Immunology Flashcards
monogenic disorder
single gene defects causing autoimmune diseases are rare
example of a monogenic autoimmune disorder
IPEX syndrome
what is IPEX syndrome
a fatal X-linked autosomal recessive disorder presenting in early childhood causing immune disregulation, enteropathy & polyendocrinopathy
what are the symptoms of IPEX syndrome?
Very early onset T1DM (before 6 months) severe malabsorption syndrome eczema autoimmune thyroid disease, autoimmune haemolytic anaemia, severe infections
what is the pathogenesis of IPEX syndrome?
Mutation in FOXP3 gene - essential for the development of regulatory T-cells which are essential in protection against auto-immunity
HLA
human leukocyte antigen complex (controls T cells)
what is the susceptibility allele associated with ankylosing spondylitis?
HLA B27
what is the susceptibility allele associated with goodpastures syndrome?
HLA DR2
what is the susceptibility allele associated with Graves disease?
HLA DR3
what is the susceptibility allele associated with SLE?
HLA DR3
what is the susceptibility allele associated with T1DM?
HLA DR3/DR4
what is the susceptibility allele associated with rheumatoid arthritis?
HLA DR4
which class of HLA do all nucleated cells express on the cell surface?
class 1
give some examples of class 1 HLA
HLA-A
HLA-B
HLA-C
which class of HLA do specialised antigen-presenting cells also express?
class 2
give some examples of class 2 HLA
HLA-DR
HLADQ
HLA-DP
why is polymorphism of HLA molecules important?
to maintain diversity
what are the 3 factors contributing to autoimmune disease?
genetics
environment
immune regulation
what pathological classification scheme is used in the classification of autoimmune disease?
Gel & Coombs classification
how are autoimmune diseases clinically classified?
organ-specific diseases or non-organ specific multi system autoimmune disease
what are hypersensitivity reactions?
Immune response that results in bystander damage to the self, usually exaggeration of normal immune mechanisms
what is the Gel & Coombs classification of hypersensitivity reactions?
Type I: Immediate hypersensitivity
Type II: Direct cell killing
Type III: Immune complex mediated
Type IV: Delayed type hypersensitivity
what type of hypersensitivity reaction according to Gel & Coombs is SLE?
type III
what is the fundamental abnormality of SLE?
disturbed regulation of B cell activity
what is SLE?
Prototypic multisystem autoimmune disease
which stage of life is frequency the highest?
2nd & 3rd decades of life
in which sex is SLE more common?
females
what is SLE characterised by?
antibodies to nuclear proteins
what does ANA bind to?
can bind to many different nuclear components
what are speckled antibodies associated with?
antibodies to extractable nuclear antigens eg Ro and La
which antibodies are more sepcific for SLE & sjorgen’s syndrome the ANA?
speckled antibodies
what do anti-centromere antibodies bind to?
chromosomes (kinetochore)
what disease are anti-centromere antibodies very specific for?
scleroderma
what are auto antigens?
proteins associated with nucleolar RNA including fibrillarin, U1RNP
what disease are neuclolar ANA associated with?
scleroderma
what are extractable nuclear antigens?
nuclear antigens that are soluble and can be extracted from the nucleus
levels of which complements can act as a surrogate marker of disease activity in SLE?
C3 & C4
- low levels = high activity
what investigations are done for type III hypersensitivity reactions?
specific IgG to putative antigen
low serum complements
characteristic biopsy features
how are type III hypersensitivity reactions managed?
decrease inflammation- corticosteroids
decrease production of antibody - immunosuppressive agents
what type of hypersensitivity is rheumatoid arthritis?
type IIII
what is rheumatoid arthritis?
Inflammatory autoimmune disease characterized by the destruction of joint cartilage and inflammation of the synovium
what are the clinical features of rheumatoid arthritis?
initially: stiffness, pain, swelling, erythema
later: osteoporosis, destruction of joint cartilage, bone resorption, displacement by ankylosing, subcutaenous nodules at pressure points
what is the immunopathogenesis of rheumatoid arthritis?
Characterised initially by infiltration of synovium by CD4+ T cells
Secondary involvement of activated B cells and antibody
what does the histology of the synovium look like in rheumatoid arthritis?
Redundant folds of synovial lining and intense infiltration with inflammatory cells
which inflammatory mediators have critical roles in the pathogenesis of rheumatoid arthritis?
IL1
TNF
how do biologicals work?
cytokine blockade by blocking the TNF network (anti-TNF)
what is a rheumatoid factor?
an antibody directed against the common (Fc) region of human IgG
what are the major indications for rheumatoid factor testing?
evaluating the prognosis of someone with rheumatoid arthritis or diagnosing sjorgen’s syndrome/cryoglobulinaemia
what is a more specific test for rheumatoid arthritis then rheumatoid factor?
anti-CCP antibody
