Cell-mediated immunity: activation and functions of T cells Flashcards
Types of cells involved
- cytotoxic T cells : kiling of infected or transformed cells
- Helper T cells (Th effectors): cytokine production, activation of macrophages
Activation of T lymphocytes
- required recognition of Antigen presented on MHC molcules by dendritic cells
- activation occurs in secondary lmyphoid Organs
- protein Antigens that cross eoithelial barriers or are produced in tissues are captured by DCs and transported to lymph nodes
- Antigens that enter circulation may be caputred by DCs in the Spleen
- After Antigen capture, DCs begin to mature and migrate to the T cell zones of peripheral lymphoid Organs
- in lymphoid Organs: DCs present Peptides in association with MHC II molcules to naive CD4+ cells and Peptides displayed by MHC I molecules to CD8+ cells
Phases of T cell responses
Antigen recognitin by T cells includes:
- cytokine IL2 secretio, particularly in CD4+ cells
- clonal Expansion as a result of cell Proliferation
- Differentiation of activated T cells into effector cells
Effectors CD4+ helper cells Respons to Antigen by producing cytokines that have several Actions:
- recruitment and acrivation of leukocytes
- activation of B lymphocytes
Effectors CD8+ CTLs Respons by killing other cells
Role of adhesion molecules in T cell activation
- adhesion molecules stabilize APC-T cell interaction
Role of co-Stimulators in T cell activation
- resting APCs Expresses no co Stimulators and Fails to activate naive T cells
- Antigen recognition without co Stimulators may make T cells anergic
- microbes and kytokines produced during innate Responses activate APCs to express co Stimulators, such as B7 molecules
- APCs become capable of activating T cells
- B7 on APC is recognized by CD28 on T cells
- Activated APCs also produce cytokines such as IL12, which stimulate the differentation of naive T cells
T cells recognize ligands on APCs
- MHC/Peptide complex
- CD4 or CD8 molecules are co receptors of TCR
- Adhesion molecules
- Cytokines
Role of IL2 in T cell activation
- after activation, T cells produce the cytokine IL2 –> express high Levels of the functional IL2 receptor
- IL2 drives the Proliferation, which can result in marked Expansion of antigen-specific clones
Types of Th effector cells
- TH1: secretes IFN-γ and mediates defense against intracellular microbes
- TH2: secretes IL4, IL5, which favor eosinophil, mast cell-mediated immune reactions against helminths
- Th17: promotes Inflammation and mediates defense against extracellular fungi and bacteria
Th cells promote Differentiation of CD8+ cells into CTL effectors
- Th cells secrete cytokines that stimulate the Differentiation of CD8+ cells
- Th cells express CD40 Ligand which binds to CD40 on APCs and activates them to stimulate Differentiation of CD8+ cells
- Differentiation involves Acquisition of the machinery to perform target cell killing: development of membrane-bound cytoplasmic granules that contain proteins (perforins and granzymes)
Memory T cells
- maintenance of Memory cells is dependenent of cytokines such as IL7
- -> promote the Expression of antiapoptotic proteins adn stimulate low Level cyclin
Types of T cell mediated immune reaction
- CD4+ T cells recognize Antigens of microbes and produce cytokines that activate the phagocytes to kill the microbes and stimulate Inflammation
- CD8+ recognize Antigens of infected cells and kill These cells
Migration of effector T cells at site of infection
- activated T cells migrate through Endothelium that is activated by cytokines
- activated endothelial cells express adhesion molecules and effector T cells express their ligands
- Chemokines Play additional roles in the Migration of T cells through walls
- T cells that specifically recognize Antigen are activated and retained
- T cells that do not Encounter the Antigen either die or return to the circulation
Activated macrophages
- produce Enzymes that catalyse Generation of toxic substances in phagolysosomes (ROS, NO, proteases)
- TH1 effectors activate the same microbe killing mechanism as in case of innate immunity
- permanent immune Response can induce chronic Inflammation –> delayed hypersensitivity reaction
function of Th2
Stimulation of IgE and eosinophil mediated reactions against helminthic infections
- helminths are too large to be phagocytosed
- secrete IL4, IL5, and IL13 –> eradicating helminths
- activate macrophages for tissue repair
Function of TH17
- secrete cytokines that recruit leukocytes, mainly neutrophils
Th17 cytokines stimulate:
–> local production of chemokines
–>production of antimicrobial Peptides (defensins)
–>promote epithelial barrier functions