Immunology of AI disease Flashcards
Does having autoimmune phenomena mean you have the disease?
No
What is HLA?
Human leukocyte antigen complex
What are the genetic influences in AI disease?
- Monogenetic disorders
- Complex genetic interplay between different immune regulating genes
- Genes determining sex
What is IPEX syndrome?
Immune dysregulation, polyendocrinopathy. enteropathy and X -linked inheritance syndrome
fatal autosomal recessive disorder presenting early in childhood
What do all nucleated cells express?
HLA class 1
How many HLA molecules can antigen presenting cells express?
12 6 HLA class 1 molecules and 6 HLA class 2 molecules
How many variants of HLA does each individual posses?
2
What can disease clustering indicate?
a genetic basis or relate to a common immune immune defect
Give some examples of initiating events in the pathogenesis of AI diseases.
EBV, Parovirus, Coxsackie, Klebsiella
What are the 3 main factors which contribute to AI disease?
- immune regulation
- infection
- HLA - association but not a prerequisite for disease
Are all autoantibodies pathogenic?
No
What do circulating auto-antibodies in autoimmune disease activate
complement
phagocytes
natural killer cells
What are the 2 clinical classifications of AI disease?
Organ specific AI disease
Multi-system AI disease
What kind of hypersensitivity reaction is SLE?
Type 3
What is the “fundamental abnormality” in SLE?
Disturbed regulation of B cell activity
In SLE what do the auto-antibodies act against?
Dead and dying nuclear material including extractable nuclear antigens
What does Normocytic normochromic anaemia indicate?
Chronic disease
What are anti-nuclear antibodies?
Group of antibodies that bind to nuclear proteins
Which autoantibodies are “speckled antibodies”? And what are they more specific for?
Anti- Ro
Anti - La
SLE and Sjogrens
What is the anti-centromere antibody specific for?
Limited scleroderma
What is the NucleolR ANA associated with?
Scleroderma
What investigations ca be used for Type 3 HSR?
Specific IgG to putative antigen
Low serum complements
Characteristic biopsy features
What is the difference between “lumpy-bumpy” and linear deposition glomerulonephritis?
lumpy bumpy - type 3 HSR - deposition of IgG ad C3 in granular pattern
linear deposition - type 2 HSR - IgG depositied along the glomerular basement membrane
How many out of 11 does a patient need to have to have according to the American Rheumatological Association criteria for SLE?
4
What kind of HSR is rheumatoid arthritis?
Type 4 - infiltartion of synovium by activated CD4+ cells –> production of cytokines, recruitment of phagocytes, activated B cells and synovial fibroblasts
Is rheumatoid factor a good/useful investigation in he diagnosis of RA?
No - Only 50% of patients with rheumatoid arthritis are positive for rheumatoid factor at the time of diagnosis
What can rheumatoid factor be used for?
evaluate prognosis in patiets with rheumatoid arthritis
may be helpful in the diagnosis of Sjogrens syndrome
What is a more specific test for RA?
Anti-CCP antibody
It is also a better predictor d an aggressive disease course
