Immune System 3/3 - Biology As Poetry

Lymphocyte

Collective name for B cells, T cells, and natural killer cells.

Lymphocytes represent a subset of leukocytes, ones that are associated with effecting adaptive immunity (B cells and T cells), though natural killer cells instead are associated with innate immunity.

Lymphocytes are the dominant cells found in lymph. Unlike basophils, eosinophils, mast cells, and neutrophils, lymphocytes are not granulocytes but instead can be described as agranulocytes.

Because lymphocytes form the core cell types that are responsible for effecting adaptive immunity, even superficial consideration of adaptive immunity involves substantial analysis of the roles of lymphocytes, and those roles are fairly complex though also moderately well understood.

The above video provides an introduction to especially B cells and T cells. Note taht "factory" B cells are just another name for "plasma cells".

Thymus

Gland in which cells responsible for cell-mediated immunity mature.

These cells in particular are the various T cells, which in addition to cytotoxic T cells also include helper T cells as well as regulatory T cells/suppressor T cells.

The T cells, though they mature in the thymus, instead originate in bone marrow. Furthermore, the time during which this maturation takes place is relatively early in life such that the thymus is more robust at young versus older ages.

The location of the thymus gland is in the chest, behind the sternum (a.k.a., the breastbone). The B cells by contrast mature, in mammals, instead in the bone marrow.

The above video provides an excellent introduction to how T cell maturation takes place in the thymus.

The above video provides a highly technical look at how T cell maturation occurs in the thymus such that these cells ultimately are able to recognize MHC but are unable to react with self antigens.

Natural killer cell

Cytotoxic lymphocyte that is associated particularly with innate rather than adaptive immunity.

Cytotoxic means cell killing, and lymphocytes can be distinguished into B cells and T cells together with natural killer cells.

Unlike T cells and B cells, which are central to adaptive immunity, natural killer cells are less involved in directly effecting adaptive immunity. Instead, they especially recognize signals that can be associated with body cell abnormalities, and they then eliminate those abnormal body cells once identified.

One of the signals natural killer cells detect is the absence of what are known as major histocompatibility complexes (MHC) on cell surfaces, which otherwise are what T cytotoxic cells recognize while detecting, for example, antigens derived from infecting viruses. MHC is also important in the matching of tissue types for transplanting tissues between individuals.

A second signal is the binding of antibodies to the surface of body cells, which should not occur unless a cell has become infected by a pathogen (such as a virus) or instead the cell possess cell-surface affecting mutations such as can be seen in cancer cells. The latter is described as antibody-dependent cellular cytotoxicity.

This video covers a lot of ground, but does nonetheless do a good job of introducing what natural killer cells are all about. Note, though, that the depiction of a virus, starting at about 17 seconds, is completely wrong since bacteriophages, as shown, are viruses of bacteria rather than of our own cells.

B cell

Lymphocytes that are responsible for producing antibodies.

The B cells are also known as B lymphocytes and they are the primary though not sole effectors of humoral immunity. These cells differentiate and then do their first-level maturation in the bone marrow. The "B" actually stands for Bursa of Fabricius, however, an organ in birds in which B cells mature, rather than Bone marrow, since B cell maturation was first observed in birds.

The process of B cell maturation actually involves additional steps that occur following exposure to antigens. Specifically, antigen binding of a B cell receptor, basically a cell-surface-associated antibody, has the effect of either activating or contributing to the activation of B cells. The result is cell division of the activated B cell and differentiation into a combination of plasma cells and memory cells as well as some change in the structure of the B cell receptor along with the structure of the antibodies subsequently produced.

The outcome is production and then secretion of large numbers of antibodies particularly by and from plasma cells, a retention of an ability to produce more such plasma cells in the future (a potential that is maintained by persistence of the memory cells), and also an increase in the total number of lymphocytes capable of recognizing a given antigen, thereby allowing for an increase in the robustness of adaptive immune responses associated with that particular specificity.

The above video continues the introduction to leukocytes, here with some emphasis on B cells.

Plasma cell

B cells that are actively producing antibodies.

Antibodies are proteins and proteins must be synthesized by cells. It is the job of plasma cells to perform this synthesis as well as subsequent antibody secretion. (Antibodies function outside of cells so therefore must be moved from inside of cells, where they are synthesized, to outside of cells, and this process of movement to outside of cells is the process of secretion.)

It is important to keep in mind that plasma cells are clonally related to the B cells that were initially stimulated to replicate as well as differentiate by the binding of their B cell receptors to a specific antigen, and also that only a very small fraction of the total number and diversity of B cells within a body will in fact be so-stimulated by a given antigen. The result of this clonality is that the specificity of the B cell receptor along with the subsequently produced antibodies will be identical, but also different from the specificity of the vast majority of other antibodies or B cell receptors present within a body.

It is equivalent to purchasing a newly manufactured product, with that purchase stimulating the maker of that product, e.g., of a car, to produce more of the product. You in this case would be the equivalent of the antigen, with your tastes and other issues associated with your selecting a car with specific characteristics equivalent to the relative antigenic uniqueness of an antigen. Cars with these specific characteristics then should increase in prevalence among cars that are produced owing to preferences among the car-buying public, and particularly so if there are a lot of people who possess similar tastes in cars. Thus, if "everybody" is buying convertibles, or cars that are painted teal, then you can be sure that the number of vehicles produced that are convertibles or which are painted teal will increase in number.

So too, if there are fairly substantial levels of a specific antigen in your body, then the result will be an increase in the prevalence of specific B cells that are able to bind to that antigen and so too a differentiation of those B cells into plasma cells that produce antibodies that similarly are able to bind to that antigen.

Memory cell

Expanded clonal lineage of B cells that can be stimulated to produce plasma cells.

When one is vaccinated it is specifically memory cells that are being increased in their prevalence to provide future protection against the pathogen in question. The same is true when one is exposed to a pathogen or parasite naturally. Indeed, the more one is exposed to a given antigen, particularly repeatedly such as one sees given vaccine boosting, or instead as one is continually exposed to a given pathogenic organism, then the more memory cells that will be produced.

The result is both a potentially more robust immune response given subsequent exposure to the same antigen, but also a potentially faster response, such that repeated exposure to the same pathogen does not result, in many cases, in repeated bouts of disease, and particularly so as memory cells divide and differentiate into additional plasma cells and memory cells.

Note that B cells are not alone in possessing memory cells, as T cells possess memory cells as well, though memory cells as a concept were originally characterized among B cells. Note too that the primary distinction between so-called passive immunization (e.g., as seen with administration of gamma globulin) and active immunization (which is the case for vaccines generally) is that active immunization involves the expansion within the body of memory cell populations, that is, stimulation of increases in numbers of specific, vaccine-recognizing memory cells.

Antibody-mediated immunity

Adaptive immune responses that are dependent on B cell proliferation and associated biosynthesis.

The B cells, a.k.a., B lymphocytes, are the producers of antibodies, with "production" representing the biosynthesis and then release of these antibodies. Antibodies, in turn and not surprisingly, form the basis of antibody-mediated immunity.

Such immunity also is typically described as humoral immunity, that is, immunity that is associated with the "humors" rather than as directly mediated by cells, even though underlying this immunity of humors is the production of antibodies by actual cells, i.e., the B cells. Non-humoral adaptive immunity nonetheless is distinguished from antibody-mediated immunity by being described as cell-mediated immunity.

Vaccine

Agent employed to artificially induce or "prime" adaptive immune responses.

Vaccines provide to the vaccinated organism at least a sampling of the immunogenicity of a microorganism, but with a lowered potential by those parasites or pathogens to cause disease. The latter is reduced either by attenuating the virulence associated with a live microorganisms (as generally mediated via mutation in that microorganism, resulting in what are described as live-attenuated vaccines), outright killing of the microorganism (resulting in what are known as whole-killed vaccines), or via a dismantling of the parasite or pathogen, resulting in a subunit vaccine (or recombinant vaccine if the dismantling is accomplished via genetic engineering).

Regardless of the form the vaccine takes, it is important to keep in mind four vaccine characteristics.

First, successful vaccination often is only possible if natural exposure to the disease-causing agent also will tend to result in immunity.

Second, vaccines don't necessarily prevent infections caused by targeted disease-causing organisms but instead tend to act only to inhibit the progression of those infections to full-blown disease.

Third, vaccination not only protects those who have been vaccinated but also those individuals who might have come into contact with an individual that has been vaccinated, a process known as herd immunity. Unvaccinated individuals, that is, have a greater potential to become infectious following exposure to a given pathogen than vaccinated individuals, thereby more effectively promoting the spread of infectious disease absent vaccination.

And fourth, the key to the ability of vaccines to interfere with the future occurrence of disease is their stimulation of the formation of memory cells within vaccine recipients.

The above video is a pretty good as well as fairly sophisticated look at what vaccines are all about.

Cell-mediated immunity

Means by which infected or otherwise abnormal body cells may be eliminated especially through the destruction of the infected cell.

Cell-mediated immunity is effected by cells, particularly though not exclusively by T lymphocytes. It is especially not directly mediated by antibodies. The prominent but not sole example of this process is the elimination of virus-infected cells by T cytotoxic cells, which can recognize processed viral antigens that have been displayed on the surface of infected cells, prompting the induction of a controlled cellular suicide of the virus-infected cell known as apoptosis.

Cell-mediated immunity is also directed against other cells that are undesirable to have present within the body, such as tumor cells or cancer cells.

Phagocytosis as directed by macrophages and neutrophils also can be viewed as cell mediated, as too are the various means of immunomodulation as directed by chemicals (cytokines) that can be released from immune system cells as a means of ramping up immune responses.

T cell

Lymphocytes that mediate cellular immunity (both helper and cytotoxic).

Along with B cells, T cells are direct effectors of adaptive immunity. T cells, however, have a greater diversity of roles in adaptive immunity. Most studied are their roles as cytotoxic cells against especially virus-infected body cells and also their roles as helper cells towards the development of adaptive immunity more generally. In either case, what these cells recognize are processed antigens as found in association with the cell-surface protein complexes known as MHC, for Major Histocompatibility Complex.

In the case of cytotoxic T cells (a.k.a., T cytotoxic cells), it specifically is MHC class I-presented antigens that are recognized. MHC class I is displayed by most body cells and serves as a window into cells, allowing for immune system recognition of the presence within body cells of abnormal proteins (often an indication that those cells are producing proteins that are other than normal body proteins, for example, virus proteins).

In the case of helper T cells (a.k.a., T helper cells), it specifically is MHC class II-presented antigens that are recognized, which are found on the surface of certain white blood cells that are known as antigen-presenting cells. In this guise, helper T cells help to motivate the progression of immune responses by recognizing foreign antigens that are presented by these other white blood cells. Most B cell stimulation, for example, requires recognition not just of antigens via their B cell receptors but also subsequent activation by T helper cells which also recognize the antigen, though within the context of MHC class II rather than MHC class I.

The "T" of T cells refers to Thymus, which is the organ within which T cells mature, there undergoing a process known as clonal deletion, that is, the elimination of T cells that are capable of recognizing self antigens.

Clonal selection

Activation of lymphocytes for mitotic expansion following their binding to antigens.

The basic principle of adaptive immunity is one of gross excess in terms of potential to recognize antigens, but with only some of that potential ever realized to combat disease. The high diversity in antigen-binding ability as found across all lymphocytes of the body, however, is not reflected by the diversity of individual lymphocytes, which instead possess only a minimum of potential to recognize antigens, ideally with an ability to recognize only a single antigen type. Most of the adaptation of adaptive immunity consequently occurs as a result of the need to increase the prevalence of specific lymphocytes from among that gross excess, lymphocytes that just happen to produce receptor variants that are able to recognize specific antigen molecules.

Lymphocyte adaptation generally requires a combination of diversity and selection, that is, a variety of different approaches to building antigen-recognizing molecules such as antibodies and then a way of increasing the numbers only of those antigen-recognizing molecules that are actually exposed to non-self antigens that they are able to recognize.

Since the process of activation of lymphocytes involves antigen-binding which is followed by the mitosis of so-activated lymphocytes, and since mitosis is a means by which cells literally clone themselves, the process of immune system adaptation is driven to a substantial extent by what can be described as clonal selection. Thus, of a huge array of antigen-recognizing diversity among lymphocytes, only those lymphocytes that actually recognize antigens are selected, with this selection involving a mitosis-driven increase in the numbers of those, specific, selected, antigen-recognizing cells.

The above video provides a pretty gorgeous view of the concept of clonal selection.

Affinity maturation

Combined mutation and selection process that results in B-cell production of antibodies that bind more strongly to antigens.

In affinity maturation, literally the affinity of the antibodies produced by a B cell lineage matures over the course of an immune response. Specifically, targeted mutations are allowed to occur within the genes encoding the antibodies, resulting in antibodies that display different affinities (binding ability) to antigens.

Those antibodies that as B-cell receptors bind most strongly to antigens result in stimulation of their producing B-cells to divide, producing an overall, selectively enhanced humoral, that is, antibody-mediated immune response which, ideally, is highly effective in contributing to the elimination of foreign antigens from the body.

T cytotoxic cells

Lymphocytes possessing the CD8 glycoprotein on their surfaces and therefore which are able to recognize major histocompatibility class I molecules.

T cytotoxic cells, a.k.a., cytotoxic T cells, are able to recognize abnormal proteins that are present within body cells. These abnormal proteins can be a consequence of mutations of a cell's own genes, as one can see in the course of development of cancers, or instead due to the invasion of body cells by pathogens, particularly viruses, that produce proteins that are simply not normal cellular proteins (but which, instead, are viral proteins).

The proteins as found within a cell are partially degraded, i.e., they are 'processed' by the cell, and then are complexed with MHC class I. Cells then display these antigen-MHC complexes on their surfaces where they can be recognized by a small subset of an otherwise huge diversity of cytotoxic T cells.

That binding of a cytotoxic T cell to these cell surface-displayed complexes stimulates the mitosis (cell division) of these T cells, their differentiation into memory cells (just as we see memory cells formation by B cells), and the destruction of the so-recognized, MHC-antigen-displaying body cell. The latter is the cytotoxic step.

The above video also very nicely illustrates the action of cytotoxic T cells against cancer cells, with less talk but even prettier action.

Interferon

Molecules produced by virus-infected and other ailing cells that are used as a means of communicating that situation to other cells so that the latter can take protective actions.

Interferon is a paracrine signaling molecule. That is, it is a hormone-like molecule that is employed particularly for cell-to-cell communication that does not involve movement of the signaling molecule through the blood.

It is a signal that is released in response to intracellular pathogens associated with the releasing cell, particularly as due to viral infection. Indeed, the name "interferon" comes from the ability of this molecule literally to interfere with viral infections. The viral infections that are interfered with, however, are not those associated with the same cell that releases interferon but instead adjacent cells, ones that could become infected as the interferon-producing cell also released viral progeny that could go on to infect these adjacent cells. (Viruses are obligate intracellularly parasites that replicate within one cell, are released from that cell, and then are able to reinitiate replication only by invading a subsequent cell.)

In a sense, the interferon molecules serve as warning signals to these adjacent cells, and the response of these cells to that warning is to modify their metabolism in such a way that they become less virus susceptible, though presumably also less functional to the body as well. The result, given viral infection of those cells, include cell death, which has the effect of killing the infecting virus as well.

Tonsils

Lymphoid tissue exposed to the back of the mouth or pharynx.

The tonsils are air-, food-, and water-exposed lymphoid tissue that sample these substances for microorganisms via associated macrophages, lymphocytes, and also macrophage-like cells known as dendritic cells. This allows the body to initiate immune responses against these organisms well prior to the body being harmed due to excessive pathogen growth and/or pathogen invasion into body tissues.

Other such microbe-sampling sites exist within the body, most notably the Peyer's patches located in the small intestine segment known as the ileum (which also happens to be the longest of the small intestine segments). Unlike the tonsils, however, Peyer's patches are not exposed to air but instead are exposed solely to chyme.

The tonsils thus are important both because of their interaction with air and therefore airborne microbes but also because of their interaction with relatively unprocessed food and water, which, following digestion, can be somewhat depleted in microorganisms as the food travels further along in the digestive tract.

The above video locates and describes the tonsils from a patient's perspective as well as discussion how they can be removed.

Lymph nodes

Key sites of development of adaptive immune responses, found in numerous, discrete locations throughout the body and that filter the drainage from body interstitium.

The lymph nodes are part of the lymphatic system, with lymph flowing through nodes in the course of its return to the blood. One-way valves within lymph vessels assure that this flow is unidirectional, entering from one end of the lymph node and exiting the other.

In between, the lymph comes into contact with leukocytes including lymphocytes and antigen-presenting cells. The latter can engulf materials from other locations within the body and then migrate to lymph nodes where they can then literally "present" (i.e., "show" or "provide") the associated antigens, in a modified form, to lymphocytes. In addition, the lymph itself can be sampled for antigens.

These processes give rise to two crucial consequences. The first is the activation of what is known as adaptive immunity, as mediated by B cells and T cells. The second is assurance that this activation occurs only under circumstances where adaptive immunity is required, particularly to fight infections, and not when it is not required (thereby, ideally, avoiding autoimmune diseases).

The above video provides a discussion of "swollen glands" and when you should or shouldn't be concerned.

If you were taking an anatomy class and if you were attempting to memorize the names and locations of major lymph nodes, a video such as the above might be helpful.

Mucociliary escalator

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Means by which smaller foreign objects are slowly moved out of the respiratory system.

The slowness of this mechanism contrasts with coughing and sneezing, which instead use air pressure to forcibly expel materials from the respiratory system.

The process by which the mucociliary escalator functions involves, not surprisingly, both mucus and cilia. The cilia line many of the surfaces making up the interior of the respiratory tract, and the beating of these cilia moves the mucus, within which they beat, towards the pharynx.

Small foreign objects become trapped in this mucus and as a consequence are moved away from where they can cause harm, which particularly is from deep within the lungs, towards where the mucus instead can be swallowed. In addition to this process, the lungs contain macrophages which engulf smaller foreign materials.

As a consequence of these mechanisms, healthy lungs generally are free of microorganisms, with the exception of those microorganisms that have recently arrived and otherwise are in the process of being removed.

The above video provides, using interesting graphics, a nice introduction into what the mucociliary transport is all about.

AIDS

Virus-induced decline in T helper cells characterized by severe immunodeficiency.

AIDS stands for Acquired ImmunoDeficiency Syndrome and is caused by a viruses known as Human Immunodeficiency Virus (or HIV). These viruses infect a variety of cell types within the body, including particularly T helper cells and macrophages.

The resulting declines in T helper cell populations results in the immunodeficiency of AIDS, though it can take years for AIDS to develop and this development occurs particularly as the resiliency of T helper cell populations, that is, ability to bounce back from virus-caused losses, is slowly depleted. At the same time, the immune system is needed to keep the HIV infection in check, and AIDS can be viewed in part as a positive feedback process whereby eventually the body's ability to hold back the replication of HIV is depleted by HIV-caused losses of T helper cells, which results in expansion of HIV populations at the further expense of T helper cells.

The resulting immunodeficiency makes the body particularly susceptible to a diversity of infectious diseases, which typically are the direct cause of death due to AIDS. Treatment for underlying HIV infections involves interfering in various ways with HIV replication using a diversity of antiviral drugs.

The above video does a good job of discussing what an HIV infection means including its symptomatic transition to AIDS; note that there is a possible "oops" at 2:00 where the narrator says, "…but as the body is forced to create new HIV cells…", presumably the word "viruses" would work better than "cells".

The above video does a good job of discussing what it means to progress from HIV infection to AIDS status.

Autoimmune disease

Lack of immune system tolerance for certain aspects of a body's own tissues, resulting in tissue destruction and/or chronic inflammation.

Autoimmune diseases result when self antigens instead are treated by the body as foreign antigens. This can occur when a pathogen produces antigens that are antigenically similar to self antigens. The pathogen may do this to increase its potential to evade the body's immune system by mimicking self antigens, which normally are ignored by the immune system ('normally', that is, given an absence of autoimmune disease).

If the pathogen stimulates an immune response in the course of infecting, and that immune response results in the generation of adaptive immune responses that also have an ability to recognize self antigens, then an autoimmune disease can commence. Examples of autoimmune diseases include type I diabetes (where the tissue attacked are the beta cells the islets of Langerhans), systemic lupus, and rheumatoid arthritis.

Allergy

Immune system hypersensitivity to a normally benign environmental component.

These environmental components are proteins that are associated with various types of organisms, including plants as well as animals. In individuals who are not allergic to the same substances, there is little or no harmful impact resulting from exposure. To individuals who are allergic, however, substantial consequences result including potentially life threatening constrictions of lung bronchioles.

These more severe allergic reactions are described as anaphylaxes (anaphylaxis is the singular) and often will increase in intensity given repeated allergen exposure. They may be treated over the short term with injections of the hormone epinephrine, which causes instead a dilation of bronchioles.

The above video provides a nice introduction to what allergies represent such as pollen allergies (this video is presented as well under the heading of allergen).

The above video does a reasonably good job of introducing the concept of food allergies, though note that the little pollen-looking things are meant to represent food allergen molecules rather than pollen grains, which are much much larger than as depicted.

Anaphylaxis

Allergic reaction that is both substantial, including to the point of being lethal, and rapid in onset.

Anaphylaxes are pathological immune responses that are stimulated by repeated exposure to allergens and are described as hypersensitivities. Life-threatening anaphylaxis responses result for example in constriction of bronchioles and consequent restriction in breathing.

As the hormone epinephrine stimulates the relaxation of bronchiole smooth muscle contraction, administration of epinephrine can result in a temporary reversal of these symptoms.

The above video walks you through what to do in response to a severe anaphylactic episode.

Adaptive Immunity