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Immune cells, which are white blood cells or leukocytes, are formed from precursors in bone marrow, primarily in the long bones of the body. These precursors, known as pluripotent hematopoietic stem cells give rise to the lymphocytes of the adaptive immune system and the granulocytes and monocytes (which mature into macrophages) of the innate immune system.
Innate immunity comprises the early phases of the host response to infection, when innate immune mechanisms recognize and respond to the presence of a pathogen. Cells involved in innate immunity include granulocytes (neutrophils, eosinophils and basophils), macrophages and Natural Killer (NK) cells. Innate immune responses are accompanied by inflammatory responses and complement activation. Innate immunity is present in all individuals at all times and does not increase with repeated exposure to a particular antigen (lacks immunological memory).
NK cells are large granular lymphocytes which are
part of the innate immune system and provide an aggressive
defense against cells infected by viruses (and other intracellular
pathogens), mutant/abnormal (cancer) cells and cells from
individuals unrelated to the responding host. They comprise
5 to 16 percent of the total lymphocyte population but have
no immunological memory. They identify then react to target
cells by attaching to them and releasing a lethal burst of
chemicals which destroys or damages the target cell. NK Cell Cytotoxic
Activity is measured by removing lymphocytes from the blood
and introducing cancer cells to them to measure the NK cells'
ability to destroy them. NK Cell Activity can be unfavorably
impacted by a variety of conditions including but not limited
to stress, chemical exposures, infections, immune deficiencies
and cancer.
Adaptive immunity is the response of antigen-specific lymphocytes to antigens and includes the development of immunological memory, in which “memory” lymphocytes are created upon first exposure to a particular antigen which enables a quicker and stronger response upon subsequent exposures. Adaptive immune responses are generated by clonal selection of antigen-specific lymphocytes and take some time to mount a defense. Lymphocytes (cells of the adaptive immune system) are comprised of B-cells and T-cells.
B-cells mature in bone marrow. When activated by an antigen, they differentiate into plasma cells that produce antibody molecules specific to that antigen. Antibodies are found in plasma (or serum which is plasma with clotting factors removed), the fluid component of blood found in extracellular fluid. Immunity mediated by antibodies is known as humoral immunity. Antibodies deal with extracellular forms of pathogens and their toxic by-products.
Major classes of circulating antibodies include IgG, IgM and IgA. The pentamer IgM antibody is the early responder. It is the first antibody to appear on the surface of activated B-cells and the first to be secreted. IgM is elevated during the early stages of an exposure to a pathogen. There are two possible outcomes, either the immune system will eradicate the pathogen or the pathogen will begin to colonize body tissues.
The IgA antibody is the intermediate responder and quantitatively the second most abundant humoral antibody. If IgA is elevated, there is presumptive evidence that an infection exists and it is transitioning from acute to chronic/long term condition.
The IgG antibody is the long term responder and the most abundant humoral antibody. IgG elevations mean that either a long term chronic infection exists that was either treated or untreated, or it is indicative of a protective antibody from a past infection that was resolved.
Immune complexes (also called antigen complexes) are formed in the normal immune response when an antibody binds to an antigen. Immune complexes are normally degraded in the liver and eliminated, unless the liver is sluggish or antigen penetration into the general circulation is at a level that overwhelms the liver's ability to process and eliminate the resulting complexes. (Refer to the section on Mucosal Immunity.) Measuring the level of circulating immune complexes is important in assessing the immune system (both the mucosal and humoral compartments) and liver function.
If the liver fails to degrade and eliminate immune complexes
efficiently, they persist and continue to circulate. These
circulating complexes are treated by the immune system as
antigens themselves and new antibodies may be formed to the
original immune complex (antigen complex). This results in
a bigger and harder to clear immune complexes. The immune
response continues and potentially escalates. Systemic physiology
becomes increasingly compensatory, and pathology can result.
This is the primary trigger for developing an autoimmune condition.
T-cells mature in the thymus. T-cells control cell-mediated immune responses and also serve to activate B cell responses to most antigens. Pathogens are only accessible to antibodies in the blood and extracellular spaces. T lymphocytes are responsible for dealing with all viruses and some bacteria and parasites that replicate inside cells, where they cannot be detected by antibodies.
Cell mediated immune response depends on direct interactions between T lymphocytes and cells bearing the antigen that the T-cells recognize. For example, cells infected with replicating viruses display antigen from the virus on their surface. Cytotoxic T-cells typically express the CD8 glycoprotein on their surface and recognize virus antigen on the surface of infected cells and control the infection by killing infected cells before viral replication is complete.
Another group of T lymphocytes typically expresses the CD4 glycoprotein on their surface. These are known as T-helper cells which recognize foreign antigens and secrete cytokines (immune cell regulating chemicals) that can activate T and B-cells. They can be divided into two subsets. T-helper 1 cells (TH1 cells) are important in the control of intracellular bacterial infections. TH1 cells activate macrophages inducing their antibacterial mechanisms and release cytokines that attract macrophages to the site of the infection.
T-helper 2 cells (TH2 cells) play a central roll in the destruction of extracellular pathogens by releasing cytokines to activate B-cells. Most antigens also require a signal from TH2 cells before they can stimulate B-cells to proliferate and differentiate into plasma cells that secrete antibody.
THI/TH2 balance is controlled by cytokines. Often, depending on the pathogen encountered, cytokines are released that promote one response while dampening the other.
T suppressor cells typically express the CD8 glycoprotein on their surface. They slow down and stop the response of B and T-cells after invading pathogens are destroyed. T suppressor cells serve to brake and/or turn off the immune response.
It is important to remember that all the cells, chemical messengers and chemical agents of the immune system work together in very complicated ways to defend the body against pathogens.
The value of immune function testing can not be overstated.
For example, an individual with a low B cell count is a low
humoral antibody producer. Therefore in evaluating the humoral
immune response to a broad range of pathogens, it is necessary
take the fact that they are a low antibody producer into account.
Specifically this means that a low antibody producer may demonstrate
a clinically significant response to a particular pathogen
or group of pathogens with a reported result that is still
in the “normal” reference range; resulting in a negative interpretation
when actually could be a "positive" given their
overall antibody production.
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