Hypersensitivities 1

Immune HypersensitivityChapter 18

Self-Test Questions:Intro: allA1-2: allA3: 1, 3, 5A4: allB: 1, 2, 4, 5C: 1 - 4D: 1 - 4

Hypersensitivities 2

What characteristics are shared by all hypersensitivies?

Immune responses: Primary (sensitization) responseSecondary (activation) response

Abnormal (hyper-) response to antigens (allergens)

Symptoms: localized or systemic

Onset can be: Early, Late or Chronic

Hypersensitivities 3

What are hypersensitivities?

4 types of hypersensitivities (Gel and Combs classification) Immune

Name system involved Effectors Effects OnsetType 1 “Atopic” Humoral (IgE) mast cells inflammation seconds

eosinophils (anaphylaxsis)

Type II “Cytotoxic” Humoral/ macrophages cell destruction hours Complement complement (hemolysis)

Type III “Im. Complex” Humoral/ granulocytes inflammation hours Complement

Type IV “Delayed type” Cell-mediated macrophages inflammation days

-- TH1

Hypersensitivities 4

Type I – Atopic hypersensitivities

AG presentationDCs, even Basos & Eosinosactivate TH2 cells

IgE productionclass switching to IgE

Mast cell sensitizationIgE binding to Fc receptors

Mast cell activationDegranulationsecretionsynthesis

Early phase& late phaseresponses

McGraw-HillType-I

Hypersensitivities 5

Early phase responses

Molecular Mediators:Primary – in granules

Secondary – synthesized later

(w/in 1- few minutes)

Localized clinical response (Atopy)atopic asthma:urticaria (hives)eczema (skin lesions)atopic rhinitisfood allergies

Systemic clinical response (anaphylaxis)anaphylatic shock

Hypersensitivities 6

e.g., Erythema, etc“peak flow rate” measurements

Due to:

-- Cytokines from mast cells

-- Recruited eosinophils & TH2

-- degranulation

Chronic Type I-- eosinophilia

-- inflammation: damaged

airways & mucous membranes

Late phase responses-- 4-6 hours later

Early phase Late phase

Hypersensitivities 7

What factors affect predisposition toward Type I hypersensitivities?

Genetic factors

Environmental factors

Hygiene hypothesis

Hypersensitivities 8

Treatment

Skin testing-- carries some risk

Drugs therapies-- Theophylline (blocks degranulation)

-- antihistamines (block histamine receptors)

-- epinephrine (reverses trachael & bronchiole SM

and contracts arteriole SM)

Desensitization

Desensitization Therapy

Hypersensitivities 9

Type II hypersensitivity-- “Cytotoxic”

Ig binding to AG on cells-- triggers cell lysisComplement mediatedMacrophage mediated

Various types of hemolytic disorderse.g., Blood transfusion incompatibility

{see section in chapter 17}

Autoimmune disorderse.g.. Goodpasture’s syndrome

RBC being phagocytosed in fetal erythroblastosis

1967 Science 158: cover

Hypersensitivities 10

Type III hypersensitivity -- “immune complex”

Localized: (Arthus reaction) -- could result from an insect bite

1)Ag-Ab complex Excess AG small complexes

complement activation2) mast cell degranulation3) neutrophil recruitment4) Triggering of inflammation

Systemic: Serum sickness Vasculitis Hypersensity pneumonitis

-- Pigeon breeders disease (pigeon feces dust)-- Farmers lung (Actinomycetes)-- Mushroom picker’s… -- Cheese washer’s…-- Chicken plucker’s…-- etc., … disease

Adapted from Majno and Joris, 2004, Cells, Tissues and Disease

Type III Hyper

C3a, C5a

Hypersensitivities 11

Type IV hypersensitivity“Delayed-type”-- slow onset ~day(s) (if sensitized)

TH1-cell mediated

Sensitization phase -- week(s) onset-- TH1 expansion

Effector stage – day(s) onset-- TH1 & macrophage activation-- inflammation

Latex type IV hypersensitivity

Hypersensitivities 12

Type IV hypersensitivities, con’t

Contact dermatis reactionsOften involves hapten productione.g. to: hair sprays, plant toxins, turpentine

TH1

Hypersensitivities 13

Tuberculosis(see Chapter 14 pp 212-213)

-- Persistent Mycobacterium tuberculosis

Granuloma (tubercule) formation TH1 cells and activated macrophages

‘caseous’ regions extended tissue destruction