Cell-Mediated Immunity Overview

Cell-Mediated Immunity: Activation and Effector Mechanisms

• Dendritic cells are primarily responsible for antigen presentation to T lymphocytes.
• Dendritic cells take up antigens in the skin and transport them to draining lymph nodes.
• Antigen presentation occurs in T-cell areas of lymph nodes.
• T cell activation is dependent upon antigen recognition and costimulation.
• T cells proliferate and differentiate upon activation, leading to effector cells.
• Effector T cells migrate to sites of infection or inflammation.
• Migration of T lymphocytes to lymph nodes involves several steps including L-selectin binding, rolling interaction, chemokine activation and firm adhesion.
• T lymphocytes circulate through lymph nodes, searching for specific antigens.
• T cell activation results from antigen recognition and costimulation.

B-cell Epitopes

• B-cell epitopes can be peptide, polysaccharide or nucleic acid structures.
• B-cell epitopes are recognized directly without antigen presentation.
• B-cell epitopes can be linear or conformational.

T-cell Epitopes

• T-cell epitopes are peptide structures.
• T-cell epitopes are recognized with the help of antigen-presenting cells.
• T-cell epitopes are only of linear type.

Sequence of Events in T Cell Responses

• Activation of macrophages and other cells, leading to inflammation.
• T cell activation by antigen in lymphoid tissues.
• CD4+ T cell differentiation into various subtypes.
• CD8+ T cell differentiation into cytotoxic T lymphocytes (CTLs).
• CTLs and memory cells develop after antigen exposure and activation.
• Production of memory cells to provide a faster response to subsequent encounters with the same antigen.
• Cytotoxic T cells eliminate infected or cancerous cells.
• The sequence involves antigen recognition, lymphocyte activation, proliferation, and differentiation into effector and memory cells.

Role of Interleukin 2

• Activated T cells produce interleukin-2 (IL-2).
• IL-2 stimulates the survival, proliferation and differentiation of other activated lymphocytes such as T-cells, B-cells and NK cells.
• IL-2 promotes the survival and function of regulatory T cells.

Different Messages of Antigen-Presenting Cells to T Lymphocytes

• MHC class II molecules present antigens in lymphoid tissues.
• Costimulatory molecules (B7.1 and B7.2) are crucial for T cell activation.
• Cytokines (IL-6, IL-12, TGF-β, IL-4) further direct differentiation to different T helper subtypes.
• The activated T cell receives multiple signals from the antigen and the antigen-presenting cell.

The Role of CTLA-4

• CTLA-4 binds B7 more strongly than CD28 and transmits inhibitory signals.
• CTLA-4 regulation of T cell activity is essential to prevent excessive immune responses.

Therapeutic Use of CTLA-4 Inhibition

• CTLA-4-Ig inhibits T cell activation by binding B7.
• Blocking B7 signalling with CTLA-4-Ig mitigates or inhibits immune activation against transplantation or tumor cells.

Different Subtypes of T Lymphocytes

• CD8+ cytotoxic T lymphocytes (CTLs) kill virus-infected cells.
• CD4+ T helper (Th) cells coordinate the immune response by providing signals to other immune cells.
• Different Th subtypes (TH1, TH2, TH17, TFH, Treg) have distinct functions in immunity.
• Subtypes include TH1, TH2, TH17, regulatory T cells, and follicular helper T cells.
• Different T cell subtypes have unique roles in host defense against pathogens, inflammation and regulation.

Effector Mechanisms of Cellular Immunity

• Phagocytosis is a process in which a cell engulfs a particle, such as a pathogen, and then digests it.
• T cell activity induces inflammation to recruit more immune cells to the infection site.
• Cellular immunity is essential to eradicate infections.

Granules of Cytotoxic T Cells

• Perforin forms pores in the target cell membrane.
• Granzymes enter the target cell and activate caspase enzymes.
• Granulysin has antimicrobial activity.

Apoptosis Induction by Killer T Lymphocytes

• Perforin/granzyme pathway forms pores in the target cell.
• Granzymes enter the target cell and activate caspases.
• Fas/FasL pathway activates caspase-8, which initiates apoptosis.

Mechanism of Killing of Target Cells

• CTLs recognize and bind to virus-infected cells.
• CTLs release granules containing perforin and granzymes into the target cell.
• Target cell DNA fragments, triggering apoptosis (cell death).

Contact Between Killer T Cell and Target Cell

• CTLs and target cells form a close contact.
• This contact is crucial to induce activation of apoptosis in the infected cell.

Activation of Macrophages

• Macrophages can be activated by Th1 cells via the release of cytokines such as IFN-γ.
• Classical activation leads to enhanced killing of microbes.
• Activated macrophages increase the killing of microorganisms.
• Enhanced microbial killing through increased reactive oxygen species production and enzyme secretion.

Granuloma Formation

• Granulomas are structures formed in response to persistent infections when cellular immunity functions are compromised.

Executive Functions of TH2 Helper T Lymphocytes

• TH2 cells provide help to B cells, particularly for antibody production that targets helminthic pathogens.
• TH2 cells induce an immune response to helminth parasites, which elicit a type 2 immune response.
• TH2 cells regulate tissue repair after inflammation and helminthic infection.

Activation of Macrophages (Classical and Alternative)

• Classically activated macrophages (M1) kill microbes via phagocytosis and inflammation and are induced by direct interaction with activated T cells.
• Alternatively activated macrophages (M2) promote tissue repair and dampen inflammation and are activated by Th2 cytokines.

Exective Functions of TH17

• TH17 cells induce inflammation and recruit neutrophils, important in fighting extracellular bacteria.
• TH17 cells promote neutrophil recruitment to sites of infection via the production of IL-17, enabling effective combat against extracellular pathogens.

Stimulation of Killer T Lymphocytes

• Specific antigens stimulate proliferation and differentiation of T cells to CTLs.
• CTLs migrate to sites of infection and kill infected cells, enabling effective host defense.

Summary of T Lymphocyte Activation

• T-cell activation requires antigen recognition and costimulation.
• T-cell activation results in the production of effector T cells and memory T cells.
• CTLs recognize and kill infected cells or tumor cells by apoptosis.
• Cytotoxic T lymphocytes induce apoptosis in target cells.

Activation of T Lymphocytes (Costimulatory Molecules and Interleukin 2)

• Costimulatory molecules (e.g., CD28 and B7) are essential for T cell activation.

• IL-2 is crucial for T cell survival, proliferation, and differentiation, including the development of memory cells.

This quiz covers the mechanisms of cell-mediated immunity, focusing on T lymphocyte activation and effector functions, as well as the role of dendritic cells in antigen presentation. Additionally, it explores the structures recognized by B-cell epitopes, highlighting their importance in the immune response. Test your knowledge on these fundamental concepts of immunology.