Immune regulation and tolerance MCQs With Answer

Immune regulation and tolerance MCQs With Answer

This question set is designed for M.Pharm students to deepen understanding of immune regulation and tolerance — key concepts in immunopharmacology and therapeutic immunomodulation. The questions cover central and peripheral tolerance mechanisms, regulatory T cells, costimulatory and checkpoint pathways, B‑cell tolerance, mechanisms of autoimmunity, and translational strategies such as tolerance induction in transplantation and immunotherapy. Each item tests conceptual knowledge and clinical relevance relevant to drug development, adverse immune responses, and novel biologic therapies. Use these MCQs as a focused review to reinforce mechanisms, molecular players (e.g., FOXP3, AIRE, CTLA‑4, PD‑1), and practical implications for designing or evaluating immunotherapeutic strategies.

Q1. What best describes central tolerance?

• Elimination or editing of self‑reactive lymphocytes during development in primary lymphoid organs
• Suppression of immune responses by peripheral regulatory cells at sites of inflammation
• Induction of anergy through lack of costimulation in mature lymphocytes
• Tolerance induced by oral administration of antigens

Correct Answer: Elimination or editing of self‑reactive lymphocytes during development in primary lymphoid organs

Q2. Which transcription factor is considered the master regulator of natural regulatory T (nTreg) cell development and function?

• T-bet
• GATA3
• FOXP3
• RORγt

Correct Answer: FOXP3

Q3. Which mechanism is a primary method of B‑cell central tolerance in the bone marrow?

• Clonal expansion
• Receptor editing of immunoglobulin light chains
• Isotype switching
• Somatic hypermutation

Correct Answer: Receptor editing of immunoglobulin light chains

Q4. Anergy in T cells is most commonly induced by which condition?

• Strong TCR stimulation plus high IL‑2
• TCR engagement in absence of costimulatory signals (e.g., CD28–B7 interaction)
• High expression of MHC class I on target cells
• Coengagement of CTLA‑4 with CD80/86

Correct Answer: TCR engagement in absence of costimulatory signals (e.g., CD28–B7 interaction)

Q5. The autoimmune regulator (AIRE) gene is crucial for tolerance because it:

• Promotes peripheral Treg differentiation in lymph nodes
• Controls expression of peripheral tissue antigens in medullary thymic epithelial cells
• Encodes a co‑stimulatory molecule on dendritic cells
• Suppresses B cell receptor signaling in the spleen

Correct Answer: Controls expression of peripheral tissue antigens in medullary thymic epithelial cells

Q6. Which cytokines are most commonly associated with regulatory T cell–mediated suppression?

• IFN‑γ and IL‑12
• IL‑4 and IL‑5
• IL‑10 and TGF‑β
• IL‑17 and IL‑22

Correct Answer: IL‑10 and TGF‑β

Q7. CTLA‑4 contributes to immune regulation primarily by which mechanism?

• Delivering activating signals to T cells via CD28
• Competing with CD28 for binding to CD80/86 and delivering inhibitory signals
• Directly killing antigen‑presenting cells through perforin release
• Enhancing IL‑2 production by T cells

Correct Answer: Competing with CD28 for binding to CD80/86 and delivering inhibitory signals

Q8. What is “infectious tolerance”?

• Transmission of tolerance between generations via DNA methylation
• Ability of one regulatory cell population to induce regulatory properties in other lymphocytes
• Loss of tolerance due to chronic infection
• Autoimmune activation following checkpoint blockade

Correct Answer: Ability of one regulatory cell population to induce regulatory properties in other lymphocytes

Q9. Which of the following best explains peripheral deletion as a tolerance mechanism?

• Activation‑induced cell death of mature self‑reactive lymphocytes in peripheral tissues
• Genetic recombination producing nonfunctional receptors in bone marrow
• Physical sequestration of antigens behind barriers like the blood‑brain barrier
• Suppression of effector cells by neutralizing antibodies

Correct Answer: Activation‑induced cell death of mature self‑reactive lymphocytes in peripheral tissues

Q10. Which checkpoint pathway is most commonly targeted by cancer immunotherapies that can cause loss of tolerance and immune‑related adverse events?

• CD28–B7
• PD‑1/PD‑L1
• IL‑2/IL‑2R
• TGF‑β receptor

Correct Answer: PD‑1/PD‑L1

Q11. “Bystander suppression” in immune tolerance refers to:

• Suppression of immune responses to unrelated antigens in the same environment by regulatory mechanisms
• Antigen cross‑presentation by dendritic cells to CD8 T cells
• Blocking of costimulation by CTLA‑4 on Tregs only for specific peptide‑MHC complexes
• Localized depletion of cytokines by effector T cells

Correct Answer: Suppression of immune responses to unrelated antigens in the same environment by regulatory mechanisms

Q12. Mixed chimerism as a strategy to induce transplant tolerance aims to:

• Replace recipient bone marrow completely with donor marrow to create permanent immunodeficiency
• Establish coexistence of donor and recipient hematopoietic cells to promote central tolerance to donor antigens
• Use high‑dose steroids to block alloreactive responses
• Induce peripheral anergy solely through costimulatory blockade

Correct Answer: Establish coexistence of donor and recipient hematopoietic cells to promote central tolerance to donor antigens

Q13. Which cell type can present antigen in a tolerogenic form and promote Treg induction under steady‑state conditions?

• Activated neutrophils
• Steady‑state dendritic cells with low costimulatory molecule expression
• Inflammatory macrophages producing IL‑12
• NK cells expressing high perforin levels

Correct Answer: Steady‑state dendritic cells with low costimulatory molecule expression

Q14. Which phenomenon describes the spread of immune responses from the initial dominant epitope to other epitopes of the same antigen or to different antigens?

• Clonal deletion
• Epitope spreading
• Receptor editing
• Immune ignorance

Correct Answer: Epitope spreading

Q15. Maternal‑fetal tolerance is facilitated in part by which mechanisms at the maternal‑fetal interface?

• High expression of classical MHC class I on trophoblasts to stimulate maternal T cells
• Local production of immunosuppressive cytokines like IL‑10 and TGF‑β and expression of nonclassical HLA‑G
• Vigorous maternal Th1 responses against paternal antigens
• Complete absence of antigen presentation in the decidua

Correct Answer: Local production of immunosuppressive cytokines like IL‑10 and TGF‑β and expression of nonclassical HLA‑G

Q16. Which assay is commonly used to measure functional T‑cell tolerance or responsiveness in vitro by assessing proliferation to alloantigen?

• Enzyme‑linked immunosorbent assay (ELISA) for cytokine only
• Mixed lymphocyte reaction (MLR)
• Flow cytometric detection of FOXP3 alone
• Western blot for TCR chains

Correct Answer: Mixed lymphocyte reaction (MLR)

Q17. Loss of peripheral tolerance leading to autoimmunity can be triggered by:

• Persistent infections that provide strong costimulation and inflammatory cytokines
• Complete absence of costimulatory signals throughout life
• Overexpression of FOXP3 in effector T cells
• Excessive IL‑10 production by macrophages

Correct Answer: Persistent infections that provide strong costimulation and inflammatory cytokines

Q18. Therapeutic use of low‑dose IL‑2 in tolerance induction aims to selectively expand which population?

• Effector CD8+ cytotoxic T lymphocytes
• FOXP3+ regulatory T cells
• Th17 proinflammatory cells
• B cell plasma cells producing autoantibodies

Correct Answer: FOXP3+ regulatory T cells

Q19. PD‑L1 on antigen‑presenting cells contributes to peripheral tolerance primarily by:

• Enhancing CD28 signaling to drive T cell activation
• Binding PD‑1 on T cells to reduce proliferation and cytokine production
• Delivering costimulation via ICOS ligand
• Activating complement on self‑tissues

Correct Answer: Binding PD‑1 on T cells to reduce proliferation and cytokine production

Q20. Which of the following best describes “immune ignorance” as a tolerance mechanism?

• Active suppression of responses by Tregs in the draining lymph node
• Lack of immune response because antigens are sequestered or present at levels below the activation threshold
• Deletion of autoreactive clones in the thymus
• Antibody‑mediated neutralization of self‑antigens

Correct Answer: Lack of immune response because antigens are sequestered or present at levels below the activation threshold

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