T-Cell Mediated Immunity: Activation and Functions of T Lymphocytes

T-Cell Mediated Immunity

• Provides defense against infections by microbes that live and reproduce inside host cells.
• Stimulates the ability of macrophages.
• Provides defense by recruiting leukocytes.
• Kills the infected cells.

Cell-Mediated Immunity

• Helps B cells to produce antibodies as part of humoral immune responses.
• Destroys cancer cells.
• Requires the interaction of T lymphocytes with other cells.

Phases of T Cell Responses

• Naive T lymphocytes recognize antigens in peripheral (secondary) lymphoid organs.
• Initiates proliferation of T cells and their differentiation into effector and memory cells.
• Effector cells perform their functions when activated by the same antigens in infected tissue.
• Phases: Migration of antigen to lymph node, Antigen recognition of naive lymphocytes, T cell expansion and differentiation, Effector T cells enter the circulation, Migration to antigen site, Antigen encounter, and Activation of T cell.

Phases of T Cell Responses (continued)

• Release of cytokines (IL-2) that stimulates proliferation of antigen-activated T cells (clonal expansion).
• Differentiation into effector T cells and memory T cells.
• Can be CD4 or CD8.

Phases of T Cell Responses (continued)

• After eliminating an infectious agent, stimuli that triggered T cell expansion and differentiation are eliminated.
• Most expanded cells die, and the immune system returns to a resting state.
• Memory cells remain in the system.

Antigen Recognition and Costimulation

• Initiation of T cell responses requires multiple receptors on the T cells recognizing their specific ligands on APCs.
• TCR – MHC, CD4/CD8 – MHC – TCR Complex, Adhesion Molecules, Costimulators, and Cytokines.

Recognition of Peptide-MHC Complexes

• TCR for antigen and CD4 or CD8 coreceptor together recognize complexes of peptide antigens and MHC molecules on APCs.
• Recognition provides the initiating, or first, signal for T cell activation.

Recognition of Peptide-MHC Complexes (continued)

• Biochemical signals that lead to T cell activation triggered by a set of proteins linked to the TCR that are part of the TCR complex and by the CD4 or CD8 coreceptor (CD3 and ζ).
• LCK - lymphocyte-specific protein tyrosine kinase, ITAM – immunoreceptor tyrosine-based activation motifs.

Role of Adhesion Molecules in T Cell Responses

• Adhesion molecules on T cells recognize their ligands on APCs and stabilize the binding of the T cells to the APCs (Integrins).
• LFA-1 – leukocyte function-associated antigen 1 (T-Cell), ICAM-1 – intercellular adhesion molecule -1; ligand from APC.

Role of Adhesion Molecules in T Cell Responses (continued)

• On naive T cells, LFA-1 integrin is in low affinity state and increases in strength when it sees an antigen.
• Integrin-mediated adhesion is critical for the ability of T cells to bind with the APC and also in the migration of effector T cells.

Role of Costimulation in T Cell Activation

• Full activation of T cells depends on the recognition of costimulators on APCs in addition to antigen.
• T cell receptor for costimulators (CD28), APC proteins (B7-1 and B7-2).
• Recognition of APC proteins is important in T cell proliferation even if there is antigen present.

Role of Costimulation in T Cell Activation (continued)

• Requirement for costimulation ensures that naive T lymphocytes are activated maximally by microbial antigens and not by harmless foreign substances or self-antigens.