MHC Flashcards
Function of MHC 1
Target of immune response in transplant
All cells have mhc which are used to present antigen eg virus to cytotoxic cells
Donor cells have different mhc1
Role MHC2
Found on APCS only
Present to CD4 (mostly helper not killer)
Direct recognition of a foreign mhc2 does not lead to death because majority of cd4 are HRLPER NOT KILLER. What actually happens is increase in IFNg which increases macro activation and secretion TNF alpha which kills donor cells
Emhances B cell response by activation CD4
What is the major way the anti transplant response is activated?
INDIRECT presentation
Re perfusion injury to the donor - dead cells taken up as APCs
Dendritic cells can present on class 1 and 2
Other APCs can only present on 2
HLA CLASS 1
A b c
HLA class 2
Dr dp dq
The patient has a donor selected with the most B AND DR in common
Strongest association with a HLA
HLA B27 and Ank spond
ANK SPOND
HLAB27- this is a class I
RA
HLA DR4
Dermatitis herpeteformis which HLA association?
HLA DR3
DM type 1
HLA DR4
(also 3)
DR3,4- DQ 2,8 –>1/25 sporadic
What are the islet cell auto Ab?
Anti GAD- sens 72% spec 99%- involved in glutamate metabolism (more in older patients- teens onwards)
Anti-insulin - sens 40% spec 90% the only Beta cell spec. More in younger patients, not really seen in adults
Anti IA-2 (tyrosine phosphatase) SEns 62% spec 96%
Zinc transporter 40-60%
AutoAb in stiff man syndrome?
Anti GAD ab
Auto Ab in MG?
Anti ACh receptor
Anti-MUSK
- more likely bulbar disease
- more resp crises
- less occular
- less thymoma
- good steroid response
- ACH response poor
- NOT for thymectomy- do not improve
AutoAb in Graves?
Anti TSH receptor (90%) Anti TPO (50%) Anti thyroglobulin (30%)
Auto Ab in hashi?
TPO - 90%
thyroglobulin - 90%
AutoAb in Addisons disease?
Anti hydroxylase Ab in 80%
What’s the deal with autoimmune diabetes in adults? (LADA)
One in 12 adults with presumed type 2 actually have type 1 /autoimmune.
Usually Anti GAD positive, IA2 and insulin Ab less common
GAD Ab is a good predictor of insulin requirement!
FAT/thin/young/old/ketoacidosis- doesn’t really matter!
What is the “thyrogastric cluster?”
autoimmune gastritis
autoimmune thyroiditis
Type 1 DM
IF find one Ab, can look for others in Juvenille onset
HLA in coeliac disease
HLA DQ 2 DQ 8- ESSENTIAL
99.6% all patients with coeliac but only 20-30% population- so if Ab negative and then DQ2/8 positive, strong grounds for recommending gastroscopy
What are the three auto Ab in coeliac?
Anti tissue transglutaminase antibody (IgA)
Anti endomysial Ab (IgA)
Anti gliadin antibodies (IgA, IgG)
tTg and AGA are epiphenomemon - not actually pathogenic
PLUS total IgA to exclude the three percent of the population with selective IgA hypogammaglobulinaemia
Usually check first or second one
Increased risk if gluten given to baby too soon or too much, rotavirus infection. Breast feeding protective.
Explain the role of Ab in pernicious anaemia?
Anti parietal cell Ab are present in 90%- against H/K ATP-ase- but also in 15% reg population
Anti-intrinsic factor Ab 60% sens but highly specific
Atrophic gastritis classically affects the body and spares the antrum.
AUTOIMMUNE GASTRITIS CAUSES IRON DEF ANAEMIA 4-6 times as much as coeliac disease.
Once get to the end stage- atrophic gastritis- with neuroendocrine G cell hyperplasia, gastrin Ab sens 90%, 100% specific
Features of Autoimmmune Polyglandular Syndromes -type 1 2 3
1- kids, AR
all have adrenal insufficiency
Vitiligo, alopecia, mucocutaneous candidiasis
Hypoparathyroid
2. Adults assoc HLA DR3/4 Adrenal insuff in all Thyroiditis 70% DM 1 in 50% Hypogonadism
- Heterogenous - thyroiditis + another autoimmune
Haemochromatosis HLA association?
HLA-A3
Becet’s HLA association?
HLA-B5
HLA DR2 two associations
narcolepsy
goodpastures
Sjogren’s HLA associations
HLA-DR3
PBC HLA association?
HLA-DR3
Explain how many copies of each HLA we get-
HLA class I- get a single chain for each molecule A,B,C, and each person gets one from mum and mum from dad
HLA class 2 has 2 chains for each DP,DQ,DR
DR- alpha is invariant but beta is highly polymorphic and may have either 1 or 2 copies of HLA DR beta on each chromosome so 2-4 possible molecules
DP- alpha and beta both plymorphic and four possible molecules (alpha and beta each chrom)
DQ- alpha and beta both polymorphic and four possible molecules (alpha and beta on each chrom)
What is the Mixed Lymphocyte Reaction test?
T cells from one person mixed with irradiated T cells from another person (irradiation prevents division)
Rate of cell division is measured and reflects recognition by T cells of MHC molecules
Way to check allogeneic recognition
DQ and DR are…
always inherited together
HLA in SLE?
DR3
Grave’s HLA?
DR3
Hashimoto’s HLA?
DR11
MOST polymorphic HLA?
B
HLA in MS?
DR2
