Lecture 3: T Cells, MHC and Lymphocyte Activation Flashcards
T Cell Receptors
T cells do not recognize native antigen. The antigen must be proceesd by the APC and recognized in conjunction with a MHC molecule
T cells are heterodimers of mostly alpha and beta chains
Each apha chain has an antigen binding site, a variable region, a constant region, and a transmembrane region
Develops in thymic cells by somatic rearangments of TCR v, D, and J gene segments
Requires RAG 1 and RAG2 enzymes
TC
Cytotoxic T cells
CD8 is the co-receptor that also binds MHC class 1
The TCR recognizes the MHC plus the peptide of the antigen on the antigen presenting cell
TC cells recognize and kill virus infected cell by releasing perforin which forms channels in the membrane or by releaseing Fas on the target cell and activating the death pathway
Viral proteins are made endogenously
TH
T helper cells
CD4 Co-receptor binds MHC Class II
Recognize exogenous peptides presented in association with MHC class II molecules of APCs
Interaction between T cells and antigen presenting cells that leads to T cell activation
Since T cells do not recognize native antibody, the native antigen protein is denatured by the antigen presenting cell and the antigen peptide complexes with the MHC molecule
Forms the tripeptide complex: T cell receptor, peptide antigen, and MHC molecule
- Cut - bacteria enters the body
- Antigen is taken to the lymph node in the context of an MHC receptor
- The T cell recognizes the peptide antigen in the context of a MHC molecule
- T cell is activated
MHC Class I Molecules
Expressed on nearly all nucleated cells (except RBCs, sperm, and ovum)
Recognized by TC cells - CD8+
TC cells recognize and kill virus infected cells - recognize the endogenous viral peptide presented in the context of MHC class 1
Intracellular antigen
MHC Class II Molecules
Expressed only on antigen presenting cells (APC) - Dendritic cells, macrophages, and B cells
Recognized by TH cells - CD4+
TH cells recognize exogenous proteins presented in association with MHC class II molecule of antigen presenting cells
T cell Education
TCR genes rearrange in the thymus
T Cells are educated to determin self antigens in the thymus
The thymus activates a gene that produces self epitopes, and if T cells bind, they are destroyed to prevent autoimmunity from developing
Positive Selection
T cells undergo positive selection in the thymus to select for T cells that recognize antigen in the context of MHC receptors
Negative Selection
T cells undergo negative selection in the thymus to eliminate T cells that react with self peptides
Gets rid of self reactive t cells due to a gene in the thymus producing self epitopes om the thymus during dedevelopment. When self reactive t cells react with the epitope, the t cells are are deleted
Prevents autoimmunity from developing
Antigens recognized by B Cell Receptors
B cell receptors recognize native antigen
Antigens recognized by T Cell Receptors
T cell receptors recognize peptide from the antigen in the context of a MHC molecule
How is an immune response initiated?
- Antigen is collected in the lymphatics and transported tot he draining lymph node by APC (dendritic cells)
- In the lymph node the activated dendritic cells (APC’s) interact with, and stimulate TH cells
- TH cells interact with, and activate antigen specific B cells
- B cells then form germinal centers and undergo germinal center reactions (isotype switch, somatic hypermutation, diffenetiation of B cells to plasma cells, and generation of memoory B-cells)
How does viral immunity develop?
- The host cell proteosome degrades viral proteins which are transported to the ER
- Peptides bind to MHC class I molecules and transport through the golgi apperatus
- MHC class I presents peptides at the cell surface and activates CD8 Tc Cells
- Activated Tc cells can kill the virus infected cell through a perforin dependent killing or through a fas dependent killing mechanism
How does immunity to extracellular pathogens develop?
- The cell engulfs the extracellular antigen in an endocytic vesicle
- Peptide is produced in a phagolysosome
- The peptide binds MHC class II molecules through vessicle fussion
- The MHC class II presents the peptiide at the cell surface and activates CD4+ Th cells
- Activated Th cells can then differentiate and prolliferate and effector Th cells will develop in response to specific cytokines released
TH Cell Activation
Costimulation (2 signals) is required for activation of TH cells
- TCR recognition of the peptide in the context of MHC receptor on an APC (often dendritic cell)
- Interaction of CD28 on T cells and B7 on APC (costimulatory molecules)
Activation of Th cells causes the release of a specific set of cytokines that stimulate proliferation and differentiation into effector T cells