Lecture 38: Antigen Presentation and Adaptive Immunity

🔹 Antigen Presentation

Q: What is antigen presentation?

A: The process by which antigen-presenting cells (APCs) display fragments of pathogens (peptides) on MHC molecules to T cells, enabling immune recognition and activation.

🔹 Antigen Presentation

Q: What benefits does antigen processing provide?

A:

• Breaks down complex pathogens into identifiable peptides

• Prevents immune evasion by hiding internal proteins

• Allows T-cell recognition of infected cells or APCs

🔹 Antigen Presentation

Q: Name three professional antigen-presenting cells.

A:

1. Dendritic cells

2. Macrophages

3. B cells

🔹 Surface vs. Internal Antigens

Q: What is the difference between surface and internal antigens?

A:

• Surface antigens bind directly to B-cell receptors (BCRs)

• Internal antigens are processed by APCs and presented via MHC molecules to T cells

🔹 T Cell Activation

Q: How do T-helper cells recognize antigens?

A: They recognize internal antigens displayed by MHC II on APCs using their T-cell receptor (TCR).

🔹 T Cell Activation

Q: What happens after T-helper cells are activated?

A: They proliferate and provide help signals (via cytokines and CD40L) to B cells, enabling antibody production.

🔹 B Cell Activation & Class Switching

Q: How do B cells become fully activated?

A:

1. Bind surface antigen via BCR

2. Process & present internal antigen on MHC II

3. Interact with activated T-helper cells recognizing the same antigen
   → Result: Differentiation into plasma cells, IgM production

🔹 B Cell Activation & Class Switching

Q: What occurs upon second exposure to the same antigen?

A:

• B cells engage CD40-CD40L signaling

• Express AID enzyme, undergo somatic hypermutation and class switching

• Produce high-affinity IgG, IgA, or IgE

🔹 B Cell Activation & Class Switching

Q: What ensures B cells only produce antibodies with T cell help?

A: A multi-factor identification scheme: B cell must present the same internal antigen that T cells recognize via MHC II, or it won’t receive activation help.

🔹 MHC Types

Q: What are the two types of MHC molecules and their functions?

A:

• MHC I: Displays endogenous peptides (from cytosol) to CD8⁺ cytotoxic T cells

• MHC II: Displays exogenous peptides (from phagolysosomes) to CD4⁺ helper T cells

🔹 MHC Types

Q: What are the sources of peptides for MHC I vs. MHC II?

A:

• MHC I: Proteasome degradation → cytosolic peptides

• MHC II: Lysosomal degradation → extracellular peptides

🔹 Specialized Proteasomes & TCR Diversity

Q: How do different proteasomes produce different peptides?

A:

• Immunoproteasomes (induced by cytokines) generate peptides optimized for MHC I loading

• Change cleavage preferences to increase epitope yield

🔹 Specialized Proteasomes & TCR Diversity

Q: How is diversity generated in T-cell receptors (TCRs)?

A: Like antibodies, TCRs undergo:

• V(D)J recombination

• Junctional imprecision

• Random nucleotide addition by TdT

🔹 T Cell Development & Selection

Q: Where do T cells mature?

A:

• Originate in bone marrow

• Mature in the thymus

🔹 T Cell Development & Selection

Q: What happens during T cell selection in the thymus?

A:

• Positive selection: Moderate affinity for self-MHC = survive

• Negative selection: High affinity for self-antigen = eliminated
  → Only ~1% survive to peripheral circulation

🔹 Immunological Memory

Q: What provides long-lasting immunity?

A:

• Memory B cells

• Memory T-helper cells
  These circulate and mount faster, stronger responses on re-infection.

🔹 Immunological Memory

Q: How do CTL and antibody titers respond to first vs. second exposure?

A:

• First exposure: slow rise in antibodies and CTLs

• Second exposure: rapid, higher response due to memory cells

🔹 Evolution of Adaptive Immunity

Q: Which organisms have adaptive immunity?

A: Jawed vertebrates (e.g., humans, fish)

🔹 Evolution of Adaptive Immunity

Q: What components define adaptive immunity?

A:

• Immunoglobulins (Ig)

• T-cell receptors (TCRs)

• MHC molecules

• RAG1/2 recombination enzymes

• Cytokines