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
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)
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
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
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)
banding: clotting green immunofluorescence
type 4
delayed
APC to Th1 cells - activation
CKs (e.g. IFNgamma, TNFalpha, IL12) act on vasc endothelium + activate macrophages - granuloma lesions form
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)
e.g. Langerhan's in skin
Therapeutic Igs
polyclonal
monoclonal
problem: admin of a foreign product
ATG from rabbits/horses
anti-D (human, for rhesus incompatibility)
OKT3
not used as much
anti T cell
once off use only or else SEs next time due to self Igs against this Ig
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
can be chimeric
10% animal (in variable region)
90% human (in constant region)
even less animal (only in 3 hypervariable regions)
not much therapeutic benefit compared to chimeric
10% make Igs against Ig (reaction)