Cells Of Adaptive Immune System Research Articles

Galectin-3 absence alters lymphocytes populations dynamics behavior and promotes functional recovery after spinal cord injury in mice

Spinal cord injury (SCI) results from various mechanisms that damage the nervous tissue and the blood-brain barrier, leading to sensory and motor function loss below the injury site. Unfortunately, current therapeutic approaches for SCI have limited efficacy in improving patients outcomes. Galectin-3, a protein whose expression increases after SCI, influences the neuroinflammatory response by favoring pro-inflammatory M1 macrophages and microglia, while inhibiting pro-regenerative M2 macrophages and microglia, which are crucial for inflammation resolution and tissue regeneration. Previous studies with Galectin-3 knock-out mice demonstrated enhanced motor recovery after SCI. The M1/M2 balance is strongly influenced by the predominant lymphocytic profiles (Th1, Th2, T Reg, Th17) and cytokines and chemokines released at the lesion site. The present study aimed to investigate how the absence of galectin-3 impacts the adaptive immune system cell population dynamics in various lymphoid spaces following a low thoracic spinal cord compression injury (T9-T10) using a 30 g vascular clip for one minute. It also aimed to assess its influence on the functional outcome in wild-type (WT)and Galectin-3 knock-out (GALNEG) mice. Histological analysis with hematoxylin-eosin and Luxol Fast Blue staining revealed that WT and GALNEG animals exhibit similar spinal cord morphology. The absence of galectin-3 does not affect the common neuroanatomy shared between the groups prompting us to analyze outcomes between both groups. Following our crush model, both groups lost motor and sensory functions below the lesion level. During a 42-day period, GALNEG mice demonstrated superior locomotor recovery in the Basso Mouse Scale (BMS) gait analysis and enhanced motor coordination performance in the ladder rung walk test (LRW) compared to WT mice. GALNEG mice also exhibited better sensory recovery, and their electrophysiological parameters suggested a higher number of functional axons with faster nerve conduction. Seven days after injury, flow cytometry of thymus, spleen, and blood revealed an increased number of T Reg and Th2 cells, accompanied by a decrease in Th1 and Th17 cells in GALNEG mice. Immunohistochemistry conducted on the same day exhibited an increased number of Th2 and T Reg cells around the GALNEG's spinal cord lesion site. At 42-day dpi immunohistochemistry analyses displayed reduced astrogliosis and greater axon preservation in GALNEG's spinal cord seem as a reduction of GFAP immunostaining and an increase in NFH immunostaining, respectively. In conclusion, GALNEG mice exhibited better functional recovery attributed to the milder pro-inflammatory influence, compensated by a higher quantity of T Reg and Th2 cells. These findings suggest that galectin-3 plays a crucial role in the immune response after spinal cord injury and could be a potential target for clinical therapeutic interventions.

Immunomodulating effects of antitumor drugs Bruton tyrosine kinase inhibitors and the possibility of their use in allergic and infectious diseases

Bruton's tyrosine kinase (BTK) inhibitors represent a class of drugs that have demonstrated their efficacy and safety in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphomas who were considered refractory to any previously used type of therapy. BTK plays a key role in all stages of B lymphocyte development, but in recent years, there have been data indicating that BTK is also involved in the activation of myeloid cells.The aim of this study is to analyze and systematize all published materials on the immunomodulatory effects of BTK inhibitors (ibrutinib, acalabrutinib, etc.).A systematic review of the scientific literature was performed using a step-by-step search process in electronic databases (PubMed, Web of Science, ScienceDirect, and Scopus). The following keywords were used in the database search: “CLL”, “BTK”, “ibrutinib”, “COVID-19”, “allergy”, “inflammation.” The search for studies was conducted from the time of the first BTK inhibitor drug (ibrutinib) appearance in 2009 until December 2022.The results of the study on the influence of BTK inhibitors on the functional state of B and T lymphocytes, neutrophils, and monocytes/macrophages are presented. The immunomodulatory effects of ibrutinib on adaptive and innate immune system cells, including CD4+ and CD8+T lymphocytes and NK cells, are described. Since BTK inhibitors alter the functional activity of phagocytic cells and the ratio of T cell populations, there is a suggestion about the possibility of using these drugs for the treatment of other nosological forms, not only B cell malignancies, which is currently being studied in clinical trials. Data on the use of BTK inhibitors to combat hyperacute inflammation and to suppress allergic reactions, including anaphylaxis, are summarized. In addition, the expediency of short-term use of BTK inhibitors to reduce the risk of side effects during oral immunotherapy and for desensitization to drugs is discussed.The presented data indicate that BTK inhibitors are promising drugs with immunomodulatory effects. However, BTK inhibitors need to increase selectivity to reduce off-target effects on other kinases.

Mesenchymal Stem Cell in Pancreatic Islet Transplantation.

Pancreatic islet transplantation is a therapeutic option for achieving physiologic regulation of plasma glucose in Type 1 diabetic patients. At the same time, mesenchymal stem cells (MSCs) have demonstrated their potential in controlling graft rejection, the most fearsome complication in organ/tissue transplantation. MSCs can interact with innate and adaptive immune system cells either through direct cell-cell contact or through their secretome including exosomes. In this review, we discuss current findings regarding the graft microenvironment of pancreatic islet recipient patients and the crucial role of MSCs operation as cell managers able to control the immune system to prevent rejection and promote endogenous repair. We also discuss how challenging stressors, such as oxidative stress and impaired vasculogenesis, may jeopardize graft outcomes. In order to face these adverse conditions, we consider either hypoxia-exposure preconditioning of MSCs or human stem cells with angiogenic potential in organoids to overcome islets' lack of vasculature. Along with the shepherding of carbon nanotubes-loaded MSCs to the transplantation site by a magnetic field, these studies look forward to exploiting MSCs stemness and their immunomodulatory properties in pancreatic islet transplantation.

A mathematical model and simulation scenarios for T and B cells immune response to severe acute respiratory syndrome-coronavirus-2

Severe acute respiratory syndrome coronavirus is a type 2 highly contagious, and transmissible among humans; the natural human immune response to severe acute respiratory syndrome-coronavirus-2 combines cell-mediated immunity (lymphocyte) and antibody production. In the present study, we analyzed the dynamic effects of adaptive immune system cell activation in the human host. The methodology consisted of modeling using a system of ordinary differential equations; for this model, the equilibrium free of viral infection was obtained, and its local stability was determined. Analysis of the model revealed that lymphocyte activation leads to total pathogen elimination by specific recognition of viral antigens; the model dynamics are driven by the interaction between respiratory epithelial cells, viral infection, and activation of helper T, cytotoxic T, and B lymphocytes. Numerical simulations showed that the model solutions match the dynamics involved in the role of lymphocytes in preventing new infections and stopping the viral spread; these results reinforce the understanding of the cellular immune mechanisms and processes of the organism against severe acute respiratory syndrome-coronavirus-2 infection, allowing the understanding of biophysical processes that occur in living systems, dealing with the exchange of information at the cellular level.

Tumor-Infiltrating B Lymphocytes: Promising Immunotherapeutic Targets for Primary Liver Cancer Treatment.

Hepatocellular carcinoma and cholangiocarcinoma are the fourth most lethal primary cancers worldwide. Therefore, there is an urgent need for therapeutic strategies, including immune cell targeting therapies. The heterogeneity of liver cancer is partially explained by the characteristics of the tumor microenvironment (TME), where adaptive and innate immune system cells are the main components. Pioneering studies of primary liver cancers revealed that tumor-infiltrating immune cells and their dynamic interaction with cancer cells significantly impacted carcinogenesis, playing an important role in cancer immune evasion and responses to immunotherapy treatment. In particular, B cells may play a prominent role and have a controversial function in the TME. In this work, we highlight the effect of B lymphocytes as tumor infiltrates in relation to primary liver cancers and their potential prognostic value. We also present the key pathways underlying B-cell interactions within the TME, as well as the way that a comprehensive characterization of B-cell biology can be exploited to develop novel immune-based therapeutic approaches.

Monocyte subpopulations display disease-specific miRNA signatures depending on the subform of Spondyloarthropathy.

Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations.

Review on Tumour Microenvironment Cell Types Associated with Metastatic Cancer

The Tumour microenvironment (TME) is a highly dynamic and perpetually altering entity of cancer development, progression, invasion, and dissemination. TME is interspersed with cellular components such as immune cells, blood vessels and stromal cells, and non-cellular components comprising extracellular matrix (ECM) and exosomes. Different cancer types possess distinct phenotypes of TME. The intricate processes of TME facilitate uncontrolled bulk formation, and chaotic vascularization, supporting oxygen and blood availability, along with the removal of metabolic wastes and aberrant metastatic colonization and seeding. Tumour masses are embedded with diverse innate and adaptive immune system cell milieu, capable of performing both pro and anti-tumorigenic effects. The nexus underpinning cancer cells and associated TME, such as cell-cell or cell-ECM interactions, play a key role in determining safe and effective therapeutic interventions. This review mainly emphasizes different roles of various cell types involved in the tumour microenvironment in the progression and promotion of metastatic potencies of tumour cells. We have further suggested that the targeting of all these cell types in the tumour microenvironment may give better cancer therapies in the near future.

Endoplasmic reticulum-Phagosome contact sites from the cradle to the grave.

Phagocytosis is a key component of the innate immune system used to ingest apoptotic cells and microorganisms for their destruction and recycling of macromolecules and the presentation of antigens to adaptive immune system cells. The newly formed vacuole or nascent phagosome undergoes a maturation process reminiscent of the classical endocytic maturation process, reaching a highly degradative phagolysosome stage before its tubulovesicular breakdown into lysosomes. The process is highly regulated and can be disrupted by various pathogenic organisms. The exchange of proteins, lipids, and other metabolites between organelles, including maturing phagosomes, is enabled by two processes, vesicular and non-vesicular transport at membrane contact sites (MCS). For decades the specific role(s) of the endoplasmic reticulum (ER) in phagocytosis has been the subject of much debate. In parallel, the last two decades have seen a burst in research on the numerous roles of ER contact sites and resident proteins in all aspects of organelle biology. Here, in this minireview, we describe ER-phagosome contact sites' functions from the early stages of particle engulfment to the phagolysosome dissolution into lysosomes. We also discuss several aspects of ER-phagosome contact sites that remain to be explored.

Cellular Immuno-Profile in Septic Human Host: A Scoping Review.

Innate and adaptive immune system cells play a critical role in the host response to sepsis. Sepsis is a life-threatening disease characterized by apoptosis-induced depletion of immune cells and immunodepression, which contribute to morbidity and mortality. Many alterations in the expression of surface markers of neutrophils and monocytes have been described in septic patients. The aim of this study was to inspect the recently published literature to inform the clinician about the most up-to-date techniques for the study of circulating leukocytes. The impact on cell phenotypes and on the function of leukocytes of extracorporeal and non-blood purification treatments proposed for sepsis were also analyzed. We conducted a systematic review using Pubmed/Medline, Ovid/Willey, the Cochrane Library, the Cochrane Controlled Trials Register, and EMBASE, combining key terms related to immunological function in sepsis and selected the most relevant clinical trials and review articles (excluding case reports) published in the last 50 years. The most important alteration in neutrophils during sepsis is that they activate an anti-apoptotic survival program. In septic monocytes, a reduced characteristic expression of HLA-DR is observed, but their role does not seem to be significantly altered in sepsis. As regards adaptive immunity, sepsis leads to lymphopenia and immunosuppression in patients with septic shock; this process involves all types of T cells (CD4, CD8 and Natural Killer), except for regulatory T cells, which retain their function. Several promising therapies that target the host immune response are currently under evaluation. During the worldwide pandemic caused by SARS-CoV-2, it was useful to study the "cytokine storm" to find additional treatments, such as the oXiris® filter. This therapy can decrease the concentration of inflammatory markers that affect the severity of the disease.

Abstract IA39: Pathology of AYA lymphomas: Creating a roadmap for translational research

Abstract Mature lymphomas of the adolescent and young adult population (AYA) are rare and clinically and pathobiologically distinct from those in the adult population. The pathobiologic aspects of lymphomas in the AYA population are largely unknown as most studies do not specify age groups and use diagnostic criteria that have been established for lymphomas in the adult population. B-cell lymphomas make up the majority of lymphomas in the AYA population and many are aggressive including Burkitt lymphoma, large/high grade B-cell lymphoma with 11q aberrations and diffuse large B-cell lymphoma (DLBCL), NOS. Most DLBCL, NOS arise as de novo lymphomas. They may occur as a secondary neoplasm after childhood cancer or in cancer predisposition syndromes, primary immunodeficiencies or other inherited genetic diseases (inborn error of immunity-associated lymphoid proliferations and lymphomas). Most DLBCL, NOS in the AYA population are of germinal center derivation, exhibit high proliferation index and while comprehensive studies are lacking, they are biologically distinct from adult diffuse large B-cell lymphomas with less cytogenetic complexity. Mature T-cell lymphomas are extremely rare in the AYA population and composed primarily of those driven by a dominant oncogenic tyrosine kinase (ALK+ anaplastic large cell lymphoma) or Epstein-Barr virus and most arise from T cells of the innate immune system. T-cell lymphomas arising from the adaptive immune system (nodal T follicular helper (TFH) cell lymphoma, peripheral T cell lymphoma, NOS) which are common in the adult population are rare in AYA. The most recent WHO Classification of Paediatric Tumors recognizes specific entities that are enriched in the AYA population with distinct genetic features including indolent B-cell lymphoma including pediatric-type follicular lymphomas, pediatric nodal marginal zone lymphoma and large B-cell lymphomas with IRF4 rearrangement, and EBV-associated T cell lymphoma such as systemic EBV-positive T-cell lymphoma of childhood, systemic chronic active EBV-positive disease and hydroa vacciniforme lymphoproliferative disorder. The distinct clinical and pathobiologic features of lymphomas in the AYA population provide unique opportunities for translational discoveries leveraging innovative technologies such as single cell sequencing, B and T cell immune repertoire analyses and circulating tumor DNA, that will provide insights into the interplay between the immune system, epigenetics, germline predisposition and viruses. These studies are poised to yield actionable information that impacts therapies and improve patient outcomes. Citation Format: Megan S. Lim. Pathology of AYA lymphomas: Creating a roadmap for translational research [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr IA39.

MiRNA-REGULATED PATHWAYS OF CD8+ T CELLS IN TNBC MOUSE MODEL

Objective: Triple negative breast cancer, which constitutes 20% of all breast cancer is the most aggressive breast cancer subtype. Although breast cancer is known as immune cold, recent studies have revealed that there is an immune response on the basis of subtypes. miRNAs are involved in regulating many biological processes of CD8+ T lymphocytes, which are adaptive immune system cells that effectively destroy tumor cells. Our aim is to examine the regulative roles of miRNAs in CD8+ T lymphocytes during the formation of triple negative breast tumors in mice. Materials and Methods:4T1 cells and Balb/c mice were used for the allograft breast cancer model. After 2 weeks, tumor-bearing and control mice were sacrificed, and spleens were harvested for CD8+ T cell isolation. Following RNA isolation, miRNA microarray analysis was performed. Differentially expressed miRNAs between the groups were detected. DIANA-mirPath web tool was used to investigate the target genes of miRNAs and in which pathways these genes are enriched. Results: Microarray analysis indicated that 41 miRNAs are differentially expressed in CD8+ T cells from tumor-bearing mice compared to the control group. The KEGG analysis results showed that the targets of differentially expressed miRNAs were significantly enriched in immune response-related pathways like ECM-receptor interaction, PI3K-Akt signaling, and tryptophan metabolism pathways. Conclusion: The pathways in which miRNA-target genes are enriched are associated with T cell metabolism and cell survival. It may be concluded that there are changes in the systemic adaptive immune response during TNBC formation and that miRNAs regulate these changes.

Serotonergic drug repurposing in multiple sclerosis: A new possibility for disease-modifying therapy.

Investigation of neuroimmune interactions is one of the most developing areas in the study of multiple sclerosis pathogenesis. Recent evidence suggests the possibility of modulating neuroinflammation by targeting biogenic amine receptors. It has been shown that selective serotonin reuptake inhibitor fluoxetine modulates innate and adaptive immune system cells' function and can reduce experimental autoimmune encephalomyelitis and multiple sclerosis severity. This brief report discusses the immune mechanisms underlying the multiple sclerosis pathogenesis and the influence of fluoxetine on them. The retrospective data on the impact of fluoxetine treatment on the course of multiple sclerosis are also presented. The results of this and other studies suggest that fluoxetine could be considered an additional therapy to the standard first-line disease-modifying treatment for relapsing–remitting multiple sclerosis.

Innate and adaptive immune system cells implicated in tendon healing and disease.

Tendons perform a critical function in the musculoskeletal system by integrating muscle with skeleton and enabling force transmission. Damage or degeneration of these tissues lead to impaired structure and function, which often persist despite surgical intervention. While the immune response and inflammation are important drivers of both tendon healing and disease progression, there have been relatively few studies of the diverse immune cell types that may regulate these processes in these tissues. To date, most of the studies have focused on macrophages, but emerging research indicate that other immune cell types may also play a role in tendon healing, either by regulating the immune environment or through direct interactions with resident tenocytes. The present review synthesises the literature on innate and adaptive immune system cells that have been implicated in tendon healing or disease, in the context of animal injury models, human clinical samples or in vitro experiments.

Associated pathogenesis of bladder cancer and SARS-CoV-2 infection: a treatment strategy.

Coronavirus disease 19 (Covid-19) is a pandemic that affects every human on Earth. Mortality rates are greater in people with both cancer and Covid-19. In comparison, patients with non-Muscle-Invasive Bladder Cancer (NMIBC) had reduced susceptibility to moderate Covid-19 mortality. The treatment and clinical management of NMIBC are consistent with BCG-mediated intravesical adjuvant therapy as a protective function against tumors. BCG vaccination exhibits a non-specific protective role against respiratory infections. This non-specific effect of BCG is partially mediated by innate immune memory due to epigenetic changes in innate and adaptive immune system cells induced by the microbe. This editorial suggests that regularly test repurposed drugs include anti-cancer drugs till the proper antiviral drugs or vaccines will be developed.

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Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease.

The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is the response of reactive CNS components to altered homeostasis, regardless of the cause to be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, or degenerative, involve direct and indirect immune-related neuroinflammation. Brain infiltrates of the innate and adaptive immune system cells appear in response to an infective or otherwise noxious agent and produce inflammatory mediators. Mediators of inflammation include local and recruited cells and signals. Processes derived from extrinsic and intrinsic CNS diseases also elicit the CNS inflammatory response. A deeper understanding of immune-related inflammation in health and disease is necessary to find potential therapeutic targets for preventing or reducing CNS damage. This review is aimed at discussing the innate and adaptive immune system functions and their roles in regulating brain cell responses in disease and homeostasis maintenance.

Autorreactividad, tolerancia y autoinmunidad

Autoimmunity is an immune response against one or several of your own antigens. Autoimmune diseases are the result of injury or loss of physiological function in organs and tissues due to an autoimmune response. This specific recognition is mediated by adaptive immune system cells, that is, T- and B-lymphocytes, though cells and molecules of the innate immune system also play a role in the mechanisms of injury. Autoimmune diseases are chronic and tend to be progressive. The persistence of the antigen, of the specific memory T and B cells, and of the powerful mechanisms of inflammatory amplification are the pathogenic mechanisms that perpetuate this disease. Mechanisms of tolerance are essential for the control of autoreactivity and mainly include those mediated in the periphery by T-lymphocytes. The etiology of autoimmune diseases has not been elucidated, although it seems clear that it is multifactorial. Genetic propensity is an important factor and certain sets of gene alleles can predispose an individual to a disease. In addition, environmental factors such as infection and tissue injury appear fundamental to its development.

Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role?

The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research.

Immunoinflammatory Aspects of Parkinson’s Disease

This review analyzes immunological impairments in Parkinson’s disease (PD). We present data on neuroinflammation, with which cell degeneration in the substantia nigra of the brain is associated and in which innate and adaptive immune system cells are involved. Brain, cerebrospinal fluid, and peripheral blood cytokine levels are analyzed. The interaction between neuroinflammation and neuron dysfunction is considered. Data on immunological impairments in people with PD and animals with models of this disease are presented. The characteristics of models of PD are discussed. Data on impairments to the blood–brain barrier are presented, along with evidence for the occurrence of autoimmune inflammation in this disease. We discuss the question of preclinical markers of PD, including immunological, i.e., cytokines, HLA-DR and HLA-DQ antigens, autoantibodies, etc. The creation of algorithms for the presymptomatic diagnosis of PD and its prophylaxis and treatment at the presymptomatic stage will lead to the cessation or slowing of neuron death.

The Good, The Bad and The Ugly: A Mathematical Model Investigates the Differing Outcomes Among CoVID-19 Patients.

The disease caused by SARS-CoV-2—CoVID-19—is a global pandemic that has brought severe changes worldwide. Approximately 80% of the infected patients are largely asymptomatic or have mild symptoms such as fever or cough, while rest of the patients display varying degrees of severity of symptoms, with an average mortality rate of 3–4%. Severe symptoms such as pneumonia and acute respiratory distress syndrome may be caused by tissue damage, which is mostly due to aggravated and unresolved innate and adaptive immune response, often resulting from a cytokine storm.Cytokine storm: A sudden acute increase in circulating levels of different inflammation causing cytokines including IL-6, IL-1, etc. Here, we discuss how an intricate interplay among infected cells and cells of innate and adaptive immune system can lead to such diverse clinicopathological outcomes. Particularly, we discuss how the emergent nonlinear dynamics of interaction among the components of adaptive and immune system components and virally infected cells can drive different disease severity. Such minimalistic yet rigorous mathematical modeling approaches are helpful in explaining how various co-morbidity risk factors, such as age and obesity, can aggravate the severity of CoVID-19 in patients. Furthermore, such approaches can elucidate how a fine-tuned balance of infected cell killing and resolution of inflammation can lead to infection clearance, while disruptions can drive different severe phenotypes. These results can help further in a rational selection of drug combinations that can effectively balance viral clearance and minimize tissue damage.