Immunology of autoimmune disease Flashcards
What is a monogenic disorder?
Single gene defect which causes the autoimmune disease.
Rare.
What is IPEX syndrome?
Immune dysregulation Polyendocrinopathy Enteropathy and X-linked inheritance syndrome.
What kind of inheritance does IPEX syndrome have?
Fatal autosomal recessive disorder
When does IPEX syndrome present?
Early childhood
What are the symptoms of IPEX syndrome?
IDDM Malabsorption Eczema Autoimmune thyroid and haemolytic anaemia Severe infections
What is the pathogenesis of IPEX syndrome?
Mutation in FOXP3 gene which is essential to develop T cells.
What does HLA stand for?
Human Leukocyte Antigen complex
What does HLA do?
???
On the surface of antigen and recognises peptides.
What are the 3 types of class I HLA?
HLA-A, HLA-B and HLA-C.
What are the specialised class II HLA?
HLA-DR
HLA-DQ
HLA-DP
True or False.
Each person has only 1 type of HLA molecule
False.
Each individual possesses 2 variants of each HLA molecule.
In what way is HLA like an enzyme?
Like lock and key mechanism.
Only a few peptides can bind to a specific molecule
What is the susceptible allele of ankylosing spondyltitis?
HLA B27
What is the susceptible allele of rheumatoid arthritis?
HLA-DR4
Which rheum disease is a type III hypersensitivity diseases?
SLE
What is a type III hypersenstivity?
Antibody-antigen complex deposition in the small vessels activating complement and macrophages to the site.
Which antibody is characterised in SLE?
ANA- anti nuclear antibodies.
What are the clinical features of SLE?
?? malar rash fatigue arthralgia weight loss depression
What other diseases is anti-ANA associated with?
Scleroderma
Sjogrens
When would you find an anti-centromere antibody?
Systemic sclerosis/ CREST.
What is the classical pathway of complement?
Centres around C3.
Formation of antibody-antigen complexes.
Why would you use C3 as a marker for disease?
It measures unactivated C3.
If C3 levels are low then C3 has been used up and would be a good marker of disease activity.
What other investigations would you do if still not sure from bloods?
Biopsy for presence of immune complexes
How does glomerulonephritis in SLE differ from that in Goodpastures (a type II)?
Goodpastures glomerulonephritis has a linear deposition of IgG on basement membrane.
SLE is bumpy.
What is the treatment for SLE?
Steroids.
Immunosuppressants
Which rheum condition is a type IV hypersensitivity?
RA
What is a type IV hypersensitivity?
Delayed type hypersensitivity.
What is RA?
Autoimmune inflammatory disease characterised by destruction of joint cartilage and inflammation of synovium
What systemic effects can poorly managed RA cause?
Osteoporosis
Bone resorption
Destruction of joint cartilage
What is the immunopathogenesis of RA?
Infiltration of CD4+ cells to synovium which produces cytokines. Causes cascade and phagocytes are recruited along with B cells.
How does the immunopathogenesis actually cause a diseased joint?
Cytokines and matrix metalloproteinase formed which directly stimulate breakdown of bone and cartilage.
Why are TNF and IL1 important in RA?
Stimulators of fibroblasts, osteoclasts and chrondrocytes and stimulate release of matrix metalloproteinases.
How does anti-TNF work?
Ab to cytokine so cytokine cannot attach to receptor.
What is rheumatoid factor?
An antibody directed against Fc region of human IgG.
True or False
If RF is negative this means the diagnosis definitely is not RA
False.
Not specific enough
