Post by Max on Jun 12, 2005 4:44:24 GMT -5
under construction
Vitamin A extensively linked to various immune-functions
The (Ro)accutane induced effects on immune function may be classified in two major categories:
1) The direct irreversible effects induced during heavy exposure which is likely to result in among other things deletion of N-glycosylation sites and thus a decreased funtion of the innate immune system
2) The secondary effects on immune function resulting from dyslipidemia, decreased NHR receptor expression and hormonal deficiencies
Vitamin A deficiency is associated with exacerbation of immunodeficiency, reduced or unbalanced levels of lymphocytes, and dysregulated production of antibodies. Animal experiments have shown that an adequate level of vitamin A is necessary to mount an efficient antibody response [1 and more]. Vitamin A status also plays an important role in reducing infectious disease morbidity and mortality by enhancing immunity, an effect that is partly mediated by macrophages [5].
The immune system can roughly be divided into two parts: the innate and adaptive. The innate immune system recognizes and initiates a response, and the adaptive part of the immune system executes the response. The principal immune effector cells of the innate immune system are monocytes/macrophages, dendritic cells (DC), natural killer cells (NK) and NK-T cells. These effector cells recognize pathogen associated molecular patterns, e.g., viral proteins, CpG DNA, or double-stranded viral RNA via a variety of pattern recognition receptors which include toll-like receptors (TLRs), NK cell receptors and mannose binding receptors. These cells then release a variety of proinflammatory cytokines and chemokines, which recruit cells to the site of infection and initiate infection and antiviral immune response. These soluble mediators also activate macrophages, NK cells and DC. Activation of the innate immune defense plays an instructive role (adjuvant effect) for the induction of virus specific, adaptive immune responses [6].
Recent research on the immune-defense
Recent research on the immune defense has brought us interestingly close to an understanding of how (Ro)accutane disrupts immune-function. Altered IgE responses have been observed post exposure in (Ro)accutane exposed animal subjects, with a lack of primary immune response, and interestingly an elevated secondary immune response [2]. The significantly altered IgE responses are suggested to be only a fraction of the alterations in immune-function induced by (Ro)accutane exposure. Many variables are yet to be measured, where significant variations are likely to be found. The result does not point out a lack of possibilty of synthesis of IgE, but rather a failure in the signaling system (a failure of recognition by the receptors which are part of mediating the innate immune response) that recognizes when antibodies are to be synthesized and released.
IgE receptor subtypes - suggested reduced affinity to LPS after heavy exposure of retinoic acid due to deletion of N-glycosylation sites
Toll-like receptor 4 (TLR4) belongs to the lipolysaccaride receptor (LPS). Mutants lacking two or more of the other N-glycosylation sites were deficient in interaction with LPS [Genecards database]. In Vero cells exposed to retinoic acid, when control and RA exposed samples were incubated with peptide N-glycosidase F (PNGase F), which removes N-glycosylated sugars, the molecular weights of the respective gB, gC and gD proteins produced were comparable in both the groups, indicating that RA did not alter the primary sequence of viral proteins during protein synthesis or increase viral protein proteolysis. RA treatment increased [3H]mannose incorporation into glycoproteins in HSV infected cells but did not change [3H]glucosamine incorporation. It is concluded that RA exposure does not reduce the synthesis of three major viral envelope glycoproteins but alters their N-glycosylation and postulate that the inhibitory effect of RA is related to its action on N-glycosylation [8].
Interaction between nuclear receptors and Toll-like receptors (TLRs)
Toll-like receptors (TLRs), play a role in recognizing when an immune response is to be initiated (innate system) [2, 3]. Possible interactions between TLRs and IgE hyperresponses have been suggested not to exist [4]. However, there is data indicating the opposite. The nuclear receptors are found to interact significantly with the TLRs [5]. The role of TLRs in human immune function is not yet fully understood.
Recent research leading to an understanding of (Ro)accutane induced alterations in immune-defense
The function of other receptor types and transcriptional activity important for the immune responses are likely to be significantly altered, due to effects from the exposure and the hormonal deficiencies discovered in exposed subjects. Also, the binding of lipids to these immune-response mediating receptors may possibly alterate their binding affinity, and the significantly observed alterations in lipid profiles observed in (Ro)accutane exposed subjects may in a near future provide an extensive explanation to the induced malfunctions regarding the immune-defense.
Vitamin A extensively linked to various immune-functions
The (Ro)accutane induced effects on immune function may be classified in two major categories:
1) The direct irreversible effects induced during heavy exposure which is likely to result in among other things deletion of N-glycosylation sites and thus a decreased funtion of the innate immune system
2) The secondary effects on immune function resulting from dyslipidemia, decreased NHR receptor expression and hormonal deficiencies
Vitamin A deficiency is associated with exacerbation of immunodeficiency, reduced or unbalanced levels of lymphocytes, and dysregulated production of antibodies. Animal experiments have shown that an adequate level of vitamin A is necessary to mount an efficient antibody response [1 and more]. Vitamin A status also plays an important role in reducing infectious disease morbidity and mortality by enhancing immunity, an effect that is partly mediated by macrophages [5].
The immune system can roughly be divided into two parts: the innate and adaptive. The innate immune system recognizes and initiates a response, and the adaptive part of the immune system executes the response. The principal immune effector cells of the innate immune system are monocytes/macrophages, dendritic cells (DC), natural killer cells (NK) and NK-T cells. These effector cells recognize pathogen associated molecular patterns, e.g., viral proteins, CpG DNA, or double-stranded viral RNA via a variety of pattern recognition receptors which include toll-like receptors (TLRs), NK cell receptors and mannose binding receptors. These cells then release a variety of proinflammatory cytokines and chemokines, which recruit cells to the site of infection and initiate infection and antiviral immune response. These soluble mediators also activate macrophages, NK cells and DC. Activation of the innate immune defense plays an instructive role (adjuvant effect) for the induction of virus specific, adaptive immune responses [6].
Recent research on the immune-defense
Recent research on the immune defense has brought us interestingly close to an understanding of how (Ro)accutane disrupts immune-function. Altered IgE responses have been observed post exposure in (Ro)accutane exposed animal subjects, with a lack of primary immune response, and interestingly an elevated secondary immune response [2]. The significantly altered IgE responses are suggested to be only a fraction of the alterations in immune-function induced by (Ro)accutane exposure. Many variables are yet to be measured, where significant variations are likely to be found. The result does not point out a lack of possibilty of synthesis of IgE, but rather a failure in the signaling system (a failure of recognition by the receptors which are part of mediating the innate immune response) that recognizes when antibodies are to be synthesized and released.
IgE receptor subtypes - suggested reduced affinity to LPS after heavy exposure of retinoic acid due to deletion of N-glycosylation sites
Toll-like receptor 4 (TLR4) belongs to the lipolysaccaride receptor (LPS). Mutants lacking two or more of the other N-glycosylation sites were deficient in interaction with LPS [Genecards database]. In Vero cells exposed to retinoic acid, when control and RA exposed samples were incubated with peptide N-glycosidase F (PNGase F), which removes N-glycosylated sugars, the molecular weights of the respective gB, gC and gD proteins produced were comparable in both the groups, indicating that RA did not alter the primary sequence of viral proteins during protein synthesis or increase viral protein proteolysis. RA treatment increased [3H]mannose incorporation into glycoproteins in HSV infected cells but did not change [3H]glucosamine incorporation. It is concluded that RA exposure does not reduce the synthesis of three major viral envelope glycoproteins but alters their N-glycosylation and postulate that the inhibitory effect of RA is related to its action on N-glycosylation [8].
Interaction between nuclear receptors and Toll-like receptors (TLRs)
Toll-like receptors (TLRs), play a role in recognizing when an immune response is to be initiated (innate system) [2, 3]. Possible interactions between TLRs and IgE hyperresponses have been suggested not to exist [4]. However, there is data indicating the opposite. The nuclear receptors are found to interact significantly with the TLRs [5]. The role of TLRs in human immune function is not yet fully understood.
Recent research leading to an understanding of (Ro)accutane induced alterations in immune-defense
The function of other receptor types and transcriptional activity important for the immune responses are likely to be significantly altered, due to effects from the exposure and the hormonal deficiencies discovered in exposed subjects. Also, the binding of lipids to these immune-response mediating receptors may possibly alterate their binding affinity, and the significantly observed alterations in lipid profiles observed in (Ro)accutane exposed subjects may in a near future provide an extensive explanation to the induced malfunctions regarding the immune-defense.