1. Hypersensitivity Flashcards
define ‘hypersensitivity’
The ANTIGEN-SPECIFIC immune responses that are either inappropriate or excessive and result in harm to the host.
describe the 2 common phases of all hypersensitivity reactions
- SENSITISATION phase
- 1st encounter with Ag
- causes activation of APCs and memory effector cells - EFFECTOR phase
- pathologic reaction upon re-exposure to same Ag and activation of memory effector cells of adaptive immunity
- causes clinical manifestation
describe the antigen and antibodies involved in the 4 types of hypersensitivity
Type I - immediate (Allergy)
- response to environmental non-infectious Ag
- involves IgE
Type II - anti-Body mediated
- response to cell-bound Ag
- involves IgG or IgM
- develops in 5-12 hrs
Type III - immune-Complex mediated
- response to soluble Ag
- involves IgG or IgM
- develops in 3-8 hrs
Type IV - cell-mediated (Delayed)
- response to environmental infectious Ag and self Ag
- involves cellular response
- develops in 24-72 hrs
what are the 2 possible mechanisms of disease involved in T2HS
- tissue/cell damage
- complement activation: cell lysis (MAC), neutrophil recruitment/activation (C3a/C5a), opsonisation
- Ab-dependent cell cytotoxicity (ADCC, IgG) - Physiological change
- receptor stimulation (e.g. Ag bind and activate TSH R - Graves’ disease)
- receptor blockade (e.g. Ag bind and block ACh R - Myasthenia gravis)
Suggest 4 possible therapeutic approaches to T2HS-mediated tissue/cell damage
- immune suppression (prevent complement activation)
- plasmapheresis (remove circulating antibodies and inflammatory mediators) - allows short-term relief and healing of damaged tissue
- splenectomy (prevent opsonisation/phagocytosis)
- intravenous immunoglobulin (IVIG, blockage of macrophage Fc Rs)
what is the pathogenesis underpinning T3HS
tissue damage caused by:
a) immune complex deposition in tissue…
b) complement activation…
c) neutrophil chemotaxis…
d) neutrophil adherence and degranulation
name 3 factors affecting IC pathogenesis in T3HS
- complex size: small and large size ICs cleared whilst intermediate size ICs persist
- host response
- low affinity antibody (form intermediate ICs)
- complement deficiency (large complement activation in T3HS causes tissue damage) - local tissue factors
- haemodynamic factors
- physiochemical factors
Result in persistence of IC deposition in joints, kidneys, small vessels and skin - multisystem disease
name 3 examples of T3HS and their causative Ag
- rheumatoid arthritis (auto-immune):
- Ag = Fc portion of altered IgG
- Ab = rheumatoid factor (IgM) - Glomerulonephritis (infectious), e.g. bacterial endocarditis, HepB infection
- Systemic lupus erythematosus
- Ag = ds-DNA
which 2 cell types are mainly involved in T4HS
lymphocytes and macrophages
describe 3 subtypes of T4HS and name examples of diseases
- contact hypersensitivity
- 48-72 hrs
- epidermal reaction (eczematous rash)
- e.g. nickel, poison ivy, organic chemicals - tuberculin hypersensitivity
- 48-72 hrs
- dermal reaction (induration and swelling)
- e.g. Mtb - granulomatous hypersensitivity (most severe)
- 21-48 days
- persistence of Ag (tissue damage) causes granuloma formation to wall off infected cells
- e.g. tuberculosis, leprosy, schistosomiasis, sarcoidosis
name 3 diseases caused by T4HS to endogenous Ag
- pancreatic islet cells - insulin-dependent diabetes mellitus
- thyroid gland - Hashimoto’s thyroiditis (involvement of CD8+ T cells and antibodies)
- IgG - RA
suggest 2 main classes of drugs used to treat T3 and T4HS
- anti-inflammatory drugs
- NSAIDs
- corticosteroids (oral prednisolone)
- 2nd drugs as steroid-sparing agents (<10mg oral steroid), e.g. azathioprine, mycophenolate mofetil, cyclophosphamide - monoclonal antibodies
- B and T cells
- cytokine network
- APCs
