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Hypersensitive ReactionsTypes II,III & IV

Hugh B. Fackrell

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Hypersensitive Reactions Assigned Reading Content Outline Performance Objectives

– Key terms– Key Concepts

Short Answer Questions

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Assigned Reading Chapter: 17 pp 413-439 Janis Kuby’s Immunology 3rd Ed

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Content OutlineGell & Coombs Classification

Type I Hypersensitivity: IgE mediatiated Type II Hypersensitivity: Antibody mediated

cytotoxic Type III Hypersensitivity: Complex mediated

cytotoxic Type IV Hypersensitivity: DTH mediated

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Type II Hypersensitivity Antibody Dependent Cytotoxicity Antibody Dependent Cell mediated

Cytotoxicity Target antigens are found on cell or tissues Antibody binds to Target Antigen

– complement activated cell destruction– Ig binds to Fc receptors on NK cells

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Type II Hypersensitivity: Antibody mediated

cytotoxic Transfusion reactions Hemolytic disease of the newborn Drug induced hemolytic anemia Nephrotoxic (Masugi type) nephtritis Autoimmune hemolytic anemias Anti receptors/ hormone autoimmune

diseases– Hashimoto’s thyroiditis myasthenia gravis

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Transfusion Reactions Major Incompatibility

– recipient has Abs to donor RBCs– chills, fever, pain & shock– large amounts of hemoglobin released– blood pressure drops, renal failure,

coagulation Minor Incompatibility

– Donor has Abs to recipient RBCs– slowly falling hematocrit

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Hemolytic disease of the newborn

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Direct Antiglobulin Test

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Nephrotoxic Nephritis Antibodies against glomerular

basement membrane– Goodpasture’s syndrome– (also lung basement membrane)

Linear binding of Ab– fixation of complement– Inflammatory cells

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Goodpasture’s syndrome

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Immune complexes in autoimmune disease

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Autoantibodies in Diabetes

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Thryoiditis Graves Disease

– Antibodies to receptor of Thyroid Stimulating Hormone (TSH-R)

– Hyperthyroidism Hashimotos Thyroiditis

– Autoantibodies to thyroid proteins– TDTH cells: lymphocyte infiltration– hypothyroidism- Goiter

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Antibodies to thyroid microsomes

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Hyperacute Graft Rejection

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Graft rejection: histology

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Acute Graft Rejection

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Acute Graft rejection: Obstructed lumen

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Acute Graft Rejection 4

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Type III Hypersensitivity Immune Complex Reactions Antigens are in solution in plasma

or interstitial fluids. Abs combine with these Ags, fix complement and initiate the consequences of the complement cascade

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Type III Hypersensitivity: Complex mediated

cytotoxic Localized reactions

– Arthus type skin reactions– complex mediated glomerulonephritis– bumpy deposits

Generalized reactions– Serum sickness

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Generalized or Systemic Type III

Acute Systemic Reactions– drug reactions penicillin– Post streptococcal acute glomerulonephritis– aggregate “anaphylaxis”- cyroprecipitates

Chronic Systemic Reactions– Infections– Auotimmune conditions SLE RA– Cutaneous vasculitis

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Serum Sickness

Time (days)

Conc

Antibodies

Ag:AB Complexes

Antigen

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Arthus Reactions

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Extrinsinic Allergic Alveolitis

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SLE: Immune complexes

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SLE ab react with nuclei

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Type IV Hypersensitivity: DTH mediated

T DTH Cells– TC

– TH1 Cytokines

– IL-2, MIF, TNF, Interferon Macrophages

– lytic enzymes

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Type IV Granulomas Effective against intracellular

parasites– Granulomatous lesions– M. leprae, M. tuberculosis

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Type IV: Contact Hypersensitivity

Small molecules complex with skin proteins– pentadecacatechol poison ivy, poison oak– cosmetics, hair dyes– solvents formaldehyde, turpentine– nickel rubber

Complex internalized by APC– MHC-II

Response 48-72 hours

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Contact Hypersensitivity

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Contact hypersensitivity histology

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Sarcoidosis

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Skin grafts

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Histology of Normal skin

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Transplanted skin histology early

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Histology of Transplanted skin late

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Tuberculin type hypersensitivity

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Performance Objectives

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Key Terms allergen, allergy, anaphylactic

shock,anaphylaxis, anergy, atopy, basophils,

contact sensitivity, degranulation, delayed type hypersensitivity,

desenstization, granulomas, homocytotropic antibodies, hypersensitivity,

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hyposensitivity, immediate hypersensitivity, late phase reaction, mast cells,

sensitization, senstizing dose, shocking dose, systemic anaphlyaxis, triple response: edema, erythema, wheal and flare,

tubercles, tuberculin skine reaction, tuberculosis, Type I hypersensitivity,

Type II hypersensitivity, Type II hypersensitivity, Type IV hypersensitivity.

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Key Concepts List the Gell & Coombs classification for

hypersensitivity reactions; give examples of each type.

Describe stimulatory hypersensitivity and give a specific example

Discuss the difference between primary and secondary exposure to antigen in imunity and in hypersensitivity

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Describe the structural and functional characteristics of IgE.

Discuss the cytotropic nature of IgE

Differentiate betweeen the cyclooxygenase and lipoxygenase pathways of mediator production

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Describe the role of mast cells in immediate hypersensitivity reactions.

Distinguish between release of preformed and newly formed mediators from mast cells and give examples of each type of mediator

Discuss the hallmarks of delayed type hypersensitivity

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Explain the mechanisms of Delayed Type Hypersensitivity induction and development

Distinguish between different types of Delayed type hypersensitivity.

Describe tuberculosis in terms of hypersensitivity reactions.

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Short Answer Questions

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By derivation, what does allergy mean and what does hypersensitivity mean? Are they synonymous?

The main difference between immediate and delayed types of hypersensivitiy is the time of appearance of the reactions. True/False? If false, name the main differences.

What is the type II reaction described by Gell & Cooombs? Does this reaction require complement?

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Is there a tendency to immediate hypersenstivity reactions? Explain?

Differentiate between antigen and allergen.

What immune and nonimmune cells are involved in immediate hypersensivity?

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What class of antibody in responsible for immediate hypersenstivity? Describe some structural and biological characteristics of this antibody?

What do we mean by homocytotropic antibodies?

Briefly describe the result of the interaction of IgE, with mast cells– a) in the presence of allergen.– b) in the absence of allergen.

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What are the chemical mediators of immediate hypersentivity reactions?

Some effector molecules of immediate hypersensitivity reactions are preformed mediators; others are newly synthesized mediators. Distinguish between the two.

Briefly describe the two pathways for the production of newly synthesized mediators.

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How can you determine whether a person is allergic to a foreign protein?

What is the triple response? Name two "in vitro" tests.

What is the mechanism for desensitization for immediate hypersensitivities? Is this desensitization lifelong? If not speculate on the reasons. What are some other modes of treatment for immediate hypersensitivity?

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Describe the differences between systemic anahylaxis and atopy?

Are the mechanisms of cell-mediated immunity and DTH the same?

Name the effector cells in DTH. What are some of the hallmarks of

DTH reactions?

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Describe contact sensitivity. How does contact sensitivity differ

from the tuberculin skin reaction? What is the mechanism of the

tuberculin skin test? If the test is positive what causes the induration (hardening) of the test site? What substances are used in this test?

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DONE!!!DONE!!!