Adaptive Immunity activation Flashcards
Class I MHC
who expresses, what do they present
all nucleated cells (obviously not RBCs)
they present peptides 8-11 amino acids in length
“present endogenously processed peptides”
How many genes do humans have for the MHC 1 complex?
3, coding for 6 alleles (one from each parents)
HLA-A
HLA-B
HLA-C
highly polymorphic and co-dominantly expressed
What is significant about polymorphic proteins?
they have the same shape but they differ by one or a few amino acids
how many allotypes of HLA-A and HLA-B are there?
200- A
400- B
what about the beta-2 protein?
it is not polymorphic.
what recognizes MHC class I?
CD8 cytotoxic lymphocytes
what does it mean to say CD*+ T cells express endogenous peptides?
these are intracellular pathogens like viruses that infect the host cell
“surface protein fragments manufactured by the cells”
MHC I hold peptides of what length?
8-9 a.a. long
what kind of bonds are at work between the peptide and the MHC and TCR?
non-covalent interactions
what components of the MHC holds to the peptide?
alpha1 and alpha2
CD8 does what
stabilizes interaction between TCR and MHC
the CDR is on the _______
TCR
is the CDR on the MHC or the TCR
TCR
where are HLA-gene coded regions on the MHC?
the alpha1 and alpha2 peptide binding region
where does CD8 bind on the MHC 1 molecule?
on the alpha3 region
what’s the order of the CDR regions from the lateral edges of the CDR regions to the most medial
CDR2-CDR1-CDR3
in the interior of the cell, what are MHC I’s doing?
sampling all the proteins
what are CTLs doing?
always sampling the MHC I of all the cells it contacts
Ag processing for class I MHC
how does it happen, what significant proteins are involved
old proteins are destroyed by the proteosome and chopped into pieces IN THE CYTOPLASM
transport proteins tap 1 and 2 carry all the garbage peptides out into the endoplasmic reticulum
these peptides become loaded into the grooves of class I MHC
Class II MHC: polymorphic or not
HIGHLY polymorphic
What size peptides do MHC II hold?
13-25 a.a.
Structure of MHC II
two non-covalently bonded peptide chains (alpha 1 and beta 1) both are highly polymorphic.
what parts of the MHC do the peptides interact with?
both the alpha 1 and beta 1 chains which have CDR
the regions where the CD4 interacts with the MHC II is called
conservative
MHC I was loaded in the endoplasmic reticulum, where are MHC II’s loaded?
in endosomes
the invariant chain: GO!
MHC II is synthesized in the endoplasmic reticulum; before it leaves, it’s loaded with an “invariant” chain to prevent it from grabbing any self-peptides as it travels around the cell.
inside the transport vesicle the invariant chain is cleaved to the “clip fragment”
clip
what remains of the invariant chain after it’s been degraded in the endosome, it’s the surrogate peptide in the MHC II until HLA-DM facilitates the release
HLA-DM
facilitates clips release from MHC II so peptides can be loaded
From where do the peptides that MHC II loads come from?
from phagocytized/endocytized/pinocytized
CD8 binds to the ____ domain of the MHC I molecule
alpha3
CD4 binds to the ___ domain of the MHC II molecule
beta2
broadly speaking, what distinguishes MHC I and II from one another apart from the big things?
MHC I seems to display intracellular pathogens and MHC II displays danger signals from outside the cell
there is the exception of cross presentation
the exogenous presentation of peptides via the MHC class 1 pathway is achieved how?
cross presentation
explain cross presentation
this is when peptides usually presented by MHC I are picked up exogenously: say a virus infected cell dies, and the cellular detritus is picked up by a professional APC….
because it’s exogenous, we expect MHC II
because these are viral materials, we also expect MHC I
the cell solves this by leaking the peptides into the cytoplasm, thus they will be treated by MHC I in an MHC II carrying cell
the “short version” of cross presentation
when professional APCs present exogenous material via the MHC I pathway.
the debris was “leaked” into the cytoplasm and thus processed via the proteosome.
Ags recognized by B cells can be in what forms
soluble are cell surface associated form
effector B cells are found where
lymphoid organs
What are the two B cell surface BCRs?
IgM and IgD
What are the components of the BCR complex?
the BCR and two other peptides: Igbeta/Igalpha
What are Igalpha/Igbeta?
they are associated disulfide linked heterodimers which, when BCRs bind an epitope, initiated an intracellular signaling cascade that leads to B cell activation
TCR’s are composed of
alpha and beta chains
what makes the TCR chains what they are
they both have constant and variable regions
TCRs are associated with what molecules?
3 invatiant domains
epsilon-delta —– gamma-epsilon and two zeta chains underneath the TCR complex
CD3
identification marker for TCR
epsilon delta and gamma epsilon
What do APCs need besides the MHC to stimulate T cells?
co-stimulators
resting-APC
MHC expression w/out co-receptor expression
activated-APC
MHC expression + co-receptor
Non-traditional gamma-delta T cells
where are they a major population, what’s interesting about their CD expressions, their significance
They don't express CD4/CD8 reside largely in epithelia tissues recognition of lipid antigens have no memory cells TCR repertoire is limited
