An Overview of Immunology

Introduction

The oral cavity is an advanced location of immunity. Systemic and mucosal immunity interact and play crucial roles in defending against damage and infections, as well as in the pathophysiology of many oral mucosal illnesses. Immunology is the study of molecular cells, organs, and systems involved in recognizing and eliminating foreign objects. Variations in immunity are caused by age, nutrition, and genetics.¹

The Roman senators' immunity from lawsuits during their tenure was originally denoted by the Latin word "immunis" (exempt), which is where the English word "immunity" (exempt) originates. Subsequently, the phrase was also used to describe the naturally developed immunity to diseases like smallpox and measles. It is implied that an individual could acquire a lifelong immunity to a disease after only one infection. The phrase "immune response" describes the immune system's coordinated reaction to foreign substances. The immune system is composed of the cells and chemicals involved in immunity.²

History of Immunology

The idea of immunity has existed for a very long time. One of the methods is the Chinese custom of protecting children from smallpox by inhaling powder created from the skin lesions of patients recovering from the disease. The oldest mention of immunity in Europe dates back to Thucydides of Athens in the fifth century BC. According to his account of the plague in Athens in 430 BC, only those who had recovered from the disease could tend to the sick because they would not become ill again. It was not long before the concept of immunity was established, and then came the controlled manipulation of immunity. The first was Edward Jenner, who successfully tested the idea of injecting cowpox pustule material into the elbow of an eight-year-old child to show that smallpox exposure did not result in the formation of any subsequent disease. Drawing from his observations that milkmaids afflicted with cowpox would never contract the more dangerous smallpox, he arrived at this conclusion. The cowpox vaccination that Jenner created and administered to patients swiftly spread throughout Europe.

But for a variety of reasons, including ignorance of clear disease targets and their origins, this approach of smallpox prevention was not adopted until nearly a century later. Emil von Behring and Shibasaburo Kitasato's 1890 experiments provided the first understanding of the immune system's functioning and earned von Behring the 1901 Nobel Prize in Medicine. Von Behring and Kitasato demonstrated that animals who had previously received diphtheria vaccination may transfer the immunological status to unimmunized animals through the serum, which is the liquid, noncellular component of coagulated blood. Since then, immunology research has made substantial advancements.²

The Skin as a Barrier to Infection: First Line of Defense

The body's surface defenses, which include the skin and the mucous membranes lining the respiratory and digestive systems, eliminate a variety of germs before they can enter the body's tissues. The skin is the largest organ in a vertebrate and accounts for 15% of the body weight of an adult human. Because of the oil and sweat glands, the skin's surface has a pH of 3 to 5, which is sufficiently acidic to inhibit the growth of most microbes.²

Cellular Counterattack: The Second Line of Defense

The body uses a range of general chemical and cellular defense systems to protect itself. All of these devices react to any microbial infection without stopping to recognize the intruder, which is one thing they have in common. The lymphatic system is a focal point for the dispersion and assembly of immune system cells. This is the site of the body's dispersion of non-specific immune response cells and chemicals (lymphatic capillaries, ducts, nodes, and lymphatic organs). These cells combat infections throughout the body in addition to being stored in lymph nodes, where foreign intruders can be removed as bodily fluids pass through.³

Types of Immunity

The initial stage of a host's immune response is the identification of foreign chemicals and bacteria. The defensive systems of the body are separated into two types of immunity: Innate (natural) and Acquired (adaptive).

Innate immunity

The innate immune system's defenses against infection can be promptly triggered by a pathogen. The goal of the innate immune system, which is essentially made up of barriers, is to either stop or lessen the ability of bacteria, viruses, parasites, and other foreign things to enter your body. One of the most important functions of innate immunity is the quick recruitment of immune cells to regions of infection and inflammation through the production of cytokines and chemokines (small proteins involved in cell–cell communication and recruitment).

The synthesis of cytokines during innate immunity mobilizes several defense mechanisms and triggers local cellular responses to infection or injury. Three key inflammatory cytokines are generated early in the response to bacterial infection: interleukin 6 (IL-6), tumour necrosis factor (TNF), and interleukin 1 (IL-1). These cytokines play a critical role in initiating the local inflammation and cell recruitment required for eliminating several infections.²

Complement system

The complement system is made up of more than 20 proteins, some of which are designated C1 through C9. Both innate immunity and adaptive immunity are used by this system to defend against microbial infections. The complement system is activated by a variety of complement protein cleavage products that result in enhanced opsonization, chemotaxis, and vascular permeability. The complement system is a biochemical cascade that recognizes and opsonizes (coats) bacteria and other pathogens. Additionally, it immediately destroys various infections and bacteria. Immune cells absorb bacteria and eliminate cell waste through a process known as phagocytosis. Phagocytic activity of the innate immune response helps eliminate dead cells or antibody complexes, as well as foreign materials present in organs, tissues, blood, and lymph.²

Adaptive Immunity

This type of immunity is organized according to the peculiarities of the pathogen producing the infection and around an ongoing infection. Because they are of the same molecular type, adaptive immunity receptors are highly pathogen-specific. Long-term immunological memory is given to the pathogen by the body retaining part of the cells selected during an adaptive immune response. A pathogen-specific adaptive immune response is initially produced during the main immune response. Vaccines must provide an innate immune response in addition to a secondary immunological response because all adaptive immune responses depend on it. Circulating lymphocytes interact with lymph-borne pathogens in draining lymph nodes. Lymphocytes remain in the node to divide and develop into effector cells when stimulated by pathogens. After draining from an infection site, lymphocytes leave the circulation and go into lymph nodes, where pathogens in the afferent lymph might activate them. The lymphatics carry lymphocytes to the thoracic duct if they are not activated after leaving the efferent lymph node.

Cells of the Immune System

The immune system's cells are divided into two primary categories: innate immunity and adaptive immunity. Innate immune cells react faster than adaptive immune cells, which have a delayed response that can take days to fully develop before going on to build immunological memory.

Inflammatory Response

Infected or damaged cells release chemical alarm signals, most notably prostaglandins and histamine, which set off a non-specific, localized inflammatory response. Additionally, they promote the dilatation of nearby blood vessels, which enhances blood flow to the site of damage or infection and results in the area being heated and red. These compounds generate the edema, or swelling of the tissues, that is often linked to infection by increasing the permeability of nearby capillaries. Some infections are accompanied with pus that is composed of tissue cells, dead or dying pathogens, and neutrophils. The neutrophils are the first to reach the area and release chemicals that kill the nearby bacteria as well as other tissue cells and themselves. Afterwards, monocytes mature into macrophages, which eliminate infection and the leftovers of deceased cells. Blood carries interleukin-1, a regulatory chemical secreted by macrophages in reaction to invasive microorganisms, to the brain.⁴

Initiating the Immune Response

When an invading germ penetrates the epidermis, histamine and prostaglandins are released, which act as chemical warning signals and induce adjacent blood vessels to enlarge. Bacterial intruders are assaulted and engulfed by a surge of phagocytic cells due to swelling caused by increased blood flow. The major histocompatibility complex (MHC) is a group of genes that produce the glycoproteins present on the surface of most vertebrate cells. These glycoproteins are known as MHC proteins or, more precisely in humans, human leukocyte antigens (HLA). The MHC proteins on tissue cells enable self-versus-non-self, recognition, which is the immune system's ability to differentiate its own cells from alien ones. Immune system T cells can distinguish between self and non-self cells, owing to the MHC proteins on the cell surface. One of the two classes of MHC proteins, MHC-1, is present in every nucleated cell in the body. Nevertheless, MHC-II is exclusively found on B cells, macrophages, and T cells that belong to the CD4+ T cell subtype. MHC-II markers allow these three cell types to recognize one other and work together in a single sort of immune response.⁴

Cell Mediated Immune Response

Cell-mediated immunity (CMI) is a particular type of acquired immunological response in which sensitized T cells, rather than antibodies, are responsible for the immune response. It is called a cell-mediated immune response because it is transferred from donor to recipient via intact lymphocytes rather than antisera. It offers defense against infections caused by obligatory intracellular bacteria, viruses, fungi, and parasites, such as those caused by Brucella, Measles (Toxoplasma gondii, Leishmania donovani, etc.), Mycobacterium leprae, and Tuberculosis. It participates in immunological surveillance and cancer immunity. It is essential to the pathophysiology of certain autoimmune disorders, such as encephalitis and thyroiditis, as well as delayed hypersensitivity reactions.⁵

Induction of CMI

Before being delivered to cells with the appropriate receptors, antigens are processed and presented in relation to self-MHC molecules. Proteins from foreign antigens, such as bacteria, can enter antigen presenting cells (APCs), such as macrophages, through endocytic vesicles. They are then exposed to intracellular vesicles that contain cellular proteases. Peptides with lengths of approximately 10–30 amino acid residues are produced by endosomal vesicles. Following their sensitization, the sensitized T lymphocytes undergo blast transformation, clonal proliferation, and differentiation into effector and memory cells such as Th, Tc, Td, and Ts. Ultimately, the physiologically active chemicals known as lymphokines which are responsible for various CMI manifestations are released by activated lymphocytes.⁶

Cytokines

Cytokines are physiologically active molecules secreted by monocytes, lymphocytes, and other cells. They are important in innate immunity, adaptive immunity, and inflammation. They actively participate in a wide range of biological functions, such as cell activation and chemotaxis. Cytokines were originally believed to be immune cells' byproducts, acting as mediators and regulators of immunological processes. It is now known that non-immune cells can be affected by cytokines, which are produced by a variety of types besides immune cells.⁷

Antibodies

IgM: This is the first class of antibodies released during the initial reaction. On the surface of lymphocytes, they function as receptors and promote agglutination processes, which cause antigen-containing particles to adhere to one another (agglutinate).

IgG: The most common form of antibody generated during a subsequent response in blood plasma.

IgD: These antibodies function on the surface of B cells as antigen-receptors.

IgA: The most common form of antibody in exogenous secretions, such as breast milk and saliva.

IgE: This kind of antibody promotes the production of extra substances, such as histamine, to aid in the pathogen attack.⁶

Unfortunately, they can sometimes trigger a severe reaction when an innocuous antigen gets into the body, leading to symptoms similar to hay fever. Antibodies do not kill invasive infections directly; rather, after IgM antibodies are created and the complement system is engaged, phagocytic cells and the complement system eliminate the pathogens. After around a week, this first wave of antibody synthesis peaks, and a much longer wave of IgG antibody production follows.²

The general structure of the antibody molecule is shown in Figure 2. The structure is made up of four polypeptide chains. The third unit (fc) binds effector molecules to eliminate antigen and mediate functions, including maternal fetal transport, whereas the other two identical fab units bind antigen. As indicated, the two identical heavy (H) and light (L) chains are positioned to span three structural units. Each antibody molecule consists of two identical short polypeptides called light chains and two identical long polypeptides called heavy chains. An antibody molecule has a Y-shaped structure due to the disulphide bonds that hold its four chains together. The polypeptide in the Y stem always has the same amino acid sequence within a particular class of immunoglobulins. Sequence variations across antibodies with varying degrees of specificity can be found in the variable region of each arm. Here, a cleft forms, that functions as the binding site for the antigen. Since both arms always have the same cleft, they bind the same antigen. The B cell receptors are found in the structure of an antibody. The receptor binds to antigens at the termini of its two variable regions. The stem is shaped by the so-called "constant" region of the heavy chains. Five different immunoglobulin classes are formed by the combination of five different heavy chain classes found in mammals - IgA, IgD, IgE, IgM, and IgG.⁸

Autoimmunity

Autoimmunity, or autoimmune illness, arises when the immune system's ability to distinguish between foreign antigens and its own constituents is compromised due to the overriding of self-tolerance mechanisms. These processes involve auto antigens, auto reactive lymphocytes (particularly helper CD4+), auto reactive lymphocytes B, and autoantibodies, which are the byproducts of these cells. Autoantigens can be found on or in the cytoplasm of normally occurring organism cells, or they can even create and excrete them on their own. Using the MHC molecule, T and B cells are able to identify their epitopes. Autoantibodies engage with auto antigens to initiate a cascade of immune responses that can lead to organ and tissue death, including complement activation, opsonization, antibody-dependent cell mediated cytotoxicity, and complex deposition.⁸

Pathogenesis of Autoimmunity

Release of sequestrated antigens

Numerous host antigens are compartmentalized to shield growing immune cells from their epitopes. Consequently, during processes of tolerance, there is no possibility of negative selection of cells with antigen receptors specific to these sequestered antigens. The source of these antigens may be "Immunologically Privileged Sites" in particular organs such as the testicles or eye that are inaccessible to the immune system. Alternatively, they can represent DNA or chromatin antigens that have been hidden in the intracellular space. However, with acute inflammatory conditions or trauma, the release of these usually contained antigens may promote the formation of auto-reactive cells.⁸

Epitope spreading

It is now known that during mechanisms of tolerance, only a tiny subset of self-epitopes referred to as "Cryptic Epitopes" are exposed to growing lymphocytes. Consequently, tolerance mechanisms may not be triggered and lymphocytes specific to these "Cryptic Epitopes" may not be subject to negative selection. Conversely, after acute inflammatory reactions, antigen presenting cells may begin to display these "Cryptic Epitopes," which would then activate auto-reactive lymphocytes against these antigens. This process of lymphocyte activation triggered by inflammation and responsive to cryptic epitopes is known as "epitope spreading".⁹

Non-specific activation

Certain highly inflammatory chemicals that appear to non-specifically activate lymphocytes may drive tolerated lymphocytes out of anergy and into a condition where they can proliferate and develop into effector cells. The finest example of one of these chemicals is lipopolysaccharide (LPS), which is generated from bacteria and polyclonally activates B cells, some of which go on to make auto-antibodies.¹⁰

Molecular mimicry

Previous microbial infection appears to be the cause of some autoimmune disorders. Antigens that closely mimic self-antigens are thought to be present in these microorganisms. During the immunological response to the pathogen, lymphocytes specific to these microbial antigens may proliferate and develop into effector cells. These surviving cells may begin organizing an immunological attack against tissues that share the same self-antigen once the pathogen has been eradicated. This "Molecular Mimicry" process may be the cause of several post-infectious autoimmune disorders.¹¹

Sequestered or hidden changes

In remote locations, the immune system is unable to reach Ag. For example: lens Ag, sperm, and thyroglobulin. Neoantigens are novel or altered antigens resulting from microbiological (intracellular viruses), chemical (drugs), or physical (irradiation) activities.¹²

Cessation of tolerance

If tolerance to self-antigens is lost, that might occur. In cross-reacting antigens, a foreign antigen mimics a self-antigen. Examples of the ex-Ag of sheep Ag and human brain include renal glomeruli, nephritogenic streptococcal strains, and streptococcal M protein and heart muscles.

Immunodeficiency

The argument that immune systems are essential because all living things devote significant resources to them ignores the significance of immune systems at different phases of life. Life does not intrinsically require a functioning immune system, and both humans and animals with weakened immune systems can grow, develop, and reproduce quite normally if they are protected from infectious agents. This raises the question of how crucial immunity is to overall health. Nature has given us a very clear answer through her experiments.¹³

Allergy

However, antigen-specific treatments have demonstrated promise in the management of allergies. Like autoimmune illness, allergy is caused by an inappropriate immune response. Instead of an autoantigen, the triggering antigen in this case is a typically benign environmental protein. Allergy reactions can be brought on by a very wide range of different triggers. These could be drugs, like the antibiotic penicillin, or chemicals, like the pollens that cause hay fever. Allergy-induced responses are very targeted because they represent an adaptive immune response. It is not a general pollen that causes hay fever in humans, but rather a particular kind of pollen. Patients who are allergic to penicillin can safely use alternative antibiotics. Allergies are the most common type of acquired immunological illness. Usually, they depend on an immunological response to the environmental antigen, mediated by IgE. Similar to when an autoimmune disease is begun, the f irst sensitizing event may not even be detected, yet it causes the formation of high-affinity IgE antibodies. By adhering to granulocyte cells, IgE functions as an allergen receptor and, when triggered, produces strong inflammatory mediators. These cells are common at mucosal surfaces, and it is thought that their main job is to get rid of toxic substances, which explains why their activation can sometimes cause sudden and acute symptoms.¹³

Transfusion and Transplantation

Complex ideas of blood circulation that gained prominence in the 17th century served as the basis for experiments involving the transfer of blood, for example, from people to animals or from one person to another. These treatments were sometimes reported as successful, despite the fact that they were often lethal. We now know that giving them a second or third time would have given the immune system enough time to create a memory, which makes this especially accurate. In 1903, Karl Landsteiner, who was investigating the source of this memory, revealed that human serum had antibodies that specifically targeted red blood cells for elimination. The rules governing red blood cell immunity were really simple. Any red cell antigen that the person did not express was neutralized by destructive antibodies. A and B were the initial antigen designations. Red blood cells expressing 'B' antigens are killed by antibodies in a patient who exhibits 'A' antigens, and vice versa. Red blood cells with blood type O that did not express either antigen could be given to any recipient. Understanding these patterns of response set the groundwork for the development of safe blood transfusion practices. Transplanting whole tissues was a far greater task. Blood group matching was not enough to guarantee acceptance.¹³

Immunotherapy

Immunotherapy is a sort of treatment that produces a medical benefit by utilizing our understanding of the immune response in animals or people. It may either stimulate or inhibit broad mechanisms such as costimulation or the specificity of the immune response. Effective immunotherapy dates back to the smallpox vaccination, which was previously addressed. However, similar techniques are also applied in a wide range of different contexts. Based on studies published in 1890, Emil Behring developed passive immunity against diphtheria toxin, which was one of the earliest therapeutic applications of immunotherapy. After immunizing guinea pigs with an attenuated toxin, Behring and Kitasato Sibasaburo discovered that their serum could treat animals infected with virulent strains of the sickness. In 1891, a youngster with diphtheria was saved using this technique (At the time, Germany was losing over 50,000 youngsters to this sickness annually). This antitoxin was originally produced commercially in Germany in 1892, and thereafter in London. These antitoxins are still utilized in modern medicine today. The goal of immunotherapy for autoimmune illnesses is to impede the immune system's response. Only the self-directed antigen-specific immune response would be the focus of the ideal therapy, allowing the remainder of the immune system to continue protecting the patient from infection.¹³

Conclusion

Immunity reacts in concert with the environment to counter a range of dangers. It is essential to good health from the time of conception, when the mother's immune system starts to safeguard the growing infant, until old age. With the advancement of medicine, medical professionals progressively discovered how to leverage an understanding of the principles of immunology to fortify and redirect the immune response, so providing increased defense against infection or cancer therapy. Immunotherapy has improved human health ever since Edward Jenner first used the term, and it will do so in the future.

Conflicts of Interest

Nil