Immunology Flashcards
definition of monogenic disorders
single gene defects causing autoimmune diseases
rare
features of IPEX syndrome
very early onset insulin dependent diabetes
severe malabsorption syndrome
eczema
autoimmune thyroid disease
mutation in what gene causes IPEX syndrome
FOXP3
what is HLA
Human leukocyte Antigen complex
what is used to control T cells
Class 1 - controls CD8 cells
Class 2 - controls CD4 cells
what diseases in HLA DR3 associated with
Graves disease
SLE
Type 1 diabetes (also DR4)
what HLA is associated with RA
HLA DR4
what is HLA B27 associated with
Ankylosing Spondylitis
what class of HLA do all nucleated cells express
Class I
what cells express Class II HLA
antigen presenting cells
why do we need polymorphism in HLA molecules
to maximise the net ability to bind peptides
only a few peptides will bind to a specific HLA
what are factors contributing to autoimmune disease
Genes
Environment
Immune regulation
what are the 4 types of hypersensitivity reactions in the Gel and Coomb’s classification
Type I: Immediate hypersensitivity
Type II: Direct cell killing
Type III: Immune complex mediated
Type IV: Delayed type hypersensitivity
what are the two clinical classifications of autoimmune diseases
Organ specific diseases
Non-organ specific or multi-system autoimmune disease
example of autoimmune diseases of Type III hypersensitivity
SLE
pathogenesis of type III hypersensitive reactions
1 - circulating antigen binds to immune complexes
2 - immune complex deposition in small vessels
3 - causes complement activation
4 - infiltration of macrophages and neutrophils
what is the abnormality in SLE
disturbed regulation of B cells activity
characterised by ANA proteins
what are antibodies are seen in SLA
Anti-DNA antibodies
Anti-nuclear antibodies
Antibodies to extractable nuclear antigens etc
in SLE, what could soft heart sounds be a sign of
pericardial effusions
anti-nuclear antibodies are very uncommon and specific for autoimmune diseases - true or false
false
very common and often found in normal individuals
associated with female sex and older age
what diseases are anti-nuclear antibodies an intrinsic part of diagnostic criteria
Mixed connective tissue disease
Autoimmune hepatic disease
what are speckled antibodies associated with
ENA e.g. Ro and La
SLE and Sjogrens
what is anti-centromere associated with
Limited scleroderma (CREST)
what is an antibody highly specific for SLE
anti-dna binding antibodies
what are the 3 pathways of complement activation
1 - classical pathway C1 C4 C2
2 - lectin
3 - alternative pathway
what complement gets switched on in complement activation
C3
what does activation of C3 lead to
Membrane attack complex
what does the formation of antibody-antigen immune complexes cause
activate complement cascade via classical pathway
causes inflammation of tissues
what can be measured to act as a marker of disease activity
unactivated C3 and C4
what is the American criteria for SLE
SOAP BRAIN MD
Serositis – pleurisy or pericarditis
Oral ulcers
Arthritis - nonerosive, 2 or more peripheral joints with tenderness or swelling
Photosensitivity
Blood disorders - Leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia
Renal involvement- proteinuria, cellular casts
Antinuclear antibodies
Immunologic phenomena - dsDNA; anti-Smith (Sm) antibodies; antiphospholipid antibodies
Neurologic disorder - Seizures or psychosis in the absence of other causes
Malar rash - Fixed erythema over the cheeks and nasal bridge
Discoid rash - Erythematous raised-rimmed lesions with keratotic scaling and follicular plugging, often scarring
how many of the criteria do you need to be diagnosed with SLE
4 out of 11
management of SLE
decrease inflammation
- corticosteroids
decrease production of antibody
- immunosuppressive agents
example of Type IV autoimmune condition
RA
what is RA characterised by
destruction of joint cartilage
inflammation of the synovium
what is Type IV pathogenesis
1 - infiltration of synovium by activated CD4+ cells
2 - production of cytokines
3 - recruitment of phagocytes and activated B cells
4 - B cells produce immunoglobulin
5 - activation of synovial fibroblasts
6 - produce additional synovium
synovial histology of RA
- intense infiltration of inflammatory cells
- intimal lining layer hyperplastic
- accumulation of CD4+ T cells, macrophages, B cells
signs of a RA joint
- Infiltration of synovium primarily with activated CD4+ cells
- Directly stimulate breakdown of bone and increased vascular formation
- Chronic production of inflammatory cytokines in synovium
- Destruction of cartillage and bone by matrix metalloproteases (MMPs)
what cytokines have a critical role in the pathogenesis of RA
TNF
IL1
what do TNF and IL1 do in RA
Potent stimulators of fibroblasts, osteoclasts and chondrocytes
Stimulate release of matrix metalloproteinases
Mediators of joint damage
new revolutionary treatment in RA and how does it work
Anti-TNF antibodies
e.g. Infliximab, adalimumab
blocks attachment of cytokine to receptor
what are serological test for RA
Rheumatoid factor
- antibody directed against the common region of human IgG
- IgM anti-IgG antibody most commonly tested
all patients with RA have Rf - true or false
false
only 50% of patients will
what is a more specific test for RA then Rf
Anti-CCP antibody
