Human Phys. Ch. 12 -- The Lymphatic System and Body Defenses

3 Important aspects of the adaptive defense system:

1) It is antigen specific -- it recognizes and acts against particular pathogens or foreign substances. 2) It is systemic -- immunity is not restricted to the initial infection site. 3) It has "memory" -- it recognizes and mounts even stronger attacks on previously encountered pathogens.

2 arms of the adaptive defense system:

- Humoral immunity (Antibody-mediated immunity) - Cellular immunity (Cell-mediated immunity)

Edema

If leaked fluid is not carried back to the blood, fluid accumulates in the tissues, producing edema. Excessive edema impairs the ability of tissue cells to make exchanges with the interstitial fluid and ultimately the blood.

Abscess

If the inflammatory mechanism fails to fully clear the area of debris, the sac of pus may become walled off, forming an abscess. Surgical drainage of abscesses is often necessary before healing can occur.

Neutrophils

In the 1st stage of inflammatory response, neutrophils, responding to a gradient of diffusing inflammatory chemicals, enter the blood from the bone marrow and roll along the blood vessel walls following the "scent"

Diapedesis

In the 2nd stage of inflammatory response, at the point where the chemical signal is the strongest, the neutrophils flatten out and squeeze through the capillary walls, a process called diapedesis.

Positive chemotaxis

In the 3rd stage of inflammatory response, still drawn by the gradient of inflammatory chemicals, the neutrophils gather in the precise site of tissue injury -- a process called positive chemotaxis. Within an hour after injury has occurred, they are busily devouring any foreign material present.

Immunodeficiencies

Include both congenital and acquired conditions in which the production or function of immune cells or complement is abnormal.

Cell-mediated immune response

Like B cells, immunocompetent T cells are activated to form a clone by binding with a "recognized" antigen. However, unlike B cells, T cells are not able to bind with free antigens. Instead, the antigens must be "presented" by a macrophage (or by other antigen-presenting cells), and a double recognition must occur. The APC engulfs an antigen, and processes it internally. Parts of the processed antigen are then displayed on the external surface of the presenting cell in combination with one of the APC's own proteins. A T-cell must recognize "nonself," the antigen fragment presented by the APC, and also "self" by coupling with a specific glycoprotein on the APC's surface at the same time. Antigen-binding alone is not enough to sensitize T cells. They must be "spoon-fed" the antigens by APCs, and something like a "double handshake" must occur.

Afferent lymphatic vessels

Lymph enters the convex side of a lymph node through afferent lymphatic vessels.

Lymphatic collecting vessels

Lymph is transported from the lymph capillaries through successively larger lymphatic vessels, referred to as lymphatic collecting vessels, until it is finally returned to the venous system through one of the 2 large ducts in the thoracic region.

Lymphoid organs

Lymph nodes are just one of many types of lymphoid organs in the body. Others are the spleen, thymus, tonsils, and Peyer's patches and the appendix of the intestine, as well as bits of lymphoid tissue scattered in the epithelial and connective tissues. The common feature of all these organs is a predominance of reticular connective tissue and lymphocytes. Although all lymphoid organs have roles in protecting the body, only lymph nodes filter lymph.

B lymphocytes (B cells)

Lymphocytes exist in two major "flavors:" - B lymphocytes (B cells) - T lymphocytes (T cells) B lymphocytes produce antibodies and oversee humoral immunity. B cells develop immunocompetence in Bone marrow. After they become immunocompetent, they migrate to the lymph nodes and spleen, where their encounters with antigens will occur.

T lymphocytes (T cells)

Lymphocytes exist in two major "flavors:" - B lymphocytes (B cells) - T lymphocytes (T cells) T lymphocytes are non-antibody producing lymphocytes that constitute the cell-mediated arm of the adaptive defense system. T cells arise from lymphocytes that migrate to the Thymus. In the thymus, they undergo a maturation process of 2-3 days, directed by thymic hormones (thymosin and others). After they become immunocompetent, they migrate to the lymph nodes and spleen, where their encounters with antigens will occur.

Immune system

Made up of the innate and the adaptive defense systems. The body's defenders against the army of hostile bacteria, viruses, and fungi that swarms on our skin and invades our inner passageways. The immune system is a functional system rather than an organ system in an anatomical sense. Its "structures" are a variety of molecules and trillions of immune cells that inhabit lymphoid tissues and organs and circulate in body fluids. The most important of the immune cells are lymphocytes, dendritic cells, and macrophages.

Germinal centers

Many follicles have dark-staining centers that enlarge when specific lymphocytes (the B cells) are generating daughter cells called plasma cells, which release antibodies.

Delayed hypersensitivities

Mediated mainly by a special subgroup of helper T cells, cytotoxic T cells, and macrophages, take much longer to appear (1-3 days) than any of the acute reactions produced by antibodies. Instead of histamine, the chemicals mediating these reactions are cytokines released by the activated T cells.

Plasma cells

Most of the B cell clone members, or descendants, become plasma cells. After an initial lag period, these antibody-producing "factories" swing into action, producing the same highly specific antibodies at an unbelievable rate of about 2000 antibody molecules per second. (The B cells themselves produce only very small amounts of antibodies.) However, this flurry of activity lasts only 4 or 5 days, then the plasma cells begin to die.

Memory cells

Most of the T cells enlisted to fight in a particular immune response are dead within a few days. However, a few members of each clone are long-lived memory cells that remain behind to provide the immunological memory for each antigen encountered and enable the body to respond quickly to subsequent invasions.

Adaptive defense system (Specific defense system)

Mounts the attack against particular foreign substances. Unlike the innate defenses, which are always prepared to defend the body, the adaptive system must first "meet" or be primed by an initial exposure to a foreign substance (antigen) before it can protect the body against the invader. What the adaptive system lacks in speed it makes up for in the precision of its counterattacks.

Autoimmune diseases

Occasionally, the immune system loses its ability to distinguish friend from foe, that is, to tolerate self-antigens while still recognizing and attacking foreign antigens. When this happens, the body produces antibodies (auto-antibodies) and sensitized T cells that attack and damage its own tissues. 5% of adults in North America -- 2/3 of them women -- are afflicted with autoimmune disease. Most common are: - Rheumatoid arthritis (RA) - Myasthenia gravis - Multiple sclerosis (MS) - Graves' disease - Type 1 diabetes mellitus - Systemic lupus erythematosus (SLE) - Glomerulonephritis

Antibody IgA

Occur in both monomer and dimer (2 linked monomers) forms. The IgA dimer, sometimes called secretory IgA, is found mainly in mucus and other secretions that bathe body surfaces. It plays a major role in preventing pathogens from gaining entry into the body.

Neutralization

Occurs when antibodies bind to specific sites on bacterial exotoxins (toxin chemicals secreted by bacteria) or on viruses that can cause cell injury. In this way, they block the harmful effects of the exotoxin or virus.

Complement fixation

Occurs when complement proteins bind to certain sugars or proteins (such as antibodies) on the foreign cell's surface. One result of complement fixation is the formation of membrane attack complexes (MAC).

Right lymphatic duct

One of the 2 large ducts in the thoracic region. Drains the lymph from the right arm and the right side of the head and thorax. Both ducts empty the lymph into the subclavian vein on their own side of the body.

Thoracic duct

One of the 2 large ducts in the thoracic region. The large thoracic duct receives lymph from the rest of the body. Both ducts empty the lymph into the subclavian vein on their own side of the body.

Self-antigens

Our own cells are richly studded with a variety of protein molecules (self-antigens). Somehow, as our immune system develops, it takes an inventory of all these proteins so that, thereafter, they are recognized as self. Although these self-antigens do not provoke an immune response in us, they are strongly antigenic to other people.

Phagocytes

Pathogens that make it through the mechanical barriers are confronted by phagocytes in nearly every body organ. A phagocyte, such as a macrophage or a neutrophil, engulfs a foreign particle. Flowing cytoplasmic extensions bind to the particle and then pull it inside, enclosing it in a vacuole. The vacuole is then fused with the enzymatic contents of a lysosome, and its contents are broken down, or digested.

Penicillin reaction

Perhaps the most dramatic and familiar example of a drug hapten's provoking an immune response involves the binding of penicillin to blood proteins, which causes a penicillin reaction in some people.

Mucosa-associated lymphoid tissue (MALT)

Peyer's patches, the appendix, and the tonsils, are part of the collection of small lymphoid tissues referred to as MALT. Collectively, MALT acts as a sentinel to protect the upper respiratory and digestive tracts from the never-ending attacks of foreign matter entering those cavities.

Humoral immunity (antibody-mediated immunity)

Provided by antibodies present in the body's "humors," or fluids.

Passive immunity

Quite different from active immunity, both in the antibody source and in the degree of protection it provides. Instead of being made by your plasma cells, the antibodies are obtained from the serum of an immune human or animal donor. As a result, your B cells are not challenged by the antigen, immunological memory does not occur, and the temporary protection provided by the "borrowed antibodies" ends when they naturally degrade in the body. Passive immunity is conferred naturally on a fetus when the mother's antibodies cross the placenta and enter the fetal circulation, and after birth during breastfeeding. For several months after birth, the baby is protected from all the antigens to which the mother has been exposed. Passive immunity is artificially conferred when a person receives immune serum or gamma globulin.

Antibody structure

Regardless of its class, every antibody has a basic structure consisting of 4 amino acid (polypeptide) chains linked together by disulfide (sulfur-to-sulfur) bonds. Two of the 4 chains are identical and contain approximately 400 amino acids each; these are the heavy chains. The other 2 chains, the light chains, are also identical to each other but are only about half as long as the heavy chains. When the 4 chains are combines, the antibody molecule formed has 2 identical halves, each consisting of a heavy and a light chain, and the molecule as a whole is commonly described as being T- or Y-shaped.

Peyer's patches

Resemble tonsils, are found in the wall of the distal part of the small intestine. The macrophages of Peyer's patches and the appendix are in an ideal position to capture and destroy bacteria (always present in tremendous numbers in the intestine), thereby preventing them from penetrating the intestinal wall.

Innate defense system (nonspecific defense system)

Responds immediately to protect the body from all foreign substances, whatever they are. Provided by intact skin and mucus membranes, by the inflammatory response, and by a number of proteins produced by body cells. This innate system reduces the workload of the second protective arm, the adaptive defense system, by preventing entry and spread of microorganisms throughout the body.

Natural killer (NK) cells

Roam the body in blood and lymph. They are a unique group of aggressive lymphocytes that can lyse and kill cancer cells, virus-infected body cells, and some other non-specific targets well before the adaptive arm of the immune system is enlisted in the fight. Unlike the lymphocytes of the adaptive system, which can recognize and eliminate only specific virus-infected or tumor cells, natural killer cells are far less picky. They can act spontaneously against any such target by recognizing certain sugars on the "intruder's" surface as well as its lack of certain "self" cell surface molecules. NK cells are not phagocytic. They attack the target cell's membrane and release lytic chemicals called perforins. Shortly thereafter, the target cell's membrane and nucleus disintegrate. NK cells also release powerful inflammatory chemicals.

Lysozyme

Saliva and lacrimal fluid contain lysozyme, an enzyme that destroys bacteria.

Tonsils

Small masses of lymphoid tissue that ring the pharynx (the throat), where they are found in the mucosa. Their job is to trap and remove any bacteria or other foreign pathogens entering the throat. They carry out this function so efficiently that sometimes they become congested with bacteria and become red, swollen, and sore, a condition called tonsillitis.

Helper T cells

The T cells that act as the "directors" or "managers" of the immune system. Once activated, they circulate through the body, recruiting other cells to fight the invaders. For example, helper T cells interact directly with B cells (that have already attached to antigens), prodding B cells into more rapid division (clone production) and then, like the "boss" of an assembly line, signaling for antibody formation to begin. The helper T cells also release a variety of cytokine chemicals that act indirectly to rid the body of antigens.

Chemotaxis

The attraction of phagocytes and white blood cells to an area. Called chemotaxis because the cells are following a chemical gradient.

Anaphylactic shock

The bodywide, or systemic, acute allergic response. Fortunately, it is fairly rare. Occurs when the allergen directly enters the blood and circulates rapidly through the body, as might happen with certain bee stings, spider bites, etc. The mechanism of anaphylactic shock is essentially the same as that of local responses, but when the entire body is involved, the outcome is life-threatening.

Medulla

The central part of the lymph node. Phagocytic macrophages are located in the medulla.

Self-tolerance

The development of self-tolerance for the body's own cells is an essential part of a lymphocyte's "education." Lymphocytes capable of binding with self-antigens (and of acting against body cells) are vigorously weeded out and destroyed.

Immunity

The highly specific resistance to disease resulting from the immune system's protective actions. immun = free

Immune response

The immune system's response to a threat. Involves tremendously increased internal nonspecific defenses (inflammatory responses and others) and also provides protection that is carefully targeted against specific antigens. Furthermore, the initial exposure to an antigen "primes" the body to react more vigorously to later meetings with the same antigen.

Efferent lymphatic vessels

The lymph exits the lymph node at its indented region, the hilum, via efferent lymphatic vessels. Because there are fewer efferent vessels draining the node than afferent vessels feeding it, the flow of lymph through the node is very slow, kind of like what happens when you pour something into a funnel. This allows time for the lymphocytes and macrophages to survey and perform their protective functions.

Lymph capillaries

The microscopic, blind-ended lymph capillaries weave between the tissue cells and blood capillaries in the loose connective tissues of the body and absorb the leaked fluid. Although similar to blood capillaries, lymphatic capillaries are so remarkably permeable that they were once thought to be open at one end like a straw.

Immediate hypersensitivity (acute hypersensitivity)

The most common type of allergy. Type of response triggered by the release of a flood of histamine when IgE antibodies bind to mast cells. Histamine causes small blood vessels in the area to become dilated and leaky and is largely to blame for the best-recognized symptoms of allergy.

Severe combined immunodeficiency disease (SCID)

The most devastating congenital condition. There is a marked deficit of both B and T cells. Because T cells are absolutely required for normal operation of both arms of the adaptive response, afflicted children have essentially no protection against pathogens of any type. Minor infections easily shrugged off by most children are lethal to those with SCID.

Allergic contact dermatitis

The most familiar examples of delayed hypersensitivity reactions are these, which follow skin contact with poison ivy, some heavy metals (lead, mercury, and others), and certain cosmetic and deodorant chemicals. These agents act as haptens; after diffusing through the skin and attaching to body proteins, they are perceived as foreign by the immune system.

Cortex

The outer part of the lymph node. Contains collections of lymphocytes called follicles. The rest of the cortical cells are lymphocytes "in transit," the so-called T cells that circulate continuously between the blood, lymph nodes, and lymphatic stream performing their surveillance role.

Clone

The resulting family of identical cells descended from the same ancestor is called a clone. Clone formation is the primary humoral response to that antigen.

Complement

The term complement refers to a group of at least 20 plasma proteins that circulate in the blood in an inactive state. However, when complement becomes attached, or fixed, to foreign cells such as bacteria, fungi, or mismatched red blood cells, it is activated and becomes a major factor in the fight against the foreign cells. Although the complement attack is often directed against specific microorganisms that have been "identified" by antibody binding, complement itself is a nonspecific defensive mechanism that "complements," or enhances, the effectiveness of both innate and adaptive defenses.

Tonsillitis

The tonsils carry out their job so efficiently that sometimes they become congested with bacteria and become red, swollen, and sore, a condition called tonsillitis.

Antigen-binding site

The variable regions of the heavy and light chains combine their efforts to form an antigen-binding site uniquely shaped to "fit" its specific antigen. Hence, each antibody has 2 such antigen-binding regions.

Lymphatic vessels (lymphatics)

Their function is to form an elaborate drainage system that picks up this excess tissue fluid (lymph), and returns it to the blood. Form a one-way system, and lymph flows only toward the heart. Like veins of the cardiovascular system, lymphatic vessels are thin walled, and the larger ones have valves.

Antigen-presenting cells (APCs)

Their major role in immunity is to engulf antigens and then present fragments of them, like signal flags, on their own surfaces where they can be recognized by T cells. In other words, they present antigens to the cells that will actually deal with the antigens. The major types of cells acting as APCs are dendritic cells (present in connective tissues and in the epidermis), macrophages, and B lymphocytes. When they present antigens, dendritic cells and macrophages activate T cells. Activated T cells, in turn, release chemicals that prod macrophages to become activated macrophages, true "killers" that are insatiable phagocytes and secrete bactericidal chemicals. Dendritic cells are the most effective antigen-presenters known -- it's their only job.

Antibody classes

There are 5 major immunoglobulin classes -- IgM, IgA, IgD, IgG, IgE (MADGE). Antibodies IgD, IgG, and IgE have the same basic Y-shaped structure described previously and are referred to as monomers. IgA antibodies occur in both monomer and dimer (two linked monomers) forms. IgM antibodies are constructed of 5 linked monomers and are called pentamers. The antibodies of each class have slightly different biological roles and locations in the body.

Secondary humoral responses

These later immune responses, are produced much faster, are more prolonged, and are more effective than the events of the primary response because all the preparations for this attack have already been made. Within hours after recognition of the "old-enemy" antigen, a new army of plasma cells is being generated, and antibodies flood into the bloodstream. Within 2-3 days, blood antibody levels peak (at much higher levels than seen in the primary response), and their levels remain high for weeks to months.

Isografts

Tissue grafts donated by a genetically identical person, the only example being an identical twin.

Xenografts

Tissue grafts harvested from a different animal species, such as transplanting a baboon heart into a human being. Although pig heart valves have been transplanted with success, xenografts of whole organs are virtually never successful.

Allografts

Tissue grafts taken from a person other than an identical twin. The graft type most used is an allograft taken from a recently deceased person. Before an allograft is even attempted, the ABO and other blood group antigens of both the donor and the recipient must be determined and must match. Then, the cell membrane antigens of their tissue cells are typed to determine how closely they match. At least 75% match is needed to attempt a graft. Good tissue matches between unrelated people are hard to find.

Autografts

Tissue grafts transplanted from one site to another in the same person.

Histamine & kinins

When cells are injured, they release inflammatory chemicals, including histamine and kinins, that: 1) Cause blood vessels in the involved area to dilate and capillaries to become leaky 2) Activate pain receptors, and 3) Attract phagocytes and white blood cells to the area. Dilution of the blood vessels increases the blood flow to the area, accounting for the redness and heat observed. Increased permeability of the capillaries allows plasma to leak from the blood into tissue spaces, causing local edema (swelling) that also activates pain receptors in the area.

Cellular immunity (cell-mediated immunity)

When lymphocytes themselves defend the body, the immunity is called cellular immunity, because the protective factor is living cells. The cellular arm also has cellular targets -- virus-infected tissue cells, cancer cells, and cells of foreign grafts. The lymphocytes act against such targets either directly, by lysing the foreign cells, or indirectly, by releasing chemicals that enhance the inflammatory response or activate other immune cells.

Precipitation

When the cross-linking process involves soluble antigenic molecules, the resulting antigen-antibody complexes are so large that they become insoluble and settle out of solution. This cross-linking reaction is more precisely called precipitation.

Active immunity

When your B cells encounter antigens and produce antibodies against them, you are exhibiting active immunity. Active immunity is: 1) naturally acquired during bacterial and viral infections, during which we may develop the signs and symptoms of the disease and suffer a little (or a lot), and 2) artificially acquired when we receive vaccines. It makes little difference whether the antigen invades the body under its own power or is introduced in the form of a vaccine. The response of the immune system is pretty much the same.

Immunocompetent

Whether a given lymphocyte matures into a B cell or a T cell depends on where in the body it becomes immunocompetent, that is, capable of responding to a specific antigen by binding to it with antigen-specific receptors that appear on the lymphocyte's surface. Once a lymphocyte is immunocompetent, it will be able to react to one distinct antigen and one only, because all the antigen receptors on its external surface are the same. Lymphocytes become immunocompetent BEFORE meeting the antigens they may later attack.

Macrophages

Within the lymph nodes are macrophages, which engulf and destroy bacteria, viruses, and other foreign substances in the lymph before it is returned to the blood. Monocytes become macrophages in immune response. The macrophages continue to wage the battle, replacing the short-lived neutrophils on the battlefield. Macrophages are the central actors in the final disposal of cell debris as the inflammation subsides.

Monocytes

A kind of leukocyte. As the counterattack continues in immune response, monocytes follow the neutrophils into the inflamed area. Monocytes are fairly poor phagocytes, but within 12 hours after entering the tissues they become macrophages with insatiable appetites.

Pus

A mixture of dead or dying neutrophils, broken-down tissue cells, and living and dead pathogens. In severely infected areas, the battle takes a considerable toll on both sides, and creamy, yellow pus may form in the wound.

Inflammatory response

A nonspecific response that is triggered whenever body tissues are injured. For example, it occurs in response to physical trauma, intense heat, and irritating chemicals, as well as to infection by viruses and bacteria. The 4 cardinal signs of an acute inflammation: - redness - heat - swelling - pain The inflammatory process begins with a chemical "alarm." Prevents the spread of damaging agents to nearby tissues, disposes of cell debris and pathogens, and sets the stage for repair.

Membrane attack complexes (MAC)

A result of complement fixation. They produce lesions, complete with holes, in the foreign cell's surface. These lesions allow water to rush into the cell, causing it to burst.

Glomerulonephritis

A severe impairment of kidney function.

Spleen

A soft, blood-rich organ that filters blood. It is located on the left side of the abdominal cavity, just beneath the diaphragm, and curls around the anterolateral aspect of the stomach. Instead of filtering lymph, the spleen filters and cleanses blood of bacteria, viruses, and other debris. As with other lymphoid organs, the spleen provides a site for lymphocyte proliferation and immune surveillance, but its most important function is to destroy worn-out red blood cells and return some of their breakdown products to the liver. Other functions of the spleen include storing platelets and acting as a blood reservoir (as does the liver).

Systemic lupus erythematosus (SLE)

A systemic disease that occurs mainly in young women and particularly affects the kidneys, heart, lungs, and skin.

Appendix

A tubelike offshoot of the first part of the large intestine where lymphoid follicles are heavily concentrated.

Lymphocytes

A type of white blood cell, collections of which are strategically located in the lymph nodes and respond to foreign substances in the lymphatic stream. Lymphocytes arise from the red bone marrow but then migrate to the lymph nodes and other lymphoid organs, where they proliferate further.

Antimicrobial proteins

A variety of antimicrobial proteins enhance the innate defenses either by attacking microorganisms directly or by hindering their ability to reproduce. The most important of these are complement proteins and interferon.

Fever

Abnormally high body temperature. A systemic response to invading microorganisms. Although high fevers are dangerous because excess heat "scrambles" enzymes and other body proteins, mild or moderate fever seems to benefit the body. Bacteria require large amounts of iron and zinc to multiply, but during a fever the liver and spleen gather up these nutrients, making them less available. Fever also increases the metabolic rate of tissue cells in general, speeding up repair processes.

Allergies (hypersensitivities)

Abnormally vigorous immune responses in which the immune system causes tissue damage as it fights off a perceived "threat" that would otherwise be harmless to the body. The term allergen is used to distinguish this type of antigen from those producing essentially normal responses.

Vaccines

Active immunity is artificially acquired when we receive vaccines. Most vaccines contain pathogens that are dead or attenuated (living, but extremely weakened). We receive 2 benefits from vaccines: 1) They spare us most of the signs and symptoms (and discomfort) of the disease that would otherwise occur during the primary response, and 2) The weakened antigens are still able to stimulate antibody production and promote immunological memory.

Sinuses

After entering the convex side of a lymph node through afferent lymphatic vessels, lymph then flows through a number of sinuses that meander through the lymph node and finally exits from the node at its indented region, the hilum, via efferent lymphatic vessels.

Hilum

After flowing through the sinuses, the lymph finally exits from the node at its indented region, the hilum.

Immunosuppressive therapy

After surgery, to prevent rejection, the patient receives immunosuppressive therapy, including one or more of the following: - corticosteroids to suppress inflammation - antiproliferative drugs - radiation (X-ray) therapy - immunosuppressor drugs Many of these drugs kill rapidly dividing cells (such as activated lymphocytes), and all of them have severe side effects. The major problem with immunosuppressive therapy is that while the immune system is suppressed, it cannot protect the body against other foreign agents.

Specific defense system

Also called the third line of defense. A functional system that recognizes foreign molecules (antigens) and acts to inactivate or destroy them. Normally it protects us from a wide variety of pathogens, as well as from abnormal body cells. When it fails, malfunctions, or is disabled, some of the most devastating diseases -- such as cancer, rheumatoid arthritis, and AIDS -- may result.

Interferons

Although the virus-infected cells in an infected person can do little to save themselves, they help defend cells that have not yet been infected by secreting small proteins called interferons. The interferon molecules diffuse to nearby cells and bind to their membrane receptors. This binding stimulates the synthesis of proteins that "interfere" with the ability of viruses to multiply within these still-healthy cells.

Clonal selection

An immunocompetent but as yet immature B lymphocyte is stimulated to complete its development (into a fully mature B cell) when antigens bind to its surface receptors. This binding event sensitizes, or activates, the lymphocyte to "switch on" and undergo clonal selection. The lymphocyte begins to grow and then multiplies rapidly to form an army of cells all exactly like itself and bearing the same antigen-specific receptors.

Monoclonal antibodies

Antibodies are prepared commercially for use in research, in clinical testing for diagnostic purposes, and in treating certain cancers. Monoclonal antibodies used for such purposes are descendants of a single cell and are pure antibody preparations that exhibit specificity for one, and only one, antigen. Besides their use in delivering cancer-fighting drugs to cancerous tissue, monoclonal antibodies are being used for early cancer diagnosis and to track the extent of cancers hidden deep within the body. They are also used for diagnosing pregnancy, hepatitis, and rabies.

Antibody function

Antibodies inactivate antigens in a number of ways: - by complement fixation - neutralization - agglutination - precipitation Of these, complement fixation and neutralization are most important to body protection.

Antigen (Ag)

Any substance capable of mobilizing our immune system and provoking an immune response. Most antigens are large, complex molecules that are not normally present in our bodies. Consequently, as far as our immune system is concerned, they are foreign intruders, or nonself. Proteins are the strongest antigens. As a rule, small molecules are not antigenic, but when they link up with our own proteins, the immune system may recognize the combination as foreign and mount an attack that is harmful rather than protective.

Hapten (incomplete antigen)

As a rule, small molecules are not antigenic, but when they link up with our own proteins, the immune system may recognize the combination as foreign and mount an attack that is harmful rather than protective. The troublesome small molecule is called a hapten, or incomplete antigen. Besides certain drugs, chemicals that act as haptens are found in poison ivy, animal dander, and even in some detergents, hair dyes, cosmetics, etc.

Interstitial fluid

As blood circulates through the body, exchanges of nutrients, wastes, and gases occur between the blood and the interstitial fluid. The fluid that remains behind in the tissue spaces, as much as 3L daily, becomes part of the interstitial fluid. This leaked fluid, as well as any plasma proteins that escape from the blood, must be carried back to the blood if the vascular system is to have sufficient blood volume to operate properly.

Graves' disease

Autoimmune disease in which the thyroid gland produces excessive amounts of thyroxine.

Type 1 diabetes Mellitus

Autoimmune disease that destroys pancreatic beta cells, resulting in deficient production of insulin.

Multiple sclerosis (MS)

Autoimmune disease that destroys the white matter (myelin sheaths) of the brain and spinal cord.

Myasthenia gravis

Autoimmune disease that impairs communication between nerves and skeletal muscles.

Rheumatoid arthritis (RA)

Autoimmune disease that systematically destroys joints.

Memory cells

B cell clone members that do not become plasma cells become long-lived memory cells capable of responding to the same antigen at later meetings with it. Memory cells are responsible for the immunological memory mentioned earlier.

Agglutination

Because antibodies have more than one antigen-binding site, they can bind to more than one antigen at a time; consequently, antigen-antibody complexes can be cross-linked into large lattices. When the cross-linking involves cell-bound antigens, the process causes clumping of the foreign cells, a process called agglutination. This type of antigen-antibody reaction occurs when mismatched blood is transfused (the foreign red blood cells are clumped) and is the basis of tests used for blood typing.

Cytotoxic (Killer) T cells

Cells that specialize in killing virus-infected, cancer, or foreign graft cells. One way a cytotoxic T cell accomplishes this is by binding tightly to a foreign cell and releasing toxic chemicals called perforins and granzymes from its granules. The perforins enter the foreign cell's plasma membrane (delivering the so-called lethal hit). Shortly thereafter, pores appear in the target cell's membrane, allowing the granzymes (protein-digesting enzymes) to enter and kill the foreign cell. The cytotoxic T cell then detaches and seeks other foreign prey to attack.

Cytokine

Chemicals released by helper T cells that act indirectly to rid the body of antigens by: 1) Stimulating cytotoxic T cells and B cells to grow and divide. 2) Attracting other types of protective white blood cells, such as neutrophils, into the area. 3) Enhancing the ability of macrophages to engulf and destroy microorganisms. As the released cytokines summon more and more cells into the battle, the immune response gains momentum, and the antigens are overwhelmed by the sheer numbers of immune elements acting against them.

Pyrogens

Chemicals secreted by white blood cells and macrophages exposed to foreign cells or substances in the body. Normally the body thermostat is set at approximately 37 C (98.6 F), but it can be reset upward in response to pyrogens.

Primary humoral response

Clone formation is the primary hormonal response to that specific antigen.

Follicles

Collections of of lymphocytes in the cortex of the lymph node. Many follicles have dark-staining centers called germinal centers.

Antibody IgM

Compared to the other antibodies, IgM antibodies are huge. They are constructed of 5 linked monomers, and are called pentamers. Only IgM and IgG can fix complement.

Lymphatic system

Consists of 2 semi-independent parts: 1) A meandering network of lymphatic vessels. 2) Various lymphoid tissues and organs scattered throughout the body. The lymphatic vessels transport back to the blood fluids that have escaped from the blood vascular system. The lymphoid tissues and organs house phagocytic cells and lymphocytes, which play essential roles in body defense and resistance to disease. The lymphatic system is a low-pressure, pumpless system.

Antibodies (Immunoglobulins or Igs)

Constitute the gamma globulin part of blood proteins. Antibodies are soluble proteins secreted by activated B cells or by their plasma-cell offspring in response to an antigen, and they are capable of binding specifically with that antigen. Antibodies are formed in response to a huge number of different antigens. Despite their variety, they all have a similar basic anatomy that allows them to be grouped into 5 Ig classes, each slightly different in structure and function.

Acquired immune deficiency syndrome (AIDS)

Currently, the most important and most devastating of the acquired immunodeficiencies. AIDS cripples the immune system by interfering with the activity of helper T cells.

Constant (C) region

Each of the 4 chains forming an antibody have a variable (V) region and a constant (C) region at the other end. Antibodies responding to different antigens have different variable regions, but their constant regions are the same or nearly so. The constant regions of the antibody chains serve common functions in all antibodies: they determine the type of antibody formed (antibody class), as well as how the antibody class will carry out its immune roles in the body, and the cells types or chemicals with which the antibody can bind.

Variable (V) region

Each of the 4 chains forming an antibody have a variable (V) region and a constant (C) region at the other end. Antibodies responding to different antigens have different variable regions, but their constant regions are the same or nearly so. The variable regions of the heavy and light chains in each arm combine their efforts to form an antigen-binding site.

Antigen presentation

Essential for activation and clonal selection of the T cells. Without the "presenters," the immune response is severely impaired.

Viruses

Essentially nucleic acids surrounded by a protein coat. They lack the cellular machinery required to generate ATP or make proteins. They do their "dirty work" in the body by entering tissue cells and taking over the cellular machinery needed to reproduce themselves.

Lymph

Excess tissue fluid. Lymph = clear water.

Rheumatoid fever

Foreign antigens can sometimes resemble self-antigens. Antibodies produced during an infection caused by streptococcus bacteria are known to cross-react with heart antigens, causing damage to both the heart muscle and its valves, as well as to joints and kidneys. This age-old disease is called rheumatoid fever.

Nonself

Foreign intruders in the body.

Regulatory T cells

Formerly called suppressor T cells, they release chemicals that suppress the activity of both T and B cells. Regulatory T cells are vital for winding down and finally stopping the immune response after an antigen has been successfully inactivated or destroyed. This helps prevent uncontrolled or unnecessary immune system activity.

Thymus

Functions at peak levels only during youth. A lymphoid mass found low in the throat overlying the heart.

Pathogens

Harmful or disease-causing microorganisms.

Antibody IgE

Has the basic Y-shape of monomers. The "troublemaker" antibodies involved in allergies.

Antibody IgD

Has the basic Y-shaped structure of monomers. Important in activating B cell.

Antibody IgG

Has the basic Y-shaped structure of monomers. The most abundant antibody in blood plasma and is the only type that can cross the placental barrier. Hence, the passive immunity that a mother transfers to her fetus is "with the compliments" of her IgG antibodies. Only IgM and IgG can fix complement.

Lymph nodes

Help protect the body by removing foreign material such as bacteria and tumor cells from the lymphatic stream and by producing lymphocytes that function in the immune response. As lymph is transported toward the heart, it is filtered through thousands of lymph nodes that cluster along the lymphatic vessels. Help rid the body of infectious agents and cancer cells, but sometimes they are overwhelmed by the very agents they are trying to destroy. For example, when large numbers of bacteria or viruses are trapped in the nodes, the nodes become inflamed and tender to the touch.