Download Hypersensitivity

Hypersensitive Reactions
Types II,III & IV
Hugh B. Fackrell
5/6/2017
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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
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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
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Major Incompatibility
–
–
–
–
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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
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Antibodies against glomerular
basement membrane
– Goodpasture’s syndrome
– (also lung basement membrane)
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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
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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
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Localized reactions
– Arthus type skin reactions
– complex mediated glomerulonephritis
– bumpy deposits
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Generalized reactions
– Serum sickness
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Generalized or Systemic Type III
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Acute Systemic Reactions
– drug reactions penicillin
– Post streptococcal acute
glomerulonephritis
– aggregate “anaphylaxis”- cyroprecipitates
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Chronic Systemic Reactions
– Infections
– Auotimmune conditions SLE RA
– Cutaneous vasculitis
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Serum Sickness
Antigen
Conc
Antibodies
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
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T DTH Cells
– TC
– TH1
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Cytokines
– IL-2, MIF, TNF, Interferon
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Macrophages
– lytic enzymes
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Type IV Granulomas
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Effective against intracellular parasites
– Granulomatous lesions
– M. leprae, M. tuberculosis
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Type IV:
Contact Hypersensitivity
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Small molecules complex with skin proteins
–
–
–
–
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pentadecacatechol poison ivy, poison oak
cosmetics, hair dyes
solvents formaldehyde, turpentine
nickel rubber
Complex internalized by APC
– MHC-II
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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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