Flashcards in L4: Antigen Presentation and the MHC Deck (17):
What is the MHC haplotype? Why is MHC polygenic? Why is MHC expression polymorphic?
- haplotype: total set of MHC genes on each chromosomes – receive MHC haplotype from each parent
- polygenic: multiple different genes within each individual
- polymorphic: multiple variants of each gene exist in the population
Structure of MHC I, MHC II
- I: alpha chain and beta-2 microglobulin
- II: alpha and beta chain
Class I MHC genes, class II MHC genes. How many are received from each parent?
- I: B, C, A
- II: D genes - DP, DQ, DR, DM
- Receive 3 different class I and 3 different class II from each parent, theoretically expressing 6 from each class, higher in class II as there are alpha and beta chains
How are the MHC genes expressed?
- Codominant fashion
MHC/HLAs associated with narcolepsy? Ankylosing spondylitis?
- HLA-DR2 associated with narcolepsy
- HLA-B27 associated with ankylosing spondylitis
What is the clinical relevance for MHC typing?
1.) Organ transplantation
2.) Paternity testing: only excludes (someone else can have that same MHC pattern)
On what cells are MHC I expressed?
- On nearly all nucleated cells
Why are RBC infections by Plasmodium undetected?
- Lack class I MHC, undetected by cytotoxic T lymphocytes
What cells recognize MHC class I?
- CD8+ T cells
On what cells are MHC II expressed?
- On APCs: DCs, macrophages, B cells. Thymic epithelial cells can express class II MHC to aid in selection of mature T lymphocytes
What cells recognize MHC class II?
- CD4+ T cells
Can T cells recognize native antigens?
- No, only able to respond to processed antigens and these processed antigens must be expressed on MHC proteins
Dendritic cells. Where are they produced, where do they reside, what is their function?
- Produced in bone marrow, circulate in blood, migrate into tissues as long-lived immature cells
- Continuously sample environment through phagocytosis and macropinocytosis. In an infection, immature DCs take up antigen, are activated and migrate to nearest lymphoid tissue. Present antigen to T-helper lymphocytes
Explain how increased level of class II MHC occurs on APCs after pathogen is recognized?
- Resting APC with low level of MHC II expression presents antigen to CD4+ T cell
- CD4+ cells are activated and release IFN-gamma
- IFN-gamma binds APC, inducing increased expression of MHC II
- Result = more antigen is presented to T cells, therefore an enhanced response
Describe the endogenous antigen processing pathway
1.) Endogenous pathogen synthesizes proteins
2.) Protein proteolysis in proteosome
3.) Transported to ER from cytosol
4.) Assembly of class I MHC in ER, loaded with foreign peptide
5.) Placed in exocytic vesicle and expressed on plasma membrane
6.) Class I MHC with endogenously processed antigen recognized by CD8+ T cells
Describe the exogenous antigen processing pathway
1.) Exogenous antigen internalized by phagocytosis (receptor-mediated, fluid-phase)
2.) Processed in endosomal/lysosomal vesicles
3.) Class II MHC synthesized in ER
4.) MHC associated with invariant chain to prevent binding of cellular/self proteins. Transported to Golgi
5.) Exocytic vesicle fuses with endosomal/lysosomal vesicle, invariant chain switched with processed foreign peptide
6.) Expressed on cell surface
7.) Class II MHC with exogenously processed antigen recognized by CD4+ T cells