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Hypersensitivity
 Altered immunologic response to an
antigen that results in disease or damage
to the host

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Hypersensitivity (cont’d)
 Allergy
 Deleterious effects of hypersensitivity to
environmental (exogenous) antigens
 Autoimmunity
 Disturbance in the immunologic tolerance of
self-antigens
 Alloimmunity
 Immune reaction to tissues of another
individual

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Hypersensitivity (cont’d)
 Characterized by the immune mechanism:
 Type I
• IgE mediated
 Type II
• Tissue-specific reactions
 Type III
• Immune complex mediated
 Type IV
• Cell mediated

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Hypersensitivity (cont’d)
 Immediate hypersensitivity reactions
 Anaphylaxis
 Delayed hypersensitivity reactions

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Type I Hypersensitivity
 IgE mediated
 Against environmental antigens (allergens)
 IgE binds to Fc receptors on surface of
mast cells (cytotropic antibody) -
“sensitized”
 Histamine release
 H1 and H2 receptors
 Antihistamines

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Type I Hypersensitivity (cont’d)
 Manifestations:
 Itching
 Urticaria
 Conjunctivitis
 Rhinitis
 Hypotension
 Bronchospasm
 Dysrhythmias
 GI cramps and malabsorption

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Type I Hypersensitivity (cont’d)
 Genetic predisposition- atopic
 Tests:
 Food challenges
 Skin tests
 Laboratory tests
 Desensitization
 Cautiously

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Type I Hypersensitivity (cont’d)

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Type II Hypersensitivity
 Tissue specific
 Specific cell or tissue (tissue-specific antigens)
is the target of an immune response

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Type II Hypersensitivity (cont’d)
 Five mechanisms:
 Cell is destroyed by antibodies and
complement
 Cell destruction through phagocytosis
 Soluble antigen may enter the circulation and
deposit on tissues; tissues destroyed by
complement and neutrophil granules
 Antibody-dependent cell-mediated cytotoxicity
(ADCC)
 Causes target cell malfunction (e.g., Graves)

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Type III Hypersensitivity
 Immune complex mediated
 Antigen-antibody complexes are formed in
the circulation and are later deposited in
vessel walls or extravascular tissues
 Not organ specific
 Serum sickness
 Raynaud phenomena
 Arthrus

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Type IV Hypersensitivity
 Does not involve antibody
 Cytotoxic T lymphocytes or lymphokine
producing Th1 cells
 Direct killing by Tc or recruitment of phagocytic
cells by Th1 cells
 Examples:
 Acute graft
rejection
 Skin test for TB
 Contact allergic
reactions
 Some autoimmune
diseases

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Allergy
 Most common hypersensitivity and usually
type I
 Environmental antigens that cause atypical
immunologic responses in genetically
predisposed individuals
 Pollens, molds and fungi, foods, animals, etc.
 Often allergen is contained within a
particle too large to be phagocytosed or is
protected by a nonallergenic coat
 Bee stings

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Autoimmunity
 Breakdown of tolerance
 Body recognizes self-antigens as foreign
 Self-antigens not normally seen by the immune
system
 Infectious disease (e.g., rheumatic fever,
glomerulonephritis)
 Antigenic mimicry
 Neoantigen
 Haptens become immunogenic when they bind
to host proteins

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Autoimmune Examples
 Systemic lupus erythematosus (SLE)
 Chronic multisystem inflammatory disease
 Autoantibodies against:
• Nucleic acids
• Erythrocytes
• Coagulation proteins
• Phospholipids
• Lymphocytes
• Platelets, etc.

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Autoimmune Examples (cont’d)
 Systemic lupus erythematosus (SLE)
 Deposition of circulating immune complexes
containing antibody against host DNA
 More common in females

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Systemic Lupus Erythematosus
 Clinical manifestations:
 Arthralgias or arthritis (90% of individuals)
 Vasculitis and rash (70%-80%)
 Renal disease (40%-50%)
 Hematologic changes (50%)
 Cardiovascular disease (30%-50%)

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Systemic Lupus Erythematosus
(cont’d)
 Eleven common findings:
 Serial or simultaneous presence of at least four
indicates SLE

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Alloimmunity
 Immune system reacts with antigens on
the tissue of other genetically dissimilar
members of the same species
 Transplant rejection and transfusion reactions:
• Major histocompatibility complex (MHC)
• Human leukocyte antigens (HLC)
 Transfusion reactions
• ABO blood groups
 Rh incompatibility
• Hemolytic disease of newborn

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Graft Rejection
 Transplant rejection is classified according
to time
 Hyperacute
• Immediate and rare
• Preexisting antibody to the antigens of the graft
 Acute
• Cell-mediated immune response against unmatched
HLA antigens

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Graft Rejection (cont’d)
 Transplant rejection is classified according
to time
 Chronic
• Months or years
• Inflammatory damage to endothelial cells of vessels
as a result of a weak cell-mediated reaction against
minor HLA antigens

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Graft-Versus-Host Disease
(GVHD)
 Immunocompromised individuals are at
risk for CVHD
 T cells in the graft are mature and capable of
cell-mediated destruction tissues within the
recipient
 Not a problem if patient is immunocompetent