T-Cell Activation and Function

T-Cell Activation

• T-cells mature in the thymus.
• Each T-cell has a unique T-cell receptor (TCR) that recognizes specific antigens.
• T-cells recognize antigens presented on the surface of infected cells.
• Effective against viruses and intracellular pathogens.
• Types:
  • Cytotoxic T cells (CD8/Tc cells): Kill cancerous or infected cells.
  • Helper T cells (CD4/Th cells): Activate the immune system via cytokines.
• T-cells recognize infected cells via antigens presented on MHC molecules (major histocompatibility complex).
• MHC Class I (MHC I): Found on all nucleated cells in the body. Presents foreign proteins.
  • Foreign proteins digested by proteasomes.
  • Foreign peptides delivered to MHC I via the endoplasmic reticulum (ER).
  • Recognized by cytotoxic T cells (Tc cells), leading to cell death.
  • Mechanism:
    1. Infected cell presents antigen on MHC I.
    2. Tc cell recognizes the antigen via its TCR.
    3. Tc cell kills the infected cell using granzymes and perforin.
• MHC Class II (MHC II): Found on dendritic cells and macrophages. Involved in surveillance and triggering immune responses.
  • Microbes digested within phagosomes.
  • Microbial peptides loaded onto MHC II and presented on the cell surface.
  • Recognized by helper T cells (Th cells), which secrete cytokines to activate antigen-presenting cells (APCs).
  • Mechanism:
    1. Dendritic cells (DCs) present antigen on MHC II in lymph nodes.
    2. Th cells are activated.
    3. Th cells release cytokines to activate immune cells.

Antigen Presentation (Summary)

• Infection occurs.
• DCs present antigens to T-cells in lymph nodes.
• T-cells are activated and released.
• Tc cells kill infected cells.
• Th cells activate DCs/macrophages presenting the antigen.
• Memory T-cells are produced.

Clonal Expansion of T-cells

• Activated by dendritic cell proliferation (1-2 days).
• Effector cells (Th CD4 and Tc CD8) leave lymphoid tissue.
• Importance of Th cells:
  • Allow B-cells to become plasma and memory cells.
  • Stimulate Tc cells to proliferate and kill infected cells (e.g., IFN-γ and TNF-α).
  • Activate macrophages to kill pathogens.
• HIV targets CD4 cells: Compromises the immune system.

B-Cell and T-Cell Activation

• Naive T-cells and B-cells migrate to lymph nodes/spleen after maturation.
• Continue circulating in the body.
• Upon infection:
  1. Microbes enter.
  2. Antigens presented in lymph nodes (by DCs).
  3. Free antigens enter the blood (spleen).
  4. T-cells and B-cells recognize and become activated.

Antigen Entering Lymph Nodes

• B-cells: Look for free antigens in lymph nodes.
  • Lymph node macrophages: viruses and large antigens.
  • Lymph fluid: soluble (small) antigens.
• T-cells: Look for DCs presenting antigens.
  • Scan all DCs within 24 hours.
  • If no antigen, move to next lymph node.
  • If antigen detected, T-cell clones are activated.
  • If soluble antigen detected, B-cells wait for Th cell activation.

B-Cell Activation

• If antigen detected, B-cell stays in lymph node.

• T-cells proliferate into Tc and Th cells (clonal selection).

• B-cell's IgD binds antigen, engulfs it, processes it, and presents it via MHC II.

• Within 48 hours, B-cell finds a Th cell with the correct TCR.

• B-cell is activated, differentiating into plasma cells.

• B-cell activation and proliferation take 4-7 days in lymph nodes, producing ~5000 plasma cells.

• Plasma cells produce 5 classes of antibodies (GAMED).