Immunology - MHC Molecules and Antigen Presentation Flashcards

5798746552	Antigenic epitopes	B cell epitope: Specific surface piece of antigen or secreted molecule/toxin that antibody binds to. Conformation or linear (RARE). T cell epitope: Specific piece of antigen held by an MHC molecule and used by an APC. MUST be linear. Can be derived from antigen surface or internal.	0
5798746553	MHC	Major histocompatibility complex Role: Present portions of antigens that are noncovalently bound to MHC gene products, (MHC class I and II molecules) to antigen-specific T cells. Any T cell recognizes foreign antigen bound to only ONE specific MHC class I or II molecule. Class I and II differ in function, tissue distribution, and biochemical composition.	1
5798746554	MHC & NK cells	NK cells destroy any cells not expressing self-MHC class I without discrimination.	2
5798746555	MHC Class I	Expressed on most nucleated cells. Restricts antigen recognition by CD8 T cells.	3
5798746556	MHC Class II	Expressed on professional APCs. Restricts antigen recognition by CD4 T helper cells.	4
5798746557	Histocompatibility	Recognition of class I or II molecules by T cell receptors. Determines tissue compatibility or incompatibility.	5
5798746558	Peptide binding cleft	Located at the amino terminal end. Cleft does NOT have fine specificity like antibodies or TCRs; ~2000 different peptides/MHC alleles.	6
5798746559	MHC Class I structure	Has 2 beta chains. Nearly all nucleated cells present this class. Noncovalently associated. Binding groove is CLOSED. Bound peptides are 8-10 AAs in length. Anchor residues: Specific AAs essential for binding peptides to a particular class I molecule. These sets of peptides have the same or similar AA residues at several defined positions. These common AA signatures bind the peptide into the MHC groove.	7
5798746560			8
5798746561	MHC Class II structure	Generally only expressed by APCs. Has 1 alpha and 1 beta chain. Cleft is open at BOTH ends. Bind peptides 10-30 AAs in length. Lack anchor residues; binding peptides have internal conserved "motifs"	9
5798746562	Capture of antigens	1: Pathogen enters through various epithelium 2: Professional APCs are in these tissues and take up/process antigen 3: Professional APCs migrate into draining lymph nodes via afferent vessels 4: After MHC-TCR engagement, antigen-specific T cells proliferate, take on effector functions, and migrate to the site of infection via efferent vessel EXCEPTION: Blood borne pathogens filter through the spleen	10
5798746563	Cytosolic pathway - MHC class I peptide loading	1: Ubiquitination of protein; proteins become target of proteasomes, which chop up proteins into peptides. 2: TAP uses ATP to translocation peptides into the ER lumen. 3: Tapasin links empty class I, which is held in the correct confirmation by chaperones, to TAP for easy access to incoming peptides. 4: Peptides fit into the binding cleft cause the release of chaperones. 5: Result is stable MHC -- peptide is transported to the surface via Golgi.	11
5798746564	Endocytic pathway - MHC Class II peptide loading	1: MHC Class II molecules are constantly made and assembled in the ER. 2: Chaperones bring alpha and beta proteins together and held together with I, the invariant chain. 3: MHC Class II with the invariant chain are transported through the Golgi to MIIC, the MHC class II compartment. 4: Extracellular protein gets taken up by APC Into endosomes. Proteins become target of proteasomes within the endosomes as pH drops. 5: Proteosomes chop up the antigenic proteins into peptides in endosomes, which then fuse with MIIC. 6: Enzymes digest the invariant chain leaving only CLIP (Class II invariant chain peptide) in the presence of free antigenic peptides. 7: HLA-DM assists in the replacement of CLIP with antigenic peptide. 8: Formation of stable MHC II: Peptide is then transferred to the surface for recognition by specific TCR.	12
5798746565	Cross-presentation	Peptides derived from the extracellular environment or from within endosomes/lysosomes get redirected into the cytosolic pathway for presentation by MHC Class I.	13
5798746566	Why does cross presentation occur?	Non-professional APCs may become unable to properly present antigen to CD8 T cells upon infection with pathogens. Dendritic cells can ingest these infected cells and stimulate helper T cells and cytotoxic Ts.	14
5798746567	CDI antigen presentation	MHC-like, but not polymorphic. Associates with Beta 2m. Involved in presentation of lipid antigens, a major constituent of some pathogens.	15
5798746568	Dendritic cells	Constitutively high in MHC II and costimulatory activity.	16
5798746569	Macrophages	Must be activated for high MHC II and costimulatory molecules.	17
5798746570	B cells	Constitutively MHC II, but activated for costimulatory molecules.	18
5798746571	Why must T cells recognize MHC + antigen?	Proximity: CD4 T cells, B cells, CD7 T cells, infected cells. Less saturation: If TCRs were saturated with free antigen, specific killing of target cells would be inhibited. Restriction: T cells see and respond only to cell associated antigen. Eliminates non-specific killing. 2 pathways; Best protection skewed to individual pathogens. Viruses and extracellular bacteria get different responses.	19
5798746572	How does the MHC haplotype determine diste susceptibility?	MHC are a complex of linked multiallelic genes located on one chromosome that code for molecules that restrict specificity of antigen recognition by T cells. MHC can determine disease susceptibility or resistance in a given host.	20
5798746573	Why is there an enormous allotropic variation of MHC molecules?	All immune systems are different, so the perfect pathogen cannot evolve to spread through a population. It may be less likely for a microbe to imitate if there is a larger variety of MHC.	21