Granuloma Formation

Figure 6 Schematic depiction of events leading to granuloma formation and SP expression in sarcoidosis. host response (92). The occasionally observed SP 65-specific B- and T-cell responses in patients with sarcoidosis may be unrelated to the disease process (20,33). Alternatively, it may reflect slight changes in some individuals in the processing presentation of bacterial or host SP, whereby normal SP tolerance, perhaps maintained via the constitutive SP expression in alveolar macrophages (see...

References

Harley, B. Singh, and R.S. Gupta, Primary structure of a human mitochondrial protein homologous to bacterial and plant chaperonins and to hsp65 kD mycobacterial antigen, Mol. Cell. Biol. 9 2279 (1989). 2. R.T. Damian, Molecular mimicry antigen sharing by parasite and host and its consequences, Am. Naturalist 98 129 (1989). 3. M.B.A. Oldstone, Molecular mimicry and autoimmune disease, Cell 50 819 (1987). 4. J.B. Winfield and W.N. Jarour, Stress proteins,...

Discussion

We have investigated in four stages the possibility that hsps are involved in the pathogenesis of BD. In stage 1, we have established that the 65-kDa hsp is found in the four species of streptococci, S. pyogenes, S. sanguis, S. faecalis, and S. salivarius, which have been implicated in the etiology of BD (8,9). In stage 2, IgA and IgG classes of antibodies to the 65-kDa hsp were found in the sera of patients with BD by immunoblotting and radioassay (14). Four B-cell epitopes were detected in...

The Cellular Basis Of Adjuvant Arthritis First Evidence For Hsps As Antigens In Arthritis

Adjuvant arthritis (AA), the most extensively studied model of arthritis, is induced in several susceptible strains of rat, usually the Lewis rat. The arthri-togenic agent, heat-killed M. tuberculosis is suspended in incomplete Freund's adjuvant (IFA) and injected intradermally at the base of the tail (0.5-1.0 mg M. tuberculosis in 100 )il IFA). Ten to 14 days later, a severe polyarthritis develops in the distal joints of the limbs which resembles RA histologically. There is inflammation of the...

Bacterial Antigens Recognized By Cd4 T Cells From Patients With

ReA-Associated with Enteric Organisms T-cell clones specific for Yersinia and Salmonella (41-44) have been reported, and they can be divided into two broad groups those showing specificity for the infecting organism and those recognizing an antigen common to the infecting organism and other enteric bacteria. Those specific for hsps would be expected to be in the latter category, and indeed hsp 60-specific clones derived from Yersinia- or Salmonella-infected patients are able to respond to...

Modulation Of Arthritis Using Recombinant Mycobacterial

The localization of the arthritis-associated T-cell epitope to hsp 65 180-188 prompted attempts to induce AA by immunization with hsp 65 alone all of which failed. Instead, immunization with hsp 65 protected rats against subsequent attempts to induce A A with whole M. tuberculosis IF A (17,48). Subsequently, vaccination with hsp 65 was found to protect against other forms of arthritis (see Table 1). The protective activity is believed to be a function of the T-cell compartment. This is based on...

Helicobacter pyloriAssociated Chronic Gastritis

University Hospital, Uppsala, Sweden The recognition that Helicobacter pylori is a major cause of chronic inflammation of the human gastric antral mucosa has revolutionized our perception of gastroduodenal disease. Once acquired, the bacteria persists for decades in the mucous layer overlaying the gastric epithelium. A high priority is being placed on studies of this new bacterial pathogen that focus on understanding the mechanisms used by the organism to induce disease (1). The importance of...

Responses To Hsp 65 In Adjuvant Arthritis And Other Arthritis Models

As T-cell responses to hsp 65 180-188 were associated with arthritis, it was of interest to examine T-cell reactivity to hsp 65 during AA and other arthritis models (Table 1). Experiments in AA rats showed clear proliferative responses to hsp 65 in lymph node and splenocyte populations (33). Responses became significant around 10 days after M. tuberculosis IFA immunization and could be detected throughout the course of AA and into remission (i.e., up to day 50). There was no correlation between...

Hsp 60 Autoimmune Diseases

In addition to the nonspecific adjuvant and regulatory effects of natural hsp 60 autoimmunity, it is clear that certain autoimmune diseases can be caused by specific hsp 60 autoimmunity. The development of type I diabetes in the NOD mouse seems to fulfill the criteria for assigning such a causal relationship anti-hsp 60 T cells can transfer diabetes (12), active immunization to the p277 epitope of hsp 60 can induce diabetes, even in mice that are not prone to dia betes (15), and the p277...

Definition Of Reactive Arthritis

Reactive arthritis (ReA) is defined as an inflammatory arthritis which occurs in relation to specific infection at a site other than the joint (1,2). The occurrence of arthritis is strongly associated with the tissue antigen HLA-B27 (3), and the classic triggering infections which have been considered are those of the gastrointestinal and genitourinary tracts. In principle, infection at any other site could give rise to a reactive process in the joints, and there are reports of ReA in...

Tcell Reactivity To Selfhsp 60 As A Protective Mechanism In Arthritis

Vaccination with hsp 65 protects rats against AA (17,33,48) and arthritis models induced using streptococcal cell walls (35), collagen type II (48), and CP20-961 (48). Hsp 65 shares 48 amino acid identity with the homologous rat hsp 60, and there have been numerous reports of cross-reactive immunorecognition of mycobacterial hsp 65 and endogenous self-hsp 60 at the T-cell level (43, 55-57). Expression of mammalian hsp 60 is known to be upregulated as a physiological response to various...

Modulation Of Adjuvant Arthritis Using The Arthritisassociated 180188 Epitope And Peptide Analogues

Once the epitope recognized by the arthritogenic T-cell clone A2b had been identified, attempts were made to induce AA with synthetic peptides of the 180-188 sequence alone. These efforts failed. Instead, repeated intraperitoneal immunization of rats with the 180-188 peptide (100 ig, emulsified in IFA, 35, 10, and 5 days prior to M. tuberculosis immunization) was reported to protect against A A induction (39). T-cell reactivity to 180-188 and M. tuberculosis was evident and protection was...