IMMUNOLOGY: Innate & Adaptive Immunity
By ¹Obiri Darko Stella, ²Sackey Lyanne, and ³Kwakye Sylvester.
Immunology is the study of the immune system in organisms. The immune system is a complex system of structures and processes in the body that has evolved to protect the body from disease. The function of these components is divided up into nonspecific mechanisms, which are innate to an organism, and responsive responses, which are adaptive to specific pathogens.
The innate immune system
The innate immune system is the first line of defence and is non-specific. That is, the responses are the same for all potential pathogens, no matter how different they may be. Innate immunity includes physical barriers (e.g. skin, saliva etc) and cells (e.g. macrophages, neutrophils, basophils, mast cells etc). These components protect an organism for the first few days of infection. In some cases, this is enough to clear the pathogen, but in other instances, the first defence becomes overwhelmed and the second line of defence kicks in.
Cells of the innate immune system
Macrophages: Macrophages, commonly abbreviated as “Mφ”, are efficient phagocytic cells that can leave the circulatory system by moving across the walls of capillary vessels. The ability to roam outside of the circulatory system is important because it allows macrophages to hunt pathogens with fewer limits. Macrophages can also release cytokines to signal and recruit other cells to an area with pathogens.
Mast cells: Mast cells are found in mucous membranes and connective tissues, and are important for wound healing and defence against pathogens via the inflammatory response. When mast cells are activated, they release cytokines and granules that contain chemical molecules to create an inflammatory cascade. Mediators, such as histamine, cause blood vessels to dilate, increasing blood flow and cell trafficking to the area of infection. The cytokines released during this process act as a messenger service, alerting other immune cells, like neutrophils and macrophages, to make their way to the area of infection, or to be on alert for circulating threats.
Neutrophils: Neutrophils are phagocytic cells that are also classified as granulocytes because they contain granules in their cytoplasm. These granules are very toxic to bacteria and fungi and cause them to stop proliferating or die on contact. The bone marrow of an average healthy adult makes approximately 100 billion new neutrophils per day. Neutrophils are typically the first cells to arrive at the site of infection because there are so many of them in circulation at any given time.
Eosinophils: Eosinophils are granulocytes that target multicellular parasites. Eosinophils secrete a range of highly toxic proteins and free radicals that kill bacteria and parasites. The use of toxic proteins and free radicals also causes tissue damage during allergic reactions, so activation and toxin release by eosinophils is highly regulated to prevent any unnecessary tissue damage.
Basophils: Basophils are also granulocytes that attack multicellular parasites. Basophils release histamine, much like mast cells. The use of histamine makes basophils and mast cells key players in mounting an allergic response.
Natural Killer cells: Natural Killer cells (NK cells), do not attack pathogens directly. Instead, natural killer cells destroy infected host cells to stop the spread of infection. Infected or compromised host cells can signal natural kill cells for destruction through the expression of specific receptors and antigen presentation.
Dendritic cells: Dendritic cells are antigen-presenting cells that are located in tissues, and can contact external environments through the skin, the inner mucosal lining of the nose, lungs, stomach, and intestines. Since dendritic cells are located in tissues that are common points for initial infection, they can identify threats and act as messengers for the rest of the immune system by antigen presentation. Dendritic cells also act as bridges between the innate immune system and the adaptive immune system.
The adaptive immune response
The adaptive immune response is the second line of defence and can be split into ¹humoral immunity and ²cell-mediated immunity.
¹Humoral immunity is due to B cells’ antibody production, which transforms to plasma cells and produces immunoglobulin (antibodies) while ²cell-mediated immunity is mediated by T cells.
Cells of the adaptive immune system
B-cells (sometimes called B-lymphocytes and often named on lab reports as CD19 or CD20 cells) are specialized cells of the immune system whose major function is to produce antibodies (also called immunoglobulins or gamma-globulins). B-cells develop in the bone marrow from hematopoietic stem cells. As part of their maturation in the bone marrow, B-cells are trained or educated so that they do not produce antibodies to healthy tissues. When mature, B-cells can be found in the bone marrow, lymph nodes, spleen, some areas of the intestine, and the bloodstream.
When B-cells encounter foreign material (antigens), they respond by maturing into another cell type called plasma cells. B-cells can also mature into memory cells, which allows a rapid response if the same infection is encountered again. Plasma cells are the mature cells that actually produce antibodies. Antibodies, the major product of plasma cells, find their way into the bloodstream, tissues, respiratory secretions, intestinal secretions, and even tears. Antibodies are highly specialized serum protein molecules.
For every foreign antigen, there are antibody molecules specifically designed to fit that antigen, like a lock and key. The variety of different antibody molecules is extensive so that B-cells have the ability to produce them against virtually all microbes in our environment. However, each plasma cell produces only one kind of antibody.
When antibody molecules recognize a microorganism as foreign, they physically attach to it and set off a complex chain of events involving other components of the immune system that work to eventually destroy the germ. Antibodies vary with respect to their specialized functions in the body. These variations are determined by the antibody’s chemical structure, which in turn determines the class of the antibody (or immunoglobulin).
There are five major classes of antibodies (IgG, IgA, IgM, IgD and IgE). IgG has four different subclasses (IgG1, IgG2, IgG3, IgG4). IgA has two subclasses (IgA1 and IgA2).
Each immunoglobulin class has distinct chemical characteristics that provide it with specific functions. For example, IgG antibodies are formed in large quantities, last in the circulation for a few weeks, and travel from the bloodstream to the tissues easily. Only IgG crosses the placenta and passes some immunity from the mother to the newborn.
Antibodies of the IgA class are produced near mucus membranes and find their way into secretions such as tears, bile, saliva and mucus, where they protect against infection in the respiratory tract and intestines. Some of the IgA also appears in the circulation.
Antibodies of the IgM class are the first antibodies formed in response to infection. They are important in protection during the early days of an infection.
Antibodies of the IgE class are responsible for allergic reactions.
Antibodies protect the body against infection in a number of different ways. For example, some microorganisms, such as viruses, must attach to body cells before they can cause an infection, but antibodies bound to the surface of a virus can interfere with the virus’ ability to attach to the host cell. In addition, antibodies attached to the surface of some microorganisms can cause the activation of a group of proteins called the complement system that can directly kill some bacteria or viruses.
Antibody-coated bacteria are also much easier for neutrophils to ingest and kill than bacteria that are not coated with antibodies. All of these actions of antibodies prevent microorganisms from successfully invading body tissues and causing serious infections.
The long life of plasma cells enables us to retain immunity to viruses and bacteria that infected us many years ago.
T-cells (sometimes called T-lymphocytes and often named in lab reports as CD3 cells) are another type of adaptive immune cell. T-cells directly attack cells infected with viruses, and they also act as regulators of the immune system.
T-cells develop from hematopoietic stem cells in the bone marrow but complete their development in the thymus. The thymus is a specialized organ of the immune system in the chest. Within the thymus, immature lymphocytes develop into mature T-cells (the “T” stands for the thymus) and T-cells with the potential to attack normal tissues are eliminated. The thymus is essential for this process, and T-cells cannot develop if the fetus does not have a thymus. Mature T-cells leave the thymus and populate other organs of the immune system, such as the spleen, lymph nodes, bone marrow and blood.
Each T-cell reacts with a specific antigen, just as each antibody molecule reacts with a specific antigen. The variety of different T-cells is so extensive that the body has T-cells that can react against virtually any antigen.
T-cells have different abilities to recognize antigens and are varied in their function. There are “killer” or cytotoxic T-cells (often denoted in lab reports as CD8 T-cells), helper T-cells (often denoted in lab reports as CD4 T-cells), and regulatory T-cells. Each has a different role to play in the immune system.
Killer, or cytotoxic, T-cells perform the actual destruction of infected cells. Killer T-cells protect the body from certain bacteria and viruses that have the ability to survive and even reproduce within the body’s own cells. Killer T-cells also respond to foreign tissues in the body, such as a transplanted kidney. The killer cell must migrate to the site of infection and directly bind to its target to ensure its destruction.
Helper T-cells assist B-cells to produce antibodies and assist killer T-cells in their attack on foreign substances.
Regulatory T-cells suppress or turn off other T-lymphocytes. Without regulatory cells, the immune system would keep working even after an infection has been cured. Without regulatory T-cells, there is the potential for the body to “overreact” to the infection. Regulatory T-cells act as the thermostat of the lymphocyte system to keep it turned on just enough — not too much and not too little.