Day 6 · Antigen Presentation, TCR and T-cell Activation

Session 2: Prof. Carla Rothlin

How the Immune System Works: Activation of Adaptive Immunity by Innate Immunity

Part I: Linking Innate and Adaptive Immune Responses

Dendritic Cells and Antigen Presentation to T Cells:
- Dendritic cells engulf bacteria through phagocytosis, leading to activation.
- Activation involves: i) MHC (Major Histocompatibility Complex) presentation. ii) Co-stimulation (e.g., CD80/CD86 on dendritic cells). iii) Release of cytokines.
Antigen Presentation Specifics:
- Exogenous antigens (bacteria) are presented via MHC II.
- Endogenous antigens (viruses) are presented via MHC I.
Intracellular Bacteria Processing:
- Pathway: Bacteria in cell → Increased mRNA → MHC II synthesis → Transport to endosome containing bacteria → Acidification of endosome → MHC II binding to bacterial antigens.
- Activated dendritic cells migrate to lymph nodes where they encounter T cells.

Part II: T Cell Maturation in the Thymus

T Cell Maturation Process:
- Origin: Bone Marrow → Common lymphoid progenitors → T cell precursors migrate to the Thymus.
- Genomic rearrangement in T cells occurs in the Thymus.
- MHC II responds to CD4, and MHC I responds to CD8.
Question: Genetic Manipulation of T Cell Genes in a Mouse:
- Answer: A mouse created with T cell genes would respond only to a specific antigen, losing the ability to combat other infections.
Why Genomic Expression Changes in T Cells Specifically:
- Answer: Altering genomic expression facilitates specific cell division processes.

Thymic Recognition of Self-Peptides and T Cell Selection

AIRE and Self-Peptide Recognition:
- AIRE (Autoimmune Regulator) allows thymic cells to express a wide range of self-peptides, crucial for negative selection.
- This process occurs before functional T cell generation to avoid self-immunity.
- Positive Selection: Promotes functional TCR.
- Negative Selection: Eliminates high-affinity reactive T cells to prevent autoimmunity.
- Many cells undergo apoptosis during thymic negative selection to ensure self-clearance.
Mechanism of T Cell Activation:
- Dendritic cell → MHC II presentation → T cell receptor binding → CD4 interaction with MHC class II.
- RTKs (Receptor Tyrosine Kinases) trigger signal amplification via phosphorylation.
Activation Requirements for T Cell Proliferation:
- Need Ca++ and DAG (Diacylglycerol).
- Phospholipase-C-gamma generates DAG and IP3.
- CD28 signaling activates effective activation and induces CD80/86 upon activation.

These notes elaborate on the activation of adaptive immunity by the innate immune system, emphasizing dendritic cell function, antigen presentation to T cells, T cell maturation in the thymus, and mechanisms behind self-peptide recognition and T cell selection.

If you require further clarification or additional details, please feel free to ask!