抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Heme oxygenase is a cytoprotective enzyme with strong antioxidant and anti-apoptotic properties. Its cytoprotective role is mainly attributed to its enzymatic activity, which involves the degradation of heme to biliverdin with simultaneous release of carbon monoxide (CO). Recent studies uncovered a new cytoprotective role for heme oxygenase-1 (HO-1) by identifying a regulatory role on the complement control protein decay-accelerating factor. This is a key complement regulatory protein preventing dysregulation or overactivation of complement cascades that can cause kidney injury. Cell-specific targeting of HO-1 induction may, therefore, be a novel approach to attenuate complement-dependent forms of kidney disease.

https://www.mdpi.com/2076-3921/10/1/60/pdf

Regulation of Complement Activation by Heme Oxygenase-1 (HO-1) in Kidney Injury.

A composition comprising iron (ferric or ferrous ions) and at least one vaccine adjuvant. The vaccine adjuvant may be LPS (lipopolysaccharide), monophosphoryl lipid A, a toll-like receptor agonists, Poly IC, a pattern recognition receptor (PRR) ligand, a NOD-like (nucleotide oligomerization domain) receptor ligand, a lectin receptor, alum, MF95, saponin, Quil-A or QS21. The iron may be iron chloride, iron oxides, iron phosphate or iron hydroxide. The composition may be suitable for use in human or veterinary medicine. The composition can be used in combination with an antigen as part of a vaccine or immunomodulatory product. Also claimed is a composition comprising monophosphoryl lipid A and iron (II) chloride (FeCl2). The composition may be used in the preparation of a vaccine or immunomodulatory product. The ambient endotoxin levels in particular matter (PM) from various environments (traffic, green and industrial) was monitored and the ability of host cell immune recognition of LPS was assessed for each sample. Analysis of metals in the environmental samples was carried out. Higher levels of iron was present in traffic samples, where there was highest levels of TLR4 stimulation by LPS.

Iron-based vaccine adjuvants

Introduction Antibody formation in transfusion-dependent thalassemia is associated with chronic hemolysis and repeated transfusions. Hemolysis produces heme, which mediates B-cell differentiation into plasma cells and produces antibodies influenced by interleukin-21 (IL-21). Objective This study aimed to compare IL-21 levels, plasma cell percentage, and red blood cell antibodies between positive and negative allo-autoantibody thalassemia before and after hemin administration. Materials and Methods This research employed a quasi-experimental nonequivalent control group pre-test and post-test design performed from April to November 2021 at Soetomo Academic Hospital in Surabaya, Indonesia. Heparinized blood samples of 5 mL and 4 mL and EDTA blood samples of 3 mL were taken from positive (29 patients) and negative (28 patients) allo-autoantibody thalassemia participants. Hemin 20 µM was added to 5 mL of heparinized blood, incubated for 2 hours, prepared into peripheral blood mononuclear cells (PBMCs), and cultured for 3 days. The percentage of plasma cells (CD38+CD184+) of cultured and uncultured PBMCs was measured by BD FACSCalibur Flow Cytometer. IL-21 levels of plasma and supernatants were measured with Sandwich Enzyme-Linked Immunosorbent Assay by Elabscience. Red blood cell antibodies were detected by QWALYS 3 E.M. Technology. Autoantibodies were determined by the Grifols gel tube method. Results IL-21 levels were significantly different in the positive and negative allo-autoantibody thalassemia groups after hemin administration. The percentage of plasma cells in the positive allo-autoantibody group increased significantly after the administration of hemin. The percentage of plasma cells between thalassemia groups was not significantly different before the hemin administration but increased significantly after it. Red blood cell antibodies after the administration of hemin were significantly different in the negative allo-autoantibody group but not significantly different in the positive allo-autoantibody group. Conclusion Hemin administration affected IL-21 levels, plasma cell percentage, and antibody formation in positive and negative allo-auto antibody thalassemia.

https://www.dovepress.com/getfile.php?fileID=86602

Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody

Antibody formation in transfusion-dependent thalassemia is associated with chronic hemolysis and repeated transfusions. Hemolysis produces heme, which mediates B-cell differentiation into plasma cells and produces antibodies influenced by interleukin-21 (IL-21).This study aimed to compare IL-21 levels, plasma cell percentage, and red blood cell antibodies between positive and negative allo-autoantibody thalassemia before and after hemin administration.This research employed a quasi-experimental nonequivalent control group pre-test and post-test design performed from April to November 2021 at Soetomo Academic Hospital in Surabaya, Indonesia. Heparinized blood samples of 5 mL and 4 mL and EDTA blood samples of 3 mL were taken from positive (29 patients) and negative (28 patients) allo-autoantibody thalassemia participants. Hemin 20 µM was added to 5 mL of heparinized blood, incubated for 2 hours, prepared into peripheral blood mononuclear cells (PBMCs), and cultured for 3 days. The percentage of plasma cells (CD38+CD184+) of cultured and uncultured PBMCs was measured by BD FACSCalibur Flow Cytometer. IL-21 levels of plasma and supernatants were measured with Sandwich Enzyme-Linked Immunosorbent Assay by Elabscience. Red blood cell antibodies were detected by QWALYS 3 E.M. Technology. Autoantibodies were determined by the Grifols gel tube method.IL-21 levels were significantly different in the positive and negative allo-autoantibody thalassemia groups after hemin administration. The percentage of plasma cells in the positive allo-autoantibody group increased significantly after the administration of hemin. The percentage of plasma cells between thalassemia groups was not significantly different before the hemin administration but increased significantly after it. Red blood cell antibodies after the administration of hemin were significantly different in the negative allo-autoantibody group but not significantly different in the positive allo-autoantibody group.Hemin administration affected IL-21 levels, plasma cell percentage, and antibody formation in positive and negative allo-auto antibody thalassemia. 

Impact of heme on specific antibody production in mice: promotive, inhibitive or null outcome is determined by its concentration

Free heme is an endogenous danger signal to provoke innate immunity. Active innate immunity is a precondition of an effective adaptive immune response. However, heme catabolites, CO, biliverdin and bilirubin trigger immunosuppression. Furthermore, free heme induces the expression of heme oxygenase-1 to reinforce the production of CO, biliverdin and bilirubin. As such, free heme can drive two antagonistic mechanisms to affect adaptive immunity. What is the outcome of animal immune response to an antigen in the presence of free heme? The question remains to be explored. Here we report the immunization results by intraperitoneal injection of the formulations containing BSA and heme. When the used heme concentrations were about less than 1μM, the production of anti-BSA IgG and IgM was unaffected; when the used heme concentrations were about more than 1μM but less than 5μM, the production of anti-BSA IgG and IgM was enhanced; when the used heme concentrations were about more than 5μM, the production of anti-BSA IgG and IgM was suppressed. The results demonstrate that heme can modulate adaptive immunity (at least humoral immunity) by the mode of double concentration-thresholds. If heme concentrations are below the first threshold, there is no effect on adaptive immunity; if between the first and second thresholds, there is promotive effect; if over the second threshold, there is inhibitive effect. A hypothesis is also presented here to explain the mode.

/pdf/heme-concentration-dependently-modulates-the-production-of-3swo6jz593.pdf

Heme concentration-dependently modulates the production of specific antibodies in murine

Application of porphyrin pigment serving as immunologic adjuvant and vaccine

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Impact of heme on specific antibody production in mice: promotive, inhibitive or null outcome is determined by its concentration

Heme concentration-dependently modulates the production of specific antibodies in murine

Application of porphyrin pigment serving as immunologic adjuvant and vaccine