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Autoimmune conditions Flashcards

1
Q

what antibodies in type 2 and 3 hypersensitivity reactions

A

IgG (type 2 also IgM)

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2
Q

what is IL-2

A

t cell growth factor produced by CD4 +T cells

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3
Q

how do T and B cells bond to antigens

A

B cells can bind to free antigens

T cells must be presented by MHC I and II

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4
Q

what is autoimmunity

A

the presence of adaptive immune responses against self tissue/cells

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5
Q

when does autoimmunity cause significant tissue/organ damage and or chronic inflammation

A

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)

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6
Q

what are the normal tolerance mechanisms for auto reactive lymphocytes

A

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

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7
Q

what does the FOXP3 gene do

A

essential for the development of CD4+ regulatory T cells

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8
Q

what happens if the FOXP3 gene is mutated

A

decreased numbers of TREGS and loss of immune regulation

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9
Q

describe four environmental factors that can initiate an autoimmune disease

A

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

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10
Q

what type of hypersensitivity is SLE

A

type 3

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11
Q

what innate and adaptive immune mediators are involved in type 3 reactions

A

B cells, IgG, complement, neutrophils

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12
Q

what innate and adaptive immune mediators are involved in type 2 reactions

A

B cells, IgG/IgM, complement, NK cells, phagocytes

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13
Q

give 2 examples of type 2 reactions

A

goodpastures syndrome, rheumatic fever

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14
Q

what happens when IgG and IgM bind to antigens on cells in the body mistakenly detected as foreign

A

complement is activated
cellular lysis or phagocytosis
(type 2 reaction)

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15
Q

describe how immune complexes formed from antigens and IgG causes type three reactions

A

deposited in the tissue, initiates complement cascade, release of lysosomal enzymes from neutrophils, cell death, inflammation, vasculitis

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16
Q

what is myasthenia gravis

A

autoimmune neuromusclar disorder characterised by severe muscle weakness and progressive fatigue caused by disrupted neurotransmission at the NMJ (due to AChR antibodies)

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17
Q

what do autoreactive antibodies in MG bind to

A

post synaptic acetylcholine receptors in muscle cells

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18
Q

what age can you get MG

A

any

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19
Q

what are the clinical manifestations of MG

A

insidious onset
fatigue after exercise- resolves after rest
progressive muscle weakness
muscles of eyes, face, mouth, throat and mouth usually affected first

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20
Q

when may symptoms of MG first appear

A

during pregnancy or after some anesthetic agents

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21
Q

what antibody in MG

A

IgG anti-AChR antibodies

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22
Q

what is the final stage of MG

A

acetylecholine receptors destroyed, paraylsis, respiratory insufficiency

AChR antibodies bind complement, leading to the destruction go the muscle endplate via membrane attack complex

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23
Q

what is the treatment of MG

A

anti cholinesterase agents (increase neurotransmission)

immunosuprpessants

complement inhibitors

surgery (thymectomy)

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24
Q

what is rheumatoid arthritis characterised by

A

destruction of joint cartilage and inflammation of the synovium

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25
what gene is associated with RA
HLA-DR4
26
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)
27
what produces rheumatoid factor
B cells
28
what produces TNF alpha in RA
synovial macrophages
29
what do pro inflammatory cytokines do in RA
act on synovial fibroblasts to promote swelling of the synovial membrane and damage to soft tissues
30
what activates osteoclasts
RANKL
31
what activates chondrocytes to destroy cartilage
TNF alpha
32
who is more likely to get autoimmune conditions
women
33
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
34
what is the general screening test for autoimmune conditions
ANA
35
what does a titre mean
higher titre (1;640) more important than lower (1;80)
36
what happens if ANA is positive
analysed for specific antibodies
37
RA: what antibodies, disease activity markers, specific associations
rheumatoid factor, anti CCP ESR/CRP CCP and erosive disease, extra articular manifestations, smoking
38
SLE: what antibodies, disease activity markers, specific associations
ANA, dsDNA, anti smith, ribosomal P low C4 (and C3), dsDNA antiphospholipid syndrome ribosomal P
39
drug induces SLE
anti-histone ESR/CRP hydralazine, cholpromazine, isoniazid, anti TNF
40
dermatomyositis/ polymyolitis: what antibodies, disease activity markers, specific associations
anti jo, anti-PM-Scl CK DM and malingnancy, anti-synthetase
41
limited sleroderma: what antibodies, disease activity markers, specific associations
anti-centromere ESR/CRP pulmonary hypertension
42
diffuse scleroderma: what antibodies, disease activity markers, specific associations
anti Scl 70, anti RNA polymerase, antifibrillarin ESR/CRP interstitial lung disease, GI, cardio, renal
43
scleroderma renal crisis
anti RNA polymerase III creatinine, BP renal crisis (hypertension, acute rise in creatone, papillodema)
44
sjogrens syndrome: what antibodies, disease activity markers, specific associations
anti-SSA (Ro), Anti-AAB (Ia), ANA, RF ESR/CRP sicca symptoms, risk lymphoma
45
congential heart: what antibodies, disease activity markers
Anti-SSA (ro) heart rate
46
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
47
Microscopic polyangiitis: what antibodies, disease activity markers, specific associations
P-ANCA (MPO+ve) ESR/CRP pulmonary, renal (puci immune focal segmental necrotising glomerulonephritis), neuro
48
churg strauss: what antibodies, disease activity markers, specific associations
p-ANCA (MPO=ve) and eosinophilia ESR/CRP asthma, eosinophilla, atopy
49
granulomatosis polyangiitiis: what antibodies, disease activity markers, specific associations
C-ANCA (PR3 +ve) ESR/CRP granulomas- renal, pulmonary
50
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
51
when does raynauds suggest underlying autoimmune disease
when in secondary, older age group
52
what is the treatment for raynauds
keep warm, vasodilators (CCN, PDE5 inhibitors)
53
what do 90% of systemic sclerosis patients present with
raynauds
54
what are the two types of systemic sclerosis
diffuse cutaneous systemic sclerosis (dsCC0 limited cutaneous systemic sclerosis (lsCC)
55
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
56
where does fibrosis occur
skin, GI tract, heart, lungs and other internal organs
57
what cell type leads to vasculopathy and tissue fibrosis in systemic sclerosis
myofibroblasts (formed from fibroblasts, firbocytes and endothelial cells)
58
describe diffuse cutaneous SSc
skin involvement on extremities above AND below elbows and knees (plus face and trunk) (everywhere)
59
describe limited cutaneous SSc
skin involvement on extremities and ONLY below elbows and knees (plus face)
60
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
61
what are pulmonary complications of systemic sclerosis
pulmonary fibrosis, pulmonary hypertension
62
what is scleroderma renal crisis
fibrinoid necrosis in the preglomerulase afferent arterioles- the normal muscle layer of the media is replaced with fibrinoid material
63
what is the treatment for digital ulcers in raynauds
prostacyclin analogues, botox injections, endothelin receptor antagonists
64
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
65
what is sjogrens syndrome
characterised by lymphocytic infiltration of exocrine glands
66
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
67
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
68
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
69
what is undifferentiated CTD
components of: MCTD, SLE, SSc, DM/PM, sjogrens
70
what is mixed connective tissue disease
components of SLE, SSc, RA and PM
71
what is polymyositis
chronic inflammation of the muscles
72
what is dermatomyositis
inflammatory disease causing skin rash, muscle weakness, inflammatory myopathy/ inflamed muscles
73
what is antiphospholipid syndrome
autoimmune disorder characterised by arterial and venous thrombosis, thrombocytopaenia, miscarriages/ pregnancy complications and raised levels of antiphospholipid (aPL) antibodies
74
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.
75
what is thrombocytopaenia
too few platelets
76
what is the difference between primary and secondary antiphopholipid antibody syndrome
primary- no other underlying autoimmune disease secondary- seen in 20% of lupus patients
77
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
78
how do you asses the severity of antiphospholipid antibody syndrome
urinalysis, CXR, pulmonary function, ECHO

MSK (71 decks)

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