Dr Alok TripathiDepartment of Biotechnology

aquaimmuno@yahoo.com

Hypersensitivities

• Immune responses to innocent antigens or self antigens that lead to symptoms or tissue

damage

• Term “hypersensitivity” originally used to denote acquired immune response, as was

“allergy”

• “Hypersensitivity” and Allergy” most commonly refer to responses to innocent

antigens

• But autoimmune diseases are sometimes subset of hypersensitivity

• Atopy is term used to describe condition of general likelihood of responding with allergic

reaction

Classified by mechanism (Gel and Coombs 1963)

• Type I, Immediate: IgE antibody triggering mast cells and eosinophils

• Type II, Antibody Mediated: IgGantibody reacting with cell surface or

matrix antigens

• Type III, Immune Complex Mediated: antigen-antibody

complexes

• Type IV: T cell mediated

Type I: allergies. IgE and mast cells

Usefulness of “Type I” IgE responses:

eliminating parasites, like helminths

Propulsive smooth muscle contraction,

mucus prevent infiltration of epithelium by parasites

About 20% of people in US have some form of allergy

• CD4 TH2 T cells cytokine profile leads to isotype switching to IgE

Sensitization phase:

• IgE triggers Mast cell degranulation

Effectorphase:

Sequence of events in Type I, “immediate hypersensitivity”

Eosinophils & Basophiles contribute to the chronic allergic reaction releasing similar chemicals mediators to IgE binding to FceeRI (which is induced in eosinophils by inflammation)

• Helper T cells (TH2) that secrete IL-4, IL-5, and IL-13 are

responsible for inducing allergen specific IgEproduction

• Non-atopic individuals also have T cells that recognize

allergens after sensitization, but in normal individuals the

T cells are kept in check by Tregs (IL-10 and TGFb) • Normal people activate TH1 helper T cells and

make IgG antibodies to same antigens

• Four distinct susceptibility genes identified so far

– G-protein coupled receptor expressed in inflamed tissue

8% of children under 3, 4% of US adults Leading cause of

anaphylaxis outside of hospitals, 30,K ER cases per year

May lead to IgE or cell mediated responses, and be expressed any of atopic sites (gut, skin, bronchi,

systemic)

Gut largest immunologic organ for Food allergy

•Systemic antigen, like bee sting

Systemic response of

IgE cross linking

receptors on connective tissue mast

cells and circulating basophils

• Desensitization with protein or peptide antigens, with or without adjuvant

• Anti-IgE antibody • – Xolair approved in 03 for asthma, but not yet

tested for peanut allergy (Genentech)

• – TNX-901 very effective in clinical trials but removed

from testing by biotech squabbling (Tanox/Genentech

legal battle)

• – Peanut allergy treated with treated with peptide plusHeatKilled Listeria, to induce TH1 response (in dogs, Frick 05)

• E.g., Arah 1,2, and 3 are peanut

proteins

• – Peptide epitopes recognized by CD4 TCRs have been determined

• – Therapy with Fel d 1 peptides increases TH1 T cellsrather then T reg T cells (Alexander 05)

Fel d 1 is component

of cat dander

generation of IgG antibodies

that prevent

allergic antigen from reaching

IgE coated mast cells

Desensitization may also be due to

Hygiene hypothesis

• Asthma and allergies increasing dramatically in recent years in

developed countries

• Exposure to pathogens (larger families, day care, farms) lowers

incidence of allergies

• Suggested that TH1 responses limit TH2responses, but TH1 and TH2

are not solely antagonistic, and basis of hygiene effects are notyet clear