MICROBIAL DISEASES is the immobilized appears to be more important. Fluorescent and agglutinating treponemal antibodies also appear. Immobilfzin is operative in the treponemal antibody immobilization test (TPI). It appears late two to three months after the infection. It is formed slowly but can persist for life as an indicator of infection. Immobilizing reflects roughly the development of host resistance, although the evidence is equivocal that it has a direct protective role. As in most infections, the principal antibodies in syphilis belong either to immunoglobulins of the IgM class of high molecular weight or to those of the IgG class of lower. molecular weight.
The immunoglobulins are formed by different sets of antibody-producing cells, generally believed to be plasmocytes. In syphilis, these are characteristically present in early lesions and in lymph nodes. Antibody demonstrated by reagin tests may belong to both IgM and IgG immunoglobulins. IgM is produced early in the infection. IgG exclusively forms the immobilizing antibody when it appears later in the infection. In immunofluorescent tests both IgM and IgG antibodies react with T. Palli-dum. Whether or not a formation of antibody continues MICROBIAL DISEASES after treponemes have been eradicated by treatment as well as the circumstances under which such eradication’ may take place is not known (see Persistence of Treponemal Forms). IgG antibodies can pass the placenta, in contrast to IgM: The presence of IgM in the serum of newborns suggests the local formation of antibodies and, therefore, prenatal active infection.
MICROBIAL DISEASES also passes the blood-brain barrier when the meninges are inflamed. This explains why serodiagnostic tests that mainly identify IgG antibody are preferred in examining the cerebrospinal fluid for syphilis of the nervous system. Cell-mediated immunity manifests itself as delayed hypersensitivity demonstrable by the response to an intradermally injected antigen after12 to 48 hours. Interaction of antigen with specifically sensitized lymphocytes and cell structures is believed to be the underlying mechanism. Al-though knowledge is very limited, cell-mediated immunity apparently does not play a major role during the secondary eruptions of syphilis (Levene, 1969). However, delayed hypersensitivity is believed to be operative in gummatous lesions.
Moreover, the striking clinical and histopathologic similarity of late destructive skin and bone lesions in, venereal syphilis, bejel, and yaws suggests a common cell-mediated or another mechanism of the host response at this stage. Immunopathologic mechanisms involving tissue damage are very little known in syphilis. Multiple humoral antibodies circulate in all phases of the disease, the antigen is present, and anti-gen-antibody complexes may have pathogenic significance. Nevertheless, a direct cytotoxic effect on host cells has not bee established. Immunopathology mechanisms have been suggested in a few and rare manifestations engendered by syphilitic infection, notably biphasic paroxysmatic cold hemoglobinuria and membranous glomerular nephritis (syphilitic “nephrosis”).
MICROBIAL DISEASES also passes the blood-brain barrier when the meninges have inflamed The occurrence of cryoglobulins in syphilis has also been reported. In recent years there have been several impor-tant scientific developments in basic immunology concerning humoral and cellular immunity and immunopathology (WHO, 1964 and 1969), which may be expected to be applied also in syphilis and other treponematoses. At present the clinical and laboratory findings can only illustrate the capacity of immunocompetent cell systems to react to antigenic stimuli in the early phase of syphilis and to generate protection against further metastatic spread and superinfection with the pathogen.
The human host can contain the infection at the time of latency by establishing a notable equilibrium be-tween the pathogenic potential of treponemes and the immune forces, as evidenced by a relatively in-frequent disturbance of this equilibrium resulting in the occurrence of late injurious manifestations. Persistence of Treponemal Forms.
Adequate penicillin therapy of early syphilis will usually heal lesions and prevent late manifestations in most instances. Symptomatic manifestations after penicillin therapy of latent syphilis are rare. When occurring, they signal survival of pathogenic treponemes notwithstanding the immune forces and therapy. When not occurring, e.g., late latency, the persistently positive serologic tests have sometimes in the past been considered to be due to persistent antibodies produced by “immunologic memory” rather than to treponemes persisting in the host.
However, the persistence of treponemal forms (treponeme-like structures) in host tissues has been observed in recent years. Thus in some instances of treated late syphilis prepone uniforms were described in lymph nodes and Cerebro-spinal fluid (Collett et al., 1962, 1968), in aqueous humor of the eye (Smith and Israel), and in trea.: congenital syphilis, as well as in ophthalmic situations apparEnl_ unrelated to syphilis. Rarely trepone have also been found (lymph nodes) treatment of early syphilis (Yobs et a: 77-paternal, forms that have been demo:1, a lowing treatment of early and late only rarely been shown by animal infest to be viable (Turner).
Others may be“dormant” T. palladium, acting like an ant-lust for continued treponemal antibody -whereas others may be saprophytic or indigenous to the human host. In some instances, these situations may Persistence of abated forms of micro-organ in the face of normally effective drugs have been studied mycobacteria and corvne. and is a phenomenon apart from drug resistance (McDermott). There is no that penicillin-nase-producing, resistant pathogenic treponeme strains have developed Knowledge concerning immunologic tissue and humoral aspects of persistent treponemal forms is extremely limited, but regardless of the extent to which such forms are viable or modified pathogenic treponemes or related indigenous organisms their role maybe