JPC SYSTEMIC PATHOLOGY
Signalment: Rhesus monkey (Macaca mulatta)
HISTORY: Tissue from the eyelid 48 hours after an intradermal injection of tuberculin.
HISTOPATHOLOGIC DESCRIPTION: Haired skin, eyelid (per contributor): The superficial and deep dermis is expanded by perivascular accumulations of large numbers of lymphocytes, fewer plasma cells, and macrophages. Multifocally, a similar infiltrate separates and isolates collagen bundles, muscle fibers, and adnexa. Associated blood vessels often contain numerous transmigrating inflammatory cells and are occasionally lined by reactive endothelial cells. Multifocally the connective tissue is loosely arranged and expanded by clear space (edema) and fibrin. The epidermis is mildly hyperplastic with parakeratosis and a serocellular crust composed of eosinophilic material (serum), degenerate neutrophils, fibrin, and erythrocytes.
MORPHOLOGIC DIAGNOSIS: Haired skin, eyelid (per contributor): Dermatitis, lymphohistiocytic, perivascular, multifocal, moderate, with hemorrhage and edema, rhesus monkey (Macaca mulatta), nonhuman primate.
CONDITION: Positive tuberculin test (type IV/delayed-type hypersensitivity)
- Intradermal tuberculin injection tests for previous exposure/sensitization to Mycobacterium tuberculosis (weakly gram-positive bacillus, acid-fast, non-spore forming); false positive tests have been reported
- Tuberculin is a protein-lipopolysaccharide component of the tubercle bacillus
- Pathogenicity is related to type IV delayed type hypersensitivity
- Initial exposure (i.e., via natural infection) of the tubercle bacilli to macrophages induces macrophages to secrete IL-12, which causes the transformation of naive CD4 T cells to TH1 cells
- Sensitized TH1 cells enter the circulation and remain in the memory pool
- Upon reexposure (i.e. via the tuberculin test) memory TH1 cells are activated by interactions with antigen presenting cells
- Activated TH1 cells secrete IFN-gamma, IL-2, TNF-alpha, and lymphotoxin
- IFN-gamma activates macrophages, improving their phagocytic ability, increases MHC II presentation, IL-12, PDGF, and TGF-beta production
- IL-2 stimulates proliferation of T-cells
- TNF-alpha and lymphotoxin stimulate endothelial cells to secrete prostacyclin, increasing blood flow and vasodilation, increase expression of the adhesion molecule, E-selectin and the chemotactic factor, IL-8
- The cumulative effect is increased microvascular permeability, fluid and fibrin leakage, and the accumulation of monocytes and lymphocytes at the site of sensitization
TYPICAL CLINICAL FINDINGS:
- Signs of sensitization, such as reddening or swelling, at the injection site appear in 8-12 hours, peak in 24-72 hours, then gradually decrease
TYPICAL GROSS FINDINGS:
- Thickened, firm, erythematous lesion at the site of injection (i.e., typically the eyelid)
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Mononuclear cell accumulations around small veins and venules (perivascular cuffing)
- Edema, hemorrhage, fibrin deposition
- Endothelial hypertrophy
- tuberculosis: Responsible for the majority of human cases; second only to HIV/AIDs in the number of human deaths caused worldwide by an infectious agent; highly contagious fatal disease in NHPs
- There are numerous pathogens and contact antigens which are commonly associated with type IV hypersensitivity reactions in domestic animals
- Bacteria: bovis, M. avium ssp. paratuberculosis, M. avium ssp., Listeria monocytogenes, Yersinia spp.
- Viruses: Lymphocytic choriomeningitis virus
- Fungi: Blastomyces dermatitidis, Histoplasma capsulatum
- Protozoa: Toxoplasma gondii, Leishmania
- Components of insecticides in flea collars, sprays, and dips
- Chemical components of plastics, leathers, metals, and dyes
- Components of shampoos, topically applied drugs and pollens
- Contact sensitivity (dermatitis) due to the urushiol (organic allergen) in poison ivy
- Delayed hypersensitivity may be involved in transplant rejection
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- McAdam AJ, Milner DA, Sharpe AH. Infectious diseases. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders; 2015:371-378.
- Snyder, PW. Diseases of immunity. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Elsevier Mosby; 2012:266-270.
- Abee RA, Mansfield K, Morris T, Tardif S, eds. Nonhuman Primates in Biomedical Research: Biology and Management. 2nd Waltham, M: Elsevier: 2012:308-310.