The importance of the adaptive immune system and various pathologies associated with it

Abstract

The immune system is an essential body system that enables the organisms to launch attacks against the pathogens. The immune system comprises two types of defenses: adaptive and innate. The innate immune system consists of physical barriers like skin, chemicals in the blood. This type of immunity system is non-specific. This means it can attack any type of pathogen whether it is a virus or bacteria. The adaptive immune system, on the other hand, can provide advanced protection from pathogens that can cause harm to the body. The adaptive immune system has its further division which indicates the difference in the adopted methods of response. These differences between the humoral and the cell-mediated response are delineated through this review paper.  There are markers on the T and B lymphocyte cells known as the MHC-class markers, that are crucial to distinguish between self and foreign cells. With these markers, the immune system can launch a response against the invaders. The two crucial markers on the surface of the T and B lymphocytes are discussed in the paper. It is very crucial for individuals to possess a healthy functioning immune system to survive in the world surrounded by pathogens and carcinogens. However, sometimes there can be cases where the adaptive immune system fails to identify the diseased cell which can lead to pathology like cancer. Recent research demonstrates that if the T-cell recognizes a cancer cell, it can launch an attack against the cancerous tumor; thus, healing cancer. Also because of certain properties of the immune system, there can be a reaction caused after a transplant which makes it important for a patient to take anti-rejection medications. There can be cases where the immune system can attack cells in the body that may result in autoimmune disease. Most importantly, this paper reviews various expert hypotheses that attempt to explore the immune system response against the Coronavirus. 

Introduction

The human body has evolved into a complex set of body systems that work in congruence for healthy functioning. The immune system is one of the body systems that protect essential organ systems from a pathogen invasion. There are two types of immune system defenses which are known as the adaptive and the immune system. This review paper elucidates the certain aspects of the adaptive immune system response. T and B-cell lymphocytes are the major component of the adaptive immune system response. These cells recognize the cell infected with a virus and initiate an immune system response. With this property of the T-cells, it is possible to treat cancer when certain antibodies as described later. However, there are cases when this cell-mediated response can be compromised. Such a case is the AIDS virus that can affect the capability of the T-cell to recognize the invader. This paper also explores the history of immunology research. 

T and B-lymphocytes

         T and B lymphocytes are essential components of the acquired immune system which are involved in the cell-mediated and humoral responses, respectively. Lymphocytes are the white blood cells that originate from the stem cells of the bone marrow. The B cells mature in the bone marrow itself whereas the T-cells migrate to the thymus for further maturation. The major difference between the two types of lymphocytes is their involvement in the varied response of the acquired immune system. The B-cells produce antibodies after exposure to the antigens whereas the T-cells attack the infected cells by activating the cytotoxic T-cells. More differences within these lymphocytes are described later in the paper. 

           

The history of immunology

            Immunology or the study of the immune system started to gain recognition when the first vaccine was developed by Edward Jenner, an English physicist. This vaccine was developed to fight against the variola virus that causes smallpox. Jenner was able to develop the vaccine as he observed that some of the milkmaids were “immune” to the smallpox disease if they were first exposed to the cowpox. However, the concept of memory formation after an initial pathogen attack was first observed in China. The early scientists were still not familiar with the concept that a microbe can cause disease as they had limitations including the incapability of not being able to observe microscopic organisms. Hence when Antoni Van Leeuwenhoek invented the microscope, the field of immunology witnessed advancements. Pasteur, who was initially interested in the process of fermentation, later developed the germ theory where he elucidated how the germs were transmitted from an infected to a healthy body (History of Immunology | Encyclopedia.Com, 2014). He also developed a vaccine against rabies. Eventually, many scientists discovered the importance of the antibodies and how they helped the immune system to launch an attack against the invaders. In the 1970s, there was an understanding of the two types of lymphocytes which included the B and T cells and originated from the bone marrow and the thymus respectively. With the advancement of technology, the T-cell interaction with various epitopes¹ was determined. The most crucial development of the immunology was the selection of the specific T-cell type and their cloning for the treatment of a specific disease. This part of the immunology is discussed later in this review paper. With the advent of molecular immunology, disease treatment with the application of T-cell is possible. This is a rapidly developing field with a promising potential for disease treatment.

The Cell-Mediated and Humoral Response of the adaptive immune system

The immune system has an essential function in protecting the body from foreign invaders. Hence there are many divisions of the immune system that ensure a healthy existence of the internal organs. The adaptive immune system has two such divisions that include the humoral and cell-mediated response. The humoral response is related to the B-cell and the formation of antibodies against the specific antigens existing in the plasma and interstitial fluid. The helper T-cells activate the B-cells which secrete antibodies. These antibodies bind to the antigens that neutralize them. The process of neutralization prevents the pathogen multiplication outside of the cells. That is why the immune response initiated to prevent a pathogen invasion outside of the cells is referred to as “humoral response” as the term “humoral” means bodily fluids.  As opposed to the humoral immune response, the cell-mediated attack is targeted towards the virus-infected or cancer cells if the immune system recognizes the tumor. When a dendritic cell or a macrophage digests an antigen, the cell presents the antigenic fragment on its surface. This cell is now referred to as the antigen-presenting cell. The MHC II marker recognizes the infected cell when it binds to the antigen-presenting cell. Cytotoxic T-cells, which are the type of T-cells that release proteins that lyse the infected cell, are released. Through this process, the immune system prevents the virus to divide through the infected cell. The MHC genes and the various types of T-cells are discussed later in this paper. The major difference between the humoral and cell-mediated response is the secretion of the antibodies. The humoral response depends upon the antibodies whereas the cell-mediated response depends upon the proteins secreted by the cytotoxic T-cells. 

Major Histocompatibility Complex

            The major histocompatibility complex or the MHC genes have the responsibility to help the immune system to recognize self from the foreign invaders. The MHC genes are polygenic, meaning there are several types of MHC genes. For instance, there are two types of MHC genes: MHC class I and class II. Most importantly, MHC genes are polymorphic. This is very crucial to understand as there are many types of this gene in a given population(Janeway et al., 2020). Thus an individual has a unique set of genes that help to sense the difference between foreign and self-cells. The MHC class I molecules are present in all the nucleated cells which present proteins made by the body’s own cells. They have the ability to present the proteins produced by the antigens attacking the body’s fluids. These MHC class I markers then bind to the cytotoxic T-cells or can lead to the activation of the B-cells that can secrete antibodies. The MHC class II markers present the antigenic proteins to the helper T-cells that activate the cytotoxic T-cells. The cytotoxic T-cells release proteins that can lead to cell death. The MHC class I molecules are involved in the humoral response and the MHC class II molecules are involved with the cell-mediated response.

 The categories of T-cells 

            There are different types of T-cells that have separate functions that make the immune response effective. One such type is the cytotoxic or CD8 T-cells. The cytotoxic T-cells directly interact with the MHC class I marker to attack the infected nucleated cells or the intracellular bacteria which have the potential to grow in the host. The cytotoxic T-cell have CD8 proteins on their surface that helps them interact with the MHC class I gene. The cytotoxic T-cell secrete proteins that form pores in the cell to lyse them. These cells are also activated by the helper T-cells. The helper T-cells are activated when they interact with the antigen-presenting cells. The MHC class II genes interact with the CD4 protein on the surface of the helper T-cells. After the activation of the helper T-cells, they may activate other cytokines, which signal the production of the antibodies by the memory B-cells or activate the cytotoxic T-cells. The other type of T-cell is memory T-cell. When the T-cells initiate an attack against the specific antigen, they might form memory by storing the antigen fragment. When the same antigen attacks the host body, the memory T-cells can turn into effector T-cells that can help coordinate an immune system attack.

Autoimmune diseases 

            Most of the time, the immune system is very accurate in recognizing foreign cells and pathogens. However, due to numerous factors, including genetic and environmental, there can be errors in identifying native cells. That is why there are many cases where the immune system attacks its own cells. This can lead to organ failure and other problems. The condition where the immune system attacks its own body is referred to as the “autoimmune diseases.” According to NEIHS, scientists are aware of 80 autoimmune diseases. Examples of autoimmune diseases include multiple sclerosis, diabetes type I, and rheumatoid arthritis. There are also cases that are often not diagnosed and the patients, hence, do not receive proper treatment. As discussed earlier, there are many factors that can contribute to this condition. These factors can include the environment and genetics. Environmental factors can consist of exposure to harmful levels of sunlight, excessive exposure to organic mercury, and improper nutrition. People may also be genetically predisposed to develop autoimmune diseases. For example, many people of European descent have inherited the predisposition to develop an autoimmune disease that attacks the muscle cells (Autoimmune Diseases, 2018). Similarly, many women with Asian-American and Hispanic descent are at risk of developing lupus. 

Lupus: An autoimmune disease 

            Lupus is a type of autoimmune disease which is commonly diagnosed in women in the reproductive ages. In this disease, the immune system starts attacking the organs which challenge the normal existence of a person. It causes inflammation in the affected part of the body. Lupus can develop in skins, joints, and vital organs. There are four types of lupus which include: systemic lupus erythematosus², Cutaneous lupus², neonatal lupus³, and drug-induced lupus⁴ (What Is Lupus? 2020). The origins of the lupus are undetermined; but, it can be deduced that genetics have a major role in this disease. For instance, women with Asian-Americans, Asian, Hispanic/Latino, Native American, and Native Pacific Islanders are at the risk of developing the diseases. Perhaps the mutation has existed in this population. This proves that genetics are prominent in the occurrence of this disease. Scientists also have reasoned the link between more women diagnosed with lupus as compared to men. Lupus is often linked with the hormone estrogen. Women express more estrogen than men and this hormone is crucial for a stronger immune system. There is no clear causal link between lupus and estrogen; however, there is a strong correlational relationship between high expression of estrogen and the onset of lupus. 

T-cells and cancer treatment

            Cancer means the rapid and uncontrolled cell division in certain areas of the body. If the tumor is undetected, then there is an increased risk of cancer spreading to the other parts of the body. This type of cancer is typically known as “metastatic.” The immune system of the body has the potential to attack the tumor as the cancer cells cannot be determined as“normal.” However, the immune system often fails to recognize these tumor cells. If the T-cells recognize the tumor, then there are chances that the immune system can launch an attack on the immune system. In his breakthrough research, Jim Allison researched a method through which the immune system can recognize the tumor. In his research, he explained how the immune system possesses a “break” that prevents any potential to develop any excessive inflammation due to the immune system response. This is why cancer escapes the careful surveillance of the immune system. Allison recognized the brakes as CTLA4 or “Cytotoxic T-lymphocyte-associated protein 4”. This protein on the surface of the T-cells serves as a check to the immune system. Allison and his team developed the drug Ipilimumab that acts as a monoclonal antibody⁶ that binds and inactivates CTLA-4. 

CAR Monoclonal anti-body and treatment of blood cancer 

            Currently, medical advancements have allowed the treatment of blood cancer through the application of monoclonal antibodies. In summary, a patient’s cell is analyzed in a lab to add a receptor that can identify cancer and signal the immune response of a potential abnormality. This receptor is known as the CAR (Chimeric antigen receptor) monoclonal antibody. It is synthesized in the lab by combining an antibody derived single chain and a transmembrane domain that links to the internal signals that can elicit the T-cell effector response (Stoiber, et.al). This increases the specificity that can attack the tumor. We can deduce that these CAR antibodies are specific to the patient and hence the lab collects the cell from the patients to ensure high specificity. The cancer cells are killed through apoptosis or cytokinesis attack. Scientists are researching whether CAR antibodies can treat other types of cancer. 

The HIV Virus and the immune system

            The HIV (human immunodeficiency virus) infection begins when the virus injects itself in the helper T-cell. The virus later replicates itself in the cell after injecting its own DNA. The infection is spread throughout the body. This weakens the immune system y as the ability to recognize the foreign pathogens is comprised. The current treatment for HIV is referred to as  “Antiretroviral therapy.” In this therapy, certain medications are administered to ensure that the virus does not replicate rapidly. With the viral replication in check, the immune system has the ability to fight the infections (HIV Treatment: The Basics  Understanding HIV/AIDS, 2020). 

Immunity suppression for transplant patients 

            As discussed earlier, the immune system is extremely efficient in recognizing any foreign molecule in the body. This property of the immune system can prove harmful to the transplant patients as the graft transplanted in them is foreign. It is very likely that the immune system will recognize the graft as a harmful foreign pathogen which is likely to harm the body. That is why the immune system can initiate an attack that can cause rejection of the organ. Thus proving to be extremely harmful. To prevent this, immunosuppression medications are administered to transplant patients that can suppress the immune system attacks. A well-known immunity suppression medication is “Tacrolimus.” The molecular formula of Tacrolimus is C₄₄H₆₉NO₁₂. When the anhydrous⁷ form of Tacrolimus forms a complex with the calcium-dependent protein, the calcineurin related activity is inhibited (PubChem, 2020). This results in the suppressed activity of the T-cells as the calcineurin related activity is crucial for the activation of the T-cells when the body senses the entry of a pathogen. Tacrolimus also inhibits the activity of several cytokines⁸. 

COVID-19 and the immune system

            Currently, the world is facing an unprecedented situation caused by the Covid-19 pandemic. In order to better understand the immune system and its involvement in the fight against this virus, this review paper has a section dedicated to the various hypothesis and statements from the experts. As this virus is genetically similar to the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), the scientists are assuming that the immune system has a reaction similar to that of the SARS-CoV.  According to Hesari, the COVID interferes with the first immune response of the body. This initial response of the body is the amplification of the interferon⁹ (IFN-1) numbers. The deactivation of the interferons allows for the rapid division of the virus with minimal checks from the immune system. Research also demonstrates that the cells with limited ATP¹⁰ have an increased risk of getting infected. The rationale behind this hypothesis is that the ATP initiates the interferon signaling pathway to help launch an attack against an invading virus. ATP depletion can lead to numerous factors that can promote the onset of the disease. The cytokine storm has the potential to increase the inflammation in the body which produces an inhospitable environment for the virus to reproduce. However, with the limited supply of ATP, the cytokine storm cannot take place. Moreover, ATP functions in the prevention of T-cell apoptosis. Hence with the inadequate amount of this important molecule, the T-cell attack is compromised (Taghizadeh-Hesary & Akbari, 2020). It is previously mentioned that the ATP depletion can prevent the cytokine storm which can lead to the disease. Nevertheless, as described by this Yale School of Medicine Immunologist,  an aggressive cytokine storm can irritate the lining of the lungs and can worsen the symptoms of the diseases (Yale Medicine Staff, 2020). The role of the immune system in fighting this virus is still under investigation. When the immunologists better understand this, there is a glimmer of hope for the production of a vaccine that can introduce a cure against the coronavirus. 

Conclusion

            The immune system is a very crucial physiological system that allows our survival in a world filled with pathogens that require nourishing hosts which are obtained in the form of our bodies. The immune system is very efficient in distinguishing self and foreign cells. However, due to some genetic or environmental factors, the immune system may not have this ability and can lead to autoimmune diseases. Moreover, the immune system may need assistance which is provided in the form of vaccinations. These vaccinations help the immune system to be more efficient in fighting some of the infections. With that being said, the most important point is to be grateful for this efficient immune system. 

           

Notes

1.      Epitopes: are parts of the protein which are derived from the antigen. These epitopes are recognized by the antibody and immune system response is initiated. 

2.      systemic lupus erythematosus: the common type of lupus; in this type of lupus the immune system can attack different internal organs and cause inflammation

3.      Cutaneous lupus: In this type of lupus, the skin is attacked by the immune system

4.      Neonatal lupus: This type of lupus is quite rare and can affect the infants of women who had lupus  

5.      Drug-induced lupus: The lupus of this type is caused by prescription drugs 

6.      Monoclonal antibody: developed in the laboratory that helps the immune system to recognize cancer. They can help the immune system to orchestrate a response  

7.      Anhydrous: a crystal structure without any hydrogen molecules

8.      Cytokines: cell signaling molecules that help in immune system communication when orchestrating an attack

9.      Interferon type 1: produced in response to a viral attack to prevent virus replication

10.  ATP: Adenosine Tri-phosphate, the energy molecule of the cell 

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