Hypersensitivity ___________________________ A situation when the immune systems cause harm to the body is referred to as a hypersensitivity a hypersensitivity

HypersensitivityHypersensitivity______________________________________________________

A situation when the immune systems cause harm to the body is referred to as A situation when the immune systems cause harm to the body is referred to as

a hypersensitivitya hypersensitivity

There are There are two categoriestwo categories of hypersensitivities: of hypersensitivities:

1. Immediate hypersensitivity and 1. Immediate hypersensitivity and 2. Delayed hypersensitivity.2. Delayed hypersensitivity.

Immediate hypersensitivitiesImmediate hypersensitivities refer to refer to humoral immunity humoral immunity (antigen/antibody reactions) causing harm; (antigen/antibody reactions) causing harm; Delayed hypersensitivitiesDelayed hypersensitivities refer to refer to cell-mediated immunity cell-mediated immunity (cytotoxic T-lymphocytes, macrophages, and cytokines) leading to harm. (cytotoxic T-lymphocytes, macrophages, and cytokines) leading to harm.

characteristics type-I

(anaphylactic)

type-II

(cytotoxic)

type-III

(immune complexes)

type-IV

(delayed type

antigen exogenous cell surface soluble tissues & organs

response time 15-30 minutes minutes – hours 3-8 hours 48 - 72 hours

appearance weal & flare lysis and necrosis

erythema and edema, necrosis

erythema, enduration

histology basophils and eosinophils

antibody and complement

complement and lymphocytes

monocytes & lymphocytes

transferred with antibody antibody antibody T-cells

examples allergic ashtma, hay fever

erythroblastosis fetalis, Goodpasture`s nephritis

SLE, farmer`s lung disease

tuberculin test, poison ivy, garanuloma

Hypersensitivity - Hypersensitivity - general characteristicsgeneral characteristics

Immediate HypersensitivityImmediate Hypersensitivity1. Type I (IgE-mediated or anaphylactic-type)1. Type I (IgE-mediated or anaphylactic-type)

GENERAL CHARACTERISTICS:GENERAL CHARACTERISTICS: the most common type of hypersensitivity, seen in about 20-the most common type of hypersensitivity, seen in about 20-

40% of the population. 40% of the population. IgEIgE is made in response to an allergen is made in response to an allergen levels of IgE may be thousands of times higher than in those levels of IgE may be thousands of times higher than in those

without allergies. without allergies. level of IgE due to a level of IgE due to a higher number of Th2 cellshigher number of Th2 cells which which

produce IL-4, a cytokine that can produce IL-4, a cytokine that can increase production of IgEincrease production of IgE and a lower number of Th1 cells that produce gamma-and a lower number of Th1 cells that produce gamma-interferon, a cytokine that decreases IgE production interferon, a cytokine that decreases IgE production

The allergen enters the body The allergen enters the body and is recognizedby sIg on a B-Ly and is recognizedby sIg on a B-Ly The B-lymphocyte then proliferates The B-lymphocyte then proliferates and differentiates into plasma cellsand differentiates into plasma cells.

The plasma cells produce and secreteThe plasma cells produce and secreteIgE which binds to receptors on mast IgE which binds to receptors on mast cells and basophils (Fccells and basophils (FcεεRI) RI) ––sensibilisationsensibilisation


MechanismMechanism


Allergen cross reacting with IgE Allergen cross reacting with IgE on mast cellon mast cell The next time the allergen enters the body,The next time the allergen enters the body,

it cross-links the Fab portions of the IgE it cross-links the Fab portions of the IgE bound to the mast cell. This triggers the mastbound to the mast cell. This triggers the mastcell to degranulate - releasecell to degranulate - release histaminehistamine and other and otherinflammatory mediatorsinflammatory mediators - bind to receptors on - bind to receptors on target cells which leads to target cells which leads to dilationdilation of blood of bloodvessels, vessels, constrictionconstriction of bronchioles, of bronchioles, excessiveexcessive mucus mucus secretionsecretion, and other symptoms of allergy., and other symptoms of allergy.


Inflammatory mediatorsInflammatory mediators platelet-activating factor, leukotreins, platelet-activating factor, leukotreins,

bradykinins, prostaglandins, and bradykinins, prostaglandins, and cytokinescytokines

TheThe early phaseearly phase appears appears

withinwithin min. after exposure to the min. after exposure to the AgAg


The Late phaseThe Late phase appears appears

several hours after exposure to Agseveral hours after exposure to Ag It is thought that basophils play a major role It is thought that basophils play a major role

here. here. Cell-bound IgE on the surface of basophils of Cell-bound IgE on the surface of basophils of

sensitive individuals binds a substance called sensitive individuals binds a substance called histamine releasing factor (possibly produced histamine releasing factor (possibly produced by Ma and B-Ly) causing further by Ma and B-Ly) causing further histaminehistamine release.release.


The The inflammatory mediatorsinflammatory mediators released or released or produced cause the following: produced cause the following:

a. a. dilationdilation of blood vesselsof blood vessels.. This causes This causes local rednesslocal redness (erythema) at the site of allergen (erythema) at the site of allergen

delivery. If delivery. If dilation is widespread, this can contribute to dilation is widespread, this can contribute to decreased vascular decreased vascular resistanceresistance, a drop in blood pressure, and , a drop in blood pressure, and shockshock. . b. b. increased capillary permeabilityincreased capillary permeability.. This causes This causes swelling of local tissuesswelling of local tissues (edema). If widespread, it (edema). If widespread, it

can can contribute to contribute to decreased blood volumedecreased blood volume and and shockshock. .


c. c. constriction of bronchial airwaysconstriction of bronchial airways. . This leads to This leads to wheezing and difficulty in breathingwheezing and difficulty in breathing. . d. d. stimulation of mucous secretionstimulation of mucous secretion.. This leads to This leads to congestion of airwayscongestion of airways. . e. e. stimulation of nerve endingsstimulation of nerve endings.. This leads to This leads to itching and pain in the skinitching and pain in the skin..


Systemic anaphylaxisSystemic anaphylaxis, the allergin is , the allergin is usually picked up by the usually picked up by the bloodblood and the and the reactions occur throughout the body. reactions occur throughout the body.

Examples: Examples: severe allergy to insect stings, severe allergy to insect stings, drugs, and antisera. drugs, and antisera.

Localized anaphylaxisLocalized anaphylaxis, the allergin is , the allergin is usually found usually found localizedlocalized in the mucous in the mucous membranes or the skin. membranes or the skin.

Examples: Examples: allergy to hair, pollen, dust, allergy to hair, pollen, dust, dander, feathers, and food. dander, feathers, and food.

Immediate HypersensitivityImmediate HypersensitivityType II (Antibody-Dependent Cytotoxicity)Type II (Antibody-Dependent Cytotoxicity)

The Fab of IgG reacts with epitopes The Fab of IgG reacts with epitopes on the host cell membrane. on the host cell membrane. Phagocytes bind to the Fc portion.Phagocytes bind to the Fc portion.

Phagocytes binding to the Fc portion Phagocytes binding to the Fc portion of the IgG and discharge theirof the IgG and discharge theirlysosomes causing cell lysis.lysosomes causing cell lysis.

Immediate HypersensitivityImmediate HypersensitivityType II (Antibody-Dependent Type II (Antibody-Dependent

Cytotoxicity)Cytotoxicity)

IgG or IgM reacts with epitopes on the IgG or IgM reacts with epitopes on the host cell membrane and activates the host cell membrane and activates the classical CP. classical CP. MAC then causes lysis of the cell.MAC then causes lysis of the cell.



The Fab portion of Ab binds to epitopes on the "foreign" The Fab portion of Ab binds to epitopes on the "foreign" cell. cell. NK cell binds to the Fc portion of AbNK cell binds to the Fc portion of AbNK cell releases NK cell releases pore-forming proteins – perforins (cell lysis)pore-forming proteins – perforins (cell lysis)proteolytic enzymes – granzymes (apoptosis), and proteolytic enzymes – granzymes (apoptosis), and chemokines. chemokines.



Examples include:Examples include:

1. AB and Rh blood group 1. AB and Rh blood group reactions; reactions;



2. autoimmune diseases such as: 2. autoimmune diseases such as: rheumatic feverrheumatic fever - Ab result in joint and heart valve damage; - Ab result in joint and heart valve damage; idiopathic thrombocytopenia purpuraidiopathic thrombocytopenia purpura - Ab result in the - Ab result in the

destruction of platelets; destruction of platelets; myasthenia gravismyasthenia gravis – Ab bind to the acetylcholine receptors on – Ab bind to the acetylcholine receptors on

muscle cells causing faulty enervation of muscles; muscle cells causing faulty enervation of muscles; Goodpasture's syndromeGoodpasture's syndrome – Ab lead to destruction of cells in the – Ab lead to destruction of cells in the

kidney; kidney; Graves' diseaseGraves' disease - Ab are made against thyroid-stimulating - Ab are made against thyroid-stimulating

hormone receptors of thyroid cells leading to faulty thyroid hormone receptors of thyroid cells leading to faulty thyroid function; function;

multiple sclerosismultiple sclerosis –Ab are made against the oligodendroglial cells –Ab are made against the oligodendroglial cells that make myelin, the protein that forms the myelin sheath that that make myelin, the protein that forms the myelin sheath that insulates the nerve fiber of neurons in the brain and spinal cord; insulates the nerve fiber of neurons in the brain and spinal cord; and and

3. some drug reactions,3. some drug reactions,4. early transplant rejections participation4. early transplant rejections participation

Immediate HypersensitivityImmediate HypersensitivityType III (Immune complex Type III (Immune complex

mediated)mediated) caused when caused when soluble antigen-soluble antigen-

antibody (IgG or IgM) complexesantibody (IgG or IgM) complexes, , which are normally removed by which are normally removed by macrophages in the spleen and liver, macrophages in the spleen and liver, form in large amountsform in large amounts and and overwhelm the body. overwhelm the body.


mediated)mediated)

Large quantities of soluble Ag-AbLarge quantities of soluble Ag-Ab complexes form in the blood and complexes form in the blood and are not completely removed by Maare not completely removed by Ma

These Ag-Ab complexes lodge in the These Ag-Ab complexes lodge in the capillaries between the endothelial cells capillaries between the endothelial cells and the basement membrane.and the basement membrane.


mediated)mediated)

These Ag-Ab complexes These Ag-Ab complexes activate the CCP leading activate the CCP leading to vasodilation.to vasodilation.

The C proteins and Ag-AbThe C proteins and Ag-Abcomplexes attract Le to complexes attract Le to the area.the area.

The Le discharge their The Le discharge their killing agents and promote killing agents and promote massive inflammation. massive inflammation. This can lead to tissue This can lead to tissue death death and hemorrhageand hemorrhage


mediated)mediated)

Examples includeExamples include

1. serum sickness, a combination type I and 1. serum sickness, a combination type I and type III hypersensitivity; type III hypersensitivity;

2. autoimmune acute glomerulonephritis; 2. autoimmune acute glomerulonephritis;

3. rheumatoid arthritis; 3. rheumatoid arthritis;

4. systemic lupus erythematosus; 4. systemic lupus erythematosus;

5. some cases of chronic viral hepatitis; and 5. some cases of chronic viral hepatitis; and

6. skin lesions of syphilis and leprosy 6. skin lesions of syphilis and leprosy

Delayed HypersensitivityDelayed Hypersensitivity

Delayed hypersensitivity Delayed hypersensitivity is cell-mediated is cell-mediated rather than antibody-mediated. rather than antibody-mediated.

Mechanism:Mechanism: Delayed hypersensitivity is Delayed hypersensitivity is the same mechanism as cell-mediated the same mechanism as cell-mediated immunity. immunity. T8-lymphocytesT8-lymphocytes become become sensitized to an antigen and sensitized to an antigen and differentiate into cytotoxic T-differentiate into cytotoxic T-lymphocyteslymphocytes while Th1 type T4-while Th1 type T4-lymphocytes become sensitized to an lymphocytes become sensitized to an antigen and produce cytokinesantigen and produce cytokines. .

CTLs, cytokines, and/or macrophages then CTLs, cytokines, and/or macrophages then cause harm rather than benefit. cause harm rather than benefit.


Binding of the CTL to a cross-reacting normal cell triggers the CTL to release Binding of the CTL to a cross-reacting normal cell triggers the CTL to release pore-forming proteins called perforins, proteolytic enzymes called granzymes,and pore-forming proteins called perforins, proteolytic enzymes called granzymes,and chemokines. Granzymes pass through the pores and activate the enzymes that lead chemokines. Granzymes pass through the pores and activate the enzymes that lead to apoptosis of the infected cell by means of destruction of its structural cytoskeletonto apoptosis of the infected cell by means of destruction of its structural cytoskeletonproteins and by chromosomal degradation. As a result, the cell breaks into fragments proteins and by chromosomal degradation. As a result, the cell breaks into fragments that are subsequently removed by phagocytes. that are subsequently removed by phagocytes.



The Mantoux skin test, the patient's arm is examined 48 to 72 hours The Mantoux skin test, the patient's arm is examined 48 to 72 hours after the tuberculin is injected. after the tuberculin is injected.

5 tuberculin units5 tuberculin units of liquid tuberculin admistered intradermally of liquid tuberculin admistered intradermally


Examples:Examples:1. Cell or tissue damage done during diseases like tuberculosis, leprosy, 1. Cell or tissue damage done during diseases like tuberculosis, leprosy,

smallpox, measles, herpes infections, candidiasis, and histoplasmosis; smallpox, measles, herpes infections, candidiasis, and histoplasmosis;

2. Skin test reactions seen for tuberculosis and other infections; 2. Skin test reactions seen for tuberculosis and other infections;

3. Contact dermatitis like poison ivy; 3. Contact dermatitis like poison ivy;

4. Type-1 insulin-dependent diabetes where CTLs destroy insulin-producing 4. Type-1 insulin-dependent diabetes where CTLs destroy insulin-producing cells; cells;

5. Multiple sclerosis, where T-lymphocytes and macrophages secrete cytokines 5. Multiple sclerosis, where T-lymphocytes and macrophages secrete cytokines that destroy the myelin sheath that insulates the nerve fibers of neurons; that destroy the myelin sheath that insulates the nerve fibers of neurons;

6. A major role in chronic transplant rejection as a result of CTL destruction of 6. A major role in chronic transplant rejection as a result of CTL destruction of donor cells (host versus graft rejection) or recipient cells (graft versus host donor cells (host versus graft rejection) or recipient cells (graft versus host rejection). rejection).

Cyclosporin A or FK-506 (Tacrolimus) are given in an attempt to prevent Cyclosporin A or FK-506 (Tacrolimus) are given in an attempt to prevent rejection. Both of these drugs prevent T-lymphocyte proliferation and rejection. Both of these drugs prevent T-lymphocyte proliferation and differentiation by inhibiting the transcription of IL-2. differentiation by inhibiting the transcription of IL-2.

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Hypersensitivity ___________________________ A situation when the immune systems cause harm to the body is referred to as a hypersensitivity a hypersensitivity