T Cells Functions PDF

T cells functions Learning Objectives On completion of this session you should be able to - Recognise the functions of different T cell subsets. - Comprehend the importance of T cells in immune regulation and defence. Effector T Cells – General Properties 1) Armed effector T cells leave the lym...

T cells functions Learning Objectives On completion of this session you should be able to - Recognise the functions of different T cell subsets. - Comprehend the importance of T cells in immune regulation and defence. Effector T Cells – General Properties 1) Armed effector T cells leave the lymphoid tissue and migrate to sites of injury/infection via the blood 2) They migrate to the tissues via activated endothelium 3) Scan tissues for MHC:antigenic peptide ligands 4) Antigen recognition triggers effector function (do not require co-stimulation) 5) Interaction of TCR with antigenic ligand has 2 effects: i) Cytoskeleton re-organises to focus effector molecules onto target cell ii) Triggers release of effector molecules 6) Effector mechanisms mediated by both cell surface and soluble molecules CD4+ T Cell Differentiation 1) Cytokines produced by APCs determine CD4+ T cell differentiation 2) Determines whether cell mediated or humoral responses dominate 3) IL-6 burst associated with TFH cell development 4) IL-12 and IFN-g associated with TH1 cell differentiation 5) IL-4 associated with TH2 cell differentiation TH1 Cell Function 1) TH1 cells produce bound TNF-a which interacts with TNF-a receptors on the macrophages 2) Activate anti-microbial properties of macrophages through: i) increasing efficiency of lysosome-phagosome fusion ii) stimulating synthesis of ROS, NOS and defensins iii) stimulating MHC class II and TNF-a receptor expression 3) Also stimulate antibody production of class that mediates pathogen destruction by phagocytes (IgG1 & 3). TH1 Cell Function 1) On recognition of MHC Class II:antigenic peptide, cytokines and cell surface effector molecules are synthesised 2) The following key cytokines are produced and their release is focused: IFN-g: activates macrophages TNF-a: acts synergistically with IFN-g; activates endothelium LT-b: (Lymphotoxin beta) kills chronically infected macrophages CD40L: with IFN-g activates macrophages TH2 Cell Function 1) Mediate anti-parasitic response 2) Migrate to epithelial sites 3) Produce IL-4, IL-13, IL-5, IL-9 & IL-10 4) Recruit, activate and promote survival of basophils, eosinophils and mast cells 5) Also activate macrophages -> alternatively activated macrophages 6) IL-4/IL-13 affect the epithelium -> increased mucous production and flow and reduces attachment of parasites TH2 Cell Function 1) IL-5, IL-9 production, survival of eosinophils, mast cells and basophils 2) IL-10 is anti-inflammatory and protects commensal bacteria in gut 3) IL-4 mediates IgE production IL-5 + TGFb stimulates IgA production TFH Cell Function 1) Mediate B cell activation 2) Remain in lymphatic tissue and migrate to edge of B cell follicles 3) B cells encounter Ag in follicles and migrate to edge of T cell area 4) Internalise, process and present antigen:MHC Class II to TFH cell 5) Binding to TFH cell rescues B cell 6) TFH expresses CD40L which binds CD40 on B cell TFH Cell Function 1) CD40L:CD40 interaction stimulates proliferation and differentiation into plasma cell in germinal centre 2) Activated B cells move to follicles and proliferate to form a germinal centre 3) In the germinal centre activated B cells undergo affinity maturation and isotype switching 4) These processes are mediated by follicular dendritic cells (FDCs) and TFH cells TFH Cell Function 1) Process is poorly understood but FDCs present antigen to B cells and rescue those expressing high affinity surface antibody 2) Cytokines mediate class switching 3) Isotype switching enables B cells to secrete other antibody isotypes (IgG, IgA, IgE) 4) Affinity maturation results in the generation of high affinity antibodies and arises by somatic hypermutation of V region genes 5) Activated B cells mature into either: 1. plasma cells - which secrete antibody 2. memory cells - retain immunological memory Tc Function 1) Preformed secretory granules in T cells contain perforins and granzymes 2) On binding ligand, secretory granules are released 3) Perforins polymerise to form a membrane pore (160 Å dia) 4) Granzymes enter cell and activate apoptosis 5) Target cell death is also induced via interactions with cell surface molecules 6) Apoptotic cell death ensures that the infectious agent is not dispersed Tc Function 1) Tc cells also release cytokines: IFN-g: inhibits viral replication, increases expression of MHC class I and TAP-1 and TAP-2 genes Activates macrophages TNF-a: synergises with IFN-g to activate macrophages TNF-b: synergises with IFN-g to kill target cell Other T cell Populations 1) Memory T cells persist after an immune response 2) Regulatory T cells (TREG) suppress responses in an antigen specific mode 3) No separate subpopulation has been identified 4) Develop from CD4+ cells in periphery or during T cell development in thymus 5) Suppress responses to autoantigen and responses to high level of antigen (limits tissue destruction from chronic activation of immune cells and effector molecules) Summary 1. Different types of T cells have specific roles in regulating the immune system and defending against pathogens. 2. Th1 Cells: Activate macrophages and cytotoxic T cells to fight intracellular pathogens. 3. Th2 Cells: Enhance antibody production by activating B cells, effective against extracellular parasites. 4. T Follicular Helper Cells (Tfh): Aid B cell activation and antibody production, crucial for memory B cell formation. 5. CD8+ Cytotoxic T Cells: Identify and eliminate infected or cancerous cells using cytotoxic molecules. 6. Regulatory T Cells (Tregs): Prevent excessive immune responses and autoimmune reactions, maintaining immune balance. 7. Memory T Cells: Respond rapidly to previously encountered pathogens, providing long-term immunity.