Cells Of Immune System Research Articles

PERBANDINGAN CD4 HIV –TB PARU SEBELUM DAN SESUDAH ARV DAN OAT

Background: Human Immunodeficiency Virus (HIV) is a viral infectious disease that attacks the immune system or white blood cells (lymphocytes). HIV, which belongs to the Retroviridae family, is lymphatic, which can damage the specific immune system, namely T-helper lymphocytes or Cluster of Differentiation 4 (CD4). The CD4 count is normal when it is 500–1400 cells/mm3, which is usually the determinant of whether a patient is infected with HIV or not. Objective: This study aims to assess the comparison of CD4 counts in HIV-TB patients before and after ARV and OAT treatment at Dr. Pirngadi Medan City. Methods: Observational analysis research with a cross-sectional design was conducted at RSUD Dr. Pirngadi Medan City in September 2022. The sample for this study was 20 patient records from the medical records of RSUD Dr. Pirngadi, Medan City. The data were analyzed using an unpaired t-test. Results: The results of the study showed that the most HIV-TB pulmonary patients at RSUD Dr. Pirngadi Medan City were aged 36-45 years (50.0%). The majority of male patients (90.0%) and the domicile of most patients in Medan City are in the Medan Tembung sub-district (15.0%). The results of the unpaired t-test obtained a p-value of 0.022, meaning that there was a significant difference between the CD4 count before and after ARV and OAT treatment in HIV-TB patients at RSUD Dr. Pirngadi Medan City. Conclusion: There were significant differences in CD4 counts before and after ARV and OAT treatment in HIV patients with pulmonary TB co-infection at Dr. Pirngadi, Medan City. Keywords: HIV, HIV-TB pulmonary, CD4

Specific Features of Juvenile Idiopathic Arthritis Patients' Cytokine Profile.

Juvenile idiopathic arthritis (JIA) is a systemic autoimmune disease that affects the joints, leading to disability. Cytokines and signaling molecules expressed by the immune system cells play a key role in JIA pathogenesis. Understanding how their content changes during pathology development can open up new opportunities for its diagnosis and treatment. The blood plasma of 30 patients with JIA (14 males and 16 females with a mean age of 12.2 ± 4.1) and 20 relatively healthy individuals (10 males and 10 females with a mean age of 10.20 ± 5.85) was analyzed to determine the levels of cytokines using the MILLIPLEX® kit. An increase in interleukins (IL)-1α, 1β, 2, 4, 5, 6, 7, 8, 9, 10, 13, 15, 17F, 22, and 27 and a decrease in IL-3 levels have been shown in patients with JIA. Levels of cytokines, which are important for B-cell activation and proliferation, are increased, while levels of T-cell activating factors remained similar to the control group. Based on our results, it can be assumed that the use of combination therapy aimed at inhibiting both nonspecific interleukins and cytokines that activate B-cells will be more effective for the treatment of JIA.

Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.

Leishmaniasis is a parasitic disease caused by the Leishmania protozoan affecting millions of people worldwide, especially in tropical and subtropical regions. The immune response involves the activation of various cells to eliminate the infection. Understanding the complex interplay between Leishmania and the host immune system is crucial for developing effective treatments against this disease. This study collected extensive transcriptomic data from macrophages, dendritic, and NK cells exposed to Leishmania spp. Our objective was to determine the Leishmania-responsive genes in immune system cells by applying meta-analysis and feature selection algorithms, followed by co-expression analysis. As a result of meta-analysis, we discovered 703 differentially expressed genes (DEGs), primarily associated with the immune system and cellular metabolic processes. In addition, we have substantiated the significance of transcription factor families, such as bZIP and C2H2 ZF, in response to Leishmania infection. Furthermore, the feature selection techniques revealed the potential of two genes, namely G0S2 and CXCL8, as biomarkers and therapeutic targets for Leishmania infection. Lastly, our co-expression analysis has unveiled seven hub genes, including PFKFB3, DIAPH1, BSG, BIRC3, GOT2, EIF3H, and ATF3, chiefly related to signaling pathways. These findings provide valuable insights into the molecular mechanisms underlying the response of immune system cells to Leishmania infection and offer novel potential targets for the therapeutic goals.

TYROBP as a molecular target in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm.

Cholangiocarcinoma occurs when there is a malignant tumor in the bile duct system. Renal cancer originates from renal tubular epithelial cells. Abdominal aortic aneurysm (AAA) is a permanently localized dilation caused by a lesion or injury to abdominal aortic wall. However, the relationship between TYROBP and cholangiocarcinoma, renal cancer and AAA remains unclear. The profiles of cholangiocarcinoma dataset GSE107943, renal cell carcinoma dataset GSE213324, and AAA dataset GSE47472 were downloaded from the GEO database using the platforms GPL18573, GPL24676, and GPL10558. DEGs were screened, WGCNA was performed as well as construction and analysis of PPI network. Functional enrichment analysis, GSEA, heat map of gene expression, survival analysis, and immune infiltration analysis were performed. The most relevant diseases to core genes were found by CTD. The GSE107943 dataset identified 3383 DEGs for cholangiocarcinoma, GSE47472 identified 95 DEGs for abdominal aortic aneurysm, and GSE213324 identified 10245 DEGs for renal cell carcinoma. For the GSE107943 cholangiocarcinoma dataset, GO analysis revealed enrichment in immune response, cell adhesion, extracellular space, and oxidoreductase activity. KEGG analysis indicated enrichment in metabolic pathways, the PI3K-Akt signaling pathway, cell apoptosis, the cell cycle, and the NF-kappa B signaling pathway. In the GSE47472 AAA dataset, GO analysis showed enrichment in neuroblast differentiation, cardiac muscle myofilament complex, and alkaline binding. KEGG analysis indicated enrichment in mRNA surveillance pathway and purine metabolism. In the GSE213324 renal cell carcinoma dataset, GO analysis indicated enrichment in immune system processes, cell adhesion, and membrane parts. KEGG analysis showed enrichment in cytokine-cytokine receptor interaction, calcium signaling pathway, and hematopoietic cell lineage. Furthermore, for cholangiocarcinoma (GSE107943), enriched terms associated with DEGs were in metabolic pathways, cell apoptosis, and the cell cycle. For AAA (GSE47472), enriched terms were in alkaline binding and cellular redox homeostasis. For renal cell carcinoma (GSE213324), enriched terms were in biological adhesion, regulation of immune system processes, and cell surface. Common core genes (ADH6, AGXT, CYP3A43, TYROBP) were identified for cholangiocarcinoma, renal cell carcinoma, and AAA. ADH6 and TYROBP were associated with cholangiocarcinoma, AAA, renal tumors, kidney diseases, atherosclerosis, and inflammation. TYROBP is abnormally expressed in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm.

Phytochemistry Profile, Antimicrobial and Antitumor Potential of the Methanolic Extract of Tabernaemontana catharinensis A DC and Eragrostis plana NEES.

Natural compounds that have the potential to act as antimicrobials and antitumors are a constant search in the field of pharmacotherapy. Eragrostis plana NEES (Poaceae) is a grass with high allelopathic potential. Allelopathy is associated with compounds generated in the primary and secondary metabolism of the plant, which act to protect it from phytopathogens. Tabernaemontana catharinensis A DC (Apocynaceae), a tree in which its leaves and bark are used for the preparation of extracts and infusions that have anti-inflammatory and antinociceptive effects, is attributed to its phytochemical constitution. The objective of this study was to elucidate the phytochemical constitution, the antibacterial potential, the toxicity against immune system cells, hemolytic potential, and antitumor effect of methanolic extracts of E. plana and T. catharinensis. The phytochemical investigation was carried out using the UHPLC-QTOF MS equipment. The antibacterial activity was tested using the broth microdilution plate assay, against Gram-negative and Gram-positive strains, and cytotoxicity assays were performed on human peripheral blood mononuclear cells (PBMC) and in vitro hemolysis. Antitumor activity was performed against the colon cancer cell line (CT26). Results were expressed as mean and standard deviation and analyzed by ANOVA. p < 0.05 was considered significant. More than 19 possible phytochemical constituents were identified for each plant, with emphasis on phenolic compounds (acids: vanillic, caffeic, and quinic) and alkaloids (alstovenine, rhyncophylline, amezepine, voacangine, and coronaridine). Both extracts showed antibacterial activity at concentrations below 500 µg/mL and were able to decrease the viability of CT26 at concentrations below 2000 µg/mL, without showing cytotoxic effect on PBMCs and in vitro hemolysis at the highest concentration tested. This is the first report of the activity of E. plana and T. catharinensis extracts against colon cancer cell line (CT26). Studies should be carried out to verify possible molecular targets involved in the antitumor effect in vivo.

Insulitis in human type 1 diabetes: lessons from an enigmatic lesion.

Type 1 diabetes is caused by a deficiency of insulin secretion which has been considered traditionally as the outcome of a precipitous decline in the viability of β-cells in the islets of Langerhans, brought about by autoimmune-mediated attack. Consistent with this, various classes of lymphocyte, as well as cells of the innate immune system have been found in association with islets during disease progression. However, analysis of human pancreas from subjects with type 1 diabetes has revealed that insulitis is often less intense than in equivalent animal models of the disease and can affect many fewer islets than expected, at disease onset. This is especially true in subjects developing type 1 diabetes in, or beyond, their teenage years. Such studies imply that both the phenotype and the number of immune cells present within insulitic lesions can vary among individuals in an age-dependent manner. Additionally, the influent lymphocytes are often mainly arrayed peripherally around islets rather than gaining direct access to the endocrine cell core. Thus, insulitis remains an enigmatic phenomenon in human pancreas and this review seeks to explore the current understanding of its likely role in the progression of type 1 diabetes.

Tumor Organoids: The Era of Personalized Medicine.

The strategies of future medicine are aimed to modernize and integrate quality approaches including early molecular-genetic profiling, identification of new therapeutic targets and adapting design for clinical trials, personalized drug screening (PDS) to help predict and individualize patient treatment regimens. In the past decade, organoid models have emerged as an innovative in vitro platform with the potential to realize the concept of patient-centered medicine. Organoids are spatially restricted three-dimensional clusters of cells ex vivo that self-organize into complex functional structures through genetically programmed determination, which is crucial for reconstructing the architecture of the primary tissue and organs. Currently, there are several strategies to create three-dimensional (3D) tumor systems using (i) surgically resected patient tissue (PDTOs, patient-derived tumor organoids) or (ii) single tumor cells circulating in the patient's blood. Successful application of 3D tumor models obtained by co-culturing autologous tumor organoids (PDTOs) and peripheral blood lymphocytes have been demonstrated in a number of studies. Such models simulate a 3D tumor architecture in vivo and contain all cell types characteristic of this tissue, including immune system cells and stem cells. Components of the tumor microenvironment, such as fibroblasts and immune system cells, affect tumor growth and its drug resistance. In this review, we analyzed the evolution of tumor models from two-dimensional (2D) cell cultures and laboratory animals to 3D tissue-specific tumor organoids, their significance in identifying mechanisms of antitumor response and drug resistance, and use of these models in drug screening and development of precision methods in cancer treatment.

Effect of intensive training on immune system cells in elite female weightlifters.

This study aimed to investigate the effects of intense weightlifting training on lymphocyte and natural killer cell subgroups, which are the major cells of the immune system, in elite female weightlifters. A total of 20 elite female weightlifters were evaluated using flow cytometry before training (pre-T), immediately after training (post-T), and after a 120-min rest period (rest-T). Post-T and rest-T showed significant decreases in helper T (Th) and cytotoxic T compared with pre-T (p=0.045, p<0.001 and p=0.05, p<0.001, respectively). B and natural killer cells were higher in post-T and rest-T than in pre-T. The increase in B cells was significant in pre-T/rest-T (p<0.001) but not in pre-T/post-T (p=0.122). Intense training significantly increased natural killer cells in both post-T and rest-T (p<0.001). CD56bright and CD56dim natural killer cell subgroups were significantly lower in post-T and rest-T than in pre-T (p=0.005, p=0.006 and p<0.001, p=0.004, respectively). This study shows that intense weightlifting alters peripheral lymphocyte and natural killer subgroup ratios, being the first investigation in this field.

A Ménage à trois: NLRC5, immunity, and metabolism.

The nucleotide-binding and oligomerization domain-like receptors (NLRs) NLR family CARD domain-containing protein 5 (NLRC5) and Class II Major Histocompatibility Complex Transactivator (CIITA) are transcriptional regulators of major histocompatibility complex (MHC) class I and class II genes, respectively. MHC molecules are central players in our immune system, allowing the detection of hazardous 'non-self' antigens and, thus, the recognition and elimination of infected or transformed cells from the organism. Recently, CIITA and NLRC5 have emerged as regulators of selected genes of the butyrophilin (BTN) family that interestingly are located in the extended MHC locus. BTNs are transmembrane proteins exhibiting structural similarities to B7 family co-modulatory molecules. The family member BTN2A2, which indeed contributes to the control of T cell activation, was found to be transcriptionally regulated by CIITA. NLRC5 emerged instead as an important regulator of the BTN3A1, BTN3A2, and BTN3A3 genes. Together with BTN2A1, BTN3As regulate non-conventional Vγ9Vδ2 T cell responses triggered by selected metabolites of microbial origin or accumulating in hematologic cancer cells. Even if endogenous metabolites conform to the canonical definition of 'self', metabolically abnormal cells can represent a danger for the organism and should be recognized and controlled by immune system cells. Collectively, new data on the role of NLRC5 in the expression of BTN3As link the mechanisms regulating canonical 'non-self' presentation and those marking cells with abnormal metabolic configurations for immune recognition, an evolutionary parallel that we discuss in this perspective review.

The role of dopamine receptors in the modulation of mononuclear phagocytes in multiple sclerosis

To investigate the role of dopamine receptor D1DR and D2DR in the production of cytokines interleukin-6 (IL-6) and IL-1β by monocytes and macrophages in patients with relapsing-remitting multiple sclerosis (MS). Ten patients with relapsing-remitting MS and 10 healthy subjects were examined. The level of IL-6 and IL-1β production was assessed in culture supernatants obtained from CD14+ monocytes or macrophages stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). To study the role of dopamine receptors in the regulation of CD14+ monocytes or macrophages, samples of cells were incubated in the presence of specific D1DR or D2DR antagonists, after which IFN-γ/LPS were added to the cultures. Levels of cytokines in culture supernatants were measured by enzyme-linked immunosorbent assay. The production of IL-6 and IL-1β by CD14+ monocytes and macrophages was comparable between the groups. Blockade of D1DR suppressed cytokine production by CD14+ monocytes and macrophages in both groups. In contrast, blockade of D2DR increased the production of cytokines by CD14+ monocytes and did not affect cytokine production by macrophages in both groups. Targeting of dopaminergic receptors could be considered as an additional mechanism of immunomodulation in MS with both pro- and anti-inflammatory effects on cells of the innate immune system.

Influences of bacterial extracellular vesicles on macrophage immune functions.

Bacterial extracellular vesicles (EVs) are crucial mediators of information transfer between bacteria and host cells. Macrophages, as key effector cells in the innate immune system, have garnered widespread attention for their interactions with bacterial EVs. Increasing evidence indicates that bacterial EVs can be internalized by macrophages through multiple pathways, thereby influencing their immune functions. These functions include inflammatory responses, antimicrobial activity, antigen presentation, and programmed cell death. Therefore, this review summarizes current research on the interactions between bacterial EVs and macrophages. This will aid in the deeper understanding of immune modulation mediated by pathogenic microorganisms and provide a basis for developing novel antibacterial therapeutic strategies.

Биохимические и иммунологические аспекты патофизиологии острого респираторного дистресс-синдрома

Aim of the study. To analyze publications of scientific studies devoted to the study of biochemical and immunological aspects of the pathophysiology of acute respiratory distress syndrome. Material and methods. An analysis of 54 sources was conducted. The search for articles was carried out in the abstract databases Scopus and Web of Science, as well as in the search engines PubMed, eLIBRARY.RU and Google Scholar, from 2000 to December 2023. Conclusions. The immunological aspect of the pathophysiology of acute respiratory distress syndrome is characterized by the activation of the innate immune system and antigen-presenting cells, which contributes to the initiation of the immune response. In turn, neutrophils release cytotoxic molecules, active oxygen metabolites, bioactive lipids and proinflammatory cytokines and trigger an inflammatory cascade. Cytotoxic molecules cause tissue necrosis, initiate apoptosis and autophagy, which maintains and enhances inflammatory reactions and lung injury, as well as the formation of a vicious circle. Damage to vascular endothelial cells initiates coagulation, promoting the activation of platelets and procoagulant cascades, which leads to the formation of microthrombi in the pulmonary microcirculatory network and fibrin deposition in the intraalveolar and interstitial compartments. The interaction of platelets and neutrophils at the site of endothelial injury is considered a humoral regulatory process. Uncontrolled immunothrombosis can cause concomitant tissue damage and contribute to organ dysfunction.

A Mathematical Model of Tumor‐Immune and Host Cells Interactions with Chemotherapy and Optimal Control

In this article, we propose the interaction of tumor cells with the immune system in the presence of chemotherapy. The existence, uniqueness, non‐negativity, and boundedness of the solutions have been established. The conditions for the existence and stability of equilibrium points have been presented in both drug‐free and treated systems. The local stability of the co‐existing equilibrium point is proved using the Routh–Hurwitz rule, and the global stability is proved using the Lyapunov function. We have used quadratic optimal control to minimize the number of tumor cells and the side effects of chemotherapy on the immune system and healthy cells. We have demonstrated the existence of optimal control and derived the corresponding optimality system using Pontryagin’s maximum principle. The optimal system is solved using the forward‐backward sweep method with fourth‐order Runge–Kutta approximation. Reduction in tumor cell growth has been observed due to the increase in recruitment of immune cells activated by tumor cell antigenicity and the rate of conversion of resting immune cells into active immune cells. Additionally, the impact of administering varying chemotherapy doses on reducing tumor cell growth has been noted. Finally, a comparison between controlled and uncontrolled dynamics has been conducted to comprehend the effect of optimal control.

Implications of tumor-infiltrating lymphocytes in early-stage triple-negative breast cancer: clinical oncologist perspectives

Implications of tumor-infiltrating lymphocytes in early-stage triple-negative breast cancer: clinical oncologist perspectives

Activation of Neurotoxic Astrocytes Due to Mitochondrial Dysfunction Triggered by POLG Mutation.

Mitochondrial diseases are associated with neuronal death and mtDNA depletion. Astrocytes respond to injury or stimuli and damage to the central nervous system. Neurodegeneration can cause astrocytes to activate and acquire toxic functions that induce neuronal death. However, astrocyte activation and its impact on neuronal homeostasis in mitochondrial disease remain to be explored. Using patient cells carrying POLG mutations, we generated iPSCs and then differentiated these into astrocytes. POLG astrocytes exhibited mitochondrial dysfunction including loss of mitochondrial membrane potential, energy failure, loss of complex I and IV, disturbed NAD+/NADH metabolism, and mtDNA depletion. Further, POLG derived astrocytes presented an A1-like reactive phenotype with increased proliferation, invasion, upregulation of pathways involved in response to stimulus, immune system process, cell proliferation and cell killing. Under direct and indirect co-culture with neurons, POLG astrocytes manifested a toxic effect leading to the death of neurons. We demonstrate that mitochondrial dysfunction caused by POLG mutations leads not only to intrinsic defects in energy metabolism affecting both neurons and astrocytes, but also to neurotoxic damage driven by astrocytes. These findings reveal a novel role for dysfunctional astrocytes that contribute to the pathogenesis of POLG diseases.

Enhancing human islet xenotransplant survival and function in diabetic immunocompetent mice through LRH-1/NR5A2 pharmacological activation.

The intricate etiology of type 1 diabetes mellitus (T1D), characterized by harmful interactions between the immune system and insulin-producing beta cells, has hindered the development of effective therapies including human islet transplantation, which requires strong immunosuppressants that impair beta cell survival and function. As such alternative immunomodulating therapies are required for successful transplantation. The discovery that pharmacological activation of the nuclear receptor LRH-1/NR5A2 can reverse hyperglycemia in mouse models of T1D by altering, and not suppressing the autoimmune attack, prompted us to investigate whether LRH-1/NR5A2 activation could improve human islet function/survival after xenotransplantation in immunocompetent mice. Human islets were transplanted under the kidney capsule of streptozotocin (STZ)-induced diabetic mice, and treatment with BL001 (LRH-1/NR5A2 agonist) or vehicle was administered one week post-transplant. Our study, encompassing 3 independent experiments with 3 different islet donors, revealed that mice treated for 8 weeks with BL001 exhibited lower blood glucose levels correlating with improved mouse survival rates as compared to vehicle-treated controls. Human C-peptide was detectable in BL001-treated mice at both 4 and 8 weeks indicating functional islet beta cells. Accordingly, in mice treated with BL001 for 8 weeks, the beta cell mass was preserved, while a significant decrease in alpha cells was observed compared to mice treated with BL001 for only 4 weeks. In contrast, vehicle-treated mice exhibited a reduction in insulin-expressing cells at 8 weeks compared to those at 4 weeks. These results suggest that BL001 significantly enhances the survival, engraftment, and functionality of human islets in a STZ-induced diabetic mouse model.

Roles in Innate Immunity.

Microglia are best known as the resident phagocytes of the central nervous system (CNS). As a resident brain immune cellpopulation, microglia play key roles during the initiation, propagation, and resolution of inflammation. The discovery of resident adaptive immune cells in the CNS has unveiled a relationship between microglia and adaptive immune cells for CNS immune-surveillance during health and disease. The interaction of microglia with elements of the peripheral immune system and other CNS resident cells mediates a fine balance between neuroprotection and tissue damage. In this chapter, we highlight the innate immune properties of microglia, with a focus on how pattern recognition receptors, inflammatory signaling cascades,phagocytosis, and the interaction between microglia and adaptive immune cells regulate events that initiate an inflammatory or neuroprotective response within the CNS thatmodulates immune-mediated disease exacerbation or resolution.

Anti-Inflammatory Immunomodulatory Activity of Valacyclovir on the in Vitro Activated Mammalian Macrophages.

Aciclovir, often known as acyclovir, is a nucleoside analog that exhibits antiviral activity in vitro against human herpesvirus 6 (HHV-6), cytomegalovirus (CMV), varicella-zoster virus (VZV), and herpes simplex virus (HSV). Valacyclovir is an amino acid ester prodrug of acyclovir. We examined valacyclovir, which is also an anti-viral agent, for its effects on inflammation. Mammalian Macrophages were activated by lipopolysaccharide (LPS) in the presence of a concentration range of Valacyclovir. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-12p40 enzyme-linked immunosorbent assay (ELISA) was performed to measure the production levels of these pro-inflammatory cytokines. Our results suggest that Valacyclovir had anti-inflammatory activity on the LPS-activated mammalian macrophages. Valacyclovir has the potential to be utilized in the clinical setting as an anti-viral drug molecule with anti-inflammatory properties. Future studies are needed to further confirm its activities on different immune system cell types.

Extracellular Traps in Patients Diagnosed With Bacterial Vaginosis, Trichomoniasis, Candidiasis, Noninfectious Vaginitis and Cytolytic Vaginosis.

Vaginal infections are a public health problem associated with serious health complications due to the exacerbated inflammation they generate. Vaginal inflammation may also occur in some noninfectious processes, such as noninfectious vaginitis and cytolytic vaginosis. Immune system cells respond to infections through various mechanisms, such as the formation of extracellular traps (ETs), which are DNA networks associated with effector proteins. Many pathogens induce ETs formation in vitro, as occurs in some natural infections. A recent report indicates that human vaginal infections in vivo generate ETs. Therefore, in this study, we aimed to identify ETs in samples from 40 donors who were diagnosed with infectious (i.e., bacterial vaginosis, candidiasis and trichomoniasis) and noninfectious (i.e., noninfectious vaginitis and cytolytic vaginosis) vaginal inflammation. We were able to observe ETs by identifying the LL-37 peptide, which is associated with DNA networks. In seven vaginal swabs from the control group (formed by 19 donors without vaginal infection symptoms), we detected at least one pathogen per sample and observed ETs; thus, these donors were considered asymptomatic. The remaining 12 donors were confirmed to be healthy, as their exudates did not present any tested pathogens, sign of inflammation or ETs. ETs in vaginal inflammatory processes can worsen inflammation but may also help control infection.

Structural and functional features of immune system cells in the dynamics of experimental temperature exposure

The body's immune response to temperature exposure is a complex multi-stage process that is controlled by a variety of reactions developing at various levels of the body. The relationship of individual cell types is the most important link in the immune regulatory mechanism. The structural changes occurring in the organs of immunity under thermal exposure are in principle identical, but the involvement of one or another organ in the process depends on the activity and strength of temperature.