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--- home:diseases:hiv_and_aids [02.17.2019] – [AIDS patients on the Marshall Protocol] sallieq
+++ home:diseases:hiv_and_aids [02.19.2019] – [More research into CD38 and immune function] sallieq
@@ Line 9: / Line 9: @@
 One of the key mechanisms that HIV fosters immune dysfunction is through completely taking over the VDR and interfering with D-binding protein. As a result, en end-stage AIDS patients levels of 1,25-D approach zero.
+===== Vitamin D metabolism =====
+<mainarticle> [[home:pathogenesis:vitamind:metabolism|Metabolism of vitamin D and the Vitamin D Receptor]] </article>
+HIV uses the VDR to recognize its own LTR promoter region in order to transcribe its own genome, thus taking over the VDR.(({{pubmed>long:17556530}}))
+{{section>:home:pathogenesis:vitamind:metabolism#hivaids&noheader&firstseconly}}
+There is no evidence that supplemental vitamin D helps HIV or AIDS patients.
+<blockquote>Vitamin D supplementation is associated with reduced immune activation levels in HIV-1-infected patients on suppressive antiretroviral therapy. (({{pubmed>long:25493593}}))
+Of note, we observed that patients with low vitamin D levels displayed a reduced CD4/CD8 ratio (P ¼ 0.03, Table 1), which is usually a sign of increased immune activation in HIV-infected patients receiving effective ART [16]. We also analyzed CD38 expression on the surface of memory CD8+ T cells as a robust marker of immune activation. Although there was substantial interindividual variability, patients with severe vitamin D deficiency displayed modest but statistically significant higher levels of CD38 expression, compared with individuals with normal vitamin D (P ¼ 0.04, Table 1).
+We thus monitored CD4/CD8 ratio, as well as cellular activation (i.e. CD38 expression) and cell cycling (i.e. Ki67 expression) of memory CD8+ T cells in vitamin D supplemented individuals. These patients presented a higher CD4/CD8 ratio post-compared with pre-supplementation (Fig. 1b). Moreover, vitamin D increase upon supplementation was associated with a reduction in cellular immune activation levels (Fig. 1c). We also found that serum levels of vitamin D and the expression of the cellular immune activation markers were inversely correlated in this longitudinal setting (Fig. 1d). Vitamin D status appears therefore to impact on cellular immune activation levels.</blockquote>
+===== HIV allows opportunistic infections to proliferate =====
+<mainarticle> [[home:diseases:co-infections|Co-infections]] </article>
+Pathogens are able spread effectively in an immunocompromised environment. This means it's possible that AIDS patients pick up substantial pathogen loads. It is further possible that it is these Th1 pathogens, which kill patients. Viral co-infections (including Epstein-Barr virus, Human Herpes Virus 6, etc.) are found in all the diseases the Marshall Protocol treats, but the viruses are not believed to bethe proximate cause of disease.
 ===== CD38 =====
@@ Line 26: / Line 53: @@
 In vitro, macrophages of CD38 KO mice were less efficient in uptake of listeria but still able to kill the bacteria. Dendritic cells also displayed enhanced CD38 expression following infection. However, absence of CD38 did not impair the capacity of mice to prime CD8+ T cells against L. monocytogenes, and CD38 KO mice could efficiently control secondary listeria infection. In conclusion, our results demonstrate an essential role for CD38 in the innate immune response against L. monocytogenes.
-CD38 and immune function:
+===== At this time there are no AIDS patients on the Marshall Protocol =====
+The ARF has no clinical experience with AIDS patients yet. However, we do believe it due time that 'post-HIV wasting disease', and many of the other post-HIV disease are found to be Th1 in pathogenesis.
+We would argue that it would make sense for an AIDS patient to strengthen his or her immune response and that the only way to do this is to kill the Th1 pathogens which dysregulate it.
+A therapeutic probe will confirm the potential efficacy of this treatment.
+===== More research into CD38 and immune function =====
 In mice, CD38 was shown to be required for immunity against S. pneumoniae, as its absence rendered mice more susceptible to infection by this pathogen. This increased susceptibility was associated with a diminished neutrophil chemotaxis in response to peptides of bacterial origin. In humans, CD38 was proposed to have a protective role in HIV infection. However, the mechanisms by which this protection is achieved are, at this point, unclear. As CD38 appears to be important in viral infections and is able to modulate immune responses, namely at the level of Th1 cytokine secretion, it is conceivable that it could also play a role in immunity against intracellular pathogens, such as mycobacteria.
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 [[https://journals.lww.com/aidsonline/Fulltext/2000/06160/Role_of_CD38_in_HIV_1_infection__an_epiphenomenon.4.aspx|Signals delivered by CD38]]
-The role of CD38 as a signaling molecule is suggested by the observation that CD38 triggering is involved in T cell costimulation, B cell maturation, and induction of cytokine production by several cell types   (Table 1). These signals are not a prerogative of a single cell lineage but are shared by B, T, and myeloid cells. CD38 signaling inhibits the growth of immature B cells in the bone marrow microenvironment, suggesting that it represents a novel regulatory mechanism of B lymphopoiesis . In mature germinal center B cells, CD38 delivers rescue signals that protect cells from apoptosis and upregulate Bcl-2 (a molecule associated with antiapoptotic effects) in a manner similar to that observed with triggering of CD40, which is known to deliver costimulatory signals to the B cell . In purified T cells, CD38 signaling induces production of high levels of interleukin (IL) 6, granulocyte-macrophage colony-stimulating factor, interferon γ, and IL-10 and low levels of IL-4 and IL-2 (i.e., a cytokine profile shared by T helper 1 and 2 cells) .
+The role of CD38 as a signaling molecule is suggested by the observation that CD38 triggering is involved in T cell costimulation, B cell maturation, and induction of cytokine production by several cell types   (Table 1). These signals are not a prerogative of a single cell lineage but are shared by B, T, and myeloid cells. CD38 signaling inhibits the growth of immature B cells in the bone marrow microenvironment, suggesting that it represents a novel regulatory mechanism of B lymphopoiesis .
-...
-CD38 expression in HIV-1-infected individuals
+In mature germinal center B cells, CD38 delivers rescue signals that protect cells from apoptosis and upregulate Bcl-2 (a molecule associated with antiapoptotic effects) in a manner similar to that observed with triggering of CD40, which is known to deliver costimulatory signals to the B cell . In purified T cells, CD38 signaling induces production of high levels of interleukin (IL) 6, granulocyte-macrophage colony-stimulating factor, interferon γ, and IL-10 and low levels of IL-4 and IL-2 (i.e., a cytokine profile shared by T helper 1 and 2 cells) .
+CD38 expression in HIV-1-infected individuals:
 As in most viral infections, HIV-1 infection causes activation of B and T cells (both CD4 and CD8 cells), which consequently upregulates the surface expression of CD38 and other activation markers. CD38 upregulation can be detected on uninfected cells, indicating that this expression is not caused by direct infection.
@@ Line 67: / Line 110: @@
-===== Vitamin D metabolism =====
-<mainarticle> [[home:pathogenesis:vitamind:metabolism|Metabolism of vitamin D and the Vitamin D Receptor]] </article>
-HIV uses the VDR to recognize its own LTR promoter region in order to transcribe its own genome, thus taking over the VDR.(({{pubmed>long:17556530}}))
-{{section>:home:pathogenesis:vitamind:metabolism#hivaids&noheader&firstseconly}}
-There is no evidence that supplemental vitamin D helps HIV or AIDS patients.
-<blockquote>Vitamin D supplementation is associated with reduced immune activation levels in HIV-1-infected patients on suppressive antiretroviral therapy. (({{pubmed>long:25493593}}))
-Of note, we observed that patients with low vitamin D levels displayed a reduced CD4/CD8 ratio (P ¼ 0.03, Table 1), which is usually a sign of increased immune activation in HIV-infected patients receiving effective ART [16]. We also analyzed CD38 expression on the surface of memory CD8+ T cells as a robust marker of immune activation. Although there was substantial interindividual variability, patients with severe vitamin D deficiency displayed modest but statistically significant higher levels of CD38 expression, compared with individuals with normal vitamin D (P ¼ 0.04, Table 1).
-We thus monitored CD4/CD8 ratio, as well as cellular activation (i.e. CD38 expression) and cell cycling (i.e. Ki67 expression) of memory CD8+ T cells in vitamin D supplemented individuals. These patients presented a higher CD4/CD8 ratio post-compared with pre-supplementation (Fig. 1b). Moreover, vitamin D increase upon supplementation was associated with a reduction in cellular immune activation levels (Fig. 1c). We also found that serum levels of vitamin D and the expression of the cellular immune activation markers were inversely correlated in this longitudinal setting (Fig. 1d). Vitamin D status appears therefore to impact on cellular immune activation levels.</blockquote>
-===== HIV allows opportunistic infections to proliferate =====
-<mainarticle> [[home:diseases:co-infections|Co-infections]] </article>
-Pathogens are able spread effectively in an immunocompromised environment. This means it's possible that AIDS patients pick up substantial pathogen loads. It is further possible that it is these Th1 pathogens, which kill patients. Viral co-infections (including Epstein-Barr virus, Human Herpes Virus 6, etc.) are found in all the diseases the Marshall Protocol treats, but the viruses are not believed to bethe proximate cause of disease.
-===== AIDS patients on the Marshall Protocol =====
-The ARF has no clinical experience with AIDS patients yet. However, we do believe it due time that 'post-HIV wasting disease', and many of the other post-HIV disease are found to be Th1 in pathogenesis.
-We would argue that it would make sense for an AIDS patient to strengthen his or her immune response and that the only way to do this is to kill the Th1 pathogens which dysregulate it.
-A therapeutic probe will confirm the potential efficacy of this treatment.

home/diseases/hiv_and_aids.txt · Last modified: 09.14.2022 by 127.0.0.1