Lecture 9 - hypersensitivity Flashcards
What is hypersensitivity
Inappropriate or exaggerated immune response against antigen or allergen
includes allergy and autoimmunity
What is consequence of hypersensitivity
Reactions against self antigen
Inappropriate reactions against microbes
Against environmental antigens
Occurs on second and subsequent exposures
Describe hypersensitivity type 1
Allergy
- Rapid
- IgE-mediates degranulation of mast cells
Describe hypersensitivity type 2
Initiated by binding of antibody to cell membrane or EM
Describe hypersensitivity type 3
Antibody binding to soluble molecules - form immune complexes
Describe hypersensitivity type 4
Attack by immune cells in absence of antibody
What initiates type 1 hypersensitivity
Activation of Th2 cell -> cytokines (IL-4, IL-5, IL13)
Drive down-stream production of IgE - binds to FcER on mast cells (degranulate)
Describe second exposure in type 1 hypersensitivity
allergen binds to IgE already on mast cells - FcER crosslinking antigen -> degranulation - release mediators (histamine)
Describe immediate response in type 1 hypersensitivity
Cause - mast cell degranulation
Peaks @ 30 mins then subsides
systemic manifestation - anaphylactic shock
Describe late response in type 1 hypersensitivity
Recruitment of effector cells - Th lymphocytes, eosinophils and neutrophils
What are eosinophils role in type 1
Release cytotoxic cationic granule proteins
- skin itching and bronchial irritability
- induce mast cell degranulation
What cytokines do Th2 cells produce
IL-4 - stimulate B cell to produce IgE
IL-5 activates eosinophils
IL-13 stimulates mucus secretion - amplifies response
TNF-alpha - promotes inflammation
What is atopy
Genetic tendency to develop allergic diseases
What are the predisposing factors to atopy
More IgE molecules/mast cells
High affinity Fc receptors for IgE on mast cells
Higher IgE levels
Genetic predisposition (80% at least 1 affected parent)
What is the ‘hygiene hypothesis’
Link between lack of exposure to infectious disease in early childhood and increase in allergy incidence
Attributed to less exposure (controversial)
What is the difference between hypersensitivity and autoimmunity
Hypersensitivity - mechanisms of how the body reacts
Most hypersensitivities manifest in autoimmune disorders (type 2 - 4)
What are the features of autoimmune diseases
Breakdown of immunologic tolerance
Systemic - affect tissues through body or localised to specific sites
Lymphocyte, macrophage and plasma cell infiltrate into lesions
More than one autoimmune condition
Female bias - familial - HLA associations - lesions classified by hypersensitivity types 2,3 & 4
What is immunologic tolerance
Billions of antigen receptors developing B and T lymphocytes - some recognise self antigen
unresponsiveness to antigen induced by exposure
prevent our bodies reacting against self antigen
What is central tolerance
Antigen induced death of self-reactive T and B cells
What is peripheral tolerance
Anergy - functional inactivation of lymphocytes
Suppression by regulatory T cells
Activation-induced cell death
Examples of local autoimmune disorders
Multiple sclerosis
Hashimoto’s thyroiditis
type 1 diabetes
chron’s disease
Myasthenia gravis
Grave’s disease
Examples of systemic autoimmune disorders
SLE
Sjogren’s syndrome
Scleroderma
Rheumatoid arthritis
describe type 2 hypersensitivity
Antibody-mediated
- targets on cell surface
- Tissue components
What are the mechanisms of tissue injury in type 2
Opsonisation and phagocytosis
Complement and Fc-mediated inflammation
Anti-body-mediated cellular dysfunction
Describe Sjogren’s syndrome
Destruction of exocrine glands (lacrimal and salivary - dry eyes and mouth)
- common in older women
Autoantibodies - FcR and induction of apoptosis and inflammation - inflammation of CD4 T cells - cytokines that contribute to inflammation