Immunology: Adaptive Immunity - T Cells

Adaptive Immunity - T Cells

• T cells are part of the adaptive immune system, specifically targeting antigens.
• They have two key functions: -Helper T cells (Th) assist immune responses. -Cytotoxic T cells (CTL) destroy infected and cancerous cells.

Immunology Lectures Outline

• Barrier Immunity: Physical, mechanical, and chemical barriers provide instant protection against infection.
• Innate Immunity: Cytokines, inflammation, complement proteins, and antigen presentation provide protection over minutes to weeks.
• Adaptive Immunity: T cells (cytotoxic and helper) respond to extracellular and intracellular infections. B cells produce antibodies.

Lecture Learning Outcomes

• Students should be able to: -Define the roles of T cells. -Describe T cell development, including receptor rearrangement. -Explain processes for T cell positive and negative selection. -Describe T cell activation. -Define T helper cell and cytotoxic T cell functions. -Identify T helper cell subsets (Th1, Th2, Th17, Treg) and their roles in infection. -Outline T cell tolerance mechanisms (central and peripheral). -List diseases due to T cell defects.

Key Roles of T Cells

• T cells are part of the adaptive immune system.
• T cells have two main functions: -Helper T cells (Th) assist with immune responses. -Cytotoxic T cells (CTL) directly kill infected or cancerous cells.

Antigen Presentation

• MHC class II and MHC class I receptors present antigens on cell surfaces.
• Only peptide antigens are presented, not whole pathogens.
• TCR recognizes the MHC-peptide complex.
• Communication about the pathogen occurs to activate the adaptive immune system.
  • MHC class II - T helper cells
  • MHC class I - Cytotoxic T cells

Unique Features of T Cells

• T cells interact with other cells to function.
• TCR recognizes antigen bound to MHC.
• Each T cell has a unique TCR.
• T cells undergo clonal expansion after activation.
• T helper and cytotoxic cells have different effector functions.
• T cells create memory cells that persist for many years.

Pertinent Questions

• Where do T cells originate?
• How do T cells express TCR with antigen-specific affinity?
• What is the T cell activation process, and why is it important?
• What are the differences between T helper and cytotoxic T cells?

T Cell Development

• Immature T cells migrate to the thymus from the bone marrow.
• In the thymus, T cells undergo development.
• Mature T cells exit the thymus and circulate as naïve cells (CD4+ or CD8+).

T Cell Checkpoints

• T cells must have a TCR.
• TCRs must recognize MHC.
• TCRs must not recognize self antigens.

T Cell Receptor (TCR)

• TCRs are membrane-bound proteins.
• TCRs are composed of an alpha and a beta chain.
• Each chain has a variable (V) region and a constant (C) region.
• The variable regions differ for each T cell clone and bind specific antigens.

How do we create T cells?

• During T cell development, V(D)J recombination randomly combines variable segments, creating a diverse repertoire of TCRs that can respond to virtually any antigen.

Life Cycle of a T Cell

• T cell development within the thymus.
• T cell activation within secondary lymphoid tissue (like lymph nodes).
• T cell effector function in peripheral tissues.

T Cell Activation (detailed)

• Naïve T cells circulate in lymph nodes.
• TCR recognizes an antigen presented by an antigen-presenting cell (APC).
• Co-stimulation signals (e.g., B7 on APC and CD28 on T cell).
• Instructive cytokines (e.g., IL-2, IL-12) shape T cell development.
• Activation leads to clonal expansion and differentiation into effector cells.

T cell effector function

• Effector T cells leave the lymph nodes and migrate to sites of infection.
• They eliminate infected cells by direct killing and immune responses.

Signals for T Cell Activation

• Signal 1: Antigen recognition. TCR on T cell binds to MHC-peptide complex.
• Signal 2: Co-stimulation. Interaction between co-stimulatory molecules (e.g., CD28 and B7.)
• Signal 3: Cytokines. Cytokine signals help shape T cell differentiation into specific subsets (Th1, Th2, etc.).

T Helper Subsets

• Different kinds of helper cells play distinct roles in immune responses: -Th1: Intracellular infections -Th2: Helminth infections -Th17: Extracellular bacterial/fungal infections

T cell Activation (further summary)

• Naïve T cells circulate in lymph nodes.
• Activation occurs when TCR recognizes antigen presented by an APC.
• Co-stimulation (signal 2) is critical for activation.
• Differentiation into specific T effector cells occurs with specific cytokines (signal 3).
• Effector T cells leave lymph nodes to carry out their functions.

Clonal Expansion

• Activated T cells rapidly increase in number (clonal expansion) producing many effector cells to fight a specific antigen.

Homeostasis

• As antigen is cleared, the majority of effector T cells die by apoptosis.
• Inhibitory pathways are activated and T regulatory cells can dampen responses.

T Cell Immunodeficiencies

• DiGeorge Syndrome: deletion on chromosome 22 affects thymus development resulting in poor T cell production.
• SCID: a diverse group of disorders caused by mutations impacting T and B cells.

Summary of T Cell Maturation

• TCR rearrangement
• Selection process in the thymus
• Differentiation into specific CD4/CD8 lineages

Summary of T Cell Activation

• T cells are activated in lymph nodes.
• Activation depends on antigen recognition, co-stimulation, and cytokine signals

Summary of T Cell Effector Function

• Effector T cells carry out functions in specific tissues.
• T helpers assist other cells and produce cytokines to direct immune responses.
• Cytotoxic T cells directly kill infected cells.

Autoimmunity and Immune Tolerance

• Self-tolerance: T cell unresponsiveness to self-antigen.
• Central tolerance: eliminates autoreactive T cells in the thymus.
• Peripheral tolerance: eliminates autoreactive T cells in peripheral tissues.