We are living in environment containing substances, capable of producing immunological responses.

Foods, drugs, dust, pollens, microbiologic agents, chemicals………….can bring hypersensitivity rn.

Type I: Immediate hypersensitivity:

Production of IgE antibody, release of vasoactive amines

and other mediators from mast cells; recruitment of other

inflammatory cells (late phase reaction).

Pathologic lesions: Vascular dilatation, edema, smooth

muscle contraction, mucus production, inflammation.

Immediate (type I) hypersensitivity:

Rapidly developing reaction

Occurring within minutes, a state of shock is produced; may

be fatal.

In individuals previously sensitized.

1. Immediate response: vasodilatation, vascular leakage,

smooth muscle spasm, glandular secretions.

2. Late phase: infiltration of tissue by eosinophils, basophils,

monocytes; tissue destruction, mucosal epithelium damage.

Antigen/ Pollen

APC

Th2 Lymphocyte

IL-4

IL-5, 13

Plasma Cells

Eosinophils

Mast Cells

Antigen

Ig E receptor

Ig E Ab

Degranulation

BM derived cells, widely distributed in tissues.

Cytoplasm bound granules +ve (metachromatic dye);

Contain:

1. Histamine,

2. Enzymes (protease, acid hydrolase),

3. Proteoglycans (Heparin, chondratin sulphate).

ACTIVATION OF ANAPHYLOTOXINS: (C5a and C3a).

Primary mediators:

Biogenic amines: Histamine: smooth muscle contraction,

increased vascular permeability.

Enzymes: Protease (chymase, tryptase) acid hydrolases :

tissue damage.

Proteoglycans: Heparin (anticoagulant) & Chondratin

sulphate.

Lipid mediators:: Leukotriens- LTC4, LTD4; Prostaglandins-

PGD2

Cytokines:: PAF, TNF, IL-1, 4, 5, 6. Eotaxin

IL-4 is mast cell regulator; released by T cells.

1. Dendritic cells—capture antigens

2. T cells differentiate to TH-2 cells

3. IL 4 activates B cells to produce Ig E

4. Ig E attracts mast cells

(Mast cells and basophils express Ig E receptors).

5. IL 5 activates eosinophils

6. IL 13 activates epithelial cells to produce mucous.

Anaphylaxis

Allergies (food allergy, allergic rhinitis and conjunctivitis)

Asthma (Bronchial)

Atopic forms (Hay fever)

Type 1: Prototype disorders: 4 A’s

ATOPY: predisposition to develop immediate hypersensitivity

reaction to a variety of inhaled and ingested allergens.

Atopic individuals have increased serum levels of Ig E levels,

and more IL 4 producing TH 2 cells.

Genetically determined

C/F: Vascular shock, wide spread edema, difficulty

in breathing, laryngeal edema, vomiting diarrhea,

even may die.

Occur after antisera, drugs (penicillin), hormones,

enzymes.

Previous history of allergy is important.

Double edged Sword

Useful????

Harmful????

Antibodies are directed against antigens present on cell surface or extracellular substances.

Three different mechanisms:

1. Opsonization & compliment & Fc-receptor –mediated phagocytosis.

2. Compliment and Fc receptor mediated inflammation.

3. Antibody mediated cellular dysfunction.

O: Autoimmune hemolytic anemia, ATP, Transfusion rn, erythroblastosis fetalis.

C: Vasculitis, Goodpasture syndrome, ARF, Glomerulonephritis.

A: Myasthenia Gravis, Grave’s disease, insulin resistant DM, Pernicious anemia, Pemphigus vulgaris.

Type II hypersensitivity:

EXAMPLES OF TYPE II REACTION: (MDP TEA)

Transfusion reaction

Erythroblastosis fetalis

Autoimmune hemolytic anemia, leukopenia,

thrombocytopenia

Drug reactions: Hemolysis following Penicillin

Pemphigus vulgaris

Myasthenia gravis, Graves disease (Ab mediated cellular

dysfunction)

IMMUNE COMPLEX MEDIATED:

Ag-Ab complexes produces tissue damage mainly by eliciting

inflammation at the site of deposition.

Circulating immune complexes are deposited typically in

vessel wall.

It represents normal mechanism of Ag removal.

Two types: Systemic/ Localized.

SP-PARAS:

S: Systemic lupus erythematosis (SLE)

P: Polyathritis nodosa (PAN)

P: Post-streptococcal GN

A: Acute GN (AGN)

R: Reactive Arthritis

A: Arthus reaction

S; Serum sickness

Phase I: Immune complex formation

Phase II: Immune complex deposition

Phase III: Immune complex mediated

inflammation

Size of immune complexes:

larger complexes –rapidly removed. So relatively harmless;

smaller –circulate longer—dangerous.

Functional status of mononuclear phagocytic system:

intrinsic dysfunction of phagocytic system—persistence of

immune complexes in circulation.

Charge, affinity, structure, hemodynamic factors…,etc.

Glomeruli

Joints

Skin

Heart

Serosal surfaces

Sites of immune complex deposition

Types:

1. Delayed- type hypersensitivity:

CD4 + T- cell mediated toxicity.

2. Direct T- cell mediated cytolysis:

CD 8 + T- cells.

CELL MEDIATED (type IV) Hypersensitivity:

1. Granulomatous Inflammation

2. Tuberculin skin test

3. Transplant rejection

4. Contact dermatitis

Examples for Type IV Hypersensitivity Rn:

To identify susceptible persons in the population prone for

tuberculosis

Screening procedure; not diagnostic of disease.

Performed in family members of patient with open

tuberculosis

To know the family members who can get afflicted, who are

already exposed and Immune.

Type I (“Allergy”) Soluble antigen: IgE: Mast cells

Atopy: Exaggerated tendency to mount an IgE response

Type II Cell associated antigen: IgG: phagocytes, NK cells

Type III Antigen-Antibody complexes

Type IV T-cell mediated

Summery of HypersensitivitiesAntibody

Cell