Activation of Adaptive Flashcards
two ways innate initiates adaptive
process/present Ag
co-stimulatory receptor molecules
MHC/HLA class I found on
all nucleated cells
MHC/HLA class II found on
professional APCs: DCs, macrophages, b lymphocytes and some thymocytes
HLA genes located on chromosome
chromosome 6
HLA alleles code for protein Ag necessary to
discriminate self and nonself
HLA from parents expressed
co-dominantly
class I HLA
class 1 == one letter (A, B, C)
code for glycoproteins expressed on all nucleated cells
present Ag to CTLs
inhibitory receptor for NK cells
class I HLA structure
alpha chain (3/4 globular domains) beta2 microglobulin (1/4 globular domain) non HLA encoded - associated noncovalently with alpha 3 domain of alpha chain
class I peptides
short - 8-10 AA
closed ends between alpha 1 and alpha 2 domains
Class I MHC synthesized in
the er
where it interacts with b2 microglobulin
class II HLA
encoded by HLA-D genes
DP, DQ, DR (class II = two letters)
membrane bound glycoproteins on APCs
present Ag to CD4+ T cells
Class II HLA structure
alpha and beta chain both encoded by HLA-D
Not covalently linked
class II peptides
13-18 AA
binds in alpha 1 beta 1 globular domains
class II HLA synthesized in
ER
interact with invariant chain - binds A/B chains and blocks peptide binding groove/ directs to endocytosis pathway (where invariant is degraded class II is free to bind whatever Ag was picked up in the endocytosed vesicle)
then transported to cell surface
MHC class I su that binds CD8
alpha 3
MHC class II su that binds CD4
beta2
after an Ag is taken up by APC
lose adhesive markers
up-regulate CCR7
increase expression of CD80
class II mhc processing
loads exogenous Ag
peptide loaded onto binding groove in late endosome
CLIP (invariant chain) protein protects binding groove until MHC is ready to receive Ag
exocytosed after association
class I MHC processing
loads cytosolic Ag TAP loads fragments from proteasome into the ER where they get trimmed and placed in peptide binding groove of MHC class I molecule (alpha chain only)
cross presentation
DCs present Ag to CTLs and CD4+ cells for most robust response
ankylosing spondylitis
inflammation of the spine
HLA-B27 gene implicated
either not binding antigenic peptide correctly for removal
or presenting something that it shouldnt
Rheumatic fever
generation of Ab against streptococci Ag that cross reacts with cardiac tissue
HLA-DR4 allele predisposes patients to RF
Bare lymphocyte syndrome
TAP nonfunctional - no peptides enter ER
Class I HLA molecules dont leave ER
cells dont present Ag
can also be caused by inherited defect in HLA class II transactivator – no class II expression on APCs