DR. SHUBHANGI V. AGALE

ASSOCIATE PROFESSOR

GRANT GOVT MEDICAL

COOLEGE

MUMBAI

HYPERSENSITIVITY

HYPERSENSITIVITY

All forms of immune-mediated injuries are collectively denoted as hypersensitivity reactions.

Subdivided into four types:

TYPE 1

Allergy and Anaphylaxis.

Allergen cross-links Ig-E ab---

release of vaso-active amines and

other mediators from mast cells and

basophils—recruitment of

inflammatory cells

eg Anaphylaxis, Br.asthama.

TYPE 2

Ab to fixed Ag:IgG or IgM binds to

Ag on cell surface --- phagocytosis

of target cell by complement or

ADCC.AIHA. Erythroblastisis

foetalis,GP synrome.

TYPE 3

Immune –complex disease: Ag-Ab

complex –activate complement---

attracts neutrophils---release of

lysosomal enzymes, oxygen free

radicals. Serum

sickness,SLE,Arthus.

TYPE 4

Cell mediated (delayed)

hypersensitivity: Sensitised T

lymphocytes---release of cytokines

& T cell mediated cytotoxicity.

Tuberculosis, contact dermatitis,

transplant rejection.

Type 1 hypersensitivity

reaction

Rapidly developing immunologic reaction occurring within minutes after the combination of an Antigen with Antibody bound to mast cells in an individual previously sensitized to the antigen.

Reaction ---- Allergy

Antigen ----- Allergen

Two reactions---- 1.systemic 2. local

Type 1 hypersensitivity

reaction

• Initial response---primary

mediators

• Late phase reaction—sec

mediators

1. Systemic reaction

Follows injection of an antigen to which host has become sensitized

Within minutes , state of fatal shock develop.

Ig G mediated antibody reaction

Mast cells

Primary mediators- histamine, enzymes (chymase, tryptase), proteoglycans

Secondary mediators- leukotriensC4,D4,B4, PG D2 , PAF, Interlukins

2. Local reaction

Skin allergy

Allergic rhinitis

Allergic conjunctivitis

Bronchial asthma

Food allergy

Hay fever

Immediate response

Evident within 5 to 30 minutes

Vasodilatation

Vascular leakage

Smooth muscle contraction

Glandular secretion

Subside within 60 minutes

Late phase reaction

Sets in 2 to 24 hrs after exposure

Without additional exposure to antigen

May last for several days

Infiltration of tissues by eosinophils

/neutrophils /monocytes/ lympocytes.

Tissue destruction, mucosal damage

E.g.- Bronchial asthma, allergic rhinitis

Type 1 hypersensitivity reaction

ATOPY

Genetically predisposed - local type

- I reaction to inhaled or ingested

allergens

E.g. pollen, house dust, food.

High Ig E levels

Family history - positive

PATHOGENESIS

Ig E mediated antibody reaction

Mast cells

Primary mediators- histamine, enzymes (chymase, tryptase), proteoglycans

Secondary mediators- leukotriensC4,D4,B4, PG D2 , PAF, Interleukins

Type 1 hypersensitivity reaction

PATHOLOGIC LESIONS

Vasodilatation

Smooth muscle spasm

Cellular infiltration

Inflammation

Mucus production

Oedema

Type-1

TYPE II - ANTIBODY MEDIATED

Mediated by Ab directed against Ag present on cell surface / extra-cellular matrix.

Secreted antibodies participate directly in injury to cells.

phagocytosis

lysis

injury to tissue by inducing inflammation.

Antibodies may also interfere with cellular functions & cause disease without tissue injury.

Type 2 hypersensitivity

reaction

Three different mechanisms

Complement---direct lysis or opsonisation.Transfusion reactions, erythroblastosis foetalis,AIHA,drugreactions,pemphigus vulgaris.

ADCC—leukocytes—neutrophils, eosinophils, macrophages & mast cells.

Ab mediated cellular dysfunction.e.g: myasthenia graves,greaves disease.

PATHOGENESIS

Production of Ig G / Ig M antibodies

Antibodies bind to antigen on target cell or tissue

Phagocytosis or lysis of target cell by complement activation

Leukocyte recruitment & inflammation

Type 2 hypersensitivity reaction

1. Opsonisation & complement

mediated cell destruction and

phagocytosis

Mismatched (Incompatible) blood transfusion- lysis of RBC (ABO incompatibility)

ERYTHROBLASTOSIS FETALIS -there is antigenic difference between mother and fetus. Ig G isoantibodies from mother cross placenta and cause destruction of fetal red cells (Rh incompatibility)

2. COMPLEMENT – AND FC

RECEPTOR MEDIATED

INFLAMMATION

Antibody deposition in extracellular matrix

Complement activation

Recruitment of neutrophils and monocytes

Release of injurious substances by activated leukocytes

Damage to tissue. e.g.-vascular rejection in organ graft.

No phagocytosis or lyses of cells.

3. ANTIBODY MEDIATED

CELLULAR DYSFUNCTION

Antibodies directed against cell-surface receptors impair or dysregulate function. Both cells & antibodies take part In diseases. (ADCC)

Examples –Myasthenia Gravis

Pemphigus vulgaris

Graves disease

Pernicious Anemia

Rheumatic fever

GRAVE’S DISEASE

Type III – IMMUNE COMPLEX

MEDIATED REACTION

Antigen – antibody complexes produce tissue damage mainly by eliciting inflammation at the site of deposition.

Antigen combines with antibody - circulate and are deposited in vessel walls, kidney & other sites.

Ag-Ab complexes are formed at extra-vascular sites where antigen may have been previously deposited.

Two types of antigens = exogenous (streptococci) and endogenous (DNA)

1. GENERALIZED (SYSTEMIC) ICD

Immune complexes are formed in circulation & are deposited in many organs.

Acute serum sickness Early 1900 Clemens von Pirquet

Pts with Diphtheria infection were being treated with serum from horses immunized with diphtheria toxin.

Pts developed fever ,skin rash & arthritis.

Symptoms appeared more rapidly with repeated injections of serum.

Conclusion : Treated pts made antibodies to horse serum proteins, & formed complexes with injected proteins.

PATHOGENESIS

Formation of ag-ab complexes in

circulation

Deposited in various tissues.

- An inflammatory reaction at the sites of

immune complex deposition. Neutrophilic

lysosomal enzyme degradation

-Complement activation

-Platelet aggregation- Micro thrombi-

ischemia- fibrinoid necrosis- vasculitis

Type 3 hypersensitivity

EXAMPLES

Systemic lupus erythematous

Acute post-streptococcal GM

Poly arteritis nodosa (PAN)

Arthus reaction

Rheumatoid arthritis

Farmer’s Lung

Henoch schonlein purpura.

SLE

Type IV –T CELL MEDIATED

(DELAYED HYPERSENSITIVITY)

Initiated by antigen-activated (sensitized)

T – lymphocytes

Delayed type reaction – CD 4 +

Direct cell cytotoxicity - CD 8 + (CTL)

Principle pattern of immunologic response

to intracellular microbiologic agents

Mycobacterium tuberculosis, viruses, fungi,

parasites & protozoa.

Tuberculosis & Leprosy

TUBERCULIN REACTION

Intracutaneous injection of tuberculin, a protein lipopolysacharide component of the tubercle bacillus.

In previously sensitized individual reddening and induration of site appear in 8 to 12 hours, & reach a peak in 24 to 72 hours.

PROCEDURE

POSITIVE REACTION

Transplant rejection

Rejection is a complex process in

which both cell mediated immunity

and circulating antibodies have a

role to play.

Transplant rejection

T cell mediated rejection: in direct recognition (activates DTH) & direct recognition. –dendriticcells express high levels of MHC1 & MHC2 mole.

Antibody mediated rejection:Anti-HLA humoralabs develop concurrently with T cell mediated rejection.

Hyperacute rejection –where preformed anti-donor abs are present.

Acute rejection: within days to weeks.combinedprocess of cellular & humoral mech contribute.

Acute cellular rejection: c/f of renal failure.Extensive CD4+ & CD8+T cells with oedema & interstitial haemorrhage.

Acute rejection vasculitis: necrotising vasculitiswith endothelial cell necrosis.

Chronic rejection ---renal ischemia.

Rejection

Rejection

ACUTE REJECTION

CHRONIC REJECTION

SUMMARY

WHAT IS HYPERSENSITIVITY?

TYPES OF HYPERSENSITIVITY?

TYPE 1

TYPE 2

TYPE 3

TYPE 4

TUBERCULIN TEST

TRANSPLANT REJECTION

THANK

YOU