Abnormal Immunity - Hypersensitivity

Question 1

Immunopathology

Answer 1

• Diseases characterized by abnormal or inappropriate immune responses
• Major Conditions include:
  
  • Hypersinsitivity reations
  • Immunodeficiency
  • Autoimmunity

Question 2

Immunopathology:

Hypersensitivity Reactions

Answer 2

• 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

Question 3

Hypersensitivity Reactions:

Answer 3

• There are 4 main immune mechanisms of hypersensitivity-induced injury
  
  • Type 1
  • Type 2
  • Type 3
  • Type 4

Question 4

Hypersensitivty Reactions:

Type 1

Answer 4

• 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

Question 5

Type 1 Hypersensitivity:

Mechanism

Answer 5

• 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

Question 6

Type 1 hypersensitivity:

Local Manifestation:

Ingested Allergens

Answer 6

• 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

Question 7

Type 1 hypersensitivity:

Local Manifestations:

Inhaled allergens

Answer 7

• 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
• Responses to some inhaled allergens are manifested in the respiratory tract
  
  • nasolacrimal urticaria

Question 8

Type 1 Hypersensitivity:

Local Manifestations

Cutaneous Allergens

Answer 8

• 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

Question 9

Type 1 Hypersensitivity:

Systemic manifestations:

Answer 9

• Anaphylaxis
• Signs and lesions are usually typical of shock
• Manifestations can include:
  
  • respiratory distress and pulmonary failure
  • Gastrointestinal dysfunction and liver failure

Question 10

Hypersensitivity Reactions:

Type 2

Answer 10

• 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

Question 11

Type 2 Hypersensitivity:

Complement-mediated mechanism

Answer 11

• Antibody binds a cell membrane or basement membrane antigen
• Classical complement cascade is activated
• Formation of the terminal membrane attack sequence and cell lysis

Question 12

Type 2 Hypersensitivity:

Leukocyte-mediated mechanism

Answer 12

• 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

Question 13

Type 2 Hypersensitivity:

Manifestation:

Reaction against Erythrocytes

Answer 13

• 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

Question 14

Type 2 hypersensitivity:

Manifestations:

Reactions against leukocytes

Answer 14

• Neonatal leukopenia
• Agranulocytosis (acquired leikopenia)

There may be increased susceptibility to infection

Question 15

Type 2 hypersenstivity:

Manifestations

Reactions against Platelets

Answer 15

• Drugs
• Infectious agents
• Autoimmunity

Thrombocytopenia is the major finding

Pathologic findings are predominately multiple petechial to ecchymotic hemorrhage

Question 16

Type 2 Hypersensitivty:

Manifestations:

Reactions agianst Basement membranes

Answer 16

• Antibodies are directed against basement membranes
  
  • glomerular and epidermal basement membranes are common targets
• Injury can be mediated by complement or leukocytes

Question 17

Hypersensitivity Reactions:

Type 3

Answer 17

• 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

Question 18

Type 3 Hypersenstivity:

Mechanisms:

Localized Hypersentitivity (arthus reaction)

Answer 18

• 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

Question 19

Type 3 Hypersensitivity:

Mechanisms:

Systemic Hypersensitivity (serum sickness)

Answer 19

• Soluble, circulating immune complexes can be deposited within vessels of multiple tissues
• Complement and leukocytes induce vessel and tissue damage

Question 20

Type 3 Hypersensitivity:

Manifestations:

Vasculitis

Answer 20

• Some degree of vasculitis occurs with al type 3 reactions
• COmmonly affected tissues include:
  
  • kidney
  • Lungs
  • joints
  • Eyes

Question 21

Type 3 Hypersensitivity:

Manifestations:

Kidney

Answer 21

• Immine complexes can be formed in many diseases, and can be deposited near glomerular basement membranes
• Complement and leukocyte-mediated damage cause glomerulonephritis

Question 22

Type 3 Hypersentivity:

Manifestations:

Lungs

Answer 22

• Deposition of immune complexes near alveolar and endothelial basement membranes
• Complement and leukocyte-mediated damage cause alveolitis

Question 23

Type 3 Hypersensitivity:

Manifestations:

Joints

Answer 23

• Immune complexes can be deposited in synovial membranes
• Complement and leukocyte-mediated damage cause synovitis and arthritis

Question 24

Type 3 Hypersensitivity:

Manifestations:

Eyes

Answer 24

• 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

Question 25

Hypersensitivity Reactions: Type 4

Answer 25

* Delayed hypersensitivity reactions mediated by antibody-independent immune responses * Key features: * Persistent antigen * T-lymphocyte proliferation and production of lymphokines * Macrophage proliferation and activation

Question 26

Type 4 Hypersenitivity: Mechanisms Tissues (delayed hypersensitivity)

Answer 26

* 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

Question 27

Type 4 Hypersensitivity: Mechanisms: Cell-mediated cytotoxicity

Answer 27

* 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.

Question 28

Type 4 Hypersensitivity: Manifestations: Tuberculin Reaction

Answer 28

* 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.

Question 29

Type 4 Hypersensitivity: Manifestation: Granulomatous Hypersensitivity

Answer 29

* 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

Question 30

Type 4 Hypersenstivity: Manifestations: Contact Hypersensitivity

Answer 30

* 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