcription factors (i.e., T-bet, GATA-3, etc.).

Accepted Answer

Naive CD4 T cells must express all of the STAT proteins to ensure they can respond to a wide range of cytokines and differentiate into any of the effector T cell subsets based on the cytokines they encounter during activation. This allows for flexibility in response to different pathogens.

Question 17

West Nile virus (WNV) is a human pathogen that is transmitted by mosquitoes, which inject the virus into the host while they are feeding. To study the immune response to WNV, mice can be infected by injecting 100 PFU of virus into the footpad. This generates a robust immune response 7 days post-infection in the popliteal lymph node (LN), located behind the knee, as indicated in Figure. Popliteal LN cells are isolated from the mouse shown above at day 7 post-infection, and the T cells are stimulated in vitro with the WNV peptide P33 plus dendritic cells isolated from a non-infected mouse of the same strain. Five hours later, the CD8 T cells in the culture are analyzed for their ability to produce the cytokine IFN-$\gamma$, and the numbers of IFN-$\gamma$-producing CD8 T cells are quantified. As a control, T cells are also stimulated with an irrelevant non-viral peptide (ova) plus dendritic cells. The results are shown in Figure. a) Why is the T cell response different between the two lymph node populations? To identify the important antigen-presenting cell required to activate WNV-specific CD8 T cells in the popliteal LN, wild-type mice and Batf3-/- mice are each immunized with 100 PFU of WNV in the left footpad, as above. Previous studies have indicated that Batf3-/- mice lack one particular subset of conventional dendritic cells, known as CD8$\alpha$+ dendritic cells (DC), but otherwise appear to have normal numbers and subsets of all other immune cell populations (e.g., T cells, B cells, macrophages, etc.). The results of this experiment are shown in Figure b) Name two possible functions of CD8$\alpha$+ dendritic cells that could account for the results seen in the Batf3^-/- mice immunized with WNV. To distinguish between the possible functions of CD8$\alpha$+ dendritic cells, another set of wild-type and Batf3^-/- mice are immunized with 100 PFU of WNV in the left footpad. At day 7 post-infection, the left popliteal LN are isolated from the mice, and the CD4 T cells in these LN populations are tested for responses to a WNV peptide bound to MHC class II (peptide Y). As a negative control, an MHC class II-binding peptide from ova is used. These results are shown in Figure . c) Do these results rule in/out either of your proposed functions of CD8$\alpha$+ dendritic cells indicated in answer to part (b)? Why or why not?

Accepted Answer

The answer of  West Nile virus (WNV) is a...

Quiz 9: T-Cell-Mediated Immunity

In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must share the same antigen specificity.

Cytotoxic granules released from cytotoxic T cells contain proteins that enter target cells and induce apoptosis. Do any of the mechanisms of apoptosis induction by cytotoxic effector T cells rely on the protein APAF-1? If so, which pathway?

Eosinophils are a subset of granulocytes that normally reside in the circulation. When activated, these cells secrete toxic compounds that are a key component in the eradication of helminthic parasite infections. Eosinophils are recruited to sites of parasite infections by:

Cytotoxic T cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes.

The Bcl-2 protein was first identified based on its overexpression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Subcellular localization experiments would show that Bcl-2 is present:

Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:

Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to:

In a lymph node, nT_reg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nT_reg cell and the naive T cell must share the same antigen specificity.