Type I Hypersensitivity (Allergy) Lecture Notes PDF

Summary I • What are the characteristics of a good allergen? What are some common allergens? ‒ Small protein or glycoprotein, metabolically active – often an enzyme, tend to be very stable (heat-, acid-, protease-resistant), encountered in low doses and typically by mucosal exposure ‒ Plant pollens...

Summary I • What are the characteristics of a good allergen? What are some common allergens? ‒ Small protein or glycoprotein, metabolically active – often an enzyme, tend to be very stable (heat-, acid-, protease-resistant), encountered in low doses and typically by mucosal exposure ‒ Plant pollens (pine, rye, mold spores), drugs (penicillin/sulfa, iodine contrast dye), foods (nuts, peas, seafood, eggs, milk, wheat), animal products (insect venom, dust mite feces, animal hair/dander) • What factors predispose a person to develop allergies? ‒ Genetics (primary factor) plus environmental exposure are required; other secondary factors can include lifestyle, dietary, infections/vaccinations • What are the cellular and soluble mediators of type 1 hypersensitivity reactions? – Cellular – CD4 Th2 cells, plasma cells, mast cells, eosinophils – Soluble – IL-4, IL-5, IL-13, IgE • What are the steps in recognition, activation, and effector function of type 1 hypersensitivity immune responses? – Allergen binds PRR; APC is activated, then activates naïve, Ag-specific CD4 cell; Th2 differentiation is induced; CD4 Th2 cell provides help to allergen-specific B cell; B cell is activated and differentiates into an IgE-producing plasma cell; secreted IgE binds FcεR on tissue-resident mast cells; at next allergen exposure, membrane-bound IgE bind allergen, crosslinking FcR and activating mast cell; mast cell degranulates, releasing histamine, leukotrienes, prostaglandins and begins to make type 2 cytokines; local symptoms are produced (itching, edema, wheezing, cough, and eos are recruited; eos degranulate and cause tissue damage • What are the 3 phases of a T1H responses, and what mediators are involved at each stage? ‒ Sensitization or induction phase – initial exposure to Ag and activation of CD4 Th2 and IgE-producing plasma cell with IgE binding FcR on mast cells ‒ Early or immediate phase – second (or 3rd, 4th, etc.) exposure to Ag binds IgE on mast cell, resulting in degranulation and mediator release ‒ Late phase – eos are recruited by mast cell cytokines, activated and degranulate; basophils may also be recruited and activated Summary II • What are general symptoms of a T1H allergic response, and what are system-specific symptoms? ‒ General – itching, mucus production, running/watery and itchy nose and eyes, rash, angioedema and IF SEVERE – anaphylaxis ‒ System-specific – urticaria/hives, scaling/thickening, oozing, edema (skin); wheezing, coughing, bronchoconstriction, asthma, mucus (resp.); vomiting, diarrhea, abd. cramps, urticaria/itching (GI) • What is the key pathologic event that leads to anaphylaxis, and what are common signs and treatment? What are common triggers of anaphylactic reactions? ‒ Key pathologic event – massive exposure to allergen leading to systemic levels of allergic mediators ‒ Common signs – system-specific symptoms, confusion, sweating, hypotension, fainting, sensation of doom ‒ Treatments – early – remove trigger, supine positioning, antihistamines; with progression – epinephrine, then more advanced medical treatment – O2, IV fluids, drugs ‒ Food, drugs, venoms • What are common testing procedures, what do they measure, and what are their diagnostic endpoints? ‒ Skin testing – intradermal injection of allergen that detects presence of sensitized mast cells in tissue and produces wheal and flare reaction ‒ RAST testing – measures levels if allergen-specific IgE in blood • What are the prevention and treatment strategies for T1H reactions? ‒ Prevention – avoid triggers; induce tolerance through immunotherapy ‒ Treatment – non-biologic (antihistamines, corticosteroids, epinephrine) and biologic (interfere with IgE and type 2 cytokine activities) Dr. Prater’s Top 10 Take-Aways • Type I hypersensitivity (allergy) is an inappropriate IgE/mast cell/eosinophil response to allergens. • Symptoms of T1H vary according to the route of exposure of the allergen. • As with other immune disorders, there is usually a genetic predisposition + environmental exposures that results in development of the allergic condition. • Allergens are usually small molecular weight metabolically active proteins, enzymes, or amino acids. • Mucosal exposure is the most common route of exposure – inhalation, direct contact, ingestion; intravenous exposure often results in a body-wide mast cell response – anaphylaxis. • First exposure to the allergen results in production of IgE which binds to mast cells with its Fc region. The second exposure to the allergen results in binding of the allergen to that IgE, resulting in mast cell degranulation. • Mast cell degranulation results in release of vasoactive amines which are responsible for the immediate response to allergens (itchy eyes, watery nose, hives, sneezing, or vomiting/diarrhea, due to dilated/leaky post cap venules). • The vasoactive amines cause inflammatory cytokine release, which stimulate eosinophils, the later response in an allergy. Eosinophils can cause additional tissue damage. • Asthma is a more serious form of allergy that occurs in the lower airways and is characterized by edema, mucous production, bronchoconstriction and inflammation. Anaphylaxis is a body-wide mast cell degranulation that can result in hypotensive shock; epinephrine, maintaining airway, fluids, steroids, etc. are used to treat anaphylaxis. • Allergy testing, antihistamines, and symptomatic/immunotherapies are used to identify the allergen, and reduce the body’s abnormal response to the allergen.