Lecture 15 - Hypersensitivity Flashcards
What is hypersensitivity
refers to undesirable reactions produced by a normal immune system, require a pre-sensitized immune state
What types of hypersensitivity are immediate
type I, type II, type III
What types of hypersensitivity are delayed
type IV
How long do immediate hypersensitivity reactions take
5 min - 10 hours
How long do immediate hypersensitivity reactions take
24-48 hours
What are common sources of allergens
inhaled: pollen, dander, mold, feces
injected: insect venoms, vaccines, drugs, therapeutics
ingested: food and orally administered drugs
contact: plant leaves, synthetic chemicals, metals
How is allergen skin testing done
the skin is scratched/poked with allergens and inflammation indicates likely allergen (type I hypersensitivity IgE mediated)
What is type I hypersensitivity
- immediate IgE mediated
- range of symptoms from minor inconvenience to death
- reaction usually takes 15-30 min following exposure
- primary cellular component is the mast cell or basophil
- reaction may involve one or more areas of the body including skin, eyes, nasopharynx, lungs and GI tract
What is the mechanism of type I hypersensitivity
- preferential production of IgE in response to certain antigens
- IgE has a very high affinity for Fc receptors on mast cells and basophils (FcERI)
- a second exposure to the same antigen cross-links cell bound IgE
- the event triggers the release of various substances from the mast cells by inducing degranulation
- the agents released from these granules include vasoactive amines and potent inflammatory mediators
What are the mediators released from mast cell granules
histamine and lipid mediators (leukotrienes, prostaglandins)
What do mediators do
- constrict smooth muscle in the lung and GI tact
- causes vasodilation
- increases the permeability of the small blood vessels
- increases mucus secretion
- prevent clotting
- production of pro-inflammatory mediators
What are platelet activating factors
attracts leukocytes, amplifies production of lipid mediators and activates neutrophils, macrophages and platelets
What do IL4 and IL13 do
amplifies the Th2 response
What does IL5 do
promote eosinophil production
What does TNF alpha do
promotes inflammation and stimulates cytokine production in many cell types
What is anaphylaxis
- a sudden severe potentially fatal allergic reaction
- can involve various areas of the body
- symptoms often occur within minutes
- reactions are mild to life-threatening
- annual incidence is about 30 per 100000 persons
- individuals with asthma or hay fever are at a greater relative risk of experiencing an anaphylactic reaction
What are areas of localized anaphylaxis
- nasal passages
- lower airways
- skin
- GI tract
What are anti-histamines
- block effects of histamines
What is epinephrine
- reduces permeability of blood vessels
- diminishes tissue swelling
- raises the blood pressure
- relaxes constricted smooth muscle
- stimulates the heart
What is type II hypersensitivity
- antibodies are generated for antigens on cell surface
- antibodies are then recognized by immune cells that have Fc receptors
- promotes destruction of the cell by antibody-dependent cell-mediated cytotoxicity
- macrophages, granulocytes and NK cells are major players
- can also activate complement
- may affect a variety of organs and tissues
What usually causes type II hypersensitivity
- drug reactions (penicillin)
- rheumatic fever
- HDFN
- blood transfusion reactions
What is type III hypersensitivity
- IgG and IgM react with soluble antigens and form immune complexes
- immune complexes are typically removed by the spleen and liver
- failure to remove immune complexes causes type III hypersensitivity
- immune complexes can be deposited in blood vessels and organs
- immune complexes activate complement and immune cells resulting in tissue damage
What does type III hypersensitivity cause
- autoimmune conditions
- persistent infections
- farmers lung
- bird fancier’s disease
What is systemic lupus erythematosus
- a chronic systemic autoimmune disease
- symptoms include butterfly-shaped rash on face, fatigue, headaches
- triggered by environmental effects
What is type IV hypersensitivity
- reaction occurs 24 hours or more after exposure
- mediated by activated immune cells only
- reaction is often initiated by the activation of T helper cells
- involved in the pathogenesis of many autoimmune and infectious diseases
What is the mechanism of type IV hypersensitivity
- following exposure T helper cells become activated
- activated T helper cells secrete cytokines that activate and recruit other immune cells such as macrophages and neutrophils
- products released from activated macrophages and neutrophils cause the majority of the tissue damage and symptoms
