Introduction: This collection of MCQs on Autoimmune diseases and mechanisms is tailored for M.Pharm students studying Immunotechnology. It focuses on core pathogenic concepts—central and peripheral tolerance, autoantibodies, genetic and environmental triggers, molecular mimicry, epitope spreading, and immune complex and cell-mediated mechanisms—along with diagnostic markers and therapeutic strategies. Each question probes mechanistic understanding and clinical relevance to help bridge fundamental immunology with pharmaceutical applications such as biologics, FcRn-targeted therapies, and immune modulation. Use these questions for self-assessment, revision, or classroom discussion to deepen your grasp of autoimmune pathogenesis and its implications for drug development and patient management.
Q1. Which molecular defect is primarily responsible for the failure of central tolerance that leads to multiorgan autoimmunity in autoimmune polyendocrine syndrome type 1?
- Defective peripheral regulatory T cell function due to FOXP3 mutation
- Mutations in AIRE causing impaired thymic expression of peripheral antigens
- Overexpression of costimulatory molecules on dendritic cells
- Gain-of-function mutation in PTPN22 increasing TCR signaling
Correct Answer: Mutations in AIRE causing impaired thymic expression of peripheral antigens
Q2. Myasthenia gravis is best classified immunologically as which type of hypersensitivity mechanism?
- Type I immediate hypersensitivity mediated by IgE
- Type II antibody-mediated cytotoxicity against cell surface receptors
- Type III immune complex–mediated tissue deposition
- Type IV T cell–mediated delayed-type hypersensitivity
Correct Answer: Type II antibody-mediated cytotoxicity against cell surface receptors
Q3. Deficiency of which complement component is most strongly associated with impaired clearance of immune complexes and an increased risk of systemic lupus erythematosus?
- Factor B
- C3
- C1q
- C5a receptor
Correct Answer: C1q
Q4. The pathogenic concept where a microbial antigen shares structural similarity with a self-antigen, triggering an autoimmune response, is called what?
- Bystander activation
- Molecular mimicry
- Epitope spreading
- Clonal anergy
Correct Answer: Molecular mimicry
Q5. Which autoantibody has the highest specificity for rheumatoid arthritis and is routinely used in diagnosis?
- Anti-nuclear antibody (ANA)
- Anti-double stranded DNA (anti-dsDNA)
- Anti-cyclic citrullinated peptide (anti-CCP)
- Anti-thyroid peroxidase (anti-TPO)
Correct Answer: Anti-cyclic citrullinated peptide (anti-CCP)
Q6. The neonatal Fc receptor (FcRn) influences autoantibody-mediated disease primarily by what mechanism?
- Presenting antigen to CD8 T cells in the thymus
- Saturating Fc gamma receptors on macrophages to block phagocytosis
- Recycling IgG and extending its serum half-life
- Promoting class switching to IgE
Correct Answer: Recycling IgG and extending its serum half-life
Q7. Epitope spreading in autoimmune disease refers to which phenomenon?
- Loss of central tolerance due to AIRE deficiency
- Expansion of an immune response from initial epitopes to other epitopes on the same or different antigens
- Direct tissue damage caused by complement membrane attack complex
- Generation of autoantibodies by molecular mimicry alone
Correct Answer: Expansion of an immune response from initial epitopes to other epitopes on the same or different antigens
Q8. A mutation in which gene causes IPEX syndrome characterized by severe early-onset autoimmunity due to dysfunctional regulatory T cells?
- PTPN22
- FOXP3
- AIRE
- CTLA4
Correct Answer: FOXP3
Q9. Which HLA alleles are classically associated with increased susceptibility to type 1 diabetes?
- HLA-B27
- HLA-DR3 and HLA-DR4
- HLA-DR2 only
- HLA-A2 and HLA-B8
Correct Answer: HLA-DR3 and HLA-DR4
Q10. The primary pathogenic mechanism of ANCA-associated small-vessel vasculitis involves which of the following?
- Deposition of large immune complexes in vessel walls
- Autoantibody-mediated activation of neutrophils leading to degranulation and endothelial injury
- IgE-mediated hypersensitivity causing mast cell degranulation
- Complement deficiency preventing opsonization
Correct Answer: Autoantibody-mediated activation of neutrophils leading to degranulation and endothelial injury
Q11. Immune checkpoint inhibitors such as anti-CTLA-4 and anti-PD-1 cause autoimmune adverse events primarily because they:
- Directly stimulate B cell class switching to pathogenic IgG
- Block co-stimulatory signals required for T cell activation
- Disrupt peripheral tolerance by inhibiting negative regulatory pathways
- Neutralize circulating regulatory cytokines like IL-10
Correct Answer: Disrupt peripheral tolerance by inhibiting negative regulatory pathways
Q12. Which autoimmune disease is prototypically mediated by circulating immune complexes that deposit in tissues, activating complement and causing inflammation?
- Type 1 diabetes mellitus
- Systemic lupus erythematosus
- Myasthenia gravis
- Hashimoto thyroiditis
Correct Answer: Systemic lupus erythematosus
Q13. Which biologic therapy depletes CD20+ B cells and is widely used for B cell–mediated autoimmune diseases?
- Infliximab
- Rituximab
- Etanercept
- Tocilizumab
Correct Answer: Rituximab
Q14. Th17 cells contribute to autoimmunity mainly by producing which proinflammatory cytokine that recruits neutrophils and promotes tissue inflammation?
- Interferon-gamma (IFN-γ)
- Interleukin-17 (IL-17)
- Interleukin-10 (IL-10)
- Transforming growth factor-beta (TGF-β)
Correct Answer: Interleukin-17 (IL-17)
Q15. Maternal autoantibodies cause neonatal disease because IgG is actively transported across the placenta via which receptor?
- Fc gamma receptor I (FcγRI)
- Polymeric Ig receptor (pIgR)
- Neonatal Fc receptor (FcRn)
- Complement receptor 1 (CR1)
Correct Answer: Neonatal Fc receptor (FcRn)
Q16. In systemic lupus erythematosus, which autoantibody correlates best with disease activity and lupus nephritis?
- Anti-centromere antibody
- Anti-double stranded DNA (anti-dsDNA)
- Anti-mitochondrial antibody
- Rheumatoid factor
Correct Answer: Anti-double stranded DNA (anti-dsDNA)
Q17. The hyperthyroidism of Graves’ disease is caused by which immunologic mechanism?
- Cell-mediated destruction of thyroid follicles by CD8 T cells
- Deposition of immune complexes in the thyroid vasculature
- Stimulating autoantibodies against the TSH receptor
- Blocking antibodies that inhibit thyroid peroxidase
Correct Answer: Stimulating autoantibodies against the TSH receptor
Q18. A genetic polymorphism in PTPN22 influences autoimmunity by altering which cellular process?
- Complement activation cascade
- Toll-like receptor ligand recognition
- T cell receptor signaling thresholds and lymphocyte activation
- Antigen presentation by MHC class I molecules
Correct Answer: T cell receptor signaling thresholds and lymphocyte activation
Q19. Central tolerance in the thymus relies on presentation of self-antigens by medullary thymic epithelial cells; which protein enables expression of peripheral tissue antigens in the thymus?
- FOXP3
- AIRE (autoimmune regulator)
- CTLA-4
- RAG1
Correct Answer: AIRE (autoimmune regulator)
Q20. Type 1 diabetes mellitus is an example of which immunopathologic mechanism underlying autoimmunity?
- Type II antibody-mediated cytotoxicity against cell-surface receptors
- Type III immune complex deposition causing vascular injury
- Type IV T cell–mediated destruction of pancreatic beta cells
- Type I IgE-mediated mast cell activation
Correct Answer: Type IV T cell–mediated destruction of pancreatic beta cells
