Cellular Immunity - 2.3.25

The Immune System: Cellular Immunity

Overview

• Focus on the anatomy and physiology of the immune system in the context of adaptive immunity.

• Date of reference: Spring 2025, February 3.

Adaptive Immunity

• Definition: Adaptive response to common environmental pathogens.

• Characteristics:

  • Systemic: Impacting the entire body.

  • Specific: Target specific pathogens.

  • Memory: Remembers past infections for a quicker response upon re-exposure.

Forms of Adaptive Immunity

• Adaptive Defenses: Divided into two main types:

  • Humoral Immunity: Involves B cells.

  • Cellular Immunity: Involves T cells.

Lymphocyte Receptors

• Interaction: T cells and B cells have unique surface receptors for antigens.

• Specificity: Each receptor can recognize only one specific antigen.

• Genetic Configuration: Receptor configurations are genetically determined, leading to thousands of possible configurations.

• Gene Influence: Genes dictate which foreign substances can be recognized by the immune system.

Cellular Immunity

• Mediated by T Cells: T cells defend against intracellular targets.

• Recognition: They only recognize processed antigens presented by antigen-presenting cells (APCs).

Antigen Presenting Cells (APCs)

• Types: Include macrophages and dendritic cells.

• Function:

  • Phagocytize antigens.

  • Display digested epitopes on cell surface using MHC proteins.

  • The process involves:

    • Phagocytosis of the antigen.

    • Fusion of lysosome with phagosome.

    • Degradation of antigen.

    • Displaying processed fragments on the surface.

Major Histocompatibility Complex (MHC) Proteins

• Role: Protein complexes on cell membranes that hold protein fragments, labeling cells as ‘self.’

• Types:

  • MHC-I: Found on every nucleated cell, displays endogenous proteins.

  • MHC-II: Found only on APCs, displays exogenous antigens.

MHC Proteins on APCs

• Function: Display epitopes on MHC proteins post-processing.

• Activation: Non-self epitopes stimulate a T cell response.

• MHC Restriction:

  • Cytotoxic T cells respond to MHC-I proteins.

  • Helper T cells respond to MHC-II proteins.

• Importance: T cells must correctly interact with MHC proteins to distinguish between self and non-self antigens.

T Cell Testing: Immunocompetence

• Location: Cortex of thymus.

• Test: Ability to bind MHC proteins on APCs:

  • Pass: T cell is immunocompetent.

  • Fail: Recombine DNA for new receptors or undergo apoptosis (positive selection).

T Cell Testing: Self-Tolerance

• Location: Medulla of thymus.

• Test: T cell receptors should not bind to self antigens:

  • Pass: T cell is self-tolerant.

  • Fail: Undergo apoptosis (negative selection).

• Outcome: Naïve T cells leave the medulla, moving to secondary lymphatic tissues.

Classes of T Cells

• Cytotoxic (killer) T (TC) Cells: Attack enemy cells directly.

• Helper T (TH) Cells: Activate TC cells, stimulate B cell proliferation, and trigger the innate immune response.

• Regulatory T (TR) Cells: Inhibit action/proliferation of other T cells.

• Memory T (TM) Cells: Responsible for cellular immune memory.

Phase 1: Recognition (TH)

• Process:

  • Antigen Presentation: Naïve TH cell binds to MHC-II with the matching receptor.

  • Co-stimulation: Completion of activation requires binding to a second protein.

  • Proliferation: Produces clones that respond to the identical epitope.

  • Outcome: Most become effector TH cells; some become memory TH cells.

Phase 1: Recognition (TC)

• Process:

  • Antigen Presentation: Naïve TC cell binds to MHC-I on APC.

  • Co-stimulation: Requires active TH to induce a second molecule on APC.

  • Proliferation: Produces clones that respond to the identical epitope.

  • Outcome: Most become effector TC cells; some will become memory TC cells.

Phase 2: Attack (Primary Response)

• TC Cells Action: Seek and identify cancerous or infected cells.

• Mechanism:

  • Bind to the MHC-I + epitope complex.

  • Deliver lethal hit using:

    • Perforin: Creates pores in target cells.

    • Granzymes: Induce apoptosis.

    • Interferons and TNF: Modulate immune response and inflammation.

TC Cells vs NK Cells

• TC Cells: Respond to specific processed antigens and require MHC-I interaction; slower response with immune memory.

• NK Cells: Can recognize and attack foreign pathogens plus infected or cancerous host cells without MHC restriction; faster initial response.

Helper T (T4) Cells and Immune Activation

• Cytokines: TH cells release interleukin and other cytokines to activate other immune cells, including:

  • Macrophages.

  • Neutrophils.

  • B cells.

• Functions:

  • Activate TC and B cells.

  • Stimulate inflammation and non-specific defenses.

Phase 3: Memory (Recall Response)

• Outcome: Following activation, some TC and TH cells become memory cells which are long-lived and more numerous than naïve T cells.

• Rapid Response: Memory cells respond quickly to antigen re-exposure, preventing noticeable illness and providing immunity.

Conclusion

• Summary: Effective immune response involves a coordinated interaction between various T cell types, antigen-presenting cells, and MHC proteins, leading to recognition, activation, and memory for future pathogen encounters.