ACTUALMENTE EMBA-RAZADA
3.11 Teorías Relativas de la Pena
Certain conditions need to prevail for successful infection via the respiratory route to occur. Key research, which established theories of airborne infection for man and animals, was reviewed by Langmuir ( 1 96 1 ) and O'Grady and Riley ( 1 963). Both reviews drew attention to the critical particle size needed for successful infection to occur in lung. In man, during speaking, coughing and sneezing, droplets are expelled into the immediate vicinity and either settle or dry out to become droplet nuclei which
can
remain suspended in air for long periods of time. From experimental infection studies in rabbits, Wellset al.
(1948) were able to show that droplet nuclei were able to reach the alveolar surfaces of the lung and they finally concluded that a few bacteria in droplet nuclei could infect, while far larger numbers of organisms in coarse particles were strained out in the upper respiratory passages and swallowed. This conclusion was supported by Lurieet al.
( 1950) who estimated that about three bacilli must beinhaled to produce a pulmonary tubercle. Particle size is critical for airborne infection. Evidence reviewed by Sonkin ( 1951) showed that particles above 5 J.lffi in diameter are trapped in the nose and that those smaller
than
0.1 J.lffi stay suspended in the alveolar air and are ultimately again removed with the expired air. The size of tubercle bacilli is about 0.5 x2
J.lffi (Schlossberg 1988). Mucosal surfaces of the respiratory and gastrointestinal systems are difficult to infect with tubercle bacilli, and very large numbers are required to do so.If not caught in the bronchial tree, an inhaled tubercle bacillus reaches the alveoli and is ingested by an alveolar macrophage. In such rnacrophages the bacillus can be destroyed or inhibited or can multiply intracellularly. If the bacillus multiplies, the alveolar macrophage dies and its bacillary load is ingested by other alveolar rnacrophages emigrating from the pool of circulating monocytes. Both types of rnacrophages are attracted to the site by released bacilli, cellular debris, and a variety of chemotactic factors of host origin. In time, rnacrophages from the circulation become completely responsible for the fate of the early lesion. The alveolar rnacrophages rarely participate in the established lesion, because they remain on the periphery rather far from the bacilli, which are almost always located more centrally (Dannenberg 1989).
The tubercle bacillus is an obligate intracellular parasite of mesenchymal cells, from which it
can penetrate into perivascular connective tissue or reticular tissue. It
has no effect on skin and mucous membrane as long as the epithelial layer is intact. However, when taken up by neutrophils or rnacrophages itcan
pass through these membranes into the corium or subepithelial tissue and become active. In cattle, a visible primary focus develops within eight days and calcification within three weeks (Jubb and Kennedy 1970). The exudative inflammatory focus is soon demarcated by granulation tissue consisting of epitheloid cells and Langhans giant cells which are againcompletely surrounded by lymphocytes. Tubercle bacilli which have multiplied in the focus are carried by monocytes to the regional lymph nodes at a very early stage, where they evoke a similar reaction. Usually, processes of the same kind occur simultaneously in the organ of entry (e.g. lungs) and in related lymph nodes. This "primary complex" is most frequently located in the respiratory tract (90 to 95% of infected cattle) or the digestive tract, or less often in the skin, genital tract and
mammary gland. In congenital tuberculosis of the calf, it is presumed that infection occurs in the majority of cases by the umbilical cord and thereby the foetal circulation to the liver and portal lymph nodes where lesions develop.
The characteristic lymph node lesion is well known, and consists of enlargement of the gland with diffuse cellular infiltration and early caseation. It is not a nodular type of lesion. A characteristic post mortem finding is early caseation of portal, caudal mediastinal, and bronchial lymph nodes with isolated nodules in lung, liver, spleen, etc (Stamp and Willson 1 946).
The fate of this focus or complex varies considerably between· species and is influenced by the condition of the animal. It may resolve into the organised connective tissue form, or become encapsulated by fibrous tissue, remaining unchanged for months or years so that the animal continues to harbour live bacilli.
M bovis
infection in cattle is considered to be always progressive, whileM tuberculosis
infection in cattle can be contained and eliminated (Cohrs 1 967).Pathology
Lesions develop most commonly in the lungs, pleura, and local lymphatic nodes (Henning 1 956; K.leeberg 1 966; Cohrs 1 967; Blood and Radostits 1 989) . The lesions may be single or multiple and may occur within a lobe, or in subpleural locations in the dorsa-caudal portions of the diaphragmatic lobes. There are almost always lesions in the regional lymph nodes, but they may be absent in some cases of chronic tuberculous pneumorua.
Lesions present a characteristic histological appearance. There may be more than one focus within a lung lobule (giving a clover-leaf appearance) and more than one lobule may be involved. The appearance of these lesions varies with their age and rate of progress. The earliest lesions are not encapsulated, but are small and surrounded by condensed alveolar tissue. The infection frequently extends from superficial pulmonary lesions to the pleura, resulting in the formation of characteristic, soft, greyish - red outgrowths of various shapes and sizes. Cauliflower-like masses are formed by the confluence of these outgrowths, producing the condition known as "pearl disease". Later there are extensive thickening of the serous membranes and even
adhesions. Chronic tuberculous pericarditis may occur in the same manner. Tuberculosis of the heart is relatively uncommon in cattle; it is characterised by calcification (McKay 1 95 9).
Tuberculosis of the alimentary tract in adult cattle, as in man, is usually an extension of pulmonary infection. In a consecutive series of 100 cattle with tuberculosis, McKay ( 1 95 9) found 2 1 cases of tuberculous enteritis, of which 12 had acute generalised infection and two chronic generalised infection. Calves which were suckled by cows with tuberculous mastitis all had extensive infection of the mesenteric lymph nodes. When present, tubercles were yellow or irregular ulcers extending deeply into the intestinal wall.
McKay ( 1 959) observed a 35% prevalence of tuberculosis of the liver among the cattle he examined. Lesions occurred on the liver capsule whenever diffuse peritonitis or miliary tuberculosis was present. Occasionally, tuberculosis of either the liver or portal lymph nodes was found without abdominal lesions other than in the mesenteric lymph nodes. Tuberculosis of the spleen is rare, and is usually a consequence of congenital infection (Jubb and Kennedy 1970).
Immunity
Viable lyrnphocytes are capable of conferring protection against tubercle bacilli (Mackaness 1 969) and other facultative intracellular parasites such as certain protozoa (Frenkel 1 967) and viruses, provided that humoral antibodies are absent.
Domestic animals develop resistance and delayed hypersensitivity after natural or artificial exposure to tubercle bacilli, but it is not known how this influences the course of the disease, because neither the degree of resistance nor the hypersensitivity has
been subjected to reliable evaluation. Tuberculosis in animals, although not always continuously progressive, is probably rarely completely overcome.
The subject of acquired immunity in tuberculosis is still highly controversial despite the use of BCG vaccine. It is known that animals infected with tubercle bacilli become more resistant to reinfection, and that animals vaccinated with viable cells of attenuated mycobacterial strains, especially when young, acquire a resistance to infection later in life (Fenner 1 95 1 ; Rich 1 95 1 ; Rosenthal 1 957; Youmans 1 957).
Actively acquired resistance is characterised by an increased capacity of macrophages to kill tubercle bacilli, and also by a greater ability of the cells to inhibit intracellular multiplication of the parasite. Such intracellular bacteriostasis is the major manifestation of acquired immunity to tuberculosis. Tubercle bacilli may remain viable in the body for years without multiplying (Youmans and Youmans, 1 969). The mechanism whereby phagocytic cells of immunised animals are able to exert such control over intracellular tubercle bacilli remains largely unknown.
The primary bacteriostatic function of the immune response in tuberculosis differs from the mechanism mediated by antibody against a bacterial cell component. The fact that immunity to tuberculosis cannot be passively transferred by antibody from tuberculous or vaccinated animals supports the minor role of antibody in the immune process (Raffle 1955). However, acquired immunity to certain other facultative intracellular parasites, such as
Salmonella typhimurium
and S.enteritidis,
may involve a cytophilic antibody (Rowleyet al.
1 964; Mitsuhashiet al.
1 965; Kurashigeet al.
1 967). A similar agent might be responsible for the increase in resistance following the transfer of macrophages from immunised animals to normal animals. This success in passively transferring immunity to tuberculosis by macrophages suggests that such cells may be solely responsible (Sever 1 960; Suter 1 96 1 ; Millman 1 96 1 ; Mackaness 1969). Large numbers of lysosomes accumulate in the cytoplasm of such cells and they are more actively phagocytic (Berthrong 1970). Thus, acquired immunity to tuberculosis might result merely from more efficient functioning of these "activated macrophages" . Nonactivated macrophages apparently cannot kill these facultative intracellular organisms. Activated macrophages are rich in lysosomal enzymes and produce relatively large amounts of reactive oxygen intermediates and other rnicrobiocidins (Dannenberg 1989).Clinical signs
Clinical signs depend upon the organs involved and the extent of the lesions. Pulmonary infection gives rise to a dry cough which increases in frequency as the disease develops and is accompanied by loss of weight. Infection of the udder sometimes produces no definite clinical signs although the tubercular mastitis may be extensive. Similarly, tuberculosis of other organs may not give rise to diagnostically reliable signs (Buxton and Fraser 1977).
Because of the universal dependence on the tuberculin test for diagnosis and the policy of slaughtering all positive reactors whether they are open cases or not, few clinico pathological tests are now carried out. Sputum or discharges may be examined by inoculation into guinea pigs but improved cultural techniques have now generally superseded animal injection tests and made them unnecessary.
The basis of all tuberculosis eradication schemes is the tuberculin test and a knowledge of the various tests used; their deficiencies and advantages is essential. Clinical examination is still of value particularly in seeking out the occasional advanced cases which do not give a positive reaction to a tuberculin test. Much attention is being directed to devising tests to detect such animals but the eye of an observant clinician