Chp 5 Flashcards
Five ways TCR are similar to BCR
TCR has similar structure to FAB on BCR
Both generated through somatic recomb
TCR - a:b chains BCR- heavy light
chains
Junctional diversity
Both require CD3
Difference b/w TCR an BCR
TCR has 1 antigen binding site
BCR has 2
TCR never se created
TCR generated in Thymus BCR-BM
TCR no effector function - only surface receptor
BCR - isotype- effector function
TcR no hypermutation
TCR
A resembles The light chains
Both contain VJ segments
TCR alpha is located on what chromosome
On chrom 14
TCR B
Resembles heavy chain on imm
On chrom 7
TCR
Not undergo isotype switching because they are not made is secreted for and their C region don’t contribute to effector function
CD3 and Zeta chain roles
On surface of the cell is to transducer signals to the interior of the TC
Conseque of SCID caused by defect in
Defect of RAG 1 or 2
lacking somatic recombination in TCR
Which of the following removes CLIP
HLA-DM
Describe MHC I
Heterodimer One a chain B2 -micro globulin A chain=1,2,3 Cytoplasmic tail
B2 microgloubulin
On mHC I
Single domain protein non cov, associated with the alpha chain
Provides support and stability
MHC I : humans
HLA- a,b,c
Polymorphic
Gut uptake of imm
Regulation of FR
Reg of NK
What chain in MHC I has greater diversity?
A- has greater diversity
B- MHC II
MHC II is made up of …
Made of a:b chain Heterodimers B chain contains b1,2 Transmembrane Cytoplasmic tail
MHC II humans
3 polymorphic class molecules
HLA- DP, DQ, DR
MHC II
B2 binds to the TC co receptor Cd4
Antigen processing
The intercellular breakdown of pathogen derive proteins into peptide frag that bind to mHC
Antigen presentation
The assembly of peptides with MHC displayed on surface of APC
TC activation must be bound on what?
TCR can bind only to peptide
Antigen must be bound on surface of APC
Endogenous Antigen processing pathway
- Proteins in the cytoskeleton are broken into small fragments in the protea some
- Transported in ER using TAP
- Peptides that bind to MHC I delivered to Er
- A chain bound to chaperone calnexin until B2 m binds
- Then are bound by the chaperones calrecticulin and tapasin until peptide binds
- Tapasin binds to tap-1 positioning the MHC near the peptide source
- peptide delivered by TAP binds to heavy chain forming the mature MHC I molecule
- MHC dissociates from the peptide loading complex and export progress to the Golgi then to be transported to cell surface
What happens if RAG is lacked?
Adaptive immunity would be compromised
SCID
Non functional TC & BC
Def in CD3?
TC have low number of of receptors that do not signal effectively
CD 3 def
Immunodeficiency
Absent of TC
Non func BC
Early death die to ScId
G:d is ass with what?
The gut mucosa
Do not require antigen processing and mhC molecules
Does not have cD8 or CD4
TCR is what?
Surface receptor - no effector fun
TCR only recognizes antigens in what form?
Of peptides bound to MHC
Cd8 binds to what?
Alpha 3
Cd4 binds to what?
Beta 2
MHC I
Greater restriction
8-10 AA (short)
Hydrophobic/basic at c-term
MHC II
More leanent
Not as restrictive
Long 13-25 AA
Calnexin is…
Lectin chaperone
Holds MHC I heavy chain
Until B2m loaded
Calrecticulin
Lectin chaperone, quality control
ERp57
Promotes folding of heavy chain
Tapasin
Transmembrane protein that tethers empty class I molecules to TAP
PDI
Protein disulfide isomerase
Catalysts disulfide bond formation
ERAP
Removed aa of peptide that is too long
Improves binding affinity
What happens if def in TAP?
Tap is the channel in the ER so if def then no peptides enter the ER
So very poor cd8 response
Chronic respiratory
MHC I
Intracellular envir
MHC II
extra cell pathogens
MhC II is ass with what chain?
Invariant chain
What does the invariant chain become?
Clip
What is the function of invariant chain?
Prevent MHC II from binding peptides in ER
Delivers MHC II to vesicles
Leaves clip
HLA-DM
What forms the central part of binding site?
CDR3- most variable
What cells are MHC I expressed on?
All cells
Cross presentation
Antigens of extra cellular origin can be presented by MHC I
What char is common to both TCR and Ig?
Somatic recom of VDJ segments is responsible for the diversity of antigen binding sites
TCR a resembles…
Light locus on Ig
TCR b chain resembles …
Ig heavy locus
MHC complex closely linked genes on what chrom…?
Chrom 6
Polgeny
Result of expression
Polymorphism
Existence within pop of many alt forms of MHC I & II
Allotypes
Polgeny
Isotypes
HLA genes of MHC I
HLA A B C E F G
HLA-E
Ligand for Nk
HLA- F
Unknown func
HLA-G
Ligand for NK
Ligand for NK
HLA
E & G
HLA genes for MHC II?
HLA DM DQ DP DR
What MHC has the greatest diversity ?
MHC 1
What is the function of g:d?
First line of defense against invading pathogens
TCR diversity is generated by…?
Gene rearrangement
What are there more forms of HLA polymorphism ? MHC I or II?
Many more forms of MHC I
Haplotype is what?
MHC genes are inherited as a group one from each parent
6M/ 6D
A heterozygous human inherits what ?
One maternal one paternal
Ea contain :
3 class I (abc) 3 class II (DP,DQ,DR)
A normal tissue type will involved how many HLA antigens ?
12
A cross over results in what?
New haplotypes
Why so many MHC alleles?
MHC most polymorphic genes known
Different pathogens generate different antigenic fragments
Other proteins involved in antigen processing and presentation ?
Tapasin
Immunoprotrasome LMP2, LMP7
HLA class I don’t involve….?
Antigen processing and presentation
HLA I functions?
Gut uptake
Reg of Fe
Ref of NK
MHC I is more evolutionary
More older
HLA region III has what ?
Components of complement sys
Cytokines (TNF)
What MHC II polymorphism not vary?
HLA-DR
Is B2 microgloubulin polymorphic?
No
TCR has what…?
Restriction responds to peptide presented by one MHC
HLA diseases
Rheum arthritisis Type I diabetes Celiac Graves MS Breast cancer
Wht are the types of MHC haplotypes?
Balancing selection
Directional selection
How are MHC alleles generated by?
Interallelic intercom version or gene conversion
Why is a transplant rejected?
The alloreactivity of TC
The MHC they were not selected for in the thymus and why the TC sees it as a foreign MHC
TC respond strongly to what..
Allografts
Cd4 are alloreactivity to what ?
Class II alloantigens
Cd8 alloreactivity to
class I alloantigens
Is MHC highly polymorphic?
Yes seen by alloreactivity TC
