Week 8 - T Cell Mediated Immunity

T Cell Receptor (TCR) recognizes the Major Histocompatibility Complex (MHC) molecule on another cell.
Upon recognition, the T cell responds by proliferating and differentiating to become an effector T cell.

Recognition: T cells identify specific antigens presented in secondary lymphoid organs.
Action: Activated T cells initiate a proliferation phase to build an army:
- Front line: The first response to infection.
- Weaponry: The tools T cells will utilize against pathogens.

Dendritic cells play a crucial role in capturing invading antigens.
- They take antigens to secondary lymphoid tissues for presentation.
- Antigens are presented on the surface of dendritic cells using MHC receptors.
- Lymphoid tissues act as the presentation location for these antigens.

Capture Process: Dendritic cells take up bacterial antigens in the skin and enter a draining lymphatic vessel.
Presentation: Dendritic cells bearing antigens enter the draining lymph node, residing in the T-cell areas.

Immature dendritic cells: Found in skin and peripheral tissues.
Mature (activated) dendritic cells: Located in lymph nodes where:
- Dendritic cells elongate.
- Macrophages assist dendritic cells by providing additional effector functions, breaking down pathogens.

Micropinocytosis: Receptor-mediated internalization of small volumes of extracellular fluid.
Macropinocytosis: Nonspecific ingestion of larger volumes, crucial for processing via the MHC class II pathway, allowing presentation to naïve T cells.
Within infected dendritic cells, processed peptides are presented on MHC class I.
- If a dendritic cell dies from a viral infection, the virus can escape and infect another dendritic cell for re-presentation.

Entry Mechanism: T cells enter lymph nodes through blood, bind to endothelial cells, and pass through the T-cell zone.
Antigen Encounter: In the T-cell zone, T cells encounter dendritic cells presenting antigens where:
- TCR inspects each MHC for presented antigens.
- If a T cell recognizes its specific antigen, it attaches to the dendritic cell.
T cells can also enter via lymphatic fluid.

Process: Naïve T cells leave the bloodstream, entering the T-cell zone through a process regulated by cytokines produced by dendritic cells.
Cell Adhesion Molecules:
- L-selectin: On T cells, binds to carbohydrates of endothelial cells.
- CD34 and ICAMs: Slow down T cells, pulling them through the endothelium.

Activation requires both TCR engagement with MHC:peptide complex and a secondary costimulatory signal.
Key Signals for Activation:
- The combined signals from TCR, co-receptors, and costimulatory receptors activate naïve T cells.
- Interleukin-2 (IL-2): Assists in T cell proliferation and differentiation, exhibiting autocrine and paracrine activity.

Escaped self-reactive T cells that encounter antigen without co-stimulation become anergic:
- Anergy Defined: A condition where T cells cannot activate, divide, differentiate, or respond.

CD4 T cells assist in the activation of other effector cells:
- TH1 Cells: Help macrophages respond to intracellular infections and induce cytotoxic T cell responses.
- TH2 Cells: Induce antibody responses against extracellular parasites.
- Treg Cells: Regulate CD8 and CD4 T cell activity to control immune responses.

TH1 Cells:
- Responsible for increasing inflammation and defending against intracellular viral and bacterial infections.
- Key cytokines: Interferon-gamma (IFN-γ) and Interleukin-12 (IL-12) supporting cell-mediated immunity.
TH2 Cells:
- Target extracellular parasites by activating antibodies.
- Key cytokine: IL-4, promoting humoral immunity.
Treg Cells:
- Control and down-regulate immune responses when they are no longer needed.
- TNF-β involvement.

Characteristics of Effector T Cells:
- TH1 Cells and TH2 Cells: Defined by their characteristic cytokines, transcription factors, and effector functions.
- TH1 Cytokines: IL-12, IFN-γ, activation of macrophages.
- TH2 Cytokines: IL-4, IL-5, amplification of humoral immune response against parasites.
Treg Characteristics:
- Transcription factor FoxP3 governs Treg function, suppressing other T cell activities.

Post-Differentiation Actions: After differentiating, T cells detach from dendritic cells and enter circulation towards infection sites.
- CD8 cytotoxic T cells trigger apoptotic responses in target cells with assistance from TH1 cells.

Functionality of Effector T Cells:
- Effector CD8 T cells search for virus-infected cells presenting the specific antigen and induce apoptosis without requiring co-receptors.
- Effector CD4 T cells recognize MHC class II molecules to activate presenting cells.

Cytotoxic Activity:
- Cytokines from T cells induce internal behavioral changes in target cells, leading to cell death via apoptosis.
- Death is triggered by the delivery of cytotoxins.
- Cytotoxic Molecules: Granzymes, perforins, and granulolysins stored in lytic granules.

Apoptosis (Programmed Cell Death):
- Prevents further pathogen spread.
- Results in a shriveled, compact cell, leading to phagocytosis by clean-up cells.

Cytotoxic T Cells: Close proximity cytokine release enables T cells to kill several target cells in succession.
- Cell Killing Process: Initial target cells undergo programmed death while the cytotoxic T cells transition to second target cells.

Role of CD4 TH1 Cells:
- Activate macrophages, enhancing phagocytosis and increasing the production of antimicrobial enzymes.
- CD40 Interaction: CD40 ligand on T cells binds to CD40 on macrophages, enhancing their ability to kill intravesicular bacteria.

TFH Cell Functionality:
- TFH cells recognize peptides derived from B cells' antigens, signaling for B cell activation.
- Interaction involves exchange of signals through CD40 and cytokines, enhancing the efficiency of antibody production.