Immunology Flashcards
HLA-DR2
Goodpastures
Graves disease HLA?
HLA-DR3
SLE HLA?
HLA-DR3
Type 1 diabetes HLA?
HLA-DR3/DR4
Rheumatoid arthritis HLA?
HLA-DR4
Which type of hypersensitivity is SLE?
Type III hypersensitivity
Symptoms of IPEX disease
- early onset insulin dependent diabetes mellitus
- severe enteropathy
- eczema
- autoimmune thyroid disease, autoimmune haemolytic anaemia,
- severe infections
Clinical classification of auto-immune diseases?
Organ-specific disease
Non-organ specific disease
Eating cells seen in type III hypersensitivity?
Macrophages and neutrophils
B or T cell dysregulation in SLE and antibodies?
B cell Antibodies to nuclear proteins: -Anti-DNA -Anti-nuclear -Anti-ENA
Name two ENAs?
anti-Ro
anti-La
What do anti-Ro and anti-La look like?
speckled!!!
What is anti-centromere antibody very specific for?
Scleroderma
What binds to kinetochore (chromosomes)?
Anti-centromere antibody
Nucleolar ANA?
Scleroderma!!
Nucleolar ANA: Autoantigens = proteins associated with nucleolar RNA including fibrillarin, U1RNP
Name 2 proteins associated with nucleolar RNA?
Fibrillarin, U1RNP
What is anti-smith antibody very specific for?
SLE
Anti-DNA antibodies in SLE
Very high titres are often associated with more severe disease, including renal or CNS involvement!!
Useful in disease monitoring
an increase in antibody titre is associated with disease activity and may precede disease relapse.
Characteristic biopsy features of type III hypersensitivity?
Immune complexes, macrophages and neutrophils, products of complement activation
Immune complex (type III) vs antibody (type II) mediated disease pathology
-Granular lumpy bumpy pattern of IgG deposition in type III
-Linear deposition along basement membrane in type II
(this can be seen in glomerulonephritis
Type III hypersensitivity management
Decrease inflammation Corticosteroids Decrease production of antibody Immunosuppressive agents Anti-proliferative agents Azathioprine Mycophenolate Cyclosphosphamide
Jaccouds arthritis?
SLE
Libmansach endocarditis?
SLE
SLE glomerulonephritis?
Proteinuria Urine sediments Urine RBC and casts Hypertension Acute renal failure Chronic renal failure
SLE cardiac features
Pericarditis
Cardiomyopathy
Pulmonary hypertension
Libman Sach endocarditis (non-bacterial endocarditis)
SLE pulmonary features
Pleurisy Infections Diffuse lung infiltration and fibrosis Pulmonary hypertension Pulmonary infarct
SLE neurological features
Depression/psychosis Not always related to disease activity Migranous headache Cerebral ischaemia TIAs or stroke Cranial or peripheral neuropathy Cerebellar ataxia
SLE haemtological features
Lymphadenopathy ~25% of all patients during their course of illness Leucopenia (low white cells) Anaemia haemolytic normochromic normocytic Thrombocytopenia (low platelets)
SLE drug treatment
-NSAID and simple analgesia
-Anti-malarials
-Steroids
-Aziathioprine
-Cyclophosphamide (IV)
-Methotrexate
-Miycophenalate mofetil
Calcineurin inhibitors (ciclosporin A, tacrolimus)
Biologics: rituximab,
How is cyclophosphamide administered?
IV
IPEX inheritence
Autosomal dominant
Ankylosing spondylitis HLA
HLA B27
Anti-nuclear antibodies associated with which conditions?
SLE Rheumatoid arthritis/autoimmune conditions HIV Hepatitis Females Older age
Speckled antibody
Ro and La
SLE, Sjogrens
Anti-centromere
Limited scleroderma (CREST)
Nucleolar ANA (fibrillarin, U1RNP)
Scleroderma
Anti-RNP
Mixed connective tissue disease and SLE
Anti-toposiomerase (Anti-Scl70)
Diffuse scleroderma, associated with more severe organ involvement, including pulmonary fibrosis
Shows activity in SLE?
Anti-dsDNA
C3 and C4 (negatively correlate)
Unactivated C3 and C4 measured in Ninewells)
GN appearance in SLE
Granular “lumpy-bumpy” (because type III duh)
GN in goodpastures?
Linear deposition
RA is which type of reacion?
Type IV hypersensitivity response
Characterised initially by infiltration of synovium by CD4+ T cells
Secondary involvement of activated B cells and antibody
Pro-inflammatory cytokines in RA
TNF and IL-1
High synovial concentrations
Potent stimulators of fibroblasts, osteoclasts and chondrocytes
Stimulate release of matrix metalloproteinases
Important mediators of joint damage
Major indications for rheumatoid factor testing?
Evaluate prognosis in patients with rheumatoid arthritis
Associated with more severe erosive disease
Associated with extra-articular disease manifestations eg nodules and vasculitis
May be helpful in the diagnosis of
Sjogren’s syndrome
cryoglobulinaemia
ANTI-CCP:
More specific test for rheumatoid arthritis than rheumatoid factor and better predictor of an aggressive disease course
In patients with undifferentiated arthritis, anti-CCP antibodies may predict those who are likely to develop rheumatoid arthritis
