What is immunity?
Think of it as the body’s personal army working from the cellular to macro level. Each cell, molecule, tissue and organ in this army plays a vital role in warding off invading pathogens, and also helps guard against internal threats like cancer.
The immune system protects the body from outside invaders such as bacteria, viruses, fungi, and parasites (types of germs) that can cause infection and disease.
The immune system also gets rid of abnormal pre-cancerous cells and cancerous cells that are growing out of control. When it works correctly, it fights off infection and keeps you healthy. However, when it does not work correctly, germs and other abnormal cells in the body can more easily cause disease.
Types of immunity
The 2 recognized types of immunity are:
- Innate
- Adaptive
Innate immunity is relatively nonspecific. It is the body’s first-line defense against many bacterial pathogens. Innate immunity resides in the skin, mucous membranes, polymorphonuclear (PMN) cells, complement system, and a select group of cells that possess cytotoxic capabilities.
The skin and mucous membranes act as physical barriers to invading microorganisms. PMN cells (ie, granulocytes, monocytes, macrophages) primarily have a phagocytic function.
Granulocytes are mobile phagocytes that travel to areas of inflammation to engulf and destroy invading microorganisms. They are relatively indiscriminate in their function. Monocytes circulate, whereas macrophages are fixed in lymphoid and mucosal tissues. They can also phagocytose foreign microorganisms. Binding of complement to a foreign substance, or antigen, amplifies and augments the body’s innate immune system by means of its role as an opsonin (a factor that enhances phagocytosis of unwanted particles) and as a chemoattractant (a factor that recruits cells to areas of inflammation). Natural-killer (NK) cells are specialized lymphocytes that have cytotoxic properties in addition to their ability to produce cytokines that assist in the orchestration of adaptive immunity.
Most infectious agents induce inflammatory responses by activating innate immunity
Microorganisms such as bacteria that penetrate the epithelial surfaces of the body for the first time are met immediately by cells and molecules that can mount an innate immune response. Phagocytic macrophages conduct the defense against bacteria by means of surface receptors that are able to recognize and bind common constituents of many bacterial surfaces. Bacterial molecules binding to these receptors trigger the macrophage to engulf the bacterium and also induce the secretion of biologically active molecules. Activated macrophages secrete cytokines, which are defined as proteins released by cells that affect the behaviour of other cells that bear receptors for them. They also release proteins known as chemokines that attract cells with chemokine receptors such as neutrophils and monocytes from the bloodstream.
The cytokines and chemokines released by macrophages in response to bacterial constituents initiate the process known as inflammation. Local inflammation and the phagocytosis of invading bacteria may also be triggered as a result of the activation of complement on the bacterial cell surface. Complement is a system of plasma proteins that activates a cascade of proteolytic reactions on microbial surfaces but not on host cells, coating these surfaces with fragments that are recognized and bound by phagocytic receptors on macrophages. The cascade of reactions also releases small peptides that contribute to inflammation.
Inflammation is traditionally defined by the four Latin words calor, dolor, rubor, and tumor, meaning heat, pain, redness, and swelling, all of which reflect the effects of cytokines and other inflammatory mediators on the local blood vessels. Dilation and increased permeability of the blood vessels during inflammation lead to increased local blood flow and the leakage of fluid, and account for the heat, redness, and swelling. Cytokines and complement fragments also have important effects on the adhesive properties of the endothelium, causing circulating leukocytes to stick to the endothelial cells of the blood vessel wall and migrate between them to the site of infection, to which they are attracted by chemokines. The migration of cells into the tissue and their local actions account for the pain. The main cell types seen in an inflammatory response in its initial phases are neutrophils, which are recruited into the inflamed, infected tissue in large numbers. Like macrophages, they have surface receptors for common bacterial constituents and complement, and they are the principal cells that engulf and destroy the invading micro-organisms. The influx of neutrophils is followed a short time later by monocytes that rapidly differentiate into macrophages. Macrophages and neutrophils are thus also known as inflammatory cells. Inflammatory responses later in an infection also involve lymphocytes, which have meanwhile been activated by antigen that has drained from the site of infection via the afferent lymphatics.
Adaptive immunity
In contrast to basic innate immunity, adaptive immunity is specific and depends on antigenic stimulation. Antigens are foreign substances that evoke an immune response. They can take on many different forms, including proteins, lipids, or carbohydrates. The generation of receptors specific for antigens is a unique and complex process that generates 1012 specific receptors for each cell type of the adaptive immune system, including T and B cells.
After a complex process of education and maturation, a circulating lymphocyte can bind to an antigen. Various cell types can process and present these antigens to T cells, or antigens may be soluble and bound to B-cell receptors. Cell-to-cell interactions set off a cascade of events that may result in T- or B-cell activation and, ultimately, host defense. The adaptive immune system consists of 2 types of lymphocytes: T-cells (70-75% of the adaptive immune force) and B cells (10-20% of the adaptive immune force). NK cells are specialized effectors of the innate immune system that destroy their targets by antibody-dependent cell-mediated cytotoxicity, have prominent antitumor effects, and are potent killers of virally infected cells.
Key Organs of the Immune System
The first line of defense against germs is the skin, the single largest organ of the body. It provides a physical barrier that keeps bacteria and viruses from entering the body. Viruses such as HIV cannot get through normal, healthy, unbroken skin. HIV can, however, get into the body through unbroken mucous membranes, which are the moist membranes of the vagina (birth canal), rectum (‘butt’), and urethra (tube that brings urine out of the body).
The internal parts of the immune system take care of germs that do get inside the body. The white blood cells that defend the body from invaders and get rid of possibly dangerous abnormal cells begin their lives in the bone marrow. Once they leave the bone marrow, they travel to the lymph organs, which serve as a home base for mature white blood cells. There, the white blood cells await instruction to go out and fight infection.
Lymph organs are spread throughout the body and include the lymph nodes, thymus, spleen, appendix, tonsils and adenoids, and clumps of tissue in the small intestine known as Peyer’s patches. Lymph nodes are located in the neck, armpits, abdomen, and groin. Each lymph node contains cells ready to fight invaders. The lymphatic vessels connect the lymph nodes and carry lymph, which is a clear fluid that “bathes” the body’s tissues and helps to clean out invaders or germs.
The spleen is an important organ for a healthy immune system. It is about the size of a fist, and it is located in the upper left of the abdomen (“belly”). One of its key roles is to filter blood and to identify and get rid of worn-out white blood cells.
Key components and antigen-receptor interaction
The adaptive immune system is composed of T and B lymphocytes. Lymphocytes constitute 40% of circulating WBCs. B cells make up 10-20% of lymphocytes, T cells account for 70-75%, and NK cells comprise 10-15%. They are considered in the context of the innate immune system above.
The cornerstone of adaptive immunity is antigen-receptor interaction. The B cell expresses surface antibody or Ig, which serves as an antigen receptor. T cells express antigen receptors. Genes for Ig and T-cell receptor (TCR) are rearranged in developing B and T cells, respectively. The variable (V), diversity (D), and junctional (J) gene recombination’s are responsible for the nearly 1012 specific receptors generated for each cell type. Recombination events of gene segments and other processes, such as the addition of nucleotides at splicing junctions and somatic hypermutation (in B-cell development), aid in diversification. The receptors created are specific for particular antigens.
B cells and their products constitute one arm of the adaptive immune system. B cells arise from hematopoietic stem-cell precursors in the bone marrow and must undergo 2 phases of maturation: an antigen-independent phase and an antigen-dependent phase. A common lymphoid progenitor gives rise to progenitor B cells (proB cells), which are the earliest identifiable cells committed to development in the B-cell lineage. These proB cells rearrange their Ig heavy-chain genetic segments to create a functional IgH gene that is then expressed as a pre–B-cell receptor.
Types and subtypes of Ig
Five types of Igs are recognized: IgG, IgM, IgA, IgD, and IgE. IgG is the most abundant antibody class. It has antitoxin, antiviral, and antibacterial functions. It makes up 80% of the total Ig concentration and is evenly divided between extravascular tissues and the circulation. IgG has a half-life of 20-25 days. It is the primary component of intravenous (IV) Ig (IVIG) used clinically. IgG crosses the placenta and has 4 subclasses: IgG1, IgG2, IgG3, and IgG4. IgG is involved in little direct killing of targets but does activate the complement system and is involved in opsonization and ADCC. The presence of IgG after an initial response to antigen is associated with immunologic memory.
Dendritic Cells and Macrophages
Dendritic cells are found mostly in the skin and mucous membranes that protect the openings of the body (e.g., nose, mouth, and throat). These cells capture and carry invaders to the lymph nodes or spleen. Macrophages (their name comes from Latin and means “big eaters”) protect different organs, including the intestines, lungs, liver, and brain. Like dendritic cells, macrophages capture and carry invaders to the lymph organs.
These two types of white blood cells are known as scavengers. They engulf (eat) foreign invaders, break them apart, and display pieces of the germs—known as antigens (from antibody-generating) —on their surfaces. The body can then make antibodies to that specific germ, which helps the body get rid of that invader faster and remember it in the future. These cells also produce chemical messengers (known as cytokines) that instruct other immune cells to go into action.
T Cells
Once antigens are processed and displayed on the surface of macrophages, they can be recognized by helper T cells (also known as CD4 cells). When CD4 cells “see” the antigens displayed, they coordinate and direct the activity of other types of immune cells—such as killer T cells, B cells, and macrophages—calling them into action to fight the intruder. CD4 cells produce many different cytokines in order to communicate effectively with other immune system cells.
Killer T cells directly attack and destroy cells infected by viruses as well as abnormal cells that may become cancerous. Suppressor T cells call off the immune system attack once the invader is conquered. This is to make sure the killer T cells stop killing once their job is done. Both killer T cells and suppressor T cells are also known as CD8 cells.
B Cells and Antibodies
B cells are another type of immune cell that is turned on by CD4 cells. When a B cell recognizes an antigen, it produces antibodies (also called immunoglobulins). An antibody is a protein that attaches to an antigen like a key fits a lock. Each antibody matches a specific antigen.
When you are exposed to a germ for the first time, it usually takes a while (several weeks to a few months) for your body to produce antibodies to fight it. But if you were exposed to a germ in the past, you will usually still have some B cells (called memory cells) in your body that recognize or ‘remember’ the repeat invader. This allows the immune system to go into action right away. This is why people get some diseases, such as chickenpox or measles, only once. This is also how vaccines work— they introduce your body to an inactive or attenuated (modified) form of a particular germ and trigger your immune system to produce antibodies to that germ.
Adaptive immunity develops over a lifetime of contact with pathogens and vaccines, preparations which help our immune systems to distinguish friend from foe.
Vaccination safely teaches our adaptive immune systems to repel a wide range of diseases, and thus protect ourselves and others.
There is currently no vaccine for coronavirus, and we may not see one for 18 months or longer. So, for now, our immune systems must adapt unaided to this potentially deadly threat.
Treatment options for immunodeficiency
Treatment options for immunodeficiency disorders may be disease-specific, whereas others may help regardless of the particular diagnosis. Patients should adhere to particular vaccination instructions. [7, 8] In some cases, prophylactic use of antimicrobial agents provides protection against bacterial, viral, and fungal pathogens. IVIG may also be used therapeutically.
Allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-identical siblings, matched unrelated donors, or haploidentical donors are sometimes used. Sources of hematopoietic stem cells are numerous and include bone marrow, peripheral blood stem cells, and umbilical-cord blood. HSCT has been used with various degrees of success. The results of transplantation depend on the timing of the procedure in relation to the patient’s disease, the type of transplant, the particular immunodeficiency, and the general health of the recipient.
Gene therapy has been used, although results are limited. Understanding and characterizing immunodeficiency at a molecular level has been extremely helpful and is likely to become even more important as clinicians attempt to tailor specific therapies for particular immunodeficiencies.
How to help your immune system
A healthy lifestyle – not smoking, drinking little or no alcohol, sleeping well, eating a balanced diet, taking regular moderate exercise and reducing stress – helps our immune systems to be in the best shape possible to tackle pathogens.