Hypersensitivity and chronic inflammation Flashcards
Hypersensitivity
Occurs when the immune system responds to antigens too vigorously
4 types
Allergy is usually type I but can be type 3/4
Type I hypersensitivity
Primary exposure to allergen stimulates a Th2 response and IgE production
Secondary exposure cross links FceRI receptors on mast cells/basophils, triggering degranulation and release of mediators
IgE
lowest abundant isotype
Tightly regulated and shortest half life
This aims to minimise IgE cross-reactivity
IgE bound to surface receptors can persist for a long time
Allergens
Trigger production of IgE in allergic people (normally a reaction against worms)
Mostly proteins or glycoproteins
Plant pollens, penicillin, nuts
Allergy symptoms
Hay fever, asthma, dermatitis
Effects can be local or systemic
Anaphylactic shock can occur when allergen enters bloodstream
Primary mediators
Released from intracellular granules (degranulation)
Histamine binds histamine receptors on various cells causing smooth muscle contraction, increased vascular permeability, vasodilation and mucous secretion
Eosinophil/neutrophil chemotactic factors also released
Secondary mediators
Platelet-activating factor, leukotrienes, prostaglandins cause further increase in vascular permeability and muscle contraction
Cytokines and chemokines also released and increase inflammation/IgE production
Chronic type I hypersensitivity
Extravasation of basophils, stimulating fibroblast to release chemokines which attract granulocytes
Leads to chronic inflammation
Antihistamines
competitive antagonism of histamine binding to cellular receptors, specifically H1 on nerve endings, smooth muscle and glandular cells
Provide symptom relief but are not used as first line therapy
Hyposensitisation treatment
Administration of small repeated doses of allergen
Results in immune tolerance via immunosuppressive cytokines TGF-beta and IL-10 (induce Treg)
Desensitisation via IgG4 antibodies competing with IgE
Hygiene hypothesis
Decreased exposure to pathogens and allergens in early life, normal maturation of immune system does not occur. Leads to increased reactivity to non-infectious antigens
Diet hypothesis
Maternal diet influences immune response of breastfed child to environmental antigens
Breast milk contains food allergens and aeroallergens
Exposure may favour oral tolerance and prevent allergy development
Type II hypersensitivity
IgG/M antibodies bind to antigens on red blood cells and induce destruction (complement, ADCC)
Can occur during blood transfusions, haemolytic disease of the newborn, and haemolytic anaemia
Type III hypersensitivity
Immune complexes of antibody/antigen which cannot be cleared by phagocytes.
Complexes can cause degranulation of mast cells and inflammation
Type IV hypersensitivity
Delayed type hypersensitivity
Contact dermatitis by poison ivy
Sensitisation occurs when bacteria (through APCs) promotes Th1 response
Effector phase occurs when re-exposure stimulates Th1 cytokine release and macrophage activation, leading to inflammation
