Abnormal Immunity - Hypersensitivity Flashcards
Immunopathology
- Diseases characterized by abnormal or inappropriate immune responses
- Major Conditions include:
- Hypersinsitivity reations
- Immunodeficiency
- Autoimmunity
Immunopathology:
Hypersensitivity Reactions
- Most immune responses to antigens are advantageous to the host
- Some immune responses can cause host injury
- Host injury due to hypersensitivity reactions occurs by several main machanisms
Hypersensitivity Reactions:
- There are 4 main immune mechanisms of hypersensitivity-induced injury
- Type 1
- Type 2
- Type 3
- Type 4
Hypersensitivty Reactions:
Type 1
- An immediate response characterized by prominent vacoactive events and teh release of inflammatory mediators
- Key features:
- Antigens that induce IgE production
- IgE-mediated mast cell degranulation
- Vascular leakage and eosinophil infiltration
Type 1 Hypersensitivity:
Mechanism
- Prior exposure to an antigen stimulates production of antigen-specific IgE
- IgE binds to Fc receptors of mast cells and basophils
- Subsequent antigen exposure results in crosslinking of IgE and cell degranulation
- Vasoactive mediators are released into the surrounding tissues
Type 1 hypersensitivity:
Local Manifestation:
Ingested Allergens
- Ingested allergens
- common inciting allergens include:
- milk, wheat products, eggs, fish, alfalfa
- Gastrointestinal signs range from mild, to severe with bloody diarrhea and vomiting.
- Approximately half of food allergies have skin anifestations
- erytherma, pruitis, urticaria
- common inciting allergens include:
Type 1 hypersensitivity:
Local Manifestations:
Inhaled allergens
- Common allergens include:
- molds, pollens, house dust, fabrics
- Responses to most inhaled allergens are manifested in the skin
- atopic dermatitis:
- lesions range from acute erytherma to chronic hyperpigmentation and pyodermas
- Pruritis is a major feature
- atopic dermatitis:
- Responses to some inhaled allergens are manifested in the respiratory tract
- nasolacrimal urticaria
Type 1 Hypersensitivity:
Local Manifestations
Cutaneous Allergens
- Common allergens include:
- insect bite, mites, fly larvae
- Most ingested or inhaled allergens result in skin responses:
- atopic dermatitis
- Locally applied allergens can also result in hypersentitivity dermatitis
Type 1 Hypersensitivity:
Systemic manifestations:
- Anaphylaxis
- Signs and lesions are usually typical of shock
- Manifestations can include:
- respiratory distress and pulmonary failure
- Gastrointestinal dysfunction and liver failure
Hypersensitivity Reactions:
Type 2
- Cytotoxicity induced by reactions against cell membrane antigens
- Key features:
- Antigens that induced IgG or IgM production against cell membrane antigens
- Antibody-mediated activation of complement or leukocytes results in cell damage
- End result is membrane damage and cell injury
- Two different mechanisms damage the cells
- complement-mediated
- Leukocye-mediated
Type 2 Hypersensitivity:
Complement-mediated mechanism
- Antibody binds a cell membrane or basement membrane antigen
- Classical complement cascade is activated
- Formation of the terminal membrane attack sequence and cell lysis
Type 2 Hypersensitivity:
Leukocyte-mediated mechanism
- Antibody binds a cell membrane or basement membrane antigen
- Leukocytes bind via their Fc receptors
- Leukocyte products damage the membrane
- lysosomal enzymes
- Oxygen free radicals
Type 2 Hypersensitivity:
Manifestation:
Reaction against Erythrocytes
- Transfusion reactions
- neonatal isoerythorlysis
- Autoimmune hemolytic anemia
- Drug-induced hemolysis
- Infectious agents
Notable clinical signs in most cases is hemolytic anemia
- Pathologic features
- icterus
- Splenomegaly
- Hemosiderosis of various tissues
Type 2 hypersensitivity:
Manifestations:
Reactions against leukocytes
- Neonatal leukopenia
- Agranulocytosis (acquired leikopenia)
There may be increased susceptibility to infection
Type 2 hypersenstivity:
Manifestations
Reactions against Platelets
- Drugs
- Infectious agents
- Autoimmunity
Thrombocytopenia is the major finding
Pathologic findings are predominately multiple petechial to ecchymotic hemorrhage
Type 2 Hypersensitivty:
Manifestations:
Reactions agianst Basement membranes
- Antibodies are directed against basement membranes
- glomerular and epidermal basement membranes are common targets
- Injury can be mediated by complement or leukocytes
Hypersensitivity Reactions:
Type 3
- Tissue damage induced by inflammatory responses to immune complexes
- Key features:
- Appropriate immune complexes
- formed in slight antingen excess
- Complement and leukocyte-induced tissue injury
- Reactions can occur to localized or circulating immune complexes
- Appropriate immune complexes
Type 3 Hypersenstivity:
Mechanisms:
Localized Hypersentitivity (arthus reaction)
- Interstitial antigen and intravascular antibody meet and precipitate within vessel walls
- Complement and leukocyets mediate vessel damage
- There is vascular necrosis, hemorrhage, thrombosis, and local tissue damage
Type 3 Hypersensitivity:
Mechanisms:
Systemic Hypersensitivity (serum sickness)
- Soluble, circulating immune complexes can be deposited within vessels of multiple tissues
- Complement and leukocytes induce vessel and tissue damage
Type 3 Hypersensitivity:
Manifestations:
Vasculitis
- Some degree of vasculitis occurs with al type 3 reactions
- COmmonly affected tissues include:
- kidney
- Lungs
- joints
- Eyes
Type 3 Hypersensitivity:
Manifestations:
Kidney
- Immine complexes can be formed in many diseases, and can be deposited near glomerular basement membranes
- Complement and leukocyte-mediated damage cause glomerulonephritis
Type 3 Hypersentivity:
Manifestations:
Lungs
- Deposition of immune complexes near alveolar and endothelial basement membranes
- Complement and leukocyte-mediated damage cause alveolitis
Type 3 Hypersensitivity:
Manifestations:
Joints
- Immune complexes can be deposited in synovial membranes
- Complement and leukocyte-mediated damage cause synovitis and arthritis
Type 3 Hypersensitivity:
Manifestations:
Eyes
- Immune complexes can be deposited in the uvea
- this is common as sequella to canine andeovirus-1 infections
- Complement and leukocyte-mediated damage cause anterior uveitis and corneal edema
Hypersensitivity Reactions:
Type 4
- Delayed hypersensitivity reactions mediated by antibody-independent immune responses
- Key features:
- Persistent antigen
- T-lymphocyte proliferation and production of lymphokines
- Macrophage proliferation and activation
Type 4 Hypersenitivity:
Mechanisms
Tissues (delayed hypersensitivity)
- Antigen persistence stimulates lymphocytes and macrophage infiltration to the site
- vasodilation and increased vascular permeability are minor parts of the typical response
- T-lymphocytes and macrophages proliferate locally and produce cytokines that mediate removal of the antigen and associated tissue damage
Type 4 Hypersensitivity:
Mechanisms:
Cell-mediated cytotoxicity
- Certain cell-associated antigens cause the generation of cytotoxic T-lymphocytes
- often these are virus infected cells and tumor cells
- Natural killer cells recognized abnormal membrane antigens
- Cytotoxic T-lymphocytes and natural killer cells bind to and destroy the abnormal cells.
Type 4 Hypersensitivity:
Manifestations:
Tuberculin Reaction
- Intradermal injection of antigen in a sensitized animal causes local swelling and macrophage infiltration
- This is used for diagnostic testing to a variety of agents
- mycobacterium sp.
Type 4 Hypersensitivity:
Manifestation:
Granulomatous Hypersensitivity
- This is a combination of delayed hypersensitivity and granulomatous inflammation
- antigen persistence is a characteristic of both
- Lymphocytes and macrophages are prominent at the site
- Common causes include:
- systemic fungal infections
- Mycobacgerial infections
Type 4 Hypersenstivity:
Manifestations:
Contact Hypersensitivity
- Dermal contact with certain antigens induces a cell-mediated delayed hypersensitivity
- Cellular infiltrate is largely lymphocytic
- Common causes:
- plants such as poison ivy
- Flea collars
- wood preservatives and waxes
- Paints, dyes, fabric chemicals
