Allergies & Hypersensitivies

Allergies & Hypersensitivies

Type I Hypersensitivity: Immediate Hypersensitivity Mediated by IgE and mast cells Reactions: Allergic rhinitis (hay fever) Pollens (ragweed, trees, grasses), dust mite feces Asthma Danders (cat), pollens, dust mite feces Systemic anaphylaxis Drugs, serum, venoms, foods (peanuts) Vomiting, diarrhea, itching, hives Food allergy (peanuts, tree nuts, shellfish, milk, eggs, etc.)

Sensitization Effector phase

Desensitization to Allergens Also known as Allergy Shots or Allergen- Specific Immunotherapy 100 years old Pioneered by Noon at St. Mary s Hospital, London in 1911 Noon and Freeman successfully treated hayfever sufferers by injecting them with pollen extracts

Desensitization Allergic diseases now considered to result from breakdown of immune tolerance to natural exposure to allergens Immune tolerance to allergens is T cell-regulated. Goal is to induce clinical tolerance (improvement in symptoms, stop progress of severe disease) Allergen specific immunotherapy used to treat Allergies to bee venom Severe upper and mild to moderate lower allergic respiratory diseases (not well controlled by drugs)

Injection Immunotherapy the Procedure Injection of allergen given subcutaneously into outer portion of upper arm. Build-up phase: Takes 3 to 7 months Shots are given one to three times a week Allergen dose is gradually increased with each shot Maintenance phase: Continues 3 to 5 years or longer Generally shots are given once a month

Soon after Th0 is Activated by its Specific Antigen, the Cell Makes a Commitment to Type of Effector Th Cell Naïve CD4+ T cell (Th0) Effector Th1 IgE antibody Effector Th2 B lymphocyte

IgE antibody on mast cells releases inflammatory mediators after binding antigen

Very Early Desensitization Effect: Tissue Mast cells Fail to Release Granules

IgE antibody on mast cells releases inflammatory mediators after binding antigen

T Cell Tolerance during Desensitization (Treg cells, suppression of Th2-Th1 cells)

Peripheral lymhoid tissue thymus Lymphoid stem cell CD8+ CD4+ CD4+ Treg CD8+ CTL + antigen Cytotoxic T lymphocyte CD4+ Th Helper T cell CD4+ Treg Regulatory T cell

Regulatory T Cell: Naïve T Cell Fails to Undergo Clonal Proliferation and Maturation Naïve CD4+ T cell Effector Th1, Th2 cell Memory Th1, Th2 Cell Treg

Soon after Th0 is Activated by its Specific Antigen, the Cell Makes a Commitment to Type of Effector Th Cell Naïve CD4+ T cell (Th0) Effector Th1 IgE antibody Effector Th2 B lymphocyte

Regulatory T Cell: Inhibits Both Th1 and Th2 Effector Cells Naïve CD4+ T cell (Th0) Effector Th1 Treg IgE antibody Effector Th2 B lymphocyte

Late Decrease in Tissue Mast Cells and Eosinophils

Acute Response in Asthma Leads to Th2-Mediated Chronic Inflammation

Late Decrease in Type I Skin Reactivity

Late Decrease in IgE Specific to Allergen

Early Increase in IgG Specific to Allergen

Immune Deviation: Allergen-Activated Th Cell Develops into Th1 Cell, with IgG4 Antibody Naïve CD4+ T cell (Th0) Effector Th1 B lymphocyte IgG antibody Effector Th2 B lymphocyte IgE antibody

Summary of Immunological Changes Accompanying Allergen-Specific Immunotherapy Very early: mast cells & basophils show much less degranulation, lower risk of anaphylaxis Result: most patients protected from bee stings soon after starting treatment Intermediate times (1 to 6 months): Regulatory T cells increase in numbers Late times (6 months to 3 years): Tissue mast cell and eosinophils decrease IgE specific for allergen decreases

Food Allergies Cause >50,000 cases of anaphylaxis a year in U.S. Cause about 100 deaths a year in U.S. Groups of foods associated with allergies: Milk & eggs Most prevalent in infants & young children (rarely cause death) Peanuts, tree nuts, fish & shellfish Cause food allergy in both children & adults More likely to cause severe shock & death

Why are Peanuts More Likely to Cause Anaphylaxis than Other Foods? Peanut allergen resists digestion Roasting process increases availability of peanut allergens

Treatment of Peanut Allergy (still Experimental) Oral immunotherapy (feed allergic children tiny amounts of peanuts, increasing dose over several months) In one study, increased tolerance for peanuts 5- fold in 18/22 allergic children In second study, successful for >90% of patients Treat with monoclonal antibody specific for IgE Treat with herbal formulation

VIDEO Dr. Wesley Burks at Duke University Oral Immunotherapy for Peanut Allergy

Is Early Peanut Consumption by Children Good or Bad? Due to rise in peanut allergies, parents were advised to delay allowing their children to eat peanuts New evidence indicates that oral exposure of children to peanuts does not cause sensitization. Rather, first exposure of children to peanut products in environment (by skin contact with peanut butter or peanut oil in lotions) causes sensitization. The oral route typically causes immune tolerance. Other routes may induce Th2 cells with IgE production.

Farm Living: effects on childhood asthma & allergy Children who grow up on farms have lower incidence of asthma & hay fever. Protection from allergies due to: Early-life contact with livestock (& their microbes) Early-life exposure to livestock feed Consumption of unprocessed cow s milk Strongest effect from exposure in utero & first few years Immune mechanisms: Increase in regulatory T cells Decreased Th2 (IgE-producing) responses to allergens

Type IV Hypersensitivity

Type IV Hypersensitivity: Delayed Type Hypersensitivity (DTH) Differs from Type I (Immediate) Hypersensitivity: Takes 12 to 48 hours for DTH allergic reaction to develop, only minutes for immediate hypersensitivity Immediate hypersensitivity is mediated by mast cells and IgE antibody specific for allergen DTH is mediated by T cells specific for allergen

Delayed Type Hypersensitivity (DTH) Reaction

Delayed Type Hypersensitivity Tuberculin test Reactions Causes skin redness, hardening or thickening, inflammation Contact sensitivity Poison ivy Small metal ions like nickel Cause skin redness, blisters, itching

Video Delayed Type Hypersensitivity Reaction

Poison Ivy Reaction

Poison Ivy

CD8 (cytotoxic T cells) mediate poison ivy reaction

CTL Typically Kill Virally Infected Cells

In Poison Ivy, CTL Kill Skin Cells Having Oily Resin (Urushiol) from Poison Ivy on Membranes