Feline Immune System

The immune system of the cat possesses no unique structural elements and it is safe to assume that in its basic features it conforms to the pattern seen in other placental mammals. Nevertheless, the feline immune system does show some interesting and unique differences, described here.

Lymphoid tissues

Cats, like ruminants and pigs, possess a population of pulmonary intravascular macrophages. These cells are considerably more important than the Kupffer cells in removing particulates from the bloodstream. Thus 86% of injected streptococci were removed in the lungs as opposed to 14% in the livers of cats. The presence of this population of cells may explain why cats are more susceptible than other mammals to septic shock mediated by macrophage-derived tumor necrosis factor (TNF). The lymph nodes, spleen, tonsils, Peyer's patches, bone marrow and thymus are of comparable structure to that seen in other mammals. The thymus appears in fetal kittens at 28 days after conception.

Feline lymphocytes

About 40–45% of feline peripheral blood lymphocytes are identifiable as B cells. The ontogeny of B cell development is similar to that seen in other animals. Pre-B cells have been identified at 42 days after conception in the fetal kitten liver. Subsequently, they are found in the spleen and bone marrow. Adult levels of B cells are reached in the kitten by 12 weeks of age.

About 32–41% of peripheral lymphocytes are identifiable as T cells. Feline T cells also form E rosettes with red blood cells from guinea pig, mouse and rat. Guinea pig erythrocyte receptors appear to be the most satisfactory T cell markers and are found on both differentiated and undifferentiated T cells. Both T helper and T suppressor cell activities have been identified in the cat. About 20% of feline peripheral blood lymphocytes lack both T and B cell markers. These null cells, found both in immune and nonimmune animals, can destroy tumor cells or virus-infected cells. They are thus assumed to be natural killer (NK) cells. NK cell activity against herpes simplex-infected target cells has been demonstrated in cats.

The mitogenic responses to phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) are primarily a property of T cells, although feline lymphocytes respond relatively poorly to PHA and lipopolysaccharide in comparison to other mammals. Feline analogs of CD4 and CD8 have been identified and several monoclonal antibodies to undefined lymphocyte cell membrane antigens have been described. fCD molecules that have been identified include CD5, CD9, CD10, CD18 (LFA-β chain) and CD45R. Such evidence as is available suggests that these molecules are very similar to their equivalents in mice and humans.

Feline cytokines

The molecular weight of feline interleukin 1 (IL-1) ranges from 15 to 20 kDa. As in other species, it occurs in three different isoforms. IL-1 is released in large quantities from peritoneal macrophages in cats infected with the coronavirus of feline infectious peritonitis and may play a part in the development of the lesions in that disease. It is also released by lipopolysaccharide-treated alveolar macrophages.

Feline IL-2, released by the action of Con A on lymphocytes, has a molecular weight of 16 kDa. It supports the proliferation of Con-A-activated feline peripheral blood lymphocytes. IL-2 production is significantly decreased in cells from cats infected with feline leukemia virus (FeLV). IL-2-containing cell supernatants can stimulate the development of cytotoxic activity (LAK) in peripheral blood lymphocytes from normal cats. The target in this case was the feline lymphoblast cell line FL74, which continuously produces FeLV.

Feline IL-6, derived from Con-A-stimulated splenocytes, has a molecular weight of 30–40 kDa. Its physicochemical properties are somwhat different from the human and mouse analogs.

Interferons α, β and γ have been characterized and resemble those in other species. Interferon produced in vitro by Newcastle disease virus-stimulated Crandall feline kidney cells will make the cells resistant to invasion by FeLV and vesicular stomatitis virus (VSV).

Feline immunoglobulins

Cats probably possess all the immunoglobulin (Ig) isotypes seen in other species, although neither IgE nor IgD have been formally identified. Adult cat sera, colostral whey, tears and nasal secretions contain IgG, IgM and IgA. Electrophoretic analysis suggests that there are at least three IgG isotypes–G1, G2 and G3–and preliminary evidence suggests the existence of a fourth. A reaginic antibody obtained from a cat infected with the microfilariae of Brugia pahangi has been characterized and had properties compatible with IgE. Given the recent evidence that some mammals, pigs for example, have no δ chain genes and cannot make any IgD, it is not unlikely that cats may also lack this isotype. Lambda (λ) is the predominant light chain type in the cat, accounting for 80–90% of light chains. In common with other mammals with placentas impermeable to immunoglobulins, female cats are obliged to transfer antibodies to their offspring through colostrum. As a result, IgG, IgM and IgA are present in colostral whey in high concentrations (Table 1 ). As lactation proceeds and immunoglobulin levels drop, IgG remains the major immunoglobulin class in cat milk. IgM and IgA are the predominant immunoglobulins in cat bile. IgA is the predominant immunoglobulin in intestinal and respiratory mucus and in tears. As in other species, cat secretory IgA is a J chain-linked dimer. Immunoglobulins cannot be detected in the urine of adult cats but may be found in the urine of suckling kittens. This may reflect the excretion of small immunoglobulin fragments absorbed by the intestine from colostrum.

Table 1.

Serum immunoglobulins in the cat (mg ml⁻¹)

Source	IgG	IgM	IgA
Serum	7.2–19.7	0.8–1.9	0.7–2.8
Colostrum	44.0	0.6	3.4
Milk	1.5	0	0.2

While IgE has been functionally identified in the cat by methods such as passive cutaneous anaphylaxis, it has not been physicochemically characterized. Feline IgE is weakly reactive with human and bovine anti-IgE, as measured by the ability of feline atopic serum to block an ELISA test for bovine IgE.

Cell-mediated immunity

Cats infected with tuberculosis respond poorly to intradermally injected tuberculin and, as a result, the tuberculin test is unsatisfactory in this species. They do not respond with delayed hypersensitivity reactions to proteins such as bovine serum albumin. Nevertheless, cats can develop a good delayed skin response to dinitrochlorobenzene, to viral antigens and to BCG vaccine, although these delayed hypersensitivity reactions are not as intense or as consistent as in other species, such as the guinea pig. Despite this lack of skin reactivity, the granulomatous reactions to tuberculosis in the cat are indistinguishable from those seen in other mammals.

Feline major histocompatibility complex (MHC) molecules

The feline histocompatibility (FLA) system has been unusually difficult to study because the conventional approach of generating lymphocytotoxic antibodies by transfusion, multiple births or skin grafting does not work well. (Only about 25% of cats rejecting allografts produce lymphocytotoxic antibodies.) It may also be difficult to produce substantial mixed lymphocyte culture reactivity between some unrelated feline cells. Although it is possible that this may be due to a lack of FLA polymorphism, it is more likely to be due to a relatively low level of MHC expression on cat mononuclear cells. Thus genetic analysis indicates that the FLA system contains 10–20 class I gene loci, of which only two are expressed. Cats also possess five class II gene loci, of which only three are expressed. Feline class I antigens display 81–82% sequence identity with the human and 73–79% identity with the mouse homologs. Analysis of the histocompatibility antigens of other felids suggests that their MHC has a similar structure. Cat class I and class II MHC genes are located on chromosome B2.

The lack of MHC polymorphism in the cat may help to account for the ease of bone marrow transplantation in this species. The success rate of bone marrow allografts in cats previously treated with X-radiation or cyclosporine is high and graft-versus-host disease is not a major problem.

Feline complement

Cats possess all the major complement components at levels comparable to those in other species of mammal. Cat complement is, however, not as hemolytic as rabbit, dog or guinea pig complement when using rabbit antibodies and sheep erythrocytes as antigens.

Feline hypersensitivity

The lungs are the primary target organ for anaphylactic shock in the cat, and serotonin release from mast cells is probably the most important mediator of anaphylaxis. Flea-bite dermatitis is the most common allergic reaction in cat skin, whereas allergic rhinitis is rarely encountered. Food hypersensitivity has been described in the cat.

Feline blood groups and hemolytic disease

There are only two feline blood group antigens, called A and B. The prevalence of each of these two antigens varies according to geographical region. Thus, in the USA, 99% of cats are group A and only 1% are group B. In contrast, in Australia, 73% of cats have group A erythrocytes, while the rest are group B. Blood group B tends to be found in more exotic breeds of cats rather than in the common domestic shorthair. Very rare AB (0.4%) cats have been described. About 20% of group A cats possess natural anti-B with titers ranging from 16 to 512. Group B cats invariably contain anti-A at high titer. Agglutination and hemolysis can be used for feline blood typing.

Neonatal isoerythrolysis has been recognized in the cat. It may be induced artificially by immunization of queens with vaccines containing feline blood components. It has also been reported to occur spontaneously when sires of blood group A are bred repeatedly to females of blood type B. The antibodies are transferred from the mothers to the kittens through their colostrum. These then cause massive erythrocyte destruction and profound anemia.

Autoimmunity in the cat

Several spontaneous autoimmune diseases have been described in the cat, including hyperthyroidism, hemolytic anemia, thrombocytopenic purpura, pemphigus vulgaris, pemphigus foliaceous, systemic lupus erythematosus, myasthenia gravis and arthritis.

Feline hyperthyroidism is recognized as an important clinical entity in older cats. The presence of autoantibodies against thyroid microsomes has been demonstrated by immunofluorescence in about one-third of these cases, while lymphoid infiltration is found in another third. Autoimmune hemolytic anemia, while usually occurring spontaneously, may also develop secondary to FeLV infection. An autoimmune thrombocytopenia has also been reported to be associated with FeLV infection.

Immunodeficiencies in the cat

Primary immunodeficiencies are rarely recorded in the cat. Thymic hypoplasia and lymphopenia have been reported in a Siberian tiger, while ‘nude’ cats – thymic aplasia and hypotrichosis – have been recorded in a litter of kittens. These kittens had no thymus, and showed lymphocyte depletion in T cell areas of the lymph nodes, spleen and Peyers patches. Their most common congenital defect in immune function is the Chédiak–Higashi syndrome. This is classically seen in some Persian cats. Affected animals show defects in pigmentation with a characteristic pale coat color and red tapetal light reflection. Their leukocytes contain enlarged lysosomal granules but increased susceptibility to infections has not been observed. Of considerably greater importance as a cause of feline disease is failure of passive transfer of colostral immunoglobulins. This results in the development of severe and intractable bacterial infections in newborn kittens. The most important cause of secondary immunodeficiency in the cat is FeLV infection. Despite its name, this virus usually causes severe immunodeficiency in infected animals. Kittens born to FeLV-infected queens may show thymic atrophy and depressed allograft responses, while infected adult cats may develop a panleukopenia. As a result, they die due to fulminating bacterial infections. Many cats with chronic bacterial or fungal infections such as pneumonias, abscesses and stomatitis are found to be FeLV infected. Feline panleukopenia, due to a parvovirus, also causes an acquired immunodeficiency syndrome with severe leukopenia and lethal secondary infections.

Feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a widespread lentivirus that infects domestic and wild cats. Infection with this virus results in progressive depletion of CD4⁺ T lymphocytes. The resulting disease in many respects resembles human acquired immune deficiency syndrome (AIDS) and is an important model of the human disease. FIV replicates preferentially in feline T lymphoblastoid cells and causes a characteristic cytopathic effect in vitro. The virus receptor is probably not mediated through fCD4 (which is expressed on only a subset of T cells) but through fCD9. Infection is also associated with a marked, polyclonal expansion of B cells and of a subset of fCD8⁺ cells. As a result the CD4:CD8 ratio can be reduced to as low as 1.6, compared with a normal ratio of 3.3. Kittens artificially infected with FIV initially exhibit few clinical signs, most notably anemia, lymphopenia, neutropenia and lymphadenopathy. Eventually a terminal AIDS-like illness develops. Natural FIV infections result in death as a result of secondary infections of the oral cavity, upper respiratory tract, gastrointestinal tract, skin or urinary system. Neurologic signs have also been described. Epidemiologic analysis suggests that FIV is mainly transmitted between cats by biting.

Gammopathies

Plasmacytomas, although uncommon, are well recognized in the cat. The great majority of these tumors secrete immunoglobulins of the IgG isotype, but IgA- and IgM-secreting myelomas have also been described. In some cases these plasmacytomas may be associated with the deposition of immunoglobulin-associated amyloidosis.

See also:

Cd Antigens; Cytokines; Leukemia Viruses.