Immunology refers to the study of physiological mechanisms that humans or other animals use to keep their bodies protected from infection by foreign invaders, such as virus, bacteria, fungi, parasites, or other pathogens. Our immune system is indispensable for our survival and without a properly functional immune system we would be susceptible to fatal illness even with a minor infection. The microorganisms that causes infectious diseases have the capability to reproduce and evolve way faster than their human host. During the course of infection, the microorganisms replicate themselves to produce a large number of its species against an individual human, in turn, human body recruits its specialized cells committed to defense, that collectively form the immune system.
Components of the immune system
The major protein components of the immune systems are – cytokines, complements, cell surface receptors, and antibodies. Whereas the cells of the immune system predominantly comprised of white blood cells or leukocytes. These cells originate from a common progenitor named hematopoietic stem cells by a developmental process called hematopoiesis. Red blood cells and platelets are also derived from the same progenitor. Since blood cells have a short lifespan, they are continuously replaced by hematopoiesis throughout life. In adults, the primary sites for hematopoiesis is the bone marrow of femur, pelvis, ribs, vertebral column, sternum, and skull. Our white blood cells are stored in different parts of the body – spleen, thymus, lymph nodes, adenoids, appendix, tonsils, and bone marrow, and Peyer’s patches, referred to as lymphoid organs.
White blood cells and their functions in immune system
Myeloid precursor
1. Granulocytes
These cells contain granules of reactive substances in their cytoplasm, hence the name granulocytes. The release of granules increases inflammation and kills microorganisms. They are also called polymorphonuclear leukocytes due to segmented nucleus of 2-5 lobes.
i. Neutrophils
-Most abundant (60%) of all white blood cells.
-Known as phagocytes as they capture, engulf, and kill microorganisms.
-Neutrophils are the effector cells of innate immunity and known as the first cell types that rapidly mobilize to the infection sites for action.
-Neutrophils die in action and forms pus, the thick yellowish exudate of pimples or boils.
ii. Eosinophils
-Regulates immune response to parasites
-The granules contain hydrolytic enzymes, histaminase, peroxidase, and neurotoxins for parasites.
-If their number increases in the blood (normal range: 1-3% of total leukocytes), it indicates allergic responses or parasitism.
iii. Basophils
-Rare in number.
-Also regulates immune response to parasites.
-The basophilic granules contain heparin and histamine that acts as an anticoagulant and vasoactive substance, respectively.
2. Mast cells
-Resident in all connective tissues
-Mast cells have basophil-like granules
-Their activation and degranulation at the site of infection is important for inflammation.
3. Agranulocytes
i. Monocytes/Macrophages
-Monocytes transmigrate from blood to tissues, where they matured to become macrophages and take up the residence.
-Macrophages are large phagocytes; plays critical role in scavenging, disposing, and phagocytosing of dead cells or cell debris, along with invading microorganisms.
-The tissue resident macrophages are usually the first cells that sense foreign pathogens when they invade tissues, and in response macrophages release cytokines to recruit neutrophils and other leukocytes to the site of infection.
ii. Dendritic cells
-Dendritic cells are also tissue resident cells.
-Share many functionalities with macrophages, however their unique role is to play as a cellular messenger that activate adaptive immune responses when required. When a tissue becomes infected, dendritic cells leave that infected tissue with a load of intact and degraded pathogens and carry it to one of the lymphoid organs that regulates the production and maturation of lymphocytes.
Lymphoid precursor
i. B lymphocytes & T lymphocytes (or B & T cells)
-Structurally similar, small lymphocytes with thin and hardly noticeable cytoplasm.
-They circulate as quiescent and immature cells and is functionally inactive. Upon pathogen recognition, these naïve B and T cells grow and differentiate into effector cells.
-B and T cells are distinguished by the cell-surface receptors they possess to interact with pathogens.
-The cell-surface receptors expressed by T cells are termed as T-cell receptors, whereas those of B-cells are called immunoglobulins (Ig). When B cells matured into effector B cells (or plasma cells), they secrete these immunoglobulins as soluble proteins, called antibodies, in contrast T-cell receptors are never found as soluble form.
-Each B and T cell expresses a single type of immunoglobulin or T-cell receptor. Thus, many millions of immunoglobulins as well as T-cell receptors are present within the population of lymphocytes in an individual human body.
-The effector T cells that are derived from T cells are further classified into two types: (i) Cytotoxic T cells, & (ii) Helper T cells. Cytotoxic T cells directly kills bacteria- or virus-infected cells during adaptive immune response. Helper T cells perform different functions. It secretes cytokines to activate other immune cells, such as secreted cytokines stimulate macrophages to become more phagocytic and B cells to differentiate into plasma cells to produce antibodies. A subset of follicular T helper cells is required for memory B cells as well as long-lived plasma cells. Another type of helper T cell comprises regulatory T cells (Treg) that sends signal to cytotoxic or other T helper cells to stop their activities when the issue is resolved, thereby prevents tissue damage from excessive immune responses.
-Naïve B and T cells are also the precursor of memory B and T cells that form during adaptive immune responses and provide long-lasting immunity.
ii. NK cells
-Natural killer cells or NK cells are large granular lymphocytes; they are also effector cells of innate immunity
-Fight against viral infections.
-They move into the viral infected tissues, secrete cytokines to stop viral replication inside the infected cells, as well as kills virus-infected cells.
Immunity
i. Innate immunity
‘Innate’ refers to inherent characteristics a person is born with, i.e. we are all born with this innate immunity that is genetically programmed for a set of responses. It is the body’s first line of defense and includes skin and mucous membranes that provides well-organized chemical, physical, and microbiological barriers to prevent microorganisms gaining access to the tissues or cells for infections. The components of the innate responses are ready to attack and halt the invading pathogens before they can barely start infections. The innate immunity happens in two phases: The first is pathogen recognition via soluble proteins and cell surface receptors that either directly binds pathogen or binds to the human cells and serum that has been transformed by the pathogens. The second phase comprises recruitment of destructive effector cells, such as neutrophils that kill virus infected cells, engulf bacteria, and eliminate pathogens. This is the non-specific and rapid mechanisms that blocks most infections.
ii. Adaptive immunity
If innate immunity fails to fight off the infections, the body mounts more flexible and forceful immune responses via adaptive immunity. The adaptive immune response is selective, considering that it targets specific problem at hand and is modified and refined in the course of infection. If succeeds, it provides long lasting immunity from recurrent infection with the same specific pathogens. That being said, the adaptive immunity made against one pathogen does not provide immunity to another pathogen. For instance, antibodies made in response to influenza infection will bind and defeat influenza virus when they try to re-infect, but the same antibodies will not bind and prevent measles infection.
How immune response works: mechanisms of inflammation
It is believed that, tissue resident macrophages are the ones that sense the infection first and in response to infection, they secrete soluble proteins known as cytokines that communicate with other immune cells to induce innate immune response. The activation of innate immune response triggers inflammation in the infected tissue. The classical signs of inflammation are heat, pain, redness, swelling, and loss of function.
The release of cytokines causes dilation of local blood capillaries, results in increased blood flow through the vessel causing skin to become warm and redden. The inner layer of the vessel comprises thin single layer of endothelial cells called endothelium. When vascular dilation occurs, it creates gaps between the endothelial cells, which makes the endothelium permeable. As a consequence, there is now increased leakages of blood plasma into the surrounding connective tissues. Increase in local fluid volume causes tissue swelling or edema, that puts pressure on the nerve endings and causes pain. Cytokines also induces expression of adhesion molecules for white blood cells on endothelium. So the white blood cells get easily attached to the endothelium and leaves blood vessels to migrate to the inflamed tissue through the gap in between endothelial cells. The process of cell Infiltration into the damaged or inflamed tissue increases swelling and some of the molecules released by them may contribute to the pain. Thus, inflammation is the immediate responses of infection by innate immune system and the discomfort they cause by inflammation helps to bring immune cells and molecules to the site of infection more rapidly and in huge numbers to fight off the infection.
When this strategy fails, the adaptive immunity adds on to the ongoing innate responses, where large number of lymphocytes (B, T, & NK cells) are called upon for more strong responses.
Immunization: How vaccine works
Any molecule, macromolecule (such as bacteria), virus particle, or even cell that has a structure that antibodies or T-cell receptor can recognize and bind to is called its corresponding antigen. So, antigen could be any substance that triggers immune response. Antibodies can reduce infection by strongly binding a site on the pathogens, forming antibody-antigen complex that inhibits pathogens’ replication or interaction with human cells. This strategy is called neutralization. The antibody-antigen complex is finally engulfed and degraded by phagocytes. In antibody mediated immunity, the most critical function of antibodies is to coat antigen surfaces so that the phagocytes can recognize, bind, digest, and degrade the antigen easily. T helper cells stimulate memory B cells and long-lived plasma cells formation that continually produces antibodies, keeping the serum antibody level constant. Memory T cells can recognize specific antigen and produce faster and forceful immune responses when they encounter with the same antigen again.
Vaccine works based on these principles. The main idea of vaccination is to train the immune system to recognize and defeat invading pathogens. For this purpose, certain molecules from the pathogens, such as DNA, proteins, carbohydrates, bacterial toxins, dead or weakened/inactivated pathogens are introduced into the body to trigger an immune response, so the immune systems safely learn to recognize the antigen, produce antibodies, and remember to defeat them in future.
For HIV, malaria, and others, a successful vaccine development programs requires that, vaccine-induced immunity will generate broadly neutralizing antibodies as well as highly functional T cell mediated long-lasting immunity.
Autoimmune disorder
An autoimmune condition arises when our immune system mistakenly attacks our own body. In this case, the immune system cannot differentiate between foreign pathogens from body’s own cells, leading to tissue damage or organ failure. The researchers still could not identify what causes this disorder, but it is believed to be linked to genetics, and external environments.
References
1. Parham, P. (2014). The immune system. Garland Science.
2. Sallusto, F., Lanzavecchia, A., Araki, K., & Ahmed, R. (2010). From vaccines to memory and back. Immunity, 33(4), 451-463.
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