Autoimmune conditions Flashcards
what antibodies in type 2 and 3 hypersensitivity reactions
IgG (type 2 also IgM)
what is IL-2
t cell growth factor produced by CD4 +T cells
how do T and B cells bond to antigens
B cells can bind to free antigens
T cells must be presented by MHC I and II
what is autoimmunity
the presence of adaptive immune responses against self tissue/cells
when does autoimmunity cause significant tissue/organ damage and or chronic inflammation
when there is high titres of autoantibodies and/or auto-reactive T cells
when there is a failure of autoimmunogical tolerance (mechanisms defective or overwhelmed)
what are the normal tolerance mechanisms for auto reactive lymphocytes
immature self reactive lymphocytes are killed as they develop in primary lymphoid tissues
activity of mature self reactive lymphocytes is suppressed by regulatory T cells in peripheral tissues
what does the FOXP3 gene do
essential for the development of CD4+ regulatory T cells
what happens if the FOXP3 gene is mutated
decreased numbers of TREGS and loss of immune regulation
describe four environmental factors that can initiate an autoimmune disease
molecular mimicry- when T and B cells with cross reactive antigen receptors are activated by non self peptides that mimic endogenous ones
intercurrent change- immune responses potential ongoing immune reactions
tissue damage- causes previosly hidden (from immune system so not deleted) self antigens to be released and exposed
superantigens- bacterial, can activate T cells non specifically which can then differentiate into effector T cells and attack tissues expressing self antigens
what type of hypersensitivity is SLE
type 3
what innate and adaptive immune mediators are involved in type 3 reactions
B cells, IgG, complement, neutrophils
what innate and adaptive immune mediators are involved in type 2 reactions
B cells, IgG/IgM, complement, NK cells, phagocytes
give 2 examples of type 2 reactions
goodpastures syndrome, rheumatic fever
what happens when IgG and IgM bind to antigens on cells in the body mistakenly detected as foreign
complement is activated
cellular lysis or phagocytosis
(type 2 reaction)
describe how immune complexes formed from antigens and IgG causes type three reactions
deposited in the tissue, initiates complement cascade, release of lysosomal enzymes from neutrophils, cell death, inflammation, vasculitis
what is myasthenia gravis
autoimmune neuromusclar disorder characterised by severe muscle weakness and progressive fatigue caused by disrupted neurotransmission at the NMJ (due to AChR antibodies)
what do autoreactive antibodies in MG bind to
post synaptic acetylcholine receptors in muscle cells
what age can you get MG
any
what are the clinical manifestations of MG
insidious onset
fatigue after exercise- resolves after rest
progressive muscle weakness
muscles of eyes, face, mouth, throat and mouth usually affected first
when may symptoms of MG first appear
during pregnancy or after some anesthetic agents
what antibody in MG
IgG anti-AChR antibodies
what is the final stage of MG
acetylecholine receptors destroyed, paraylsis, respiratory insufficiency
AChR antibodies bind complement, leading to the destruction go the muscle endplate via membrane attack complex
what is the treatment of MG
anti cholinesterase agents (increase neurotransmission)
immunosuprpessants
complement inhibitors
surgery (thymectomy)
what is rheumatoid arthritis characterised by
destruction of joint cartilage and inflammation of the synovium
what gene is associated with RA
HLA-DR4
what type of reaction is RA
type 4, infiltration of synovium by self reactive CD4+T cells (and lymphocytes, plasma cells, dendritic cells and macrophages)
what produces rheumatoid factor
B cells
what produces TNF alpha in RA
synovial macrophages
what do pro inflammatory cytokines do in RA
act on synovial fibroblasts to promote swelling of the synovial membrane and damage to soft tissues
what activates osteoclasts
RANKL
what activates chondrocytes to destroy cartilage
TNF alpha
who is more likely to get autoimmune conditions
women
what symptoms should make you suspect an autoimmune conditions
arthralgia, arthritis, muscle pain/ weakness, photosensitivity, raynauds, sicca symptoms (dry eyes/mouth/throat/vagina), dysphagia, SOB, neurological symptoms, recurrent pregnancy loss
what is the general screening test for autoimmune conditions
ANA
what does a titre mean
higher titre (1;640) more important than lower (1;80)
what happens if ANA is positive
analysed for specific antibodies
RA:
what antibodies,
disease activity markers,
specific associations
rheumatoid factor, anti CCP
ESR/CRP
CCP and erosive disease, extra articular manifestations, smoking
SLE:
what antibodies,
disease activity markers,
specific associations
ANA, dsDNA, anti smith, ribosomal P
low C4 (and C3), dsDNA
antiphospholipid syndrome ribosomal P
drug induces SLE
anti-histone
ESR/CRP
hydralazine, cholpromazine, isoniazid, anti TNF
dermatomyositis/ polymyolitis:
what antibodies,
disease activity markers,
specific associations
anti jo, anti-PM-Scl
CK
DM and malingnancy, anti-synthetase
limited sleroderma:
what antibodies,
disease activity markers,
specific associations
anti-centromere
ESR/CRP
pulmonary hypertension
diffuse scleroderma:
what antibodies,
disease activity markers,
specific associations
anti Scl 70, anti RNA polymerase, antifibrillarin
ESR/CRP
interstitial lung disease, GI, cardio, renal
scleroderma renal crisis
anti RNA polymerase III
creatinine, BP
renal crisis (hypertension, acute rise in creatone, papillodema)
sjogrens syndrome:
what antibodies,
disease activity markers,
specific associations
anti-SSA (Ro), Anti-AAB (Ia), ANA, RF
ESR/CRP
sicca symptoms, risk lymphoma
congential heart:
what antibodies,
disease activity markers
Anti-SSA (ro)
heart rate
mixed connective tissue disease:
what antibodies,
disease activity markers,
specific associations
anti-U1RNP (daDNA must be negative)
ESR/CRP
puffy hands, overlap with other CTD
Microscopic polyangiitis:
what antibodies,
disease activity markers,
specific associations
P-ANCA (MPO+ve)
ESR/CRP
pulmonary, renal (puci immune focal segmental necrotising glomerulonephritis), neuro
churg strauss:
what antibodies,
disease activity markers,
specific associations
p-ANCA (MPO=ve) and eosinophilia
ESR/CRP
asthma, eosinophilla, atopy
granulomatosis polyangiitiis:
what antibodies,
disease activity markers,
specific associations
C-ANCA (PR3 +ve)
ESR/CRP
granulomas- renal, pulmonary
what causes raynauds
vasospasm of artery= vascular occlusion= digital ischemia
cyanosis as capillaries and venules are filled with deoxygenated blood
rubor as vasospasm releases and capillaries still dilated filled with oxygenated blood
when does raynauds suggest underlying autoimmune disease
when in secondary, older age group
what is the treatment for raynauds
keep warm, vasodilators (CCN, PDE5 inhibitors)
what do 90% of systemic sclerosis patients present with
raynauds
what are the two types of systemic sclerosis
diffuse cutaneous systemic sclerosis (dsCC0
limited cutaneous systemic sclerosis (lsCC)
what is systemic sclerosis (scleroderma)
autoimmune disease in which there is increased fibroblast activity resulting in abnormal growth of connect tissue= vascular damage and fibrosis
where does fibrosis occur
skin, GI tract, heart, lungs and other internal organs
what cell type leads to vasculopathy and tissue fibrosis in systemic sclerosis
myofibroblasts (formed from fibroblasts, firbocytes and endothelial cells)
describe diffuse cutaneous SSc
skin involvement on extremities above AND below elbows and knees (plus face and trunk) (everywhere)
describe limited cutaneous SSc
skin involvement on extremities and ONLY below elbows and knees (plus face)
what are the limited (CREST) symptoms of systemic sclerosis (scleroderma)
CREST
Calcinosis (calcium deposits in the skin)
Raynauds phenomenon- spasm of blood vessels in response to cold or stress
Esophageal dysfunction (acid reflux, decreased motility of esophagus)
Sclerodactyly- thickening and tightening of the skin on the fingers and hands
Telangiectasias- dilation of capillaries causing red marks on surface of the skin
what are pulmonary complications of systemic sclerosis
pulmonary fibrosis, pulmonary hypertension
what is scleroderma renal crisis
fibrinoid necrosis in the preglomerulase afferent arterioles- the normal muscle layer of the media is replaced with fibrinoid material
what is the treatment for digital ulcers in raynauds
prostacyclin analogues, botox injections, endothelin receptor antagonists
what is the management for systemic sclerosis
yearly echo and PFTs
treat raynauds and digital ulcers
treat reflux woth PPi +/- rantidine +/-gaviscon
pulmonary fibrosis- immunosuppession
PHT- [rostacyclin analogues, endothelin receptor anatagonists, PDE5 inhibitors
BP- ACE INHIBITORS
what is sjogrens syndrome
characterised by lymphocytic infiltration of exocrine glands
what are the symptoms of sjorgens
keratoconjuctivitis sicca
- gritty eyes
- thirsty
- dry mouth
- vaginal dryness
- blepharitis
- salivary gland inflammation
- tooth decay
- lymphoma
- dry cough
- multisystem involvement
describe the antibodies, blood marjers and diagnostic markers of sjorgens
usually ANA positive
anti ro and anti La-more specific than sensitive
if antibodies negative salivary gland ultrasound and biopsy
usually high ESR/ PV
raised IgG
cytopaenias
what is the treatment of sjogrens syndrome
artificial tears and salivary supplements, vaginal lubricants
good dental hygiene- strong fluoride toothpaste
hydroxychloroquine for fatigue and arthralgia
immunosuppressants for major organ involvement
what is undifferentiated CTD
components of: MCTD, SLE, SSc, DM/PM, sjogrens
what is mixed connective tissue disease
components of SLE, SSc, RA and PM
what is polymyositis
chronic inflammation of the muscles
what is dermatomyositis
inflammatory disease causing skin rash, muscle weakness, inflammatory myopathy/ inflamed muscles
what is antiphospholipid syndrome
autoimmune disorder characterised by arterial and venous thrombosis, thrombocytopaenia, miscarriages/ pregnancy complications and raised levels of antiphospholipid (aPL) antibodies
what biochemical markers are seen in antiphopholipid antibody syndrome
Presence of antiphospholipid antibodies on 2 occasions 12 weeks apart-
Anti cardiolipin antibody(IgM and IgG)
Lupus anticoagulant.
Beta 2 glycoprotein.
what is thrombocytopaenia
too few platelets
what is the difference between primary and secondary antiphopholipid antibody syndrome
primary- no other underlying autoimmune disease
secondary- seen in 20% of lupus patients
what is the management for antiphopholipid antibody syndrome
lifelong anticoagulants if thombosis
pre pregnancy- LMWH and aspirin into post partum period
if major organ invlovement- immunosuprpession. if not- Hydroxychloroquine, symptomatic treatment
how do you asses the severity of antiphospholipid antibody syndrome
urinalysis, CXR, pulmonary function, ECHO
