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M Arala-Chaves

Publications and source records attributed to M Arala-Chaves.

9 recordsLinked to original sources
PubMed1992

V-region-related and -unrelated immunosuppression accompanying infections.

This paper discusses current evidence for the relationship between polyclonal lymphocyte activation, specific immunosuppression with decreased resistance, and autoimmune pathology, that are all often found associated with infections by a variety of virus, bacteria and parasites. The central question of class determination of immune effector activities is considered in the context of the cellular targets for nonspecific mitogenic activities associated with infection. A model is presented to integrate these findings: mitogens produced by the microorganism or the infected cells are preferentially active on CD5 B cells; the resulting over-production of IL-10 will tend to bias all immune activities into a Th2-mode of effector functions, with high titers of polyclonal antibodies and little or no production of gamma IFN and other "inflammatory" lymphokines that often mediate resistance. In turn, these conditions allow for parasite persistence and the corresponding long-term disregulation of self-directed immune reactivities, resulting in autoimmunity in the chronic phase. This model would predict that selective immunization with the mitogenic principles involved in deregulation, could stand better chances than strategies of vaccination based on immunopotentiation against other, functionally neutral antigenic epitopes. It is argued, however, that the complexity of immune responses and their regulation, together with our ignorance on the genetic controls of class-determination, offer poor prospects for a scientifically-based, rational development of vaccines in the near future. It is suggested that empirically-based and technologically developed vaccines might succeed, while basic scientific approaches are reinforced and given the time to provide a better understanding of those processes.

Animals↗
PubMed1991

Susceptibility to infection with Mycobacterium avium is paradoxically correlated with increased synthesis of specific anti-bacterial antibodies.

A comparison was made between the levels of splenic and intestinal (Peyer's patches and thin intestinal epithelium) Ig production of C57BL/6 germ free and conventional C57BL/6, BALB/c, DBA/2 and C3H/He mice and the susceptibility to Mycobacterium avium infection, evaluated by the number of bacterial colony-forming units (CFU) found in the liver and in the spleen of the animals. Mice received an i.p. injection of either 5 x 10(6), 10(7) or 10(8) bacteria, or were given the larger inoculum intragastrically. Alternatively, mice were treated with an i.p. injection of M. avium bacterial sonicates. A marked increase of splenic IgA production, quantitatively associated with the size of the inoculum and thus with the degree of infection, was observed in susceptible compared to relatively resistant mice. This increase was observed at an earlier time following infection with the larger rather than with the smaller inocula. Consistent significant increases in splenic production of IgG isotypes were only observed in the susceptible mice after infection with the intermediate and larger inocula whereas a comparative increase of IgM was only clearly observed after infection with the larger inoculum. Intestinal Ig production remained unchanged, however, in both susceptible and relatively resistant mice after i.p. infection. Also, all mice were resistant to M. avium infection by the intragastric route and with this site of entry splenic and intestinal Ig production remained unchanged. Susceptibility to M. avium infection was also quantitatively associated with increased levels of circulating specific anti-bacterial antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Recombinational biases in the rearranged C1-inhibitor genes of hereditary angioedema patients.

DNA structural changes responsible for hereditary angioedema were sought in the C1-inhibitor gene, which contains unusually dense clusters of Alu repeats in various orientations. Among patients belonging to 45 unrelated families, eight partial C1-inhibitor gene deletions and a partial duplication were found. Four deletions had one of the boundaries within the gene and the other in extragenic regions--in three cases 5' of the gene and in one case 3' of the gene. The boundaries of the partial duplication and of the remaining four deletions mapped instead within a few kilobases of exon 4. The same element--Alu 1--the first of three tandem Alu repeats preceding exon 4, contained one of the breakpoints of each of these five rearrangements. Moreover, these recombination breakpoints spread over the entire length of Alu 1, in contrast with the tight clustering observed near the 5' end of Alu sequences rearranged in other human genes. Thus, two uncommon recombinational biases are observed in the Alu rearrangements of hereditary angioedema patients; one promotes the occurrence of intragenic breakpoints in a single Alu repeat, and the other allows the breaks to be distributed over the entire Alu structure rather than within the hot spot of the left Alu monomer. A region of potential Z-DNA structure, located 1.7 kb upstream of Alu 1, may contribute to both peculiarities.

Angioedema↗
PubMed1990

Low T- and B-cell reactivity is an apparently paradoxical request for murine immunoprotection against Streptococcus mutans. Murine protection can be achieved by immunization against a B-cell mitogen produced by these bacteria.

C57BL/6 mice thymectomized as adults or depleted of CD4+ cells were much less susceptible than intact conventional mice to the B-cell mitogenic and specific immunosuppressive effects of a protein designated as F5'EP-Sm secreted by Streptococcus mutans. These mice were also considerably more resistant to infection by these bacteria than intact individuals. The immunosuppressor effect of F5'EP-Sm was also abrogated, however, in conventional intact mice when immunized intraperitoneally against heat-inactivated F5'EP-Sm. On the other hand, resistance to bacterial infection could be achieved by immunization of conventional intact C57BL/6 mice against heat-inactivated F5'EP-Sm by intraperitoneal or intradermal routes even when the animals were infected 3 months after immunization and even when the immunization procedure did not include Freund's adjuvant, which was the case with the intradermal route. Interestingly, the protection against the bacterial infection was accompanied by only a minor increase in specific serum antibodies against F5'EP-Sm. These results are discussed in the context of adequate strategies for immunoprotection against Streptococcus mutans and other micro-organisms which are secretors of substances that share both B-cell mitogenic and immunosuppressive properties and which are thus able to suppress the immune response by overstimulation of the immune system of the host.

Animals↗
PubMed1990

Erythema multiforme associated with autoreactivity to 17 alpha-hydroxyprogesterone.

We report a case of a 23-year-old woman who was afflicted with disseminated skin erythema multiforme-like eruptions that started at the menarche, relapsed at the premenstrual periods, dramatically spread during two pregnancies and cleared after abortion; the skin lesions responded dramatically to thalidomide treatment. A high-affinity binding factor to 17 alpha-hydroxyprogesterone (17-OHP) was found in the serum of this patient. Her lymphocytes did not proliferate in vitro after exposure to exogenous 17-OHP but showed significant chromatin activation. There was a decreased expression of HLA antigens at the surface of the patient's blood lymphocytes. This is a unique well-documented case of erythema multiforme most possibly due to autoreactivity to 17-OHP; the precise mechanism(s) of this autoreactivity has not been established.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Correlation between specific immunosuppression and polyclonal B cell activation induced by a protein secreted by Streptococcus mutans.

The relationship between polyclonal B cell activation and immunosuppressor effects induced by F5'EP-Sm, a non-cytotoxic protein secreted by Streptococcus mutans, was studied in C57BL/6 mice. Mice treated with F5'EP-Sm exhibited a considerable increase in splenic nonspecific Ig plaque-forming cells (PFC) compared with untreated mice. The isotypic pattern of non-specific PFC responses favours IgG2a approximately equal to IgG2b greater than IgG3 greater than IgG1 approximately equal to IgM, when taken as a ratio between treated and untreated animals. When F5'EP-Sm was administered 2 days before immunization with sheep red blood cells (SRBC), the non-specific PFC production was accompanied by an ephemeral increase in specific PFC against SRBC 1 day after immunization, which was quickly replaced by a strong immunosuppression. In contrast, when F5'EP-Sm was injected after priming, there was little or no demonstrable suppression of specific PFC, and the increase of non-specific PFC was much less evident. The kinetic curves representing increase or decrease in relation to controls of specific and non-specific PFC are almost mirror images in each of the isotypes. The in vivo suppressor effect was abrogated in thymectomized mice, although the involvement of the T cell compartment is probably secondary to the B cell mitogen effect, since T-depleted spleen cells proliferate and synthesize non-specific Ig when stimulated in vitro with F5'EP-Sm.

Animals↗
PubMed1976

Chronic mucocutaneous candidiasis treated with transfer factor.

A patient with chronic mucocutaneous candidiasis resistant to all tropical therapy has had extensive tests of immunological function carried out before and after administration of transfer factor. Immunological testing has been both specific, directed at responses to candida antigen, and non-specific, directed at general assessment of the patient's immune status. Transfer factor has been administered on three occasions in the past year. After each treatment temporary clinical improvement accompanied by changes in both specific and non-specific immunological responses have been observed. The possible mode of action of transfer factor in this case is discussed.

Adult↗