Immunopathology: Hypersensitivity Flashcards
What is Immunopathology
- Disease characterized by abnormal or inappropriate immune responses
- Reactions involve coordinated and integrated contribution from both immune and inflammatory responses
- Major conditions include:
- hypersensitivity reactions
- Immunodeficiency
- autoimmunity
Wht are Hypersensitivity reactions?
- Most immune responses to antigens are advantageousto the host
- Some immune responses can cause host injury (hypersensitivity reactions)
- Host injury due to hypersensitivity reactions occurs by several main mechanisms
- Type I
- Type II
- Type III
- Type IV
What is Type I hypersensitivity reaction?
- An immediate response characterized by prominent vasoactive events and the release of inflammatory mediators
- Key features:
- Antigens that induce IgE production
- IgE-mediated mast cell degranulation
- Vascular leakage and eosinophil infiltration
What is the mechanism of Type I hypersensitivity reactions?
- 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 ini crosslinking of IgE and cell degranulation
- Vasoactive mediators are releaed into the surrounding tissues
What are the local manifestations of Type I hypersensitivity reactions to ingested allergens?
- Ingested allergens (food alergies)
- Gastrointestinal sign range from milkd, to severe with bloody diarrhea and vomiting
- ~1/2 of food allergies have skin manifestations
- erythema, pruritis, urticaria
What are the local manifestations of Type I hypersensitivity reactions to inhaled allergens?
- Inhaled allergens (respiratory allergies)
- Responses to most inhaled allergens are manifested in the skin
- Atopic dermatitis:
- lesions range from acute erythema to chronic hyperpigmentation and pyodermas
- Pruritis is a major feature
- Atopic dermatitis:
- Responses to some are manifested in teh respiratory tract
- Nasolacrimal urticaria (hay fever)
- Responses to most inhaled allergens are manifested in the skin
What are the local manifestations of Type I hypersensitivity reactions to cutaneous allergens?
- Cutaneous allergens (skin allergies)
- Most ingested or inhled allergens result in skin responses
- atopic dermatitis
- Locally applied allergens can also result in hypersensitvity dermatitis
- Most ingested or inhled allergens result in skin responses
What are the systemic manifestations of Type I hypersensitivity reactions?
- Anaphylaxis:
- Signs and lesions are usually typical of shock
- Include:
- Respiratory distress and pulmonary failure
- Gastrointestinal dysfunciton and liver failure
What are Type II Hypersensitivity reactions?
- Cytotoxicity induced by reactions against cell membrane antigens
- Key features:
- Antigens that induce IgG or IgM production against cell membrane antigens
- Antibody-mediated activation of complement or leukocytesz results in cell damage
- End result is membrane damage and cell injur
- 2 different mechanisms damage cells:
- Complement-mediated
- Leukocyte-mediated
What is the Cmplement-mediated mechanism of Type II hypersensitivity?
- Antibody binds a cell membrane or basement membrane ntigen
- Classical complement cascade is activated
- Formation of the terminal membrane attack sequence and cell lysis
What is the leukocyte-mediated mechanism of Type II hypersensitivity?
- Antibody binds a cell membrane or basement membrane antigen
- Leukocytes bind ia their Fc receptors
- Leukocyte products damage he membrane
- Lysosomal enzymes
- Oxygen free radicals
What are the manifestation of Type II hypersentitivities against erythrocytes?
- Common targets are circulating cells, epidermis and basement membranes
- Reactions against erythrocytes:
- Transfusion reactions
- Neonatal isoerythrolysis
- Autoimmune hemolytic anemia
- Drug-induced hemolysis
- Infectious agents
- The notable clinical sign in most cases is hemolytic anemia
What are the pathologic features of reaction against erythrocytes?
- Icterus
- Splenomegaly
- Hemosiderosis of various tissues
What are the manifestations of Type II hypersensitivity against Leukocytes?
- Reactions against Leukocyctes
- Neonatoal leukopenia
- Agranulocytosis (acquired leukopenia)
- There may be increased susceptibility to infection
What are the manifestations of Type II hypersensitivity against platelets?
- Reactions against platelets
- Drugs
- Infectious agents
- Autoimmunity
- Thrombocytopenia is the major finding
- Pathologic findings are predominately multiple petechial to ecchymotic hemorrhages
What are the manifestations of Type II hypersensitivity reactions against basement membranes?
- Reactions against basement membranes
- Antibodies are directed against basement membrane components
- Glomerular and epidermal basement membranes are common targets
- Injury can be mediated by complement or leukocytes
- Antibodies are directed against basement membrane components
What are Type III Hypersensitivity Reactions?
- Tissue damage induced by inflammatory responses to immune complexes
- Key Features:
- Appropriate immune complexes
- formed in slight antigen excess
- Complement and leukocyte-induced tissue injury
- Reactions can occur to localized or circulating immune complexes
- Appropriate immune complexes
What are the mechanisms of Type III hypersensitivity reactions?
- 2 different pathways of injury are described, based on the location of the immue complex
- Localized hypersensitivity (Artus reaction)
- Systemic Hypersensitivity (Serum sickness)
What is the Arthus reaction?
- Interstitial antigen and intravascular antibody meet and precipitate within vessel walls
- Complement and leukocytes mediate vessel damage
- There is vascular necrosis, hemorrhage, thrombosis and local tissue damage
What is Serum Sickness?
- Soluble, circulating immune complexes can be deposited within vessels of mutiple tssues
- Complement and leukocyte induce vessel and tissue damage
What are the manifestations of Type III hypersentivity reactions?
- Vasculitis
- Some degree occurs with all Type III reactions
- Commonly affected tissues include:
- Kidney
- Lungs
- Joints
- Eyes
How are Kidneys affected by Type III hypersensitivity reactions?
- Immune complexes can be formed in many diseases, and can be deposited near glomerular basement membranes
- Complement and leukocyte-mediated damage cause glomerulonephritis
How are lungss affected by Type III hypersensitivity reactions?
- Deposition of immune complexes near alveolar and endothelial basement membranes
- Complement and leukocyte-mediated damage cause alveolitis
How are joints affected by Type III hypersensitivity reactions?
- Immune complexes can be deposited in synovial membranes
- Complement and leukocyte-mediated damage cause synovitis and arthritis
How are eyes affected by Type III hypersensitivity reactions?
- Immune complexes can be deposited in the uvea
- this is common as a sequella to canine adenovirus-1 infection
- Complement and leukocyte-mediated damage cause anterior uveitis and corneal edema
What are Type IV hypresensitivity reactions?
- A delayed hypersensitivity reaction medited by antibody-independent immune responses
- Key Features:
- Persisten antgen
- T-lymphocyte proliferation and production of lymphokines
- Macrophage proliferation and activation
- 2 pathways of damage are described:
- One for tissue
- One for cells
What is the mechanism of delayed Type IV hypersensitivity?
- Antigen persistence stimulates lymphocyte and macrophage infiltration to the site
- Vasodiltion and increased vascular permeability are minor parts of the typical response
- T-lymphocytes and macrophges proliferate locally and produce cytokines that mediate removal of the antigen and associated tissue damage
What is the mechanism of cell-mediated cytotoxicity?
- Certain cell-associated antigens cause the generation of cytotoxic T-lyphocytes
- Often these are virus infected cells and tumor cells
- Natural killer cells recongized abnormal membrane antigens
- Cytotoxic T-lymphocytes and natural killer cells bind to and destroy the abnormal cells
What are Tuberculin reaction of Type IV hypersensitivity reactions?
- 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.
What is Granulomatous hypersensitivity?
Type IV 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
- Mycobacterial infections
What is Contact hypersensitivity?
Type IV hypersensitivity
- Dermal contact with certain antigens induces a cell-mediated delayed hypersensitivity
- Cellular infiltrate is largely lymphocytic
- Common causes:
- Plants (poison ivy)
- Flea collars
- Wood preservatives and waxes
- Paints, dyes, fabric chemicals
What is Autoimmunity?
- Immune responses directed against self
- The immune mechanisms that mediate autoimmunity are the same that mediate reactions against exogenous antigens
- The only difference is the source of the antigen
What are the mechanisms of Autoimmunity?
- Several general theories have been made about the origin of autoreactive immunity
- Release of sequestered antigens
- Alteration of self antigens
- Alteration of immune reactivity
What is the Release of sequestered antigens autoimmunity mechanism?
- Some substances in the body are not normally exposed to the immune system
- Includes:
- Myelin
- Lens
- Sperm
What is the alteration of self antigens autoimmunity mechanism?
- Sel antigens may be modified so that they are no longer recognized as self
- Viral alteration of cell membrane features
- Chemical alteration of cell membranes
What is the alteration of immune reactivity autoimmunity mechanism?
- There is a loss of tolerane to self antigens
- Autoreactive B- and T-lymphocytes are normally present, but non-functional
- Changes may occur that allow functions of these cells to be manifested
What are the predisposing factors of Autoimmunity?
- Genetic predisposition:
- certain conditions have definite inherited patterns of breed or familial occurrence
- Gender predisposition:
- More common in females
- over 75% of cases os systemic lupus erythematosis are diagnosed in females
- Comparative levels of estrogen and testosterone can influence autoimmunity
- More common in females
What are the manifestations of Autoimmunity?
- Autoimmune thyroiditis
- Periodic ophthalmia
- Autoimmune skin disease
- Autoimmune hemolytic anemia
- Autoimmune thrombocytopenia
- Myasthenia gravis
- systemic lupus erythematosis
What is Autoimmune thyroiditis?
- Antibodies are produced against thyroid epithelium or thyroglobulin
- A common cause of hypothyroidism in dogs
What is periodic ophthalmia?
- Anti-leptospiral antibodies that are cross reactive with corneal self antigens cause anterior uveitis and vision deficiencies
What is Autoimmune skin disease?
- Antibodies are produced to various components of the epidermis
- A variety of different syndromes exist
- Pemphigus vulgaris
- Pemphigus foliaceous
What is autoimmune hemolytic anemia?
- Antibodies against erythrocytes result in complement or leukocyte-mediated hemolysis
What is Autoimmune thrombocytopenia?
- Anti-platelet antibodies destroy platelets and predispose to hemorrhage
What is myasthenia gravis?
- antibodies are produced against acetylcholine receptors of neuromuscular junctions causing weakness and muscle atrophy
What is systemic lupus erythematosis?
- Autoantibodies are directed against a variety of tissues most likely due to a loss of immunoregulation
- Antibodies are commonly formed against nucleic acids, erythrocytes, platelets, muscle, skin, lymphocytes
What is immunodeficiency?
- Immunological defects thatlead to depression of certain immune functions and increase susceptibility to infectious disease
- Any component ofthe immune system can be affected?
What are the mechaisms of immunodeficiency?
-
Inherited defects
- gnetic abnormalities result in the failure of proper development of the immune system
-
Acquired defects
- expsure to certain infectious agents or chemicals, or nutritional deficiencies
What is Combined Immunodeficiency (CID)
- Manifestation of Immunodeficiency
- SOme inherited defects involve multiple immune cells
- CID is most common in Arab foals, but similar syndromes are reported in dogs, mice and other species
- Functional B- and T-lymphocytes are absent or decreased
- Affected animals usually die before 6 months of age due to infectious disease
What is selective immunodeficiency?
- Manifestation of immunodeficiency
- Certain geneti defects involve specific immune cells
- B-lymphocytes
- IgM deficiency in Arabs and Doberman pinschers
- IgG deficiencyin dogs and cattle
- T-lymphocytes
- Trait A-46 in Friesian cattle
- B-lymphocytes
What is viral-induced immunodeficiency?
- Immunodeficiency manifestation
- A large number of viruses can alter immune functions
- Some viruses destroy lymphoid cell and tissues
- Some viruses cause lymphocyte dysfunction
What Viruses that destroy lymphoid cells and tissues?
- canine parvovirus
- Canine distemper virus
- Feline panleukopenia virus
- Bovine virus diarrhea virus
What viruses cause lyphocyte dysfunction?
- Feline leukemia virus
- Feline immunodeficiency virus
- Bovine leukosis virus
- Equine infectious anemia virus
- Mareks disease virus
What is chemical-induced immunodeficiency?
- Immunodeficiency manifestation
- Various chemicals reportedly induce immunosuppresion
- Include:
- Halogenated biphenyls
- Certain Heavy metals
- Mycotoxins
What is nutrition-induced immunodeficiency?
- Immunodeficiency manifestation
- Severe malnutrition or starvation will depress immune function
- Deficiencies of certain vitamins or minerals can suppress immune responses
- Zinc, magnesium
- Vitamins A and B
What is Failure of passive transfer?
- Immunodeficiency manifestation
- Colostral antibodies are not obtained by the newborn
- Neonates not receiving colostrum are predisposed to infections early in life
