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25 Cards in this Set

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  • Back
what are the three general steps in antigen processing and presentation?
1) Ag protein is in the cell
2) Ag protein is broken up
3) pieces are displayed by transmembrane MHC to an Ab
What are the three professional APCs?
macrophage
dendritic cells
B cells
Where does antigen presentation take place?
secondary lymph tissue
What are the two main classes of T cells?
based on CD4 and CD8 coreceptors

CD4 - helper T cells (TH1, TH2) assist with extracellular infections. "4 help call helper T cells"

CD8 - cytotoxic T cells assist with intracellular pathogens. "stack two o's in 'cytotoxic' and you have an 8"
What are the roles of the two types of helper T cells?
TH1 - activate tissue macrophages
TH2 - stimulate B cells to make antibodies. "B = 2nd letter in alphabet, TH2 has 2 in it"
what is the role of MHCs?
MHCs will activate T cell coreceptors and cause an immunologic response by presenting Ags on the surface of APCs.
What are the two types of MHCs?
MHC class I - activates CD8 cytotoxic T cells
MHC class II - activates CD4 helper T cells
what is the rule of 8?
MHC class I = CD8 because 1*8 = 8
MHC class 2 = CD4 because 2*4 = 8
how are MHC I and II molecules different structurally?
MHC I - one transmembrane domain (alpha-3) with one separate beta group and alpha-1, alpha-2 creates Ag presenting groove

MHC II - two transmembrane domains (alpha-2, beta-2) with alpha-1, beta-1 creating Ag presenting groove

(pic)
how do MHC I and II molecules bind with CD4 and CD8 T cell coreceptors and T cell receptors?
MHCI - alpha-1, alpha-2, Ag complex binds TCR while CD8 alpha group binds alpha-3 of MHCI

MHCII - alpha-1, beta-a, Ag complex binds TCR while CD4 binds beta-2 of MHCII

(pic)
What length of peptides (Ag fragment) can MHC I and MHC II display?
MHC I - small 8-10 AAs in length
MHC II - larger 13 - 25 AAs in length
What types of cells can display MHC I and MHC II cells?
MHC I - all cells in the body
MHC II - only professional APCs (dendritic, macrophage, B cells)
What are the steps of MHC I peptide processing?
1) proteasome degrades pathogen into fragments in the cytosol
2) fragments are transferred from cytosol to ER by TAP (transporter protein)
3) calnexin stabilizes MHC I alpha complexes until beta-domain binds
4) calnexin releases complex and calreticulin-MHC-tapasin-TAP copmlex is formed and stabilized MHC to accept peptide fragment of Ag
5) peptide binds MHC I from TAP
6) calreticulin-MHC-tapasin-TAP complex dissociates to release MHC I-Ag complex
7) MHCI-Ag complex is packaged and released from ER to cell surface
What is Bare Lymphocyte Syndrome relevant to MHC I?
defect in TAP protein so that protein fragment cannot be moved from cytosol to ER and MHCI will not appear on the cell surface.
What are symptoms of Bare Lymphocyte Syndrome?
chronic respiratory infections, poor response to viruses (intracellular pathogens)
What do MHC I display when there are no Ag fragments to display?
self fragments that do not provoke an immune response. if they do provoke an immune response, then this is autoimmunity... bummer.
What are the steps of MHC II Ag processing and presentation?
1) MHC II is assembled in the ER with the addition of the "invariant chain." the "invariant chain" blocks binding to endogenous peptide fragments until MHC II is ready to bind Ag fragments
2) MHC II-invariant chain complex is packages and released from the ER
3) in the vessicle, the invariant chain is cleaved into pieces leaving behind only one CLIP fragment bound to the binding site of the MHC II
4) extracellular Ag has been phagocytized and process into fragments by phagolysosomes and exists in an endocytic vessicle, the endocytic vessicle and the MHC II vessicle unite
5) upon exposure to the Ag fragments, MLA-DM is recruited to stabilize MHC II and release CLIP to allow a binding site for the Ag fragment
6) once the Ag fragment is bound, MLA-DM dissociates, and MHC II-Ag complex is expressed on the cell surface for presentation
(pic)
What is Bare Lymphocyte Syndrome relevant to MHC II?
CIITA is a complex that turns on MHC II transcription. in this version of Bare Lymphocyte Syndrome, CIITA is defective and MHC II are not made, so cannot be expressed on the cell surface.
What is the functional definition of MHC diversity?
the ability to bind and present diversity of Ag
What are the two main forms of MHC diversity?
Polymorphism and polygeny
MHC restriction
for a T cell receptor to be activated it has to recognize the proper peptide being presented as well as the presentation must occur by the proper MHC molecule. highly specific.
heterozygote advantage
the principle that if there is no overlap between the maternal and paternal contribution to MHC diversity, then there is the maximum amount of diversity with offspring MHC diversity and capacity.
what is the only cell in the body that does not express MHC I?
RBC
gene polymorphisms
a phenomena that creates MHC diversity because of the presence within a population of multiple alternative forms of a single gene
polygeny
multiple loci that can be co-expressed in different combination to provide MHC diversity