McQs on T cell Development & Activation: Immunology


Multiple Choice Question on T cell Development, Differentiation, and Activation


1) T cells (T lymphocytes) are crucial in the recognition of antigens presented by self-MHC. The T cell progenitors undergo proliferation and differentiation in the thymus and form a mature T cell. 
Which of the following organ is the origin of T cell progenitors?
a) Thymus
b) Hepatocytes
c) Bone marrow
d) None of the above

2) What is the characteristic feature of progenitor T cells that have migrated to the thymus?
a) They express T cell receptor/CD3 complex
b) They express CD28 cell adhesion molecule
c) They express CD4 or CD8 co-receptor
d) None of the above

3) Which of the following cell adhesion molecule is present in the T cell progenitors required for homing these cells into the thymus?
a)CD25
b) CD44
c) IL-2
d) CTLA-4

4) Pre- T cell receptor complex consists of the β chain of TCR & CD3 molecules that are formed during the proliferation of T cells. 
 The function of the pre-TCR complex includes all of the following, except?
a) signal productive rearrangement of TCR β for further proliferation
b) suppress further rearrangement of β chain (allelic exclusion)
c) prepare cells for rearrangement of α chain
d) commit T cells for CD4 or CD8 positive T cells

5) Which of the following is the process for T cell development and maturation?
a) Rearrangement of T cell receptor and expression of coreceptors
b) Positive selection of thymocytes bearing receptors that are capable of binding to self-MHC molecules (MHC restriction)
c) Negative selection ensures the affinity receptor self MHC or MHC antigen complex is eliminated (self-tolerance)
d) All of the above

6) During the differentiation of T lymphocytes, the double-positive cells are directed to become CD4 + T cells & CD8+ T cells which are MHC II & MHC I restricted respectively. 
Which of the following process might be the correct for T cell differentiation?
a) Intrinsic model- multiple interactions of MHC with double-positive (CD4+ & CD8+) instruct the cell to differentiate
b) Stochastic model- CD4 or CD8 expression in switched of randomly
c) Both A and B
d) None of the above

7) The activation of T cell requires the interaction of MHC/peptide of TCR/CD3 complex activation requires the expression of.................................................
a) Transcription factors such as c-Fos, c-Myc, c-Jun, etc.
b) Interleukins such as IL-2, IL-3, and IL-6
c) Adhesion molecules such as CD28, CTLA-4
d) All of the above

8) Which of the following cytoplasmic tail of CD4 or CD8 coreceptors are required for phosphorylation of ITAM present in CD3 molecules?
a) Lck
b) ZAP70
c) LAD
d) None of the above

9) The cell surface proteins on T cell bind to B7 on the antigen-presenting cells and serve as a secondary signal. 
Which of the following statement is true regarding the secondary signal?
a) CD28 is a protein that binds to B7 on APC that acts as costimulatory signals for T cell activation
b) CTLA-4 is a protein that binds to B7 on APC that acts as a suppressor signal for T cell activation
c) Both
d) None

10) Which of the cytokines function in an autocrine manner and induce T cell proliferation after engagement of TCR with antigens interaction and presence of secondary signal?
a) IL-1
b) IL-2
c) IL-3
d) IL-4

11) Cytokines such as IL-2, IFN-γ, and TNF-β, play an important role in cell-mediated cytotoxicity, and delayed hypersensitivity. 
Which of the following subset of T helper cells are involved in the process?
a) T helper 1 CD4+
b) T helper 2 CD4+
c) T helper 1 CD8+
d) T helper 2 CD8+

12) Cytokines such as IL-4, IL-5, IL-6 & IL-10 play an important role in B cell activation and humoral immune response
a) T helper 1 CD4+
b) T helper 2 CD4+
c) T helper 1 CD8+
d) T helper 2 CD8+

13) The regulatory or suppressor T cells express the specific cell surface marker for its function. It is
a) CD4+ CD25+
b) CD4+ CD25-
c) CD4 - CD8 - CD25 +
d) CD4 + CD8 + CD25 +

14) The activated T cells undergo activation-induced cell death (AICD). 
Which of the following is the effector molecule that is a response for AICD?
a) IL-2
b) Fas/Fas ligand
c) IL-4
d) INF-γ

15) T-cell receptor engagement with antigenic peptide MHC may induce T cell activation or the clonal anergy. 
Which of the following interaction favors T cell activation?
a) Fas/Fas ligand
b) B-7 & CTLA-4 interaction
c) B-7 & CD28 interaction
d) B-7 & CD 8 interaction


Multiple Choice Answers with Explanation:
1-c) Bone marrow
The origin of T cell progenitors is the bone marrow. However, these progenitor cells migrate to the thymus where they undergo proliferation and differentiation to form mature T cells.

2-d) None of the above
Progenitor T cells that have migrated to the thymus do not express any of the markers listed in the answer choices. These cells are called double-negative thymocytes because they do not express either CD4 or CD8 co-receptors, which are required for T cell activation. These cells undergo further differentiation in the thymus, and some of them develop into T cells that express either CD4 or CD8 co-receptor, which are involved in the recognition of antigen presented by MHC class II or MHC class I molecules, respectively. The expression of T cell receptor/CD3 complex is a characteristic feature of all T cells, including progenitor T cells that have migrated to the thymus. CD28 cell adhesion molecule is expressed on T cells after activation and is involved in T cell activation and co-stimulation.

3-b) CD44
CD44 is a cell adhesion molecule that is expressed on the surface of T cell progenitors and is required for homing these cells into the thymus. CD25 is the alpha chain of the IL-2 receptor and is expressed on activated T cells. IL-2 is a cytokine that is produced by activated T cells and is important for the proliferation and survival of T cells. CTLA-4 is a protein receptor that is expressed on activated T cells and regulates T cell activation by competing with CD28 for binding to CD80 and CD86 on antigen-presenting cells.

4-d) commit T cells for CD4 or CD8 positive T cells
The pre-TCR complex plays an essential role in T cell development. It consists of the TCR β chain and CD3 molecules, and its function includes the following:
a) Signal productive rearrangement of TCR β for further proliferation b) Suppress further rearrangement of β chain (allelic exclusion) c) Prepare cells for rearrangement of α chain
However, the pre-TCR complex does not commit T cells for CD4 or CD8 positive T cells. The commitment of T cells to the CD4 or CD8 lineage occurs after successful rearrangement of the α chain and positive selection in the thymus.5-d) All of the above

6-c) Both A and B
The activation of T cells requires a complex series of interactions and signaling events. The primary signal for T cell activation is the interaction of the T cell receptor (TCR) with a peptide antigen presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APCs). This interaction activates the TCR/CD3 complex, which in turn triggers a series of intracellular signaling events. One of the earliest events is the activation of transcription factors such as c-Fos, c-Myc, and c-Jun, which help to initiate T cell proliferation and differentiation. Additionally, the activation of T cells requires the presence of certain cytokines, such as interleukins like IL-2, IL-3, and IL-6, which play important roles in promoting T cell growth and differentiation. Finally, adhesion molecules such as CD28 and CTLA-4 are also involved in T cell activation, as they facilitate the interactions between T cells and APCs that are necessary for proper T cell function.
 
7-d) All of the above
The phosphorylation of ITAMs (Immunoreceptor Tyrosine-based Activation Motifs) present in the CD3 complex is critical for T cell activation. CD4 and CD8 coreceptors do not directly phosphorylate the ITAMs but instead play a role in enhancing T cell receptor (TCR) signaling.
The cytoplasmic tail of CD4 and CD8 coreceptors binds to the non-catalytic region of Lck, a Src family tyrosine kinase that is constitutively associated with the cytoplasmic tails of the CD4 and CD8 molecules. Upon TCR engagement, the Lck kinase activity is activated, leading to the phosphorylation of ITAMs present in the CD3 complex.
Once phosphorylated, the ITAMs serve as docking sites for the recruitment and activation of ZAP70 (Zeta-chain-associated protein kinase 70), another tyrosine kinase that propagates downstream signaling events leading to T cell activation.

8-a) Lck
The cytoplasmic tail of CD4 and CD8 coreceptors do not directly phosphorylate the ITAMs (Immunoreceptor Tyrosine-based Activation Motifs) present in the CD3 complex. Instead, the phosphorylation of ITAMs is carried out by the Lck kinase, which is constitutively associated with the cytoplasmic tails of CD4 and CD8 coreceptors.
Upon engagement of the T cell receptor (TCR) with its antigen, Lck is activated and phosphorylates the ITAMs present in the CD3 complex. Once phosphorylated, the ITAMs act as docking sites for ZAP70 (Zeta-chain-associated protein kinase 70), which is recruited and activated by the phosphorylated ITAMs.
ZAP70 then phosphorylates downstream signaling molecules, ultimately leading to T cell activation. Therefore, the correct answer to the question is (a) Lck, as it is the kinase responsible for the initial phosphorylation of ITAMs present in the CD3 complex.

9-c) Both
Both CD28 and CTLA-4 can bind to B7 on antigen-presenting cells (APCs) and modulate T cell activation in different ways.
CD28 is a costimulatory receptor on T cells that binds to B7 molecules (CD80 or CD86) on APCs. This interaction provides a crucial "second signal" that is necessary for full T cell activation and promotes the proliferation, survival, and cytokine production of activated T cells. Without this costimulatory signal, T cell activation can be aborted, leading to tolerance and immune suppression.
On the other hand, CTLA-4 (cytotoxic T-lymphocyte antigen 4) is another receptor on T cells that also binds to B7 molecules on APCs. However, CTLA-4 has a higher affinity for B7 molecules than CD28 and acts as a negative regulator of T cell activation. When CTLA-4 is engaged by B7 molecules, it inhibits T cell activation, leading to T cell anergy (inactivation) or apoptosis (cell death).
Therefore, both CD28 and CTLA-4 can bind to B7 on APCs and modulate T cell activation in different ways: CD28 acts as a costimulatory signal for T cell activation, while CTLA-4 acts as a suppressor signal for T cell activation. 

10-b) IL-2
IL-2 (Interleukin-2) is a cytokine that is produced by activated T cells and plays a critical role in T cell proliferation and differentiation. After the engagement of TCR with antigens and the presence of a secondary signal (e.g., CD28-B7 interaction), activated T cells upregulate the expression of IL-2 and its receptor (IL-2R) on their surface.
IL-2 binds to the IL-2R on the surface of the same T cell (autocrine signaling) and induces a signaling cascade that leads to T cell proliferation, survival, and differentiation into effector T cells. The autocrine production of IL-2 is critical for the expansion and maintenance of antigen-specific T cells during an immune response.

11- a) T helper 1 CD4+
T helper 1 (Th1) CD4+ cells are a subset of helper T cells that secrete cytokines such as IL-2, IFN-γ, and TNF-β. These cytokines promote cell-mediated immunity, including the activation and differentiation of cytotoxic T lymphocytes (CTLs) and the induction of delayed-type hypersensitivity (DTH) reactions.
IL-2, produced by Th1 cells, is critical for the expansion and differentiation of both CD4+ and CD8+ T cells during cell-mediated immunity. IFN-γ and TNF-β, also produced by Th1 cells, enhance the cytotoxic activity of CTLs and macrophages, leading to the destruction of infected or cancerous cells.
In contrast, T helper 2 (Th2) CD4+ cells primarily secrete cytokines such as IL-4, IL-5, and IL-13, which promote humoral immunity and eosinophil-mediated responses. Therefore, Th2 cells are not involved in cell-mediated cytotoxicity and delayed hypersensitivity.
T helper 1 CD8+ cells and T helper 2 CD8+ cells do not exist as distinct subsets. CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), directly mediate cell-mediated immunity and cytotoxicity, but do not produce cytokines in the same way that CD4+ helper T cells do.

12-b) T helper 2 CD4+

T helper 2 (Th2) CD4+ cells are a subset of helper T cells that secrete cytokines such as IL-4, IL-5, IL-6, and IL-10. These cytokines play a critical role in the activation and differentiation of B cells, leading to the production of antibodies and the promotion of humoral immunity.
IL-4, produced by Th2 cells, stimulates B cell proliferation, class switching to IgE and IgG1, and differentiation into plasma cells. IL-5, also produced by Th2 cells, promotes the survival, proliferation, and activation of eosinophils and plays a critical role in the defense against helminthic parasites.
IL-6, produced by both Th2 and Th1 cells, stimulates the differentiation of B cells into antibody-secreting plasma cells and the production of acute-phase proteins by hepatocytes. IL-10, produced by Th2 cells, inhibits the activation of macrophages and dendritic cells, leading to a decrease in pro-inflammatory cytokine production.
In contrast, T helper 1 (Th1) CD4+ cells primarily secrete cytokines such as IFN-γ, TNF-β, and IL-2, which promote cell-mediated immunity and the activation of macrophages and cytotoxic T cells.
T helper 1 CD8+ cells and T helper 2 CD8+ cells do not exist as distinct subsets. CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), directly mediate cell-mediated immunity and cytotoxicity, but do not produce cytokines in the same way that CD4+ helper T cells do.

13- a) CD4+ CD25+
The specific cell surface marker expressed by regulatory or suppressor T cells is (a) CD4+ CD25+.
Regulatory T cells (Tregs) are a subset of CD4+ T cells that play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. They express high levels of CD25, the alpha chain of the interleukin-2 receptor (IL-2Rα), which is required for their development and function.
CD25 is also expressed by other activated T cells, but Tregs express it constitutively at high levels, allowing them to compete for limited amounts of IL-2 and thereby suppress the activation and proliferation of other T cells.

14-b) Fas/Fas ligand
The effector molecule that is responsible for activation-induced cell death (AICD) in activated T cells is Fas/Fas ligand.
Fas (also known as CD95) is a cell surface receptor that belongs to the tumor necrosis factor (TNF) receptor superfamily. Its ligand, Fas ligand (FasL), is expressed on activated T cells, natural killer (NK) cells, and some other cell types.
When FasL binds to Fas on the surface of a target cell, it triggers a signaling cascade that leads to caspase activation and apoptosis (programmed cell death). This process is important for regulating the immune response and preventing the proliferation of autoreactive T cells that could cause autoimmune disease.

15-b) B-7 & CTLA-4 interaction
B7 molecules (B7-1 and B7-2) are expressed on the surface of antigen-presenting cells (APCs) and bind to CD28 on the surface of T cells. This interaction provides the second signal required for T cell activation, which is necessary in addition to the first signal provided by T cell receptor engagement with antigenic peptide MHC.
CD28 is a costimulatory receptor that enhances T cell proliferation and survival by inducing the production of cytokines such as IL-2. In contrast, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is another receptor on T cells that binds to B7 molecules, but it has an inhibitory effect on T cell activation by competing with CD28 for binding to B7 and signaling for T cell anergy.


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