This chapter will provide information on different types of hypersensitivity reactions, mediators of these reactions, the consequent tissue damages. A clear knowledge of the various mechanisms described in this chapter will help in understanding of the various hypersensitivity diseases that occur in domestic animals. A more elaborate discussion on specific hypersensitivity diseases occurring in domestic animals will be offered in Spring Semester (Microbiology 202). After studying this chapter one should be able to answer the following questions:
A state where immunological responses become inappropriate or exaggerated and result in tissue damage.
The response is not a general one but is characteristic of an individual, and usually occurs following a second exposure with a particular antigen (allergen).
There are two major categories:
The Coombs-Gell Classification Schema was introduced in 1963 in which hypersensitivity reactions have been classified into 4 types: Types I, II, III, and IV. First three types are mediated by antibody and the fourth is mediated by T cells and macrophages.
22.214.171.124 Type I: Immediate hypersensitivity:
Reaction occurs within minutes.
Inhaled antigen - Hay fever, tracheobronchial constriction (asthma).
Aerosolized antigen - Conjunctivitis, lacrimation.
Ingested antigen - diarrhea, colic.
Skin contact - urticarial lesions, rash, wheel & flare reaction.
Atopic Diseases in domestic animals:
canine allergic inhalant dermatitis, allergic rhinitis.
ectoparasites, pollens, mold, household dust
Bovine atopy, atopic rhinitis, milk allergy.
Tests for Type I hypersensitivity
Schultz-Dale Reaction - uterine or intestinal tissue is isolated from a sensitized animal. Upon in vitro exposure with the specific antigen, smooth muscle contraction occurs.
Passive Cutaneous Anaphylaxis (PCA)- serum from a sensitized animal is injected into the skin of a normal recipient. A mixture of antigen and Evans Blue dye is injected intravenously 3-6 hours later. A blue patch of reactivity at the skin site indicates specificity.
Prausnitz-Kustner Reactions (P-K test): serum for an atopic patient is injected into the skin of a normal recipient. The assay is positive if a wheal with erythema develops immediately after injection of the offending allergen at the same site.
Radioallergoimmunosorbent test (RAST): an in vitro assay to measure antigen-specific IgE levels in test serum. Patient's serum is added to wells in 96-well plates coated with suspected allergen. After washing to removed unattached antibodies, an isotopically-labeled anti-species IgE serum is allow to react. A positive test can be determined using a counter to determine amount of isotope present.
These hypersensitivities are associated with antibody-mediated blood cell destruction. The reaction involves a combination of IgG or IgM antibodies with the antigenic determinants on the cell membrane.
Cytotoxicity as a result of blood transfusions and incompatibilities including hemolytic disease of the newborn. The following is an example of incompatibility for B system antigen resulting in the destruction of piglet RBC's.
Sow(B) b/b X Boar (B) a/b after breeding, the sow is immunized with blood from the boar 7 piglets given colostrum 4 (b/b) 3 (a/b) no effect hemolytic disease Hemolytic disease of newborn is not uncommon in foals but may occur in other animals.
Mare gets sensitized to fetal erythrocytes during pregnancy and parturition and produces antibodies which accumulate in colostrum. When the newborn foal ingests this colostrum these antibodies enter the circulation and cause erythrocyte hemolysis.
Examples of drugs: Penicillin, quinine, aminosalicylic acid.
Examples of infections: Equine infectious anemia, Aleutian disease of minks, Salmonella lipopolysaccharides.
126.96.36.199 Type III. Immune Complex-mediated hypersensitivity
When complement-activating immune complexes (antigen-antibody complexes) are deposited in tissues chemotactic factors are released with accumulation of PMN. These cells release inflammatory mediators causing tissue destruction.
The Arthus Reaction
A rabbit given small doses of innocuous proteins may develop an erythema followed by edema with subsequent necrosis at the injection site. The first injection of antigen induces the primary response i.e, sensitization of the subject. Each subsequent injection with the same antigen provokes a secondary response so that high levels of serum antibodies to the antigen develop.
The antibodies circulate in the blood and react with antigen. Antigen-antibody complexes fix onto complement and initiate platelet agglutination and mast cell degranulation.
Note: IgE can react with platelets causing the release of platelet activating factor inducing a nonimmunological but similar clinical manifestation.
Serum sickness is not an uncommon iatrogenic complication of serum therapy. The disease is initiated by the protracted interaction between antigen and antibody in circulation with complement. Associated inflammatory and proliferative lesions develop in connective tissue. After elimination of the complexes from circulation, the lesions may disappear and in most instances, healing is complete.
Immune complex-mediated glomerulonephritis, arthritis, and vascultis are other complications of Type III hypersensitivity. These conditions are observed in many viral and bacterial diseases of domestic animals.
188.8.131.52 Type IV. Delayed Type Hypersensitivity (DTH) or cell-mediated hypersensitivity.
The central feature common to all DTH reactions is that specifically sensitized lymphocytes interact with antigen locally and evoke an inflammatory response at the reaction site. These events involve the production and release of lymphokines and do not involve either circulating antibody or complement. Thus it is a cell-mediated response and typically occurs after 24-48 hours (delayed-type) Important example: Tuberculin reaction.
Tuberculin reaction occurs only in animals that have or have had tuberculosis. This test is the basis for eradication of tuberculosis. Single intradermal test - 0.05 ml of purified protein derivative (PPD) tuberculin is injected into anal-fold and the site is examined 72-96 hours later. Positive reaction is confirmed when there is a diffuse, indurated swelling.
Examples of Tissue Damage
Allergic contact Dermatitis - a result of the continual exposure to a variety of substances ranging from oily resins of plants (poison ivy) to simple chemicals employed for domestic, industrial and medical purposes (paints, chemicals in flea collars). In both examples, the reaction involves antigen attaching to homologous receptors on sensitized T lymphocytes. This leads to the production of lymphokines that acts on other cells including macrophages.
1. What are the roles of complement components C3a and C5a in immediate hypersensitivites?
REFERENCES Type I and Type IV
Hypersensitivities in Animals. K. T. Schultz, JAVMA 181:
1083, 1982. Veterinary Clinical Immunology
by Halliwell and Goram.
Bach, M. K. Mediators of
Anaphylaxis and Inflammation. Ann. Rev. Microbial.
Type I and Type IV Hypersensitivities in Animals. K. T. Schultz, JAVMA 181: 1083, 1982.
Veterinary Clinical Immunology by Halliwell and Goram.