Determinación de Parámetros de TI

INTRODUCTION.

The pathogenicity of mycobacteria is determined by the host's immune responses to either all or some of their antigens. Similarly, protection from mycobacterial disease relies on immune recognition of various antigens. Which antigens evoke such a protective response is open to debate, but it would appear that recognition of the common mycobacterial antigens facilitates protective immune responses. These common antigens are referred to as the group i antigens and they are shared by all species of mycobacteria (Stanford and Grange, 1974). At least some of these antigens are also shared by Nocardia, Listeria and Corynebacteria (Stanford et al, 1978; Grange, 1985). Evidence to support the role of common antigens in immunogenicity is shown in that BCG can be protective against both leprosy and tuberculosis in man (Brown et al, 1968). However, as Rook (1987) points out, immunisation with common antigens may provoke protective immune responses by promoting a rapid recognition of the species specific ones and this latter response may be the target for bactericidal effector mechanisms.

BCG is the vaccine strain of H.tuberculosis used in man. It is named after the workers Albert Calmette and Camille Gudrin. They produced the vaccine strain at Lille in France, where they subcultured the bovine tubercle bacilli repeatedly on medium containing ox bile every three weeks from 1906 until 1918. It has now been in use since 1921 and is widely used despite setbacks, like the one at Liibeck where a

batch of vaccine was accidently prepared from virulent ft.tuberculosis, resulting in the deaths of 72 children.

In man BCG is administered as a live vaccine. Live vaccines have long been considered most immunogenic, suggesting that the ability to survive in vivo is required for appropriate protective immune responses (Collins, 1971). As most invading potentially infective living organisms are overcome, this would appear to be the case.

The work of Lefford et al (1980) showed BCG to protect mice from ft.avium infection. As has been discussed in Chapter four, BCG has also been used with varying degrees of success to protect chickens from avian tuberculosis. Although duck immunology differs somewhat from that of chickens, BCG was chosen in this study as a potential vaccine to protect wildfowl from the disease.

It would appear that all species of mycobacteria are capable of inducing some level of mycobacterial immunity in mammals. Whereas the slow growers may produce more necrotic and less protective responses, some fast growers can suppress necrotic responses and induce bactericidal mechanisms (Stanford, 1983b). Certainly the role of environmental saprophytic mycobacteria in 'immunising' individuals prior to BCG vaccination has been described (Palmer and Long, 1966; Comstock and Webster, 1969).

The potential use of ft.vaccae as a vaccine against both leprosy and tuberculosis has been recognised where immune recognition is elicited by its high concentration of group i common antigens (Stanford et al, 1978; Swinburne et al, 1985; Stanford et al, 1989; Ghazi-Saidi et al, 1989). ft.vaccae, named in 1964 by Bdnicke and Juhasz, is a rapidly growing variably chromogenic environmental saprophyte. It bears an

antigenic similarity with M.leprae in that it possesses the antigens common to all mycobacteria but lacks groups ii and iii antigens associated with either the slow growing or rapid growing mycobacteria respectively (Stanford and Grange, 1974; Stanford et al, 1975b).

The synergistic effect of M.vaccae on the outcome of BCG vaccination has also been documented (Stanley et al, 1981; Bahr et al, 1986; Stanford et al, 1989). Indeed the immunogenicity of M.vaccae has warranted its use as an immunotherapeutic agent for leprosy and tuberculosis (Stanford et al, 1988a; Stanford et al, 1990; Bahr et al, 1990a; Bahr et al, 1990b). There have been no reported cases of M.vaccae infections in birds so this non-pathogenic saprophytic mycobacterium was chosen as a potential vaccine for the wildfowl in this study.

Whilst many vaccines are attenuated live vaccines e.g. BCG, poliomyelitis and smallpox, killed vaccines have been shown to produce specific protection (Weiss, 1959; Rook, 1980). As previously mentioned, the ability of a vaccine to survive in vivo may be linked to immunogenicity. However, the work of Youmans and Youmans (1969) showed that protection could be afforded in CF 1 mice when they were immunised with M.tuberculosis H37Ra; a strain that has limited ability to multiply in the host. Stanford et al (1990) used M.vaccae, killed by irradiation, as an immunotherapeutic agent in the treatment of pulmonary tuberculosis in humans and similarly this killed organism has been used in the prevention of bovine tubercle bacilli infection in badgers Meles meles (Stainsby, 1989). Sinha et al (1987) also found that killed M.vaccae was better at sensitising guinea pigs and mice for delayed-type hypersensitivity than the live bacilli. Killed M.vaccae was therefore tried as a potential vaccine in this study.

Mammalian immunity to mycobacteria is mediated by specific antigen responsive T-cells, which in turn release lymphokines which then activate non-specific killing mechanisms of macrophages. The inability as yet, to distinguish between T and B cells in wildfowl, and the difficulty in demonstrating the presence of cytokines, may suggest different protective mechanisms. However, it is plausible to assume that wildfowl immune responses are somewhat similar, if less sophisticated, to those found in mammals and chickens. Within wildfowl no work has as yet, been carried out to determine which epitopes are recognised by appropriate lymphocytes. It is hoped that if an optimal vaccine is to be produced, then all individuals will recognise the same, or a similar, set of antigenic determinants rather than different epitopes being recognised by different individuals.