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Pathology > Immunopathology > Flashcards

Immunopathology Flashcards

1
Q

Immunopathology

A

Disease where the response to foreign or self antigens is abnormal or inappropriate

  • hypersensitivity rxns
  • autoimmunity
  • immunodeficiency
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2
Q

Hypersensitivity

A

Inappropriate or exaggerated response to certain antigens

  • 1: immediate
  • 2: cytotoxic
  • 3: immune complex
  • 4: delayed
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3
Q

Type 1 hypersensitivity

A

Develops rapidly (within minutes) following exposure to an antigen binding to IgE

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4
Q

Type 1 mechanism

A

Prior exposure to an antigen stimulates production of IgE –> specific IgE binds to Fc receptor of mast cells/basophils –> subsequent exposure to antigen causes binding and crosslinking of IgE on surface of mast cells –> degranulation occurs with release of mediators into surrounding tissue
*mediators: vasodilation, increased vascular permeability, bronchial smooth muscle constriction

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5
Q

What antigens are involved with type 1?

A
  • pollen
  • parasite
  • insect venom proteins
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6
Q

Factors that determine a type 1 hypersensitivity

A
  • genetic component
  • dose/route of exposure
  • antigen processing –> if IL-4 predominates then Th2 lymphocytes will induce B cells to produce IgE
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7
Q

Anaphylactoid reactions

A

Others substances that can activate mast cells (not by the IgE receptor)
- cytokines, complement, drugs, physical stimuli (heat, cold, trauma)

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8
Q

Type 1 hypersensitivity results in ________

A

Anaphylaxis or anaphylactic shock (systemic)

- drop in bp, bronchoconstriction, laryngeal edema, pulmonary congestion

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9
Q

Signs of shock

A
  • cattle/sheep: respiratory distress, pulmonary hypertension, lung is shock organ with severe pulmonary edema
  • horse: diarrhea and coli, lung and intestine are shock organs = bronchoconstriction with edema and edematous/hemorrhagic entercolitis
  • dog: abdominal pain with vomiting, muscle weakness and collapse, portal hypertension and systemic hypotenesion, liver is shock organ
  • cat: lung is shock organ
  • pig: lung and intestine is shock organ
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10
Q

Type 1 hypersensitivity usually has ______ lesions

A

Localized

  • restricted to specific tissue (commonly epithelial)
  • ex: mites, chemicals, flea allergy dermatitis
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11
Q

Allergic dermatitis

A

Route of exposure may be inhalation, ingestion, or percutaneous absorption

  • most inhaled or ingested antigens result in dermatitis
  • acute inflammatory rxn, often perivascular
  • red raised areas, often around muzzle, periocular area, conjunctiva, interdigital areas
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12
Q

Atopic dermatitis

A

Genetic predisposition

- production of IgE antibodies after exposure to common environmental allergens

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13
Q

Angioedema

A

Swelling of skin and mucous membranes

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14
Q

Type 2 hypersensitivity - cytotoxic

A

Cell destruction mediated by presence of antibodies directed against cell surface antigens
- antibodies are endogenous (directed against self antigens) or exogenous (directed against foreign antigens)

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15
Q

Type 2 mechanisms

A
  • complement mediated cytotoxicity (MAC –> cell lysis)
  • leukocyte mediated cytotoxicity (cell mediated, opsonization by antibody –> phagocytosis)
  • antibody against cell surface receptor (altered cell function –> may function as agonist or antagonist
  • results in decrease or loss of population of cells*
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16
Q

Rxns against erythrocytes - transfusion rxn

A

When an animal receives blood from an incompatible donor

  • acute hemolytic anemia
  • splenomegaly and hemosiderosis of various tissues
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17
Q

Rxns against erythrocytes - hemolytic disease of newborn

A

Neonatal isoerythrolysis

  • mother develops antibodies against fetal erythrocytes
  • leakage of fetal erythrocytes across placenta, antibodies to fetal RBCs are concentrated in the colostrum
  • absorption of colostrum results in acute hemolytic crisis in the newborn
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18
Q

Autoimmune hemolytic anemia

A

Autoantibodies are made to self-antigens on erythrocytes

- hemolytic anemia occurs due to complement mediated erythrocyte destruction

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19
Q

Drug induced hemolysis

A

Certain drugs can alter erythrocyte membranes

- immunoglobulin binding and complement activation

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20
Q

Infectious diseases (type 2)

A

Certain viral, bacterial, protozoal antigens can adhere to erythrocytes and initiate hypersensitivity
- ex: anaplasmosis, EIA

21
Q

Neonatal leukopenia

A

Antibodies produced against fetal leukocyte antigens that cross placenta during gestation
- neutropenia

22
Q

Thrombocytopenia (immune mediated)

A

Anti-platelet antibodies are formed

  • antibody formation may be autoimmune or caused by drug-induced membrane alteration
  • chemical: petechiae and purpuric hemorrhage
23
Q

Myasthenia gravis

A

Antibodies block acetylcholine receptors causing muscle weakness and paralysis

  • autoimmune
  • no gross or microscopic lesions
24
Q

Type 3 hypersensitvity

A

Antigen-antibody complexes that form in circulation or in tissues become stuck or lodged in tissue

  • develop from antibody response to endogenous or exogenous antigens
  • Fc segment activates complement and leukocytes = damage to cell and tissue
25
Q

Size of immune complex

A
  • determines pathogenicity
  • immune complexes formed during antibody excess are insoluble and phagocytosed
  • immune complexes formed with a large excess of antigen are usually too small to be trapped in tissue
  • complexes formed with slight antigen excess are most pathogenic
26
Q

Predilection sites for immune complexes

A
  • kidney and glomeruli
  • eye
  • skin
27
Q

Localized type 3 hypersensitivity

A

Localized area of tissue necrosis from acute necrotizing vasculitis (Arthus rxn)

  • antigen-antibody complexes formed at site of injection and within blood vessel
  • complement and neutrophil mediated damage to vessel occurs
  • tissue damage dependent of quantity of complexes formed
  • vascular necrosis, increased vascular permeability, hemorrhage, thrombosis, local tissue necrosis
28
Q

Systemic type 3 hypersensitivity

A

Deposition of soluble, intravascular immune complexes within multiple organs

  • antibodies form complexes with intravascular antigens
  • immune complexes are deposited within blood vessel of many tissues (kidney, joints, cardiovascular)
  • complement and neutrophil-mediated damage to tissue
  • macrophages produce pro-inflammatory cytokines
  • *result of persistent infections, autoimmune disease or inhalation to foreign antigens
29
Q

Local or systemic immune complexes result in ______ and ______

A

Tissue damage; inflammation

30
Q

Vasculitis

A

Occurs to a degree in all type 3 rxns

  • immune complex within the vessel wall
  • induces damage to adjacent tissue (ischemia)
  • systemic viral diseases, systemic lupus erythematosus, food hypersensitivity, drug rxn
  • vessel wall thickened by eosinophilic material (fibrin)
31
Q

Systemic lupus

A

Presence of autoantibodies against DNA, nucleoproteins, cell surface antigens, etc
- glomerulonephritis, arthritis, vasculitis

32
Q

Pupura hemorrhagica

A

Occurs in horses following infection with streptococcus equi

- swelling and hemorrhage, skin may slough, affects all organs

33
Q

Type 3 - renal immune complexes

A

Deposition of soluble immune complexes in the glomerulus = glomerulonephritis

  • damage to filtration structure
  • component of many diseases with constant antigenic stimulation
  • viral: EIA, feline leukemia, FIP
  • bacterial: pyometra, endocarditis
  • parasitic: heartworm
34
Q

Type 3 - respiratory complexes

A

Hypersensitivity penumonitis

  • immune complex formation involving a variety of inhaled antigens
  • diffuse alvelitis following inhalation of antigens by a sensitized animal
  • type 1 sensitivity contributes
  • inhalation of fungal spores in cattle
35
Q

Type 3 - ocular complexes

A

Viral antigen-antibody complexes in the eye, causes anterior uveitis and damage to corneal endothelium (corneal edema)
- inflammation secondary to infection or vaccination with canine adenovirus type 1

36
Q

Type 4 hypersensitivity

A

Delayed hypersensitivity mediated by specific T cells following exposure to antigen

  • chronic and antibody independent - cell mediated hypersensitivity
  • result of interaction of T cells and specific antigen to which they have been sensitized
  • rxn to persistent antigens
37
Q

Delayed hypersensitivity

A

Persistent antigen stimulates the infiltration of lymphocytes and macrophages to the site
- macrophages and lymphocytes coordinate to remove the inciting antigen

38
Q

Direct cytotoxicity

A

Certain cell associated antigens result in the generation of cytotoxic T cells
- targets are virus infected cells and tumor cells

39
Q

Tuberculin rxn

A

Local swelling of macrophage infiltration following intradermal injection of antigen in sensitized animal

  • following intradermal injection of tuberculin, a sensitized host will develop a localized type 4 rxn with 24-72 hrs
  • antigen taken up by dendritic cell and presented to antigen-specific CD4 cell, activated to produce and secrete cytokines that attract other inflammatory cells
  • used to diagnostic testing
40
Q

Granulomatous hypersensitivity

A

Persistent antigen that results in granulomatous and lymphocytic inflammation

  • macrophages, giant cells, lymphocytes, necrosis and fibrosis
  • bacteria, fungi, and certain parasites
41
Q

Contact dermatitis

A

Antigen too small to elicit immune response by itself

  • antigens are complexed with larger proteins
  • processing and presentation by APCs
  • in a sensitized host repeat exposure = effector phase response = epidermal vesicle formation with mononuclear cell infiltration
  • causes: poison ivy, flea collars, paints, dyes
42
Q

Autoimmunity

A

Production of antibody and T cells that are reactive to self antigens
- many autoimmune diseases are type 2 or 3

43
Q

Mechanisms of autoimmunity

A
  • release of sequestered antigens (substances not normally exposed to immune system)
  • alteration of self antigens (normal proteins are altered, chemicals can alter cell surfaces)
  • alteration of immune reactivity (loss of tolerance to self antigens, self reactive B and T cells are present in normal animals, but are non functional)
44
Q

Susceptibility

A
  • genetic: species and breed (systemic lupus erythematosus common in collies and shelties)
  • gender: more frequent in females
45
Q

Autoimmunity is a _______ hypersensitivity

A

Type 2

46
Q

Autoimmune skin disease

A

Antibodies directed against epidermal antigens activate complement then neutrophil-mediated skin damage

47
Q

Pemphigus foliaceious

A

Autoantibodies against adhesion molecules on keratinocytes

48
Q

Pemphigus vulgaris

A

Autoantibodies against antigens in or near the epidermal-dermal junction
- severe and rare

49
Q

Bullous pemphigoid

A

Autoantibodies against basement membrane antigens

- vesicles then ulceration

Pathology (19 decks)

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