HYPERSENSITIVITY

Type I : Type II : Type III : Type IV : Type V :

Immediate (allergies) Cytotoxic (ITH) Toxic Complex (ITH) T Cell-Mediated (DTH) Stimulatory

Type I
Ag that trigger allergies allergens Allergies : allergens bind to Ig E Clinical syndrome :
Asthma Hay fever Urticaria

Diagnosis : skin testing

Cytotoxic Hypersensitivity (Type II)

Characteristics of Cytotoxic Hypersensitivity

Directed against cell surface or tissue antigen Characterized by complement cascade activation and various effector cells

Complement
Formation of membrane attack complex (lytic enzymes) Activated C3 forms opsonin recognized by phagocytes Formation of chemotactic factors Effector cells possess Fc and complement receptors
macrophages/monocytes neutrophils NK cells

Examples of Type II Hypersensitivity

Blood transfusion reactions Hemolytic disease of the newborn (Rh disease) Autoimmune hemolytic anemias Drug reactions Drug-induced loss of self-tolerance Hyperacute graft rejection Myasthenia gravis (acetylcholine receptor) Sensitivity to tissue antigens

ABO Blood Group Reactivity

blood group genotypes antigens antibodies to (phenotype) ABO in serum A AA, AO A anti-B B BB, BO B anti-A AB AB A and B none O OO H anti-A/B

Hemolytic Disease of the Newborn

first birth RhD negative mother
RhD positive red cells
B cell

post partum

subsequent

anti-RhD

RhD positive fetus

anti-RhD

Lysis Of RBCs

RhD positive fetus

Drug-Induced Reactions: Adherence to Blood Components

blood cell adsorbed drug or antigen drug metabolite antibody to drug

complement

lysis

Toxic Complex Hypersensitivity (Type III)

Diseases associated with immune complexes Persistent infection

microbial antigens deposition of immune complexes in kidneys

Autoimmunity
self antigens deposition of immune complexes in kidneys, joints, arteries and skin

Extrinsic factors
environmental antigens deposition of immune complexes in lungs

Inflammatory Mechanisms in Type III

Complement activation
anaphylatoxins Chemotactic factors

Neutrophils attracted
difficult to phagocytize tissue-trapped complexes frustrated phagocytosis leads to tissue damage

Disease Models
Serum sickness Arthus reaction

Arthus Reaction

T-Cell Mediated Hypersensitivity (Type IV / Delayed-Type)

Manifestations of T-Cell Mediated Hypersensitivity Allergic reactions to bacteria, viruses and fungi Contact dermatitis due to chemicals Rejection of tissue transplants

General Characteristics of DTH

An exaggerated interaction between antigen and normal CMI-mechanisms Requires prior priming to antigen Memory T-cells recognize antigen together with class II MHC molecules on antigen-presenting cells Blast transformation and proliferation Stimulated T-cells release soluble factors (cytokines) Cytokines
attract and activate macrophages and/or eosinophils help cytotoxic T-cells become killer cells, which cause tissue damage

Inducers of Type IV Hypersensitivity

Types of Delayed Hypersensitivity

Delayed Reaction reaction time Jones-Mote Contact tuberculin granulomatous days maximal
24 hours 48-72 hours 48-72 hours at least 14

Contact Hypersensitivity
Usually maximal at 48 hours Predominantly an epidermal reaction Langerhans cells are the antigen presenting cells
a dendritic antigen presenting cell carry antigen to lymph nodes draining skin

Associated with hapten-induced eczema

nickel salts in jewellry picryl chloride acrylates p-Phenylene diamine in hair dyes chromates chemicals in rubber poison ivy (urushiol)

Poison Ivy contact dermatitis

Tuberculin Hypersensitivity
Maximum at 48-72 hours Inflitration of lesion with mononuclear cells First described as a reaction to the lipoprotein antigen of tubercle bacillus Responsible for lesions associated with bacterial allergy
cavitation, caseation, general toxemia seen in TB

May progress to granulomatous reaction in unresolved infection

Granulomatous Hypersensitivity
Clinically, the most important form of DTH, since it causes many of the pathological effects in diseases which involve T cell-mediated immunity Maximal at 14 days Continual release of cytokines Leads to accumulation of large numbers of macrophages Granulomas can also arise from persistence of indigestible antigen such as talc (absence of lymphocytes in lesion)

Granuloma Formation

Examples of Microbial-Induced DTH

Viruses (destructive skin rashes)
smallpox measles herpes simplex

Fungi
candidiasis dematomycosis coccidioidomycosis histoplasmosis

Parasites (against enzymes from the eggs lodged in liver)

leishmaniasis schistosomiasis

Type V Stimulatory Hypersensitivity

Interaction of autoantibodies with cellular receptors Antibody binding mimics receptor-ligand interaction Examples
thyroid stimulating antibody (mimics thyroid stimulating hormone [TSH] of pituitary binds to thyroid cell receptor activation of B-cell by anti-immunoglobulin

Innate Hypersensitivity Reactions

Toxic shock syndrome (S. aureus TSS toxin)
hypotension, hypoxia, oliguria and microvascular abnormalities excessive release of TNF, IL-1, IL-6 intravascular activation of complement

Septicemia - Septic Shock

primarily due to lipopolysaccharide

Adult respiratory distress syndrome

overwhelming accumulation of neutrophils in lung

Platelet aggregation/adherence to macrophages by grampositive bacteria Superantigens

Gram positive enterotoxins react directly with T-cell receptors and induce massive cytokine release