Hypersensitive Reactions

Types 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 Outline
Gell & 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

Antigen

Antibodies
Conc

Ag:AB
Complexes

Time (days)

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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!!!

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