Section B: step by step

Question 1

What mechanisms generate BCR and TCR diversity?

Answer 1

V(D)J recombination, Junctional diversity, Combinatorial diversity, Somatic hypermutation, Class switch recombination

• V(D)J recombination: randomly joins V, D (heavy chain only), and J gene segments.
• Junctional diversity: imprecise joining, nucleotide addition (TdT).
• Combinatorial diversity: random pairing of light + heavy or α + β chains.
• Somatic hypermutation (B cells only): mutations improve affinity.
• Class switch recombination (B cells): changes antibody isotype.

Question 2

What determines antibody specificity for antigens?

Answer 2

Fab region, Complementarity-determining regions (CDRs), Non-covalent binding, High structural complementarity

• Fab region contains variable domains from heavy and light chains.
• CDRs in the variable domain bind antigen.
• Binding is non-covalent: H-bonds, van der Waals, ionic.

Question 3

What are the main antibody classes and their functions?

Answer 3

IgM, IgG, IgA, IgE, IgD

• IgM: first produced; pentameric; complement activation.
• IgG: main serum antibody; crosses placenta; opsonisation.
• IgA: mucosal immunity; found in secretions.
• IgE: allergies and parasites; binds FcεRI on mast cells.
• IgD: role unclear; present on naïve B cells.

Question 4

How do CD8+ T cells kill virus-infected cells?

Answer 4

Recognise viral peptides on MHC I, Release perforin and granzymes, Trigger apoptosis via Fas–FasL binding, Release IFN-γ, Form memory T cells

• Induce apoptosis.

Question 5

How do dendritic cells activate naïve T cells?

Answer 5

Capture antigen, Migrate to lymph nodes, Present antigen on MHC I and MHC II, Provide co-stimulatory signals, Secrete cytokines

• Chemokine signals: CCR7.
• Co-stimulatory signals: CD80/CD86.
• Example cytokine: IL-12 for Th1.

Question 6

How does the innate immune system respond to viruses?

Answer 6

PRRs detect viral RNA/DNA, Infected cells release Type I IFNs, Activate NK cells, Dendritic cells bridge to adaptive response

• Example PRRs: TLR3, RIG-I.

Question 7

How does the adaptive immune system respond to viruses?

Answer 7

CD8+ T cells kill infected cells, CD4+ T cells help B cells and cytotoxic T cells, B cells produce neutralising antibodies, Memory cells provide long-term immunity

Question 8

How is a latent viral infection resolved?

Answer 8

Virus reactivates, Antigen presented on MHC I, Cytotoxic T cells destroy infected cells, Antibodies neutralise extracellular virus, CD4+ cells support memory

• Cytokine production.

Question 9

How does IgE mediate allergic reactions (Type I hypersensitivity)?

Answer 9

Allergen exposure triggers IgE production, IgE binds FcεRI receptors, Re-exposure triggers degranulation

• Degranulation releases histamine, leukotrienes, prostaglandins.
• Causes inflammation, vasodilation, bronchoconstriction (anaphylaxis).

Question 10

What are examples of inherited immunodeficiencies?

Answer 10

SCID, X-linked agammaglobulinaemia, CGD

• SCID: lack of functional T and B cells.
• X-linked agammaglobulinaemia: no mature B cells → no antibodies.
• CGD: phagocytes can’t produce ROS → recurrent infections.

Question 11

What are examples of acquired immunodeficiencies?

Answer 11

HIV/AIDS, Cancer, Immunosuppressive drugs

• HIV/AIDS: infects and kills CD4+ T cells.
• Cancer: tumours or chemotherapy suppress immunity.
• Immunosuppressive drugs: used in transplant patients.

Question 12

What are treatments for immunodeficiencies?

Answer 12

Gene therapy, Antiretroviral therapy, IVIG, Bone marrow transplant, Cytokine or monoclonal antibody therapy

Question 13

What are consequences of immune dysfunction?

Answer 13

Recurrent infections, Poor vaccine responses, Autoimmune disease, Opportunistic infections

• Example: PCP in AIDS.