Immune System Overview

Perforins

• Perforins create holes in target cell membranes, allowing granzymes to enter.
• Granzymes activate enzymes leading to DNA degradation and cell death.

Cell Mediated: T-Cell Roles

• FAS receptor signaling leads to apoptosis.
• Apoptosis is a programmed cell death characterized by cell shrinkage and DNA fragmentation.
• Osmotic lysis occurs when perforins allow fluids to enter the target cell, leading to swelling and rupture.
• Apoptosis is faster and more efficient than osmotic lysis.

Humoral Immune Response

• Main function: destroy extracellular pathogens or prevent the spread of internal ones.
• Achieved by producing antibodies or immunoglobulins.

B Cell Surface Molecules

• B-cell receptor (BCR): present on immature B cells, predominantly IgM.
• CD40: essential for interaction with T cells.
• MHC II: presents antigens to T helper cells.

B Cell Activation

• Signal 1: Antigen binds to BCR, activating B cells. B cells engulf, degrade, and present antigens on MHC II.
• Signal 2 (co-stimulatory): Peptide-MHC II complex recognized by T helper cells.
  • CD40L binds to CD40 on B cell surface.
  • T helper cells secrete cytokines (IL-4, 5, 6, & 10) to activate B cell differentiation into plasma cells.

T-Cell Dependent vs. T-Cell Independent Antigen Activation

• T-cell dependent antigens: require T helper cells for B cell activation.
• T-cell independent antigens: directly activate B cells without T cells, but only produce IgM and no memory cells.

T Helper Cells (Th)

• Th1 cells: stimulate macrophages to kill intracellular pathogens (e.g., Mycobacterium tuberculosis).
• Th2 cells: assist in destroying extracellular pathogens by activating B cells to produce antibodies.

T Cytotoxic Cells (Tc)

• Function: eliminate virus-infected cells and tumor cells.

Lymphocyte Subsets

• Common Lymphoid Progenitor (CLP): gives rise to both T and B cells.
• T cells: mature in the thymus.
  • T helper cells: secrete cytokines.
  • Cytotoxic T cells: kill infected cells.
• B cells: mature in the bone marrow.
  • Plasma cells: secrete antibodies.

T Cells

• Major role in cell-mediated immunity.
• Identified by the presence of the T-cell receptor (TCR) on the cell surface.
• T helper cells: secrete cytokines to assist other immune cells.
• T cytotoxic cells: kill infected cells and tumor cells.

Mechanism of Macrophage Activation by Th1 Cells

• Infected macrophages present peptide-MHC II complexes to effector Th1 cells.
• Th1 cells release interferon-gamma (IFN-γ) causing macrophage activation.
• Activation leads to:
  • Enhanced fusion of phagosomes and lysosomes.
  • Increased production of reactive oxygen species, nitric oxide, and antibacterial enzymes.

MHC Display Properties

• MHC I: Found on all nucleated cells and presents antigens to CD8+ T cytotoxic cells.
• MHC II: Found on antigen-presenting cells (APCs) and presents antigens to CD4+ T helper cells.

Cell Mediated: T-Cell Roles

• Activated T helper cells interact with antigen-presenting B cells.
• Release cytokines that stimulate B cell maturation and antibody production.

Function of Effector CD8+ T cells (Cytotoxic T Cells)

• Eliminate abnormal cells like virus-infected cells and tumor cells.
• Recognize viral peptides presented on MHC I molecules.

Mechanism of Killing by Cytotoxic T Cells

• Induction of apoptosis:
  • Release of cytoplasmic granules: Perforins and granzymes.
  • Perforins create pores in the target cell membrane.
  • Granzymes activate enzymes leading to DNA degradation and cell death.
• Osmotic lysis: Perforins allow fluids to enter the target cell, leading to cell swelling and rupture.

CD28 Molecule

• Binds to B7 molecule on antigen-presenting cells (APCs) during antigen recognition.
• Provides the second signal for T cell activation.

CD40 Ligand (CD40L)

• Present on activated T helper cells.
• Involved in B cell activation by binding to CD40 on B cells.