Immunodeficiency disease Presented by saddock muperi Reg number b200231a IMMUNODEFICIENCY DISEASES DEFINITION :Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Defence mechanisms of body are impared which results in repeated microbioal infections. Specific immunofunctions. Immunodeficiency can be Primary or Secondary . Immunodeficiency can arise as a result of inherited defects in development of the immune system ,of defects secondary to other cause or of tumours of the immune system. Any failure of the immune system is usually manifested in an increased susceptibility to infectious disease. Immunodeficiencies have been investigated largely in human medicine since animals are unlikely to receive the attention necessary to keep immunodeficient individuals alive. The type of deficiency that have been studied seem to be similar in animals and man. INHERITED DEFECTS IN ANTIGEN PROCESSING Chronic granulomatous Disease in humans is characterised by impairment of the bactericidal efficiency of neutrophils, patients suffer from recurrent infections and develop septic granuloma in lymph nodes, lungs, bones and skin. Chediak Higashi syndrome is described in people but also reported in Hereford cattle ,Aleutian mink, Persian cats, White tigers and killer whales. It is associated with the defect in cell structure which results in the production of abnormality large granules in neutrophils monocytes and eosinophils and in enlarged melanocyte granules. The leucocyte granules of affected animals are fragile than those of normal cells rupturing spontaneously and causing tissue damage such as cataracts. The leucocytes also have decreased chemotactic response and a reduced capacity for intracellular killing. The gene influences the increased susceptibility to tumours and to some viruses. Affected animals commonly succumb to recurrent pyogenic bacterial infections or to lymphoid tumours The canine granulopathy syndrome is an autosomal recessive condition observed in Irish setters. Affected dogs suffer from recurrent bacterial infections due to abnormal neutrophil function in killing phagocytosed bacteria. Mac 1 deficiency is known from humans and has been reported in a dog .Mac-1 is a glycoprotein found on the surface of macrophages,monocytes,granulocytes ,large granular lymphocytes which function as complement receptor for phagocytosis. In addition deficient cells can no longer bind to vascular endothelium and emigrate from the blood stream into infected tissue. The neutrophils cannot be mobilised to contain bacterial infections and recurrent infection are seen. In man this is an autosomal recessive condition. Gray Collie Syndrome: This defect of neutrophil function is seen in collie dogs with abnormal skin pigmentation ,eye lesions and cyclical neutropenia. Such animals suffer from infections during the periods of low neutrophil levels. INHERITED DEFICIENCIES IN THE IMMUNE SYSTEM The consequences of inherited immunological defects have provided us with great deal of information on the site of the lesion Horses: They are among the few domestic animals whose economic worth has permitted a though analysis of neonatal mortality so that primary immune deficiencies could be identified Combined immunodeficiency occurs in 2% of Arabian Foals they fail to either produce T or B cells and have few circulating lymphocytes. They maybe kept alive for a short period by maternal antibodies but they cannot produce their own and they die from infections within a few months. The gene is an autosomal recessive one ,meaning that it must be present in both parents an exact diagnosis becomes important as it affects the economic value of the parents Agammaglobunaemia has been described in foals they lacked identifiable B cells and immunoglobulins.Their lymphoid tissues had no primary follicles ,germinal centres and plasma cells. They survived for many months but suffered from recurrent bacterial infections. Selective IgM and IgG deficiencies are rare but reported transient hypergammaglobulinaemia is seen in some foals at two or three months of age as a result of delayed onset of immunoglobulin synthesis. In this period they will be susceptible to infections . A more common immunodeficiency affecting up to 10% of all foals is due to failure to adsorb sufficient colostrum. CATTLE Trait A-46 is carried by certain field black Friesian cattle and it is an autosomal recessive gene causing thymic and lymphocytic hypoplasia. There is depletion of lymphocytes in the gut associated lymphoid tissue and atrophy of the thymus ,spleen and lymph nodes. They have depressed cell mediated immunity but rather normal antibody levels. Zinc supplementation corrects the condition. Zinc is required for the thyroxine hormone thymulin and these animals probably have a decreased capacity to absorb it from the intestine. Selective IgG2 deficiency is a complete absence of this immunoglobulin class and has been reported in the 2% of Danish Red cattle, which levels them with an increased susceptibility to pneumonias and gangrenous mastitis .In addition up to 15% of these animals have subnormal IgG2 levels but do not seem to suffer any ill consequences from it . DOGS A family of dogs with inherited dwarfism and T cell deficiency has been reported ;their thymuses lacked a cortex and there was probably a deficiency in growth hormone as a result of a lesion in the hypothalamus. Combined immunodeficiency has been seen in one dog ,a puppy suffering from severe bacterial infections. Several litters from the same mating have been studied and it was a sex linked disorder with few lymphocytes unresponsive to the stimulation and undeveloped lymphoid organs. Selective IgM deficiency was seen in dogs with only a chronic nasal discharge . Selected IgA deficiency was found in animals unresponsive to vaccination against kennel cough and suffering from recurrent respiratory tract infections eczema and otitis.Their T and B lymphocytes were normal but there were no IgA secreting plasma cells and no IgA in the serum .The condition was not sex linked but both parents had low IgA. Transient hypergammaglobulinaemia has been seen in litter of puppies at the age of six months ;IgG level later rose to normal . Acrodermatitis is an inherited disease of Bull Terriors with growth retardation ,a skin lesion and severe immunodepression.This autosomal recessive condition results in no or very little thymus development and a T cell deficiency. CHICKENS Birds of the hypothyroid OS strain have a selective IgA deficiency. Birds of UCD 140 cell line have a selective IgG deficiency known as hereditary dysgammaglobulinaemia.Their Ig levels are normal until about 50 days after hatching ,then IgG drops and IgA and IgM rise ,specific suppressor cells are thought to be responsible .This may be mediated by vertically transmitted virus. SECONDARY DEFECTS- MALNUTRITION It has been long realized that famine and disease are closely associated and tend to assume that malnutrition leads to increased susceptibility to infection. Malnutrition can include not only deficiencies but excess or imbalance of specific nutrients .In general severe nutritional deficiencies reduce T cell function ,impairing cell mediated responses but sparing B cell function and humeral immunity . Starving results rapidly in thymus atrophy , a drop in T cell numbers produced and found in the secondary lymphoid tissues .Serum immunoglobulin may rise due to lack of suppressor T cells .Eventually starvation will result in depressed complement levels and decreased phagocyte function. Specific nutritional deficiencies have a range of effects. Regulatory T cell function can be decreased by lack of some B vitamins, deficiency of Vitamin A or of polyunsaturated fatty acids. Magnesium deficiency affects B cells . Cell mediated immune responses are depressed in deficiencies of Vitamin A ,B12 and Folic acid. Zinc is critical for normal immune functions as seen in trait A -46 . Vitamin E also affects immune functions ;deficient animals are suppressed while it is claimed that Vitamin E supplemented animals are immunostimulated and have increased resistance to disease. VIRUS INDUCED DISORDERS The effect of the viruses that affect the immune system can be on the primary or on the secondary organs. In poultry Infectious Bursal disease virus acts primarily on the lymphoid cells of the Bursa of Fabricuis to cause necrosis. There may also be damage to the spleen and thymus but these recover while the bursa atrophies. Birds affected soon after hatching will not develop B cell responses while those infected once enough B cells have been produced will suffer less. AIDS in man is also an important virus induced immunodeficiency disease and similar disease in animals occur in animals. There is Simian immunodeficiency virus very similar to the human virus and it occurs in Rhesus monkeys(Macaca mulata ) upon infection with the virus. Both humeral and cell mediated immunity are affected and the histopathology is similar to that of human AIDS. Half of the animals die of septicemia or diarrhea with wasting. Opportunistic infections are common and some monkeys develop tumours such as fibrosarcomasa.African green monkeys however which have been exposed to the virus in nature and seem to have developed resistance to it can be infected but apparently suffer no disease. Other similar viruses infect cats ,Feline Immunodeficiency Virus and cattle (BIV) CONT. Other viruses destroy secondary lymphoid organs e.g. canine distemper virus spreads first to lymphoid tissue where virus replication virus replication causes lymphocyte destruction ;shedding these tissues enables the virus to invade the epithelial tissues and the brain. Not only is there lymphopenia but macrophage function is depressed and suppressor cell activity increased. Secondary infections are then important in the clinical signs of infection. Depletion of lymphoid tissues is seen with Feline panleukopenia, Canine parvo virus Infection, feline leukemia and African Swine fever ,Feline Leukaemia, African Swine fever . Bovine virus diarrhea can cause lymphopenia ,destruction of T and B cells in secondary lymphoid tissues .Peyers patch destruction and depression of local B cell function permit local ulceration and bacterial invasion. Equine herpes virus 1 causes T cell lymphopenia and consequent depression of cell mediated immunity in foals. Parainfluenza 3 and Infectious bovine rhinotracheitis viruses can interfere with alveolar macrophage function opening the door to secondary infections with Pasteurella in stressed calves. In Visna a neurological disease of sheep ,cell mediated immunity is depressed but B cell responses are enhanced. Immunosuppression also generally accompanies infection with other organisms such as Demodex,Toxoplasmas,trypnosomes,Trichinella and some bacteria. Toxin induced immunosuppression and other secondary immunodeficiencies Many environmental toxins have a suppressive effect on the immune system. These include :polychlorinated biphenlys,iodine,lead,cadium,methyl mecury and DDT.Mycotoxins from mouldy grain such as T2 toxin from Fusarium or aflatoxins may also have the same effect Other secondary immunodeficiencies :Animals suffering from absolute protein loss with nephrotic syndrome ,heavy parasite loads or tumors will have decreased antibody production .Other stresses can also be immunosuppressive e.g crowding ,rapid weaning, prolonged transportation and trauma. Neoplasma of Lymphoid cells The immune system requires that antigen sensitive cells stimulated by the appropriate exposure to antigen respond in a controlled fashion by division and the system is complex because of the need for rigid control. If it fails uncontrolled lymphocyte proliferation may result. The neoplastic transformation may occur in both branches of the lymphoid cell system at any stage of their maturation process. The stage of the maturation of the tumour differentiation cell can also be determined by the surface markers it bears. Lymphoid tumors usually cause immunodepression ;T cell tumors interfere more with cell mediated immunity and B cell tumors more with the production of antibody by other B cells. Lymphomas The enzootic form of bovine lymphosarcoma is caused by infection with bovine leukemia virus which infects primarily B lymphocytes. In sheep lymphomas are divided evenly between B and T cells. B cell lymphoma is inherited in swine . Horses carrying lymphorsarcomas account for about 57% of canine malignancies and there is no evidence that these are virus induced. Lymphosarcomas account for 57% of canine malignancies and there is no evidence that these are virus induced. Cats probably have the highest incidences of lymphoid tumours of any animal. Most of these are due to feline leukemia virus an oncogenic retrovirus that can cause a number of different syndromes in cats including both proliferative and generative conditions. Of cats exposed to the virus 30% become neither infected nor immune and 40% immune and develop high titres of neutralizing antibodies and eliminate the virus.30% do not mount any effective immune response against the virus and maintain a persistent infection.Pesistantly infected cats will suffer from destruction of lymphocytes esp T cells and interfere with their function .Secondary infections are common and inhibition of bone marrow cells leads to anemia. There is a vaccine against this infection prepared from persistently infected cell lines in culture. Avian lymphoid tumors include Marek’s disease and Lymphoid leucosis. Marek’s is an infection of the T Lymphocytes leading to immunodepression of cell mediated response while the Avian lymphoid leucosis is a tumor of B lymphocytes resulting in depressed antibody responses . Polyclonal gammopathies They are observed in a wide variety of pathological conditions. The most resembling myeloma is Aleutian disease of mink in which there is marked plasmacytosis and polyclonal gammopathy. Systemic disease like systemic lupus erythematosus and rheumatoid arthritis as well as infections like tropical pancytopenia of dogs and African trypanosomiasis can also give polyclonal activation of B cells. Prolonged antigenic stimulation in chronic bacterial infections leads to hypergammaglobinaemia G. In Horses parasitized with Stronglylus vulgaris ,IgG(T) levels rise significantly .Virus infections like feline infectious peritonitis and African Swine fever can produce polyclonal gammopathy as do conditions in which extensive liver damages occur. THE END Myelomas They are a result of malignant transformation of single B cell ,producing a clone of immunoglobulin producing tumour cells with appearance of plasma cells. Arising from one cell myelomas produce one type of immunoglobulin in large quantities known as myeloma protein or M protein. They maybe of any type ,the frequency of each correlates with its relative amount in normal serum.Occasinally cells produce only light chains .Myelomas are reported to occur in people,mice,dogs,cats,horses,pigs, ferrets and rabbits. The most common clinical signs in dogs are bleeding as a result of hyper viscosity and an effective loss of clotting components which bind to the myeloma protein. The hyper -viscousity also causes other clinical signs due to the extra strain on the heart . Animals with myelomas are profoundly immunosuppressed because of its commitment of resources to the neoplastic cells and the negative feedback effects of high serum immunoglobulin levels. Pyogenic infections are the common cause of death.
