Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
38 Cards in this Set
- Front
- Back
- 3rd side (hint)
|
Where is the MHC complex found?
|
Short arm of 6th chromosome
It can be divided into 3 region Region I Region II Region III < graft rejection (tightly packed, most dense in the entire genone) |
|
|
|
How many genes are in the MHC
|
180 genes
40% are immune response |
|
|
|
Region I
|
Class I transplantation antigens
Structure: A chain + B chain Theres a groove, 35 AA with 20 variable AAs < this determines differnces |
|
|
|
Region II
|
Class I transplantatoin antigens
|
|
|
|
How does CD8 recognize MHC
|
Cd8 recognizes a constant region of the MHC I
|
|
|
|
Does the B2-microglobin play role a rejection grafts
|
No.
It does make sure however, that the conformation/structure of the MHC stays intact |
|
|
|
What encodes for transplantation antigens
CLass I - all nu. cells Class II - more limited distb. |
B locus
A locus C locus Multiple alleles on each |
|
|
|
WHere does the Tubercle bacilis reside?
|
Macrophages
Which cells destory these |
CD4 cells
|
|
|
What is special about the B locus?
|
780 alleles - like a chinese menu
At c -230 genes A a -450 genes |
Can you see the tremendous polymorphism ability
We're talking billion trillion combos |
|
|
Class II loci
|
dp 39 alleles
dq 71 alles - only dq has variability on both alpha and beta chains, dr -438 alleles |
since on the dq u have polymorphism on the a and b chains , they can combine to get cis and trans, they are codiminate, they express mhc of mother and father.
|
|
|
Would u want to expression transplantation antigens on the plancenta during pregnancy? No
|
Hell no.
However a class I like antigen is expression. the reason is: the NK cell needs to make sure sees it or eles it'll kill it |
|
|
|
What's Mic1 and Mic2?
|
Mic 1 and Mic 2 ligands are encouded in the MHC which tell NK cells not to kill cells which express these
|
|
|
|
The entire HLA on the 6th chromosome is called a haplotype.
|
When u get on the wards they ask - what's the dq haplotype (fault of harrision)
|
For our purpose its the entire consetellation of mhc products on a single chromosome
|
|
|
The answer is always...
|
25%
|
on the Boards the answer is always 25%
|
|
|
A3 and A19 what is going to be the DR
|
4?
9? 2? 3? |
The entire constellation is inherited in blocks, low incidence of crossover but it can occur
|
|
|
Type offspring B7 and B27
What is the HLA A type of this individual? |
what?
|
The entire constellation is inherited in blocks, low incidence of crossover but it can occur
|
|
|
Linkage Disquilibrium
HLA A1 and B7 11% and 17% So what is the chances of invididuals being A1 and b7 |
2% (just product)
But when you look at populations its actually 8% which is a 4x increase. |
Example of linkage disquilibrium
|
|
|
Hemochromatosis
incrased iron abs by gut liver - cirrosis panc - diabetes skin - brown discoloration When u look at patients they have a higher incidence of HLA... |
HLA A3
Why? Where is the gene that encodes for for the iron transporter in the gut? |
In the MHC (Chrome A)
And so where is the A locus? Not too far apart. |
|
|
read harrisons
|
308 - to 316?
|
|
|
|
Linkage disequilibrium
Disease Association |
Linkage disequilibrium
Disease Association |
What
|
|
|
What does the TCR see?
|
It sees both H antigen and a peptide.
It has to see both. |
CONCEPT OF MHC RESTRICTION
|
|
|
TheMHC peptide binding groove
|
What peptides are bound? does a given mhc molecule bind all peptides? theres some specificity. only certain peptides are bound to certain mhc products. if we have three peptides that are quite differnt -a
|
it's not exquisite though, prob can bind 5 -7 diff ones
|
|
|
Not all kids who die, get cerebral malaria? in gambia
|
the kids who get malaria, w/o cerebral have a specific HLA b53 when typing is performed
so the b53 allows binding to malaria peptide for presentation |
B53 can be isolatd and marla peptide is found on it
if the patient was hla b8, it wouldn't bind, parasite would live in liver, get into blood stream, to to ceregrum and kid would die |
|
|
Why is there a difference between HLA distribution in coast vs inland in papau new guinea
|
Captain Cook - brought EBV
People would are HLA11 didn't succumb to disease The HLA11 prob bound peptide, presented to immune system, which destroyed virus. |
If you go there today you'll find that there are HLA11 individuals who do get EBV - why?
The virus has changed or mutated. |
|
|
Celiac sprue is associated with a specific HLA-DQ which one?
|
DQ2
|
* Genetics play an important role in celiac sprue. The incidence of celiac disease in relatives of patients with celiac sprue is significantly higher than in the general population. The prevalence in first-degree relatives of patients with celiac sprue is approximately 10%. Concordance for the disease in monozygotic twins approaches 75% and is approximately 30% for first-degree relatives.
* Gliadin binds to HLA-DQ2 heterodimers or HLA-DQ8 heterodimers found in 90-95% and 5-10% of patients with celiac disease, respectively. HLA-DQ2 and HLA-DQ8 are present on the surface of antigen-presenting cells in the lamina propria, and binding of gliadin leads to expression of the proinflammatory cytokine interferon gamma and activation of CD4+ T lymphocytes. |
|
|
Antigenic determinant
|
Toyota Logo
|
|
|
|
Looking at HLA B27.
found antigenic determinant interacting with anti-sera |
if we look at molecules theres 27 different molecules - toyotas are not all the time
|
|
|
|
If you have hla b*5701
which drug shouldn't you give |
Abacavir
|
Abacavir is used in combination with other medications to treat human immunodeficiency virus (HIV) infection
|
|
|
How do proteosomes affect antigen presentation
|
They can influence what peptides are being made
Different proteosome chop different antigens Protesome genes are located in HLA!? |
psorasis
nickel hypersensitivy ankalosing spondalytis |
|
|
TAP1 and TAP1
ER transporters Where are TAPs encoded? |
In the MHC Complex
|
ankalosing spondalytis
uvittis |
|
|
Viruses can downregulate...
|
TAP
|
To prevent Class I presentation and prevent CTL attack
But Gamma-interferon can upregulate the TAP and overcome the block |
|
|
What is Tapasin
|
This gene encodes a transmembrane glycoprotein that mediates interaction between newly-assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane.
|
|
|
|
5 Year Graft Survival Rate
Living vs Cadaver Grafts Have different Rates of survival time |
Serotypes although the same,
the genotypes might be different For example just cause serotypes are matched, the genotypes might be mismatched. Serotype - using LOGO Genotype - actual car |
|
|
|
What do B cell and T Cell activation need?
|
They both need HELP!
|
|
|
|
what is indirect allorecognition vs direct recognition?
|
Allogenic MHC molecules or other donor alloantigens are processed and presented by recipient APCs. This is the normal mechanism of T -cell stimulation by nominal antigens. as processed peptides associated with self (recipient) MHC class II molecules. Alloantigens shed from a graft will in general be treated as exogenous antigens by recipient APCs , leading to a dominance of th cells recognizing allopeptides bound to MHC self class II molcules. The observations made thus far indicate That T cells sensitized by the direct pathway might initlaly dominate the rejection process occuring in nonimune recipients bu that T cells sensitized by indirect allorecognition might contribute substantially to continuing long -term or chronic graft dmange after the allograft has lost its DC pop and direct alloreactiv eT cells have been rendered hyporesponsive.
|
Direct allorecognition is defined as the recognition by recipient T cell sof the intact MHC alloantigens displayed at the surface of donor (dendritic) cells carried within the graft. No other cells intervene in the initial step of the direct pathway
|
|
|
semi direct allorecogntion
|
re macrophage will eat graft cell membranes and some antigens end up on on the macrophage
|
|
|
|
Possible explanation
|
1. recipient T cells are looking at the foreign MHC W/O the peptide
2. recept t cell needs both foriegn MHC with peptide, ????? |
|
|
|
Important concept
|
Know t cell shows MHC restiction
(unique mhc peptide comobo MHC products can only bid some peptides |
|
