Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Review Article - (2024)Volume 15, Issue 2
The area of genetics known as immunogenetics focuses on comprehending the immune system's genetic foundation and how it interacts with the human genome. It looks into how immune response to pathogens, immune-related disorders and the efficacy of immunotherapies are affected by genetic variations. In order to protect the body from infectious agents like bacteria, viruses and parasites, the immune system is essential. Additionally, it detects and gets rid of aberrant cells like cancer cells. The immune response is a very intricate process that requires multiple cell types, molecules and signaling pathways to work in unison. The immune system's diversity and functionality are largely influenced by genetic factors.
Immunogenetics; Human leukocyte antigens; Major histocompatibility complex; Cytokines
The Major Histocompatibility Complex (MHC), also referred to as the Human Leukocyte Antigen (HLA) system in humans, is the collective name for the genes that regulate immune responses. The immune system can identify and react to foreign substances thanks to the proteins that the MHC genes encode presenting antigens to the immune system [1-7].
The study of immunogenetics examines how genetic variation within the MHC affects immune response and susceptibility to disease. A person's capacity to mount a successful immune response can be influenced by different alleles (different versions of a gene) within the MHC, which can increase or decrease their susceptibility to specific infections or autoimmune diseases [8].
The genetics of immune-related illnesses, such as autoimmune diseases like rheumatoid arthritis, multiple sclerosis and type 1 diabetes, is another area of study for immunogenetics. Researchers hope to learn more about the underlying genetics of these disorders, find potential biomarkers for diagnosis and prognosis and create targeted therapies by delving into these genetic factors [9].
Immunogenetics is also very important in the field of transplant medicine. To reduce the chance of transplant rejection, organ donors and recipients must have MHC profiles that match. Transplantation success rates for organs and tissues can be raised by having a better understanding of the genetic variables that affect transplantation outcomes. In order to better understand the genetic foundation of the immune system, the multidisciplinary field of immunogenetics combines genetics, immunology and molecular biology. It offers important insights into disease susceptibility, immune response mechanisms and the creation of customized immunotherapies [10].
Significance of studying genetic variations in the immune system
Disease susceptibility: A person's susceptibility to different diseases can be influenced by genetic variations in immunerelated genes. The chance of contracting infectious diseases, autoimmune disorders and even some forms of cancer can all be raised by specific genetic variations. Researchers can identify people who are more vulnerable and create targeted therapies or preventive measures by knowing these genetic variations [11].
The field of immunogenetics has been instrumental in the development of personalized medicine. Genetic profiling can be used to forecast a person's reaction to particular immunotherapies or drugs. Healthcare providers can maximize therapeutic efficacy and reduce side effects by customizing treatments based on an individual's genetic composition [12].
Transplantation compatibility: Researching immune system genetic variations is crucial for the transplantation of organs and tissues. Successful transplantation depends on the recipient's and donor's immune systems getting along, especially when it comes to gene matching within the MHC. Reducing the risk of transplant rejection by identifying appropriate matches through an understanding of genetic variations in the MHC [13].
Vaccine development: Genetic variations can affect an individual's response to vaccines. Some individuals may have genetic variants that alter their immune response to specific vaccine components, leading to differences in vaccine efficacy. By studying these genetic variations, researchers can develop more effective vaccines or tailor vaccination strategies for different population groups [14].
Drug development: Genetic variations can influence an individual's response to drugs, including immunomodulatory agents. Understanding the genetic factors that affect drug metabolism, efficacy and toxicity can help optimize drug selection and dosing for individual patients. This field known as pharmacogenomics leverages genetic information to guide personalized drug therapy.
Basic immunology research: Understanding the immune system's genetic variations helps to understand the underlying mechanisms of immune responses. It aids in the understanding of how immune system regulation, signaling pathways and immune cell development are impacted by genetic factors. This information advances our understanding of immunology [15].
Understanding disease susceptibility, creating personalized medicine strategies, enhancing the effectiveness of vaccines, directing drug therapy, improving transplantation outcomes and expanding our basic knowledge of the immune system all depend on our ability to study genetic variations in the immune system. It has important ramifications for the diagnosis, treatment and prevention of disease in many medical specialties.
This review's main goal is to present a thorough examination and synopsis of the field's current level of understanding in immunogenetics.
Human Leukocyte Antigens (HLA)
A collection of genes known as Human Leukocyte Antigens (HLA) are found on chromosome 6 of the human genome. They encode proteins that present antigens to immune cells and control immune responses, two essential functions of the immune system. The major histocompatibility complex in humans is made up of HLA genes [16].
The human population's HLA system is highly polymorphic, displaying a significant amount of genetic variation. The immune system needs this diversity in order to identify and react to a broad variety of pathogens. Nearly all nucleated cells in the body have expressed HLA proteins on their surface, which enables immune cells to interact with them [17].
Presenting antigens to T cells, a subset of white blood cells involved in immune responses, is the main job of HLA proteins. Small molecules called antigens, like proteins or peptides, are produced by pathogens or other foreign substances. These antigens are brought to the cell surface by HLA proteins, where T cells are exposed to them. T cells need this procedure in order to identify foreign antigens and launch an immune response against them [18,19].
The distinction between self and non-self is another function of HLA proteins. They aid in the differentiation of foreign and native cells in the body. This is particularly important for organ and tissue transplantation, as the compatibility between the HLA profiles of the donor and recipient is critical to minimize the risk of transplant rejection [20].
Thousands of distinct HLA alleles have been discovered to date, demonstrating the great polymorphism of the HLA system. Each person inherits one set of HLA genes from their mother and one set from their father. These alleles are inherited in a Mendelian fashion. The distinctiveness of each person's immune profile is influenced by the variety of HLA alleles [21].
Finding a person's unique HLA alleles through HLA typing is crucial in a number of clinical contexts. It lowers the risk of rejection in organ and tissue transplantation by matching donors and recipients. HLA typing is also used to assess whether a blood transfusion is compatible and to diagnose and treat specific autoimmune diseases [22].
A collection of genes called HLA encode proteins that are essential for immune responses. They participate in the presentation of antigen to T cells and are extremely polymorphic. Immune recognition, transplant compatibility and clinical uses like HLA typing all depend on the HLA system [23].
Human Leukocyte Antigens (HLA) genes and their role in immune responses
The human genome's chromosome 6 contains a collection of genes referred to as HLA genes or human leukocyte antigen genes. HLAs, which are proteins encoded by these genes are critical for immune responses [24]. The Major Histocompatibility Complex (MHC), a section of the genome involved in immune system regulation and the recognition of self and non-self-antigens, includes the HLA genes. HLA genes are divided into two classes in humans, class I and class II. HLA-A, HLA-B and HLA-C are examples of class I HLA genes. Nearly every nucleated cell in the body has proteins expressed on its surface that are encoded by these genes. They are essential in providing CD8+ T cells, also referred to as cytotoxic T cells, with antigens derived from intracellular pathogens, such as viruses and intracellular bacteria [25]. Typically, class I HLA molecules present short peptides that are derived from intracellular proteins as antigens. A cell that has contracted a virus or other intracellular pathogen uses class I HLA molecules to present the pathogen's proteins on its surface after breaking them down into peptides. The presentation of this antigen enables cytotoxic T cells to identify and eradicate infected cells [26].
HLA-Dorsalis Pedis (DP), HLA-DQ and HLA-Disease Resistant (DR) are examples of class II HLA genes. These genes code for proteins that are predominantly expressed on the surface of antigen-presenting cells, including B cells, dendritic cells and macrophages. They are involved in presenting helper T cells or Cluster of Differentiation (CD4+) T cells, with antigens derived from extracellular pathogens like bacteria and parasites.
Antigens that have been taken up and processed by antigenpresenting cells attach to class II HLA molecules. The class II HLA molecules are then used to present the antigens on the cell surface. Helper T cells use this interaction to identify antigens and trigger immune responses, such as the activation of other immune cells and the synthesis of antibodies [27].
Because the HLA genes are highly polymorphic, there are numerous variations or alleles of them in the human population. The diversity of immune responses and the capacity to identify a broad spectrum of antigens are facilitated by this genetic variation. The ability of the immune system to effectively combat different infections depends on the diversity of HLA genes [28].
By presenting antigens to T cells, which are essential components of adaptive immunity, HLA genes and the proteins they encode play a critical role in immune responses. Maintaining immune homeostasis and enabling the immune system to identify and eradicate pathogens depend on the interaction between T cells and HLA molecules. HLA genes are important in transplant medicine as well because successful organ and tissue transplantation and lowering the risk of rejection depend on the donor and recipient's HLA profiles matching [29].
Relevance of Human Leukocyte Antigen (HLA) typing for organ transplantation and disease susceptibility
Identification of a person's unique Human Leukocyte Antigen (HLA) alleles is known as HLA typing and it is crucial for two main purposes, organ transplantation and disease susceptibility [30]. The development of certain infectious diseases, autoimmune disorders and even some types of cancer are all influenced by an individual's HLA typing. Because the HLA genes are highly polymorphic, there are many distinct alleles of them in the human population. Disease susceptibility may be impacted by these genetic differences in HLA alleles, which may affect the immune system's capacity to identify and react to infections or self-antigens.
For instance, certain HLA alleles have been linked to a higher chance of developing autoimmune conditions like celiac disease, multiple sclerosis, rheumatoid arthritis and type 1 diabetes. Under these circumstances, some HLA alleles may make people more susceptible to an immune reaction directed against their own tissues or cells [31]. Infectious diseases may also be relevant to HLA typing. Diverse HLA alleles can bestow differing degrees of vulnerability or defense against specific pathogens. For example, elevated vulnerability to infections such as Human Immunodeficiency Virus (HIV), hepatitis B and C, malaria and tuberculosis has been associated with specific HLA alleles.
Researchers and medical professionals can gain a better understanding of the genetic components that contribute to disease susceptibility by using typing to determine an individual's HLA alleles. This information can support early detection, risk assessment and individualized treatment plans for a range of illnesses.
To guarantee compatibility between the donor and recipient, HLA typing is crucial. Reducing the chance of graft rejection, which happens when the recipient's immune system attacks the transplanted organ because it perceives it as foreign, is essential to the success of organ transplantation [32]. HLA molecules are essential to this procedure. The HLA molecules on the surface of the transplanted organ's cells are recognized by the recipient's immune system, should these HLA molecules exhibit a notable dissimilarity from the recipient's HLA profile the organ could be viewed a alien by the immune system, triggering an immunological reaction that could result in organ rejection [33].
The level of HLA compatibility can be ascertained by transplant specialists by performing HLA typing on both the donor and the recipient. Reducing the risk of organ rejection and increasing the likelihood of a successful transplant are achieved by matching the HLA profiles of the donor and recipient, especially with regard to class I and class II HLA alleles. HLA typing is commonly carried out prior to transplant procedures in order to determine appropriate donor-recipient matches and improve the likelihood of long-term graft survival.
HLA typing has a big impact on organ transplantation and disease susceptibility. In particular, it aids in understanding how immune responses and autoimmune and infectious disease development are influenced by genetic factors. Furthermore, in order to guarantee compatibility between donors and recipients, lower the risk of graft rejection and enhance transplant outcomes, HLA typing is essential in the organ transplant process [34].
HLA gene associations with autoimmune disorders
The relationship between HLA genes and autoimmune disorders has been the subject of much research. When the immune system unintentionally targets the body's own tissues and cells, autoimmune diseases result. HLA genes are excellent candidates for genetic susceptibility to autoimmune disorders because they are essential for immune regulation and for presenting antigens to T cells [35].
Advances in HLA genotyping techniques
HLA typing and understanding the HLA associations can aid in risk assessment, early diagnosis and potentially personalized treatment approaches for individuals with autoimmune diseases. It is worth noting that while HLA genes are strongly associated with autoimmune diseases, they are not the sole determinant. Other genetic and environmental factors also contribute to disease development [36].
Polymerase Chain Reaction (PCR): HLA genotyping was transformed by PCR-based techniques. HLA alleles can be found and identified by using PCR, which amplifies particular DNA regions of interest. Sequence-Specific Primers (SSP) and Sequence-Specific Oligonucleotide (SSO) probes were first created created to distinguish between particular HLA alleles according to their DNA sequences [37].
Sanger sequencing: This DNA sequencing technique is popular and has been used for HLA genotyping. To ascertain the precise nucleotide sequence, amplified HLA Deoxyribonucleic Acid (DNA) fragments must be sequenced. Although Sanger sequencing yields accurate and high-resolution results, it can be expensive and time-consuming, especially when used for largescale genotyping [38].
Next-Generation Sequencing (NGS): By enabling the parallel sequencing of millions of DNA fragments, NGS technologies have completely changed HLA genotyping. NGS provides enhanced resolution, high throughput and simultaneous detection of multiple HLA alleles. Comprehensive HLA genotyping, including the discovery of unique or uncommon alleles and haplotypes, has been made possible by it. For HLA genotyping, NGS-based techniques like hybrid capture-based methodologies and amplicon-based sequencing are frequently employed [38].
Sequence-Specific Primed-PCR (SSP-PCR): SSP-PCR is a PCRbased method that amplifies HLA alleles using particular primers. It offers an easy-to-use and reasonably priced approach to HLA genotyping, especially in environments with limited resources. SSP-PCR is frequently used for HLA typing in blood transfusion and transplantation settings and it can be utilized for high-volume genotyping [39].
Microarray-based methods: HLA genotyping has made use of microarray technology. Immobilized probes that can hybridize with amplified HLA DNA fragments make up microarrays. It is possible to detect multiple HLA alleles at once using this method. Microarray-based methods can produce thorough HLA genotyping results and have high throughput capabilities [40].
High-Resolution Melting (HRM): HRM is a quick and affordable method that uses the distinct melting characteristics of DNA fragments to identify between various HLA alleles. It can yield precise genotyping results and doesn't require sequencing. Finding polymorphisms and identifying known HLA alleles are two areas where HRM is especially helpful. Our capacity to precisely identify HLA alleles and haplotypes has greatly increased as a result of these advancements in HLA genotyping techniques. They have improved patient care and tailored treatment plans in a variety of clinical contexts by deepening our understanding of HLA diversity, disease associations and transplantation compatibility [41].
Small proteins called cytokines are essential for immune system cell-to-cell communication and immune system regulation. They are produced by non-immune cells like fibroblasts and epithelial cells, as well as a variety of immune cells like T cells, B cells, macrophages and dendritic cells. As signaling molecules, cytokines facilitate the coordination of immune responses by passing messages from immune cells to one another [42]. The immune system relies on cytokines to mediate and regulate a wide range of functions, including Interleukin-1 (IL-1), Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) are cytokines that play a role in both initiating and promoting inflammation. They promote the activation of inflammatory responses and aid in the recruitment of immune cells to areas of infection or tissue damage [43].
Cytokines are essential for the growth, differentiation and maturation of immune cells. For instance, Interleukin-2 (IL-2) stimulates T cell proliferation and differentiation, whereas B cell activation and differentiation are mediated by Interleukin-4 (IL-4) and Interleukin-5 (IL-5) [44].
Cytokines are in charge of immune cell activation and proliferation. Natural Killer (NK) cells can be activated and their cytotoxic activity against cancerous or infected cells can be enhanced by Interleukin-12 (IL-12) and Interferon-gamma (IFN- γ). T cells require Interleukin-7 (IL-7) and Interleukin-15 (IL-15) to survive and proliferate [45].
To guarantee a suitable and controlled response, cytokines aid in the balancing and regulation of immune responses. To prevent excessive inflammation and tissue damage, regulatory T cells, for instance, produce cytokines like Transforming Growth Factor-beta (TGF-β) and Interleukin-10 (IL-10), which suppress immune responses.
Cytokines serve as intermediaries between distinct immune cells, promoting intercellular communication and the synchronization of immune responses. They aid in the intricate coordination of immune system cell interactions, resulting in a well-coordinated and potent defense against infections [46].
Certain cytokines, such as interferons, have direct antiviral and antimicrobial effects. They can strengthen the capacity of immune cells to eliminate pathogens, strengthen the antiviral defenses of infected cells and stop viruses from spreading [47].
It's crucial to remember that cytokines can have pleiotropic effects, which means that, depending on the situation and the cells involved, a single cytokine may have multiple purposes. Furthermore, immune homeostasis depends on the balance and control of cytokine production and dysregulation of cytokine signaling can lead to the onset of a number of diseases, such as cancer, inflammatory diseases and autoimmune disorders because they coordinate and modify immune responses, cytokines are essential for immune regulation. Their complex web of interactions and roles guarantees that the immune system will operate as it should in preventing infections, preserving tissue homeostasis and fostering immune surveillance [48-52].
The study of genetic variables that influence the onset and course of immune-related disorders is known as immunogenetics. Understanding how genetic variations affect the immune system's response to pathogens and how autoimmune disorders, immunodeficiencies and other immunemediated diseases develop are the main areas of focus.
The structure, expression and function of immune-related genes can be impacted by genetic variations, including Single Nucleotide Polymorphisms (SNPs), insertions, deletions and Copy Number Variations (CNVs), presentation, immune cell activation and regulation of immune responses.
These arise when healthy cells and tissues are unintentionally attacked by the immune system. Certain genetic variations have been linked to an increased risk of autoimmune diseases, according to immunogenetic studies. For instance, there is a strong correlation between certain variations of the Human Leukocyte Antigen (HLA) gene and conditions like type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus. These HLA variations are essential for controlling the immune system and presenting antigens.
People with immunodeficiencies have weakened immune systems, which leaves them more vulnerable to infections. Certain genetic mutations affecting genes related to immunoglobulins, T-cell receptors, complement pathways or other immune system components can result in certain primary immunodeficiencies. An increased vulnerability to infections can arise from these genetic variations if they cause abnormalities in immune cell development, function or signaling.
An individual's susceptibility to infectious diseases is influenced by genetic factors. The ability of the immune system to identify and mount a successful defense against pathogens can be impacted by variations in genes involved in immune recognition, signaling or response pathways. For instance, altered immune responses to particular infections have been linked to variations in the genes encoding Toll-Like Receptors (TLRs), which are essential for pathogen recognition.
Genetic differences can also have an impact on immune-related diseases' severity, course or clinical results. These moderators may have an impact on the way a disease presents, how well a treatment works and whether complications arise. For example, in the case of autoimmune diseases, certain genetic variations have been found to predict the response to immunosuppressive therapies or to modify the course of the disease in HIV/AIDS.
Research on immunogenetics can shed light on how a person's genetic makeup affects how they react to immunomodulatory treatments. Genetic variations pertaining to drug metabolism, drug targets or immune pathways may influence the efficacy or unfavorable outcomes of immunosuppressive or immunomodulatory drugs. Pharmacogenomic testing can improve therapy outcomes and serve as a guide for treatment decisions.
Gaining knowledge about the immunogenetic foundation of disease susceptibility facilitates enhanced risk evaluation, timely identification and customized therapeutic approaches. It is crucial to remember that gene-gene interactions, environmental factors and epigenetics all play important roles in the complex puzzle of disease susceptibility, genetic variations are just one piece. To better understand disease mechanisms and create targeted therapies, more research is required to untangle the complex interactions between genetics and the immune system.
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Citation: Atsbeha A, Bekele D (2024) A Review on Unlocking the Secretes of Immunogenetics. J Clin Cell Immunol. 15:708.
Received: 23-Feb-2024, Manuscript No. JCCI-24-29746; Editor assigned: 26-Feb-2024, Pre QC No. JCCI-24-29746 (PQ); Reviewed: 11-Mar-2024, QC No. JCCI-24-29746; Revised: 18-Mar-2024, Manuscript No. JCCI-24-29746 (R); Published: 25-Mar-2024 , DOI: 10.35248/2155-9899.24.15.708
Copyright: © 2024 Atsbeha A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.