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Immunology 6 - Hypersensitivity (ii) (type 4 (anti-phospholipid syndrome…
Immunology 6 - Hypersensitivity (ii)
type 2
Ig-mediated
binds to tissues + activates complement
inflamm cell influx + tissue damage
e.g. in autoimmunity
anti-glomerular basement membrane disease
green immunofluorescence on membrane = IgG inflamm rim
Dx
lab test = tissue-specific Igs
100% sensitive (esp in acute untreated disease)
Bx (look for Ig deposition)
Pemphigus + Pemphigoid
rare autoimmunity affecting skin + mucous membranes
lab test less sensitive
penicillin allergy
Igs made in response to penicillin coated RBCs
activates complement
MAC - haemolysis
C3b - opsonisation + phagocytosis
"special' type 2 hypersensitivity
Igs bind to functionally important Rs as agonists or antagonists
antagonising = MG
ACh R
muscle fatiguability
agonising = Grave's
TSH R
hyperthyroidism + non-thyroid effects (e.g. exophthalmos)
type 3
Ig binds to antigen either in blood or tissue
activates complement (release of inflamm mediators, C3a,4a,5a which induces mast cell degranulation)
rheumatoid vasulitis
SLE
banding: clotting green immunofluorescence
immune complexes are normal
supposed to be removed by the reticuloendothelial system (phagocytes in liver + spleen)
abnormal when there's too many
instead deposited in tissue + blood vessels (! occlusion)
lab tests
complement studies (look for low C3+4 due to increased consumption)
complement degradation product studies (not routinely available)
CH100 (rule out complement deficiency)
look @ connective tissues (ANF, rheumatoid factor, cryoglobulins-abnormal Igs, anti-dsDNA, anti-extractable nuclear antigen/ENA)
type 4
delayed
APC to Th1 cells - activation
CKs (e.g. IFNgamma, TNFalpha, IL12) act on vasc endothelium + activate macrophages - granuloma lesions form
e.g. Langerhan's in skin
RA
cellular rejection
antineutrophil cytoplasmic antibodies (ANCAs)
increase neutrophil's ability to damage endothelium via activating resp burst
aid neutrophil adhesion to endothelium (common in vasculitis)
anti-phospholipid syndrome
anti-cardiolipin antibodies contribute to thrombosis
autoimmune hypercoaguable state
mechanism poorly understood
passive transfer induces disease (animal studies)
Therapeutic Igs
polyclonal
ATG from rabbits/horses
anti-D (human, for rhesus incompatibility)
monoclonal
OKT3
anti T cell
once off use only or else SEs next time due to self Igs against this Ig
not used as much
can be humanised
infliximab (anti-TNF)
Natalizumab/Tysabri
how is this done?
fuse mouse B cells with antigen + myeloma cells (malignant immortal plasma cells)
grow on medium selective to hybrid cells
grow on antigen-specific medium
clone
labour intensive
even less animal (only in 3 hypervariable regions)
not much therapeutic benefit compared to chimeric
can be chimeric
10% animal (in variable region)
90% human (in constant region)
problem: admin of a foreign product
10% make Igs against Ig (reaction)