Anatomy test 4 chapter 21

passive/active/natural/artificial immunity types*

Natural active immunity. This is the production of one's own antibodies or T cells as a result of natural exposure to an antigen. Artificial active immunity. This is the production of one's own antibodies or T cells as a result of vaccination. A vaccine consists of either dead or attenuated (weakened) pathogens that can stimulate an immune response but cause little or no discomfort or disease. In some cases, periodic booster shots are given to restimulate immune memory and maintain a high level of protection. Natural passive immunity - temporary immunity that results from acquiring antibodies produced by another person. The only natural way for this to happen is for a fetus to acquire antibodies from the mother through the placenta before birth, or for a baby to acquire them during breast-feeding. Artificial passive immunity - a temporary immunity that results from the injection of an immune serum obtained from another person or from animals that have antibodies against a certain pathogen.

Acquired Immunodeficiency Syndrome (AIDS)

a group of conditions in which infection with the human immunodeficiency virus (HIV) severely depresses the immune response. HIV has an inner core consisting of a protein capsid that encloses two molecules of RNA, two molecules of an enzyme called reverse transcriptase, and a few other enzyme molecules. The capsid is enclosed in another layer of viral protein, the matrix. External to this is a viral envelope composed of phospholipids and glycoproteins derived from the host cell. Like other viruses, HIV can be replicated only by a living host cell. It invades helper T (CD4) cells, dendritic cells, and macrophages. HIV adheres to a target cell by means of one of its envelope glycoproteins and "tricks" the target cell into internalizing it by receptor-mediated endocytosis. Within the host cell, reverse transcriptase uses the viral RNA as a template to synthesize DNA—the opposite of the usual process of genetic transcription. Viruses that carry out this RNA → DNA reverse transcription are called retroviruses. The new DNA is inserted into the host cell's DNA, where it may lie dormant for months to years. When activated, however, it induces the host cell to produce new viral RNA, capsid proteins, and matrix proteins. As the new viruses emerge from the host cell, they are coated with bits of the cell's plasma membrane, forming the new viral envelope. The new viruses then adhere to more host cells and repeat the process. By destroying TH cells, HIV strikes at a central coordinating agent of innate, humoral, and cellular immunity. After an incubation period ranging from a few months to 12 years, the patient begins to experience flulike episodes of chills and fever as HIV attacks TH cells. At first, antibodies against HIV are produced and the TH count returns nearly to normal. As the virus destroys more and more cells, however, the signs and symptoms become more pronounced. A normal TH count is 600 to 1,200 cells/µL, but a criterion of AIDS is a count less than 200/µL.

imflammation**

a local defensive response to tissue injury of any kind, including trauma and infection. general purposes: (1) to limit the spread of pathogens and ultimately destroy them (2) to remove the debris of damaged tissue (3) to initiate tissue repair. Inflammation is characterized by four cardinal signs: redness, swelling, heat, and pain.

Mobilization of Defenses (inflammation)

first priority: get defensive leukocytes to the site quickly. Damaged tissues release cytokines that stimulate the red bone marrow to release neutrophils. Certain cells secrete vasoactive chemicals that dilate the blood vessels in the area of injury. Among these are histamine, leukotrienes, and other cytokines secreted by basophils, mast cells, and cells damaged by the pathogens that triggered the inflammation. The resulting increase in local blood flow is called hyperemia. Hyperemia not only results in the more rapid delivery of leukocytes, but also washes toxins and metabolic wastes from the tissue more rapidly. In addition to dilating local blood vessels, the vasoactive chemicals stimulate endothelial cells of the blood capillaries and venules to contract slightly, widening the gaps between them and increasing capillary permeability. This allows for the easier movement of fluid, leukocytes, and plasma proteins from the bloodstream into the surrounding tissue. Among the helpful proteins filtering from the blood are complement, antibodies, and clotting factors, all of which aid in combating pathogens. Endothelial cells actively recruit leukocytes. In the area of injury, they produce cell-adhesion molecules called selectins, which make their membranes sticky, and snag leukocytes arriving in the bloodstream. Leukocytes adhere loosely to the selectins and slowly tumble along the endothelium, sometimes coating it so thickly they obstruct blood flow. This adhesion to the vessel wall is called margination. The leukocytes then crawl through the gaps between the endothelial cells—an action called diapedesis or emigration—and enter the tissue fluid of the damaged tissue

Lymphocytes and APCs talk to each other with cytokines called

interleukins -- chemical signals from one leukocyte (or leukocyte derivative) to another

components of the lymphatic system

(1) lymph, the recovered fluid; (2) lymphatic vessels, which transport the lymph; (3) lymphatic tissue, composed of aggregates of lymphocytes and macrophages that populate many organs of the body 4) lymphatic organs, in which these cells are especially concentrated and which are set off from surrounding organs by connective tissue capsules.

five types of leukocytes.

---Neutrophils spend most of their lives wandering in the connective tissues killing bacteria. One of their methods is simple phagocytosis and digestion—engulfing microbes with their pseudopods and destroying them with lysosomal enzymes. The other is a more complex process that produces a cloud of bactericidal chemicals. When a neutrophil detects bacteria in the immediate area, its lysosomes migrate to the cell surface and degranulate, or discharge their enzymes into the tissue fluid. Here, the enzymes catalyze a reaction called the respiratory burst: The neutrophil rapidly absorbs oxygen and reduces it to superoxide anions (O2•-), which react with H+ to form hydrogen peroxide (H2O2). Another lysosomal enzyme produces hypochlorite (HClO), the active ingredient in chlorine bleach, using chloride ions in the tissue fluid. Superoxide, hydrogen peroxide, and hypochlorite are highly toxic; they form a chemical killing zone around the neutrophil that destroys far more bacteria than the neutrophil can destroy by phagocytosis alone. Unfortunately for the neutrophil, it too is killed by these chemicals. These potent oxidizing agents can also damage connective tissues and sometimes contribute to rheumatoid arthritis. ---Eosinophils are found especially in the mucous membranes, standing guard against parasites, allergens (allergy-causing antigens), and other foes. They congregate especially at sites of allergy, inflammation, or parasitic infection. They help to kill parasites such as tapeworms and roundworms by producing superoxide, hydrogen peroxide, and various toxic proteins including a neurotoxin. They promote the action of basophils and mast cells (see next paragraph). They phagocytize and degrade antigen-antibody complexes. Finally, they secrete enzymes that degrade and limit the action of histamine and other inflammatory chemicals that, unchecked, could cause tissue damage. ---Basophils secrete chemicals that aid the mobility and action of other leukocytes: leukotrienes that activate and attract neutrophils and eosinophils; the vasodilator histamine, which increases blood flow and speeds the delivery of leukocytes to the area; and the anticoagulant heparin, which inhibits the formation of blood clots that would impede leukocyte mobility. These substances are also produced by mast cells, a type of connective tissue cell similar to basophils. Eosinophils promote basophil and mast cell action by stimulating them to release these secretions. ---Lymphocytes all look more or less alike in blood films, but there are several functional types. Three basic categories have already been mentioned: natural killer (NK) cells, T cells, and B cells. In the circulating blood, about 80% of the lymphocytes are T cells, 15% B cells, and 5% NK and stem cells. The roles of these lymphocyte types are too diverse for easy generalizations here, but are described in later sections on NK cells and adaptive immunity. NK cells are part of our innate immunity and the others function mainly in adaptive immunity. Certain lymphocytes called helper T cells function in both innate and adaptive immunity. ---Monocytes are leukocytes that emigrate from the blood into the connective tissues and transform into macrophages. All of the body's avidly phagocytic cells except leukocytes are called the macrophage system. Dendritic cells are included even though they come from different stem cells than macrophages and employ receptor-mediated endocytosis instead of phagocytosis to internalize foreign matter. Some phagocytes are wandering cells that actively seek pathogens, whereas reticular cells and others are fixed in place and phagocytize only those pathogens that come to them—although they are strategically positioned for this to occur. Macrophages are widely distributed in the loose connective tissues, but there are also specialized forms with more specific localities: microglia in the central nervous system, alveolar macrophages in the lungs, and hepatic macrophages in the liver, for example.

three functions of lymphatic system

--Fluid recovery. Fluid continually filters from blood capillaries into the tissue spaces. The capillaries reabsorb about 85% of it on average, but the 15% they don't absorb would, over the course of a day, amount to 2 to 4 L of water and one-quarter to one-half of the plasma protein. One would die of circulatory failure within hours if this water and protein were not returned to the bloodstream. One task of the lymphatic system is to reabsorb this excess and return it to the blood. --Immunity. As the lymphatic system recovers tissue fluid, it also picks up foreign cells and chemicals from the tissues. On its way back to the bloodstream, the fluid passes through lymph nodes, where immune cells stand guard against foreign matter. When they detect anything potentially harmful, they activate a protective immune response. --Lipid absorption. In the small intestine, special lymphatic vessels called lacteals absorb dietary lipids that are not absorbed by the blood capillaries.

three lines of defense against these environmental agents of disease

--The first line of defense consists of epithelial barriers, notably the skin and mucous membranes, which are impenetrable to most of the pathogens that daily assault us. --The second line of defense consists of protections against pathogens that break through those external barriers. These defenses include leukocytes and macrophages, antimicrobial proteins, natural killer cells, fever, and inflammation. --The third line of defense is adaptive immunity, a group of mechanisms that not only defeat a pathogen but leave the body with a "memory" of it, enabling one to defeat it so quickly in future encounters that the pathogen causes no illness. Such defenses collectively compose the immune system

three characteristics of adaptive/acquired immunity (the third line of defense)**

1) It has a systemic effect. When an adaptive response is mounted against a particular threat such as a bacterial infection, it acts throughout the body to defeat that pathogen wherever it may be found. 2) It exhibits specificity. Adaptive immunity is directed against a specific pathogen. Immunity to one disease such as chickenpox does not confer immunity to others such as tetanus. 3) it has a memory. When reexposed to the same pathogen, the body reacts so quickly that there is no noticeable illness. The reaction time for inflammation and other innate defenses, by contrast, is just as long for later exposures as for the initial one.

three characteristics of innate immunity**

1) It is a local effect, in most cases, warding off a pathogen at the point of invasion (ex. rash or mosquito bite) with little effect anywhere else. Fever is an exception, having a systemic (body-wide) effect. 2) It is nonspecific. Each mechanism of innate immunity acts against a broad spectrum of disease agents, not against one particular pathogen (ex. the physical barrier of the skin and the antiviral effect of fever) Innate immunity used to be called nonspecific defense. 3)It lacks memory of any prior exposure to a pathogen - it is no easier to defeat the same pathogen in later exposures Much of our innate immunity employs three basic kinds of defense: (1) protective proteins such as keratin, interferons, and complement; (2) protective cells such as neutrophils and macrophages; and (3) protective processes such as fever and inflammation

four types of hypersentivity (distinguished by the types of immune agents (antibodies or T cells) involved and their methods of attack on the antigen. Type I is also characterized as acute (immediate) hypersensitivity because the response is very rapid, whereas types II and III are characterized as subacute because they exhibit a slower onset (1-3 hours after exposure) and last longer (10-15 hours). Type IV is a delayed cell-mediated response, whereas the other three are quicker antibody-mediated responses.)

1) Type I (acute) hypersensitivity includes the most common allergies. Some authorities use the word allergy for type I reactions only, and others use it for all four types. Type I is an IgE-mediated reaction that begins within seconds of exposure and usually subsides within 30 minutes, although it can be severe and even fatal. Allergens bind to IgE on the membranes of basophils and mast cells and stimulate them to secrete histamine and other inflammatory and vasoactive chemicals. Anaphylaxis is an immediate and intense type I reaction. Local anaphylaxis can be relieved with antihistamines. Anaphylactic shock is a severe, widespread acute hypersensitivity characterized by bronchoconstriction, dyspnea (labored breathing), widespread vasodilation, circulatory shock, and sometimes sudden death. Antihistamines are inadequate by themselves to counter anaphylactic shock, but epinephrine relieves the symptoms by dilating the bronchioles. -Examples of Type I Hypsensitivity: asthma/food allergies. 2) Type II (antibody-dependent cytotoxic) hypersensitivity occurs when IgG or IgM attacks antigens bound to cell surfaces. The reaction leads to complement activation and either lysis or opsonization of the target cell. Macrophages phagocytize and destroy opsonized platelets, erythrocytes, or other cells. -Examples of cell destruction by type II hypersensitivity: blood transfusion reactions, pemphigus vulgaris, and some drug reactions. In some other type II responses, an antibody binds to cell surface receptors and either interferes with their function as in myasthenia gravis, or overstimulates the cell as in toxic goiter. 3) Type III (immune complex) hypersensitivity occurs when IgG or IgM forms antigen-antibody complexes that precipitate beneath the endothelium of the blood vessels or in other tissues. At the sites of deposition, these complexes activate complement and trigger intense inflammation, causing tissue destruction. -Examples of type III hypersensitivity: the autoimmune diseases acute glomerulonephritis and systemic lupus erythematosus, a widespread inflammation of the connective tissues. 4) Type IV (delayed) hypersensitivity is a cell-mediated reaction in which the signs appear about 12 to 72 hours after exposure. It begins when APCs in the lymph nodes display antigens to helper T cells, and these T cells secrete interferon and other cytokines that activate cytotoxic T cells and macrophages. The result is a mixture of nonspecific and immune responses. -Examples of Type IV hypersensivity: allergies to haptens in cosmetics and poison ivy; graft rejection; the tuberculosis skin test; and the beta cell destruction that causes type 1 diabetes mellitus.

lymphatic cells (lymphocytes and other cells)

3 lymphocytes: --Natural killer (NK) cells are large lymphocytes that attack and destroy bacteria, transplanted tissues, and host cells (cells of one's own body) that have either become infected with viruses or turned cancerous. --T lymphocytes (T cells) are lymphocytes that mature in the thymus and later depend on thymic hormones; the T stands for thymus-dependent. There are several subclasses of T cells that will be introduced later. --B lymphocytes (B cells) are lymphocytes that differentiate into plasma cells—connective tissue cells that secrete antibodies. They are named for an organ in chickens (the bursa of Fabricius) in which they were first discovered. However, you may find it more helpful to think of B for bone marrow, the site where these cells mature in humans. other cells: --Macrophages are large, phagocytotic cells of the connective tissues. They develop from monocytes that have emigrated from the bloodstream. They phagocytize tissue debris, dead neutrophils, bacteria, and other foreign matter. They also process foreign matter and display antigenic fragments of it to certain T cells, thus alerting the immune system to the presence of an enemy. Macrophages and other cells that do this are collectively called antigen-presenting cells (APCs). --Dendritic cells are branched, mobile APCs found in the epidermis, mucous membranes, and lymphatic organs. They play an important role in alerting the immune system to pathogens that have breached the body surfaces. They engulf foreign matter by receptor-mediated endocytosis rather than phagocytosis, but otherwise function like macrophages. After internalizing an antigen, they migrate to a nearby lymph node and activate an immune reaction to it. --Reticular cells are branched, stationary APCs that contribute to the connective tissue framework (stroma) of the lymphatic organs.

autoimmune diseases

A disease in which the immune system fails to distinguish self-antigens from foreign ones and produces autoantibodies that attack the body's own tissues. Autoimmunity is usually prevented by negative selection of developing T and B cells, but there are at least three reasons why self-tolerance may fail: 1) Cross-reactivity. Some antibodies against foreign antigens react to similar self-antigens. In rheumatic fever, for example, a streptococcus infection stimulates production of antibodies that react not only against the bacteria but also against antigens of the heart tissue. It often results in scarring and stenosis (narrowing) of the mitral and aortic valves. 2) Abnormal exposure of self-antigens to the blood. Some of our native antigens are normally not exposed to the blood. For example, a blood-testis barrier (BTB) normally isolates sperm cells from the blood. Breakdown of the BTB can cause sterility when sperm first form in adolescence and activate the production of autoantibodies. 3) Change in the structure of self-antigens. Viruses and drugs may change the structure of self-antigens and cause the immune system to perceive them as foreign. One theory of type 1 diabetes mellitus is that a viral infection alters the antigens of the insulin-producing beta cells of the pancreatic islets, which leads to an autoimmune attack on the cells.

Severe combined immunodeficiency disease (SCID)

A group of disorders caused by recessive alleles that result in a scarcity or absence of both T and B cells. Children with SCID are highly vulnerable to opportunistic infections and must live in protective enclosures. Children with SCID are sometimes helped by transplants of bone marrow or fetal thymus, but in some cases the transplanted cells fail to survive and multiply, or transplanted T cells attack the patient's tissues (the graft-versus-host response).

Antigen-presenting cells (APCs)*

Although the function of T cells is to recognize and attack foreign antigens, they usually can't do this on their own. They require the help of antigen-presenting cells (APCs). Dendritic cells, macrophages, reticular cells, and B cells function as APCs. APC function hinges on a family of genes called the major histocompatibility complex (MHC) on chromosome 6. These genes code for MHC proteins—proteins on the APC surface that are shaped a little like hotdog buns, with an elongated groove for holding the "hotdog" of the foreign antigen. MHC proteins are structurally unique to every person except for identical twins. They act as "identification tags" that label every cell of your body as belonging to you. When an APC encounters an antigen, it internalizes it by endocytosis, digests it into molecular fragments, and displays the relevant fragments (its epitopes) in the grooves of the MHC proteins. These steps are called antigen processing. Wandering T cells regularly inspect APCs for displayed antigens. If an APC displays a self-antigen, the T cells disregard it. If it displays a nonself-antigen, however, they initiate an attack. APCs thus alert the immune system to the presence of a foreign antigen. The key to a successful defense is then to quickly mobilize immune cells against it.

Recognition phase of humoral immunity

An immunocompetent B cell has thousands of surface receptors for one antigen. B cell activation begins when an antigen binds to several of these receptors, links them together, and is taken into the cell by receptor-mediated endocytosis. One reason small molecules are not antigenic is that they are too small to link multiple receptors together. After endocytosis, the B cell processes (digests) the antigen, links some of the epitopes to its MHC-II proteins, and displays these on the cell surface. Thus, the B cell itself acts as an antigen-presenting cell. Usually, the B cell response goes no further unless a helper T cell binds to this Ag-MHC protein complex. (Some B cells are directly activated by antigens without the help of a TH cell.) When a TH cell binds to the complex, it secretes interleukins that activate the B cell. This triggers clonal selection—B cell mitosis giving rise to a battalion of identical B cells programmed against that antigen. Most cells of the clone differentiate into plasma cells. Plasma cells develop mainly in the germinal centers of the lymphatic nodules of the lymph nodes. About 10% of them remain in the lymph nodes, but the rest leave the nodes, take up residence in the bone marrow and elsewhere, and there produce antibodies until they die. The job of a plasma cell is to synthesize and secrete antibodies. It creates antibodies at a fast rate of 2,000 molecules per second over a life span of 4 to 5 days. These antibodies travel throughout the body in the blood and other body fluids. The first time you are exposed to a particular antigen, your plasma cells produce mainly an antibody class called IgM. In later exposures to the same antigen, they produce mainly IgG.

two types of adaptive/acquired immunity*

Cellular (cell-mediated) immunity employs lymphocytes that directly attack and destroy foreign cells or diseased host cells. It is a means of ridding the body of pathogens that reside inside human cells, where they are inaccessible to antibodies: intracellular viruses, bacteria, yeasts, and protozoans, for example. Cellular immunity also acts against parasitic worms, cancer cells, and cells of transplanted tissues and organs. Humoral (antibody-mediated) immunity employs antibodies, which don't directly destroy pathogens but tag them for destruction by mechanisms described later. The expression humoral refers to antibodies dissolved in the body fluids ("humors"). Humoral immunity is effective against extracellular viruses, bacteria, yeasts, protozoans, and molecular (noncellular) pathogens such as toxins, venoms, and allergens. In the unnatural event of a mismatched blood transfusion, it also destroys foreign erythrocytes.

Most lymphocytes in the deep cortex are T cells. Lymph nodes are widespread but especially concentrated in the following locations:

Cervical lymph nodes occur in deep and superficial groups in the neck, and monitor lymph coming from the head and neck. Axillary lymph nodes are concentrated in the armpit (axilla) and receive lymph from the upper limb and breast. Thoracic lymph nodes occur in the thoracic cavity, especially in the mediastinum, and receive lymph from the mediastinum, lungs, and airway. Abdominal lymph nodes occur in the posterior abdominopelvic wall and receive lymph from the urinary and reproductive systems. Intestinal and mesenteric lymph nodes are found in the mesenteries and adjacent to the appendix and intestines; they receive lymph from the digestive tract. Inguinal lymph nodes occur in the groin and receive lymph from the entire lower limb. Popliteal lymph nodes occur at the back of the knee and receive lymph from the leg proper.

Attack phase of cellular immunity

Helper and cytotoxic T cells play different roles in the attack phase. Helper T (TH) cells are necessary for most immune responses. They play a central coordinating role in both humoral and cellular immunity. When a TH cell recognizes an Ag-MHC protein complex, it secretes interleukins that exert three effects: (1) to attract neutrophils and natural killer cells; (2) to attract macrophages, stimulate their phagocytic activity, and inhibit them from leaving the area; and (3) to stimulate T and B cell mitosis and maturation. Cytotoxic T (TC) cells are the only T lymphocytes that directly attack and kill other cells. When a TC cell recognizes a complex of antigen and MHC-I protein on a diseased or foreign cell, it "docks" on that cell, delivers a lethal hit of chemicals that will destroy it, and goes off in search of other enemy cells while the chemicals do their work. Among these chemicals are: --perforin and granzymes, which kill the target cell in the same manner as we saw earlier for NK cells. --interferons, which inhibit viral replication and recruit and activate macrophages, among other effects; --tumor necrosis factor (TNF), which aids in macrophage activation and kills cancer cells. As more and more cells are recruited by helper T cells, the immune response exerts an overwhelming force against the pathogen. The ***primary response***, seen on first exposure to a particular pathogen, peaks in about a week and then gradually declines.

five classes of antibodies

IgA, IgD, IgE, IgG, and IgM (after the structures of their C regions (alpha, delta, epsilon, gamma, and mu) IgD, IgE, and IgG are monomers; IgA has a monomer form as well as a dimer composed of two cojoined monomers; and IgM is a pentamer composed of five monomers. The surface antigen receptors of B cells are IgD and IgM molecules. IgG is particularly important in the immunity of the newborn because it crosses the placenta with relative ease. Thus, it transfers immunity from the mother to her fetus. In addition, an infant acquires some maternal IgA through breast milk and colostrum

active vs. passive immunity*

In active immunity, the body makes its own antibodies or T cells against a pathogen. In passive immunity, the body acquires them from another person or an animal that is immune to the pathogen

innate and adaptive (acquired) immunity*

Innate immunity - defenses we're born with (hence innate) that protect us from a broad spectrum of disease agents; it encompasses the first and second lines of defense Adaptive immunity - third line of defense: a group of mechanisms that not only defeat a pathogen but leave the body with a "memory" of it, enabling one to defeat it quickly in future encounters

Humoral immunity

Instead of directly attacking enemy cells, the B lymphocytes of humoral immunity produce antibodies that bind to antigens and tag them for destruction. Like cellular immunity, humoral immunity works in three stages: recognition, attack, and memory.

B Lymphocytes (B Cells)*

Less is known about B cell maturation than about T cells, but the B cell process occurs entirely within the red bone marrow. Adults produce about 50 million B cells per day, but only 10% enter the general circulation. The other 90% are apparently destroyed in the course of positive and negative selection in the bone marrow. Self-tolerant B cells that survive selection go on to multiply and generate immunocompetent B cell clones. These cells disperse throughout the body and colonize the same organs as T cells. They are abundant in the lymphatic nodules of the lymph nodes and in the spleen, bone marrow, and mucous membranes.

Lymph Nodes and Metastatic Cancer

Metastasis is a phenomenon in which cancerous cells break free of the original primary tumor, travel to other sites in the body, and establish new tumors. Because of the high permeability of lymphatic capillaries, metastasizing cancer cells easily enter them and travel in the lymph. They tend to lodge in the first lymph node they encounter and multiply there, eventually destroying the node. Once a tumor is well established in one node, cells may emigrate from there and travel to the next. However, if the metastasis is detected early enough, cancer can sometimes be eradicated by removing not only the primary tumor, but also the nearest lymph nodes downstream from that point.

tissue repair

Monocytes are major agents of tissue cleanup and repair. They arrive within 8 to 12 hours, emigrate from the bloodstream, and turn into macrophages. Macrophages engulf and destroy bacteria, damaged host cells, and dead and dying neutrophils Edema also contributes to tissue cleanup. The swelling compresses veins and reduces venous drainage, while it forces open the valves of lymphatic capillaries and promotes lymphatic drainage. The lymphatics can collect and remove bacteria, dead cells, proteins, and tissue debris the battle progresses, all of the neutrophils and most of the macrophages die. These dead cells, other tissue debris, and tissue fluid form a pool of yellowish fluid called pus, which accumulates in a tissue cavity called an abscess Blood platelets and endothelial cells in an area of injury secrete platelet-derived growth factor, an agent that stimulates fibroblasts to multiply and synthesize collagen. At the same time, hyperemia delivers oxygen, amino acids, and other necessities of protein synthesis, while the heat of inflamed tissue increases metabolic rate and the speed of mitosis and tissue repair. The fibrin clot in the tissue may provide a scaffold for reconstruction. Pain also contributes importantly to recovery. It is an important alarm signal that calls our attention to the injury and makes us limit the use of a body part so it has a chance to rest and heal.

Attack phase of humoral immunity

Once released by a plasma cell, antibodies use four mechanisms to render antigens harmless: 1) Neutralization means the masking of critical regions of an antigen molecule by antibodies. Only certain regions of an antigen are pathogenic—for example, the parts of a toxin molecule or virus that enable these agents to bind to human cells. Antibodies can neutralize an antigen by masking these active regions. 2) Complement fixation is an action in which antibodies bind complement proteins to an enemy cell, leading to its destruction. IgM and IgG bind to enemy cells and change shape, exposing their complement-binding sites. This initiates the binding of complement to the enemy cell surface and leads to inflammation, phagocytosis, immune clearance, and cytolysis, as described earlier. Complement fixation is the primary mechanism of defense against foreign cells such as bacteria and mismatched erythrocytes. It opsonizes bacteria and makes it easier for phagocytes to ingest and destroy them. 3) Agglutination is the clumping of enemy cells by antibodies, described earlier in the discussion of ABO and Rh blood types. It is effective not only in mismatched blood transfusions, but more importantly as a defense against bacteria. An antibody molecule has 2 to 10 binding sites; thus, it can bind to antigen molecules on two or more enemy cells at once and stick them together. This immobilizes microbes and other alien cells and prevents them from spreading through the tissues. Further, neutrophils and macrophages can phagocytize agglutinated clusters of bacteria more efficiently than phagocytizing bacteria one at a time. 4) Precipitation is a similar process in which antigen molecules (not whole cells) are clumped by adhesion to antibodies. This creates large Ag-Ab complexes that can be removed by immune clearance or phagocytized by eosinophils.

T Lymphocytes (T Cells)*

T cells are produced in the red bone marrow by the hemopoietic stem cells. Newborn T cells enter the bloodstream and travel to the thymus—the "school" where they mature into fully functional T cells and face two harsh "graduation exams" that test their usefulness to the immune system. On arrival, T cells go first to the thymic cortex and cluster on the cortical epithelial cells. The epithelial cells test these young lymphocytes to see which ones will be capable of later recognizing foreign antigens and antigen-presenting cells (APCs). If a T cell possesses the proper receptors to recognize them, it receives a protective signal from the epithelial cell that spares its life. T cells that cannot recognize them receive no life-sparing signal. They get a chance to "retake the test"; they can reshuffle the DNA for their antigen receptors and try again. But if they fail once more, they are doomed. Within 3 or 4 days, these useless T cells die by apoptosis and the cortical macrophages phagocytize them. T cells that pass the test and can properly respond to respond to antigens are called immunocompetent. The T cells in the medulla face yet another difficult test and even more of them are doomed to fail and possibly die. Here, their examiners are macrophages and reticular cells. Unlike the cortical epithelial cells, these are derived from bone marrow and test the T cells in a different way. Their role is to weed out T cells that react to the antigens of one's own body or to one's own APCs even in the absence of antigen. Macrophages and reticular cells present the T cells with self-antigens and antigen-binding proteins called MHCs (explained shortly). In one theory, T cells that react too strongly to these are killed by apoptosis. There is also evidence, however, that the thymic corpuscles secrete a signal (cytokine) that renders these self-reactive T cells permanently inactive (a state called anergy) or converts them to regulatory T cells that moderate the activity of the cytotoxic (killer) T cells that actually attack foreign cells (all explained later). In any event, elimination or conversion of self-reactive T cells is called negative selection, and it leaves the immune system in a state of self-tolerance—restraint from attacking one's own tissues. Only about 2% of the T cells survive both positive and negative selection; 98% are eliminated, especially by positive selection. The few survivors multiply and form clones of identical T cells programmed to respond to a particular antigen. These cells, which are immunocompetent but have not yet encountered an enemy (foreign antigen), constitute the naive lymphocyte pool. Naive T cells leave the thymus by way of blood and lymphatic vessels (there is no blood-thymus barrier in the medulla), disperse throughout the body, and colonize lymphatic tissues and organs.

spleen*

The body's largest lymphatic organ - measures up to 12 cm long and usually weighs about 150 g. It is located in the left hypochondriac region, just inferior to the diaphragm and posterolateral to the stomach. It is protected by ribs 10 through 12. The spleen fits snugly between the diaphragm, stomach, and kidney and has indentations called the gastric area and renal area where it presses against these adjacent viscera. It has a medial hilum penetrated by the splenic artery, splenic vein, and lymphatic vessels. The parenchyma exhibits two types of tissue named for their appearance in fresh specimens (not in stained sections): red pulp, which consists of sinuses gorged with concentrated erythrocytes; and white pulp, which consists of lymphocytes and macrophages aggregated like sleeves along small branches of the splenic artery. In tissue sections, white pulp appears as an ovoid mass of lymphocytes with an arteriole passing through it. However, the three-dimensional shape is not egglike but cylindrical. These two tissue types reflect the multiple functions of the spleen. Its blood capillaries are very permeable; they allow red blood cells (RBCs) to leave the bloodstream, accumulate in the sinuses of the red pulp, and reenter the bloodstream later. The spleen is an "erythrocyte graveyard"—old, fragile RBCs rupture as they squeeze through the capillary walls into the sinuses. Macrophages phagocytize their remains, just as they dispose of blood-borne bacteria and other cellular debris. The spleen produces blood cells in the fetus and can resume this role in adults in the event of extreme anemia. Lymphocytes and macrophages of the white pulp monitor the blood for foreign antigens, much like the lymph nodes do the lymph. The spleen is a reservoir for a large "standing army" of monocytes, waiting in a state of emergency preparedness. In such events as microbial infection, myocardial infarction, or gaping wounds, angiotensin II stimulates the spleen to release great numbers of monocytes into the bloodstream. The monocytes help to combat pathogens and repair damaged tissues. The spleen also helps to stabilize blood volume by transferring excess plasma from the bloodstream into the lymphatic system. The spleen is highly vascular and vulnerable to trauma and infection. A ruptured spleen can hemorrhage fatally, but is difficult to repair surgically. Therefore, a once-common procedure in such cases was its removal, splenectomy. A person can live without a spleen, but people with splenectomies are more susceptible to infections and premature death, and splenectomy is now performed less commonly than it used to be.

lymph nodes*

The most numerous lymphatic organs, numbering about 450 in a typical adult. Two functions: to cleanse the lymph and to act as a site of T and B cell activation. A lymph node is an elongated or bean-shaped structure, usually less than 3 cm long, often with an indentation called the hilum on one side. It is enclosed in a fibrous capsule with trabeculae that partially divide the interior of the node into compartments. Between the capsule and parenchyma is a narrow, relatively clear space called the subcapsular sinus, which contains reticular fibers, macrophages, and dendritic cells. Deep to this, the gland consists mainly of a stroma of reticular connective tissue and a parenchyma of lymphocytes and antigen-presenting cells. The parenchyma is divided into an outer C-shaped cortex that encircles about four-fifths of the organ, and an inner medulla that extends to the surface at the hilum. The cortex consists mainly of ovoid to conical lymphatic nodules. When the lymph node is fighting a pathogen, these nodules acquire light-staining germinal centers where B cells multiply and differentiate into plasma cells. The medulla consists largely of a branching network of medullary cords composed of lymphocytes, plasma cells, macrophages, reticular cells, and reticular fibers. The cortex and medulla also contain lymph-filled sinuses continuous with the subcapsular sinus. Several afferent lymphatic vessels lead into the node along its convex surface. Lymph flows from these vessels into the subcapsular sinus, percolates slowly through the sinuses of the cortex and medulla, and leaves the node through one to three efferent lymphatic vessels that emerge from the hilum. No other lymphatic organs have afferent lymphatic vessels; lymph nodes are the only organs that filter lymph as it flows along its course. The lymph node is a bottleneck that slows down lymph flow and allows time for cleansing it of foreign matter. Macrophages and reticular cells of the sinuses remove about 99% of the impurities before the lymph leaves the node. On its way to the bloodstream, lymph flows through one lymph node after another and thus becomes quite thoroughly cleansed of impurities. Blood vessels also penetrate the hilum. Arteries follow the medullary cords and give rise to capillary beds in the medulla and cortex. In the deep cortex near the junction with the medulla, lymphocytes emigrate from the bloodstream into the parenchyma of the node.

Memory phase of cellular immunity

The primary response is followed by immune memory. Following clonal selection, some T cells become memory cells. These cells are long-lived and much more numerous than naive T cells. Aside from their sheer numbers, they also require fewer steps to be activated, and therefore respond to antigens more rapidly. Upon reexposure to the same pathogen later in life, memory cells mount a quick attack called the T cell recall response. This time-saving response destroys a pathogen so quickly that no noticeable illness occurs, so the person is immune to the disease.

tonsils**

The tonsils are patches of lymphatic tissue located at the entrance to the pharynx, where they guard against ingested and inhaled pathogens. Each is covered by an epithelium and has deep pits called tonsillar crypts lined by lymphatic nodules. The crypts often contain food debris, dead leukocytes, bacteria, and antigenic chemicals. Below the crypts, the tonsils are partially separated from underlying connective tissue by an incomplete fibrous capsule. There are three main sets of tonsils: (1) a single median pharyngeal tonsil (adenoids) on the wall of the pharynx just behind the nasal cavity; (2) a pair of palatine tonsils at the posterior margin of the oral cavity; and (3) numerous lingual tonsils, each with a single crypt, concentrated in patches embedded in each side of the root of the tongue The palatine tonsils are the largest and most often infected. Tonsillitis is an acute inflammation of the palatine tonsils, usually caused by a Streptococcus infection. Surgical removal = tonsillectomy. Tonsillitis is now usually treated with antibiotics.

lymphadenitis / lymphadenopathy

When a lymph node is under challenge by an antigen, it may become swollen and painful to the touch—a condition called lymphadenitis. Physicians routinely palpate the accessible lymph nodes of the cervical, axillary, and inguinal regions for swelling. The collective term for all lymph node diseases is lymphadenopathy

Memory phase of humoral immunity *

When a person is exposed to a particular antigen for the first time, the immune reaction is called the primary response. The appearance of protective antibodies is delayed for 3 to 6 days while naive B cells multiply and differentiate into plasma cells. As the plasma cells begin secreting antibody, the antibody titer (level in the blood plasma) begins to rise. IgM appears first, peaks in about 10 days, and soon declines. IgG levels rise as IgM declines, but even the IgG titer drops to a low level within a month. The **primary response*, however, leaves one with an immune memory of the antigen. During clonal selection, some members of the clone become memory B cells rather than plasma cells. Memory B cells, found mainly in the germinal centers of the lymph nodes, cause a quick --**secondary, or anamnestic response**, if reexposed to the same antigen. Plasma cells form within hours, so the IgG titer rises sharply and peaks within a few days. The response is so rapid that the antigen has little chance to exert a noticeable effect on the body, and no illness results. A low level of IgM is also secreted and quickly declines, but IgG remains elevated for weeks to years, conferring lasting protection. Memory does not last as long in humoral immunity as it does in cellular immunity.

interferons*

When certain cells are infected with viruses, they secrete proteins called interferons. They alert neighboring cells and protect them from becoming infected. They bind to surface receptors on those cells and activate second-messenger systems within. This induces the synthesis of dozens of antiviral proteins that defend a cell by such means as breaking down viral genes and preventing viral replication. Interferons also activate NK cells and macrophages, which destroy infected cells before they can liberate a swarm of newly replicated viruses. Interferons also confer resistance to cancer, since the activated NK cells destroy malignant cells.

lymph

a clear, colorless fluid, originating as tissue fluid taken up by the lymphatic vessels. Lymph leaving the lymph nodes contains a large number of lymphocytes—this is the main supply of lymphocytes to the bloodstream. Lymph may also contain macrophages, hormones, bacteria, viruses, cellular debris, or even traveling cancer cells.

Cellular (cell-mediated) immunity / types of t cells *

a form of adaptive immunity in which T lymphocytes directly attack and destroy diseased or foreign cells, and the immune system remembers the antigens of those invaders and prevents them from causing disease in the future. Cellular immunity employs four classes of T cells: --Cytotoxic T (TC) cells are the "effectors" of cellular immunity that carry out the attack on foreign cells. --Helper T (TH) cells promote the action of TC cells as well as playing key roles in humoral and innate immunity. All other T cells are involved in cellular immunity only. --Regulatory T (TR) cells, or T-regs, limit the immune response by inhibiting multiplication and cytokine secretion by other T cells. Once a pathogen is defeated, it is important to down-regulate TC activity, because otherwise TC cells would continue to produce inflammatory cytokines that could cause extensive tissue damage in the long term. TR cells prevent this and reduce the risk of developing autoimmune diseases. --Memory T (TM) cells are descended from TC cells and are responsible for memory in cellular immunity. Thus, they sustain the body's vigilance against a given pathogen without causing the damage that a persistent population of TC cells would do.

complement system**

a group of 30 or more globulins that make powerful contributions to both innate and adaptive immunity. Complement proteins are synthesized mainly by the liver. They circulate in the blood in inactive form and are activated in the presence of pathogens. The inactive proteins are named with the letter C and a number, such as C3. Activation splits them into fragments, which are further identified by lowercase letters (C3a and C3b, for example). Activated complement contributes to pathogen destruction by four methods: inflammation, immune clearance, phagocytosis, and cytolysis. There are three pathways of activation: the classical, alternative, and lectin pathways. The classical pathway requires an antibody to get it started; thus it is part of adaptive immunity. The antibody binds to an antigen on the surface of a microbe and changes shape, exposing a pair of complement-binding sites. Complement C1 binds to these sites and sets off a reaction cascade. Like the cascade of blood-clotting reactions, each step generates an enzyme that catalyzes the production of many more molecules at the next step; each step is an amplifying process, so many molecules of product result from a small beginning. In the classical pathway, the cascade is called complement fixation, since it results in the attachment of a chain of complement proteins to the antibody. The alternative and lectin pathways require no antibodies and thus belong to our innate immunity. Complement C3 slowly and spontaneously breaks down in the blood into C3a and C3b. In the alternative pathway, C3b binds directly to targets such as human tumor cells, viruses, bacteria, and yeasts. This, too, triggers a reaction cascade—this time with an autocatalytic effect in which C3b leads to the accelerated splitting of more C3 and production of even more C3b. Lectins are plasma proteins that bind to carbohydrates. In the lectin pathway, a lectin binds to certain sugars of a microbial cell surface and sets off yet another reaction cascade leading to C3b production. As we can see, the splitting of C3 into C3a and C3b is an intersection where all three pathways converge. These two C3 fragments then produce, directly or indirectly, the end results of the complement system: -Inflammation. C3a stimulates mast cells and basophils to secrete histamine and other inflammatory chemicals. It also activates and attracts neutrophils and macrophages, the two key cellular agents of pathogen destruction in inflammation. The exact roles of these chemicals and cells are explained in the section on inflammation to follow. -Immune clearance. C3b binds antigen-antibody (Ag-Ab) complexes to red blood cells. As these RBCs circulate through the liver and spleen, the macrophages of those organs strip off and destroy the Ag-Ab complexes, leaving the RBCs unharmed. This is the principal means of clearing foreign antigens from the bloodstream. -Phagocytosis. Bacteria, viruses, and other pathogens are phagocytized and digested by neutrophils and macrophages. However, those phagocytes cannot easily internalize "naked" microorganisms. C3b assists them by means of opsonization—it coats microbial cells and serves as binding sites for phagocyte attachment. The way Elie Metchnikoff described this, opsonization "butters up" the foreign cells to make them more appetizing to phagocytes. -Cytolysis. C3b splits another complement protein, C5, into C5a and C5b. C5a joins C3a in its proinflammatory actions, but C5b plays a more important role in pathogen destruction. It binds to the enemy cell and then attracts complements C6, C7, and C8. This conglomeration of proteins (now called C5b678) goes on to bind up to 17 molecules of complement C9, which form a ring called the membrane attack complex. The complex forms a hole in the target cell up to 10 nm wide, about the diameter of a single protein molecule. The cell can no longer maintain homeostasis; electrolytes leak out, water flows rapidly in, and the cell ruptures.

thymus*

a member of the endocrine, lymphatic, and immune systems. It houses developing lymphocytes and secretes hormones that regulate their later activity. It is a bilobed organ located between the sternum and aortic arch in the superior mediastinum. The thymus shows a remarkable degree of degeneration (involution) with age The fibrous capsule of the thymus gives off trabeculae (septa) that divide the gland into several angular lobules. Each lobule has a light central medulla populated by T lymphocytes, surrounded by a dense, darker cortex. Both cortex and medulla have a branching network of interconnected epithelial cells that play important roles in lymphocyte development; their roles differ in the two regions, so they are separately described as cortical epithelial cells and medullary epithelial cells. In the cortex, cortical epithelial cells and capillary pericytes surround the blood capillaries and form a blood-thymus barrier, which isolates developing lymphocytes from premature exposure to blood-borne antigens. After developing in the cortex, T cells migrate to the medulla, where they spend another 3 weeks. There is no blood-thymus barrier in the medulla; mature T cells enter blood or lymphatic vessels here and leave the thymus. Some of the medullary epithelial cells are arranged in keratinized whorls called thymic corpuscles, which may play a role in the immune system's self-tolerance (restraint from attacking the body's own tissues) and are useful for identifying the thymus histologically. Epithelial cells of the thymus secrete several signaling molecules that promote the development and action of T cells both locally (as paracrines) and systemically (as hormones); these include thymosin, thymopoietin, thymulin, interleukins, and interferon

neutrophils

accumulate in the inflamed tissue within an hour. After emigrating from the bloodstream, they exhibit chemotaxis—attraction to chemicals (chemotactic factors) such as bradykinin and leukotrienes that guide them to the site of injury or infection. As they encounter bacteria, neutrophils avidly phagocytize and digest them Neutrophils also recruit macrophages and additional neutrophils by secreting cytokines, like shouting to bring in reinforcements. Activated macrophages and T cells in the inflamed tissue secrete cytokines called colony-stimulating factors, which promote the production of more leukocytes (leukopoiesis) by the red bone marrow. Within a few hours of onset, the neutrophil count in the blood can rise from the normal 4,000 or 5,000 cells/µL to as high as 25,000 cells/µL, a condition called neutrophilia. In the case of allergy or parasitic infection, an elevated eosinophil count, or eosinophilia, may also occur

Lymphatic Tissues

aggregations of lymphocytes in the connective tissues of mucous membranes and various organs In some places, lymphocytes and macrophages congregate in dense masses called lymphatic nodules (follicles).

Fever

an abnormal elevation of body temperature. It is also known as pyrexia, and the term febrile means pertaining to fever. People with colds, for example, recover more quickly and are less infective to others when they allow a fever to run its course rather than using antipyretic (fever-reducing) medications such as aspirin and ibuprofen. Fever is beneficial in that it (1) promotes interferon activity, (2) inhibits reproduction of bacteria and viruses, and (3) elevates metabolic rate and accelerates tissue repair. Fever is typically initiated by exogenous ***pyrogens***—fever-producing agents originating outside the body, such as the surface glycolipids of bacteria and viruses. As neutrophils and macrophages attack such pathogens, they secrete a variety of polypeptides that act as endogenous pyrogens. These in turn stimulate neurons of the anterior hypothalamus to raise the set point for body temperature—say, to 39°C instead of the usual 37°C. Prostaglandin E2 (PGE2), secreted in the hypothalamus, enhances this effect. Aspirin and ibuprofen reduce fever by inhibiting prostaglandin synthesis, but in some circumstances, using aspirin to control fever can have deadly consequences. When the set point rises, a person shivers to generate heat and the cutaneous arteries constrict to reduce heat loss. In the stage of fever called onset, one has a rising temperature, yet experiences chills and feels cold and clammy to another's touch. In the next stage, stadium, the temperature oscillates around the higher set point for as long as the pathogen is present. The elevated temperature enhances the action of interferons and other antimicrobial proteins, and it inhibits bacterial reproduction. When the infection is defeated, **pyrogen** secretion ceases and the hypothalamic thermostat is set back to normal. This activates heat-losing mechanisms, especially cutaneous vasodilation and sweating. The skin is warm and flushed during this phase. The phase of falling temperature is called defervescence in general, crisis (flush) if the temperature drops abruptly, or lysis if it falls slowly. Even though most fevers are beneficial, excessively high temperature can be dangerous because it speeds up different enzymatic pathways to different degrees, causing metabolic discoordination and cellular dysfunction. Fevers above 105°F can make one delirious. Convulsions and coma ensue at higher temperatures, and death or irreversible brain damage commonly results from fevers that range from 111° to 115°F.

hypersensitivity

an excessive, harmful immune reaction to antigens. It includes reactions to tissues transplanted from another person (alloimmunity), abnormal reactions to one's own tissues (autoimmunity), and allergies, which are reactions to environmental antigens.

antigens

any molecule that triggers an immune response (ex. toxins, food allergens) Some antigens are free molecules such as venoms, toxins, and food-borne substances; others are components of plasma membranes and bacterial cell walls. Small universal molecules such as glucose and amino acids are not antigenic; if they were, our immune systems would attack the nutrients and other molecules essential to our very survival. Most antigens have molecular weights over 10,000 amu and have enough structural complexity and variability to be unique to each individual: proteins, polysaccharides, glycoproteins, and glycolipids. Only certain regions of an antigen molecule, called epitopes (antigenic determinants), stimulate immune responses (antibodies) Some molecules, called haptens19 (incomplete antigens), are too small to be antigenic in themselves, but they can stimulate an immune response by binding to a host macromolecule and creating a unique complex that the body recognizes as foreign

Natural killer (NK) cells

cells that patrol the body for pathogens or diseased host cells. They attack and destroy: -bacteria -cells of transplanted organs and tissues -cells infected with viruses -cancer cells. What happens when enemy cell is recognized? -the NK cell binds to it -releases proteins called perforins, which polymerize in a ring and create a hole in its plasma membrane. -the hole allows a rapid inflow of water and salts (this will sometimes kill the cell) -the NK cell also secretes granzymes (a group of protein-degrading enzymes) -granzymes enter the pore made by the perforins, destroy the target cell's enzymes, and induce apoptosis (programmed cell death)

The lymphatic capillaries converge to form

collecting vessels. These often travel alongside veins and arteries and share a common connective tissue sheath with them. At irregular intervals, they empty into lymph nodes. The lymph trickles slowly through each node, where bacteria are phagocytized and immune cells monitor the fluid for foreign antigens. It leaves the other side of the node through another collecting vessel, traveling and often encountering additional lymph nodes before it finally returns to the bloodstream

the lymphatic system

consists of a network of vessels that penetrate nearly every tissue of the body, and a collection of tissues and organs that produce immune cells. These include the lymph nodes, spleen, thymus, tonsils, and red bone marrow.

lymphatic (lymphoid) organs

include the red bone marrow, thymus, lymph nodes, tonsils, and spleen. The red bone marrow and thymus are regarded as primary lymphatic organs because they are the sites where B and T lymphocytes, respectively, become immunocompetent—that is, able to recognize and respond to antigens. The lymph nodes, tonsils, and spleen are called secondary lymphatic organs because immunocompetent lymphocytes migrate to these organs only after they mature in the primary lymphatic organs.

The route from the tissue fluid back to the bloodstream is:

lymphatic capillaries → collecting vessels → six lymphatic trunks → two collecting ducts → subclavian veins

the collecting vessels converge to form

lymphatic trunks

Cancer of a lymph node is called

lymphoma

pathogens

microbes that cause disease (ex. viruses, bacteria, fungi)

three major processes of imflammation*

mobilization of the body's defenses; containment and destruction of pathogens; tissue cleanup and repair.

three types of lymphocytes

natural killer (NK) cells, T lymphocytes, and B lymphocytes

when microbes get past epithelial barriers, they are attacked by

phagocytes.

antibodies (Abs), also called immunoglobulins (Igs)*

proteins in the gamma globulin class that play a variety of roles in defense. Some of them are integral proteins in the plasma membranes of basophils and mast cells and thus function in innate immunity. Others, with roles in adaptive immunity, are membrane proteins of B lymphocytes or are soluble antibodies dissolved in body fluids such as blood plasma, lymph, mucus, saliva, intestinal secretions, tears, and breast milk. The basic structural unit of an antibody, called an antibody monomer, is composed of four polypeptides linked by disulfide (—S—S—) bonds. These include two heavy chains about 400 amino acids long and two light chains about half that long. Each heavy chain has a hinge region where the antibody is bent, giving the monomer a T or Y shape. All four chains have a variable (V) region that gives an antibody its uniqueness. The V regions of each heavy and light chain pair combine to form an antigen-binding site on each arm. These sites are where the antibody attaches to the epitopes of antigen molecules. The rest of each chain is a constant (C) region, which has the same amino acid sequence, or nearly so, in all antibodies of a given class (within one person). The C region determines the mechanism of an antibody's action—for example, whether it can bind complement proteins. The human immune system is believed capable of producing at least 10 billion and perhaps up to 1 trillion different antibodies. How can so few genes generate so many antibodies? One means of generating diversity is that the genome contains several hundred DNA segments that are shuffled and combined in various ways to produce antibody genes unique to each clone of B cells. This process is called somatic recombination, because it forms new combinations of DNA base sequences in somatic (nonreproductive) cells. Another mechanism of generating diversity is that B cells in the germinal centers of lymphatic nodules undergo exceptionally high rates of mutation, a process called somatic hypermutation—not just recombining preexisting DNA but creating wholly new DNA sequences. These and other mechanisms explain how we can produce such a tremendous variety of antibodies with a limited number of genes.

three purposes and four signs of imflammation*

purposes: (1) to limit the spread of pathogens and ultimately destroy them (2) to remove the debris of damaged tissue (3) to initiate tissue repair. signs: redness, swelling, heat, and pain Words ending in the suffix -itis denote inflammation of specific organs and tissues. Inflammation can occur anywhere in the body, but it is most common and observable in the skin. Many of the chemicals that regulate inflammation and immunity are in a class called cytokines—small proteins that serve as a chemical communication network among immune cells. Cytokines usually act at short range, either on neighboring cells (a paracrine effect) or on the same cell that secretes them (an autocrine effect); these terms are distinguished from the long-distance endocrine effects of hormones. Cytokines include interferons, interleukins, tumor necrosis factor, chemotactic factors, and other chemicals Inflammation involves three major processes: mobilization of the body's defenses, containment and destruction of pathogens, and tissue cleanup and repair.

Recognition phase of cellular immunity

recognition phase consists of: antigen presentation and T cell activation. Antigen Presentation When an antigen-presenting cell (APC) encounters and processes an antigen, it typically migrates to the nearest lymph node and displays it to the T cells. Cytotoxic and helper T cells patrol the lymph nodes and other tissues as if looking for trouble. When they encounter a cell displaying an antigen on an MHC protein, they initiate an immune response. T cells respond to two classes of MHC proteins: 1) MHC-I proteins occur on every nucleated cell of the body (not erythrocytes). These proteins are constantly produced by the cell and transported to the plasma membrane. Along the way, they pick up small peptides in the cytoplasm and display them once they are installed in the membrane. If the peptides are normal self-antigens, they don't elicit a T cell response. If they are viral proteins or abnormal antigens made by cancer cells, however, they do. In this case, the Ag-MHC protein complex is like a tag on the host cell that says, "I'm diseased; kill me." Infected or malignant cells are then destroyed before they can do further harm to the body. 2) MHC-II proteins (also called human leukocyte antigens, HLAs) occur only on APCs and display only foreign antigens. As T cells mature in the thymus and undergo the positive and negative selection described earlier, they become limited to recognizing a specific class of MHC protein. This process, called MHC restriction, results in TC cells responding only to MHC-I proteins and TH cells only to MHC-II T Cell Activation begins when a TC or TH cell binds to an MHC protein displaying an epitope that the T cell is programmed to recognize. Before the response can go any further, the T cell must bind to another protein, related to interleukins, found on the surface of APCs in damaged or infected tissues. In a sense, the T cell has to check twice to see if it really has bound to an APC displaying a suspicious antigen. This signaling process, called costimulation, helps to ensure that the immune system doesn't launch an attack in the absence of an enemy, which could turn against one's own body with injurious consequences. Lack of costimulation drives the T cell into anergy, a state of inactivity and ineffectiveness. Successful costimulation, in contrast, activates the process of clonal selection: The T cell undergoes repeated mitosis, giving rise to a clone of identical T cells programmed against the same epitope. Some cells in the clone become effector cells that carry out an immune attack, and some become memory T (TM) cells.

three stages of cellular immunity

recognition, attack, memory

red bone marrow

red bone marrow - an important supplier of lymphocytes to the immune system. It is involved in hemopoiesis (blood formation) and immunity. Red bone marrow is In children, it occupies the medullary spaces of nearly the entire skeleton. In adults, it is limited to the axial skeleton and the proximal heads of the humerus and femur

first line of defense

the skin and mucous membranes. Its surface is composed mainly of keratin, a tough protein that few pathogens can penetrate. Furthermore, with exceptions such as the axillary and pubic areas, it is too dry and poor in nutrients to support much microbial growth. Even those microbes that do adhere to the epidermis are continually cast off by the exfoliation of dead surface keratinocytes The skin also is coated with diverse antimicrobial chemicals. Sweat and sebum coat it with a protective acid mantle—a thin film of lactic and fatty acids that inhibit bacterial growth. Sweat also contains an antibacterial peptide called dermicidin. Keratinocytes, neutrophils, macrophages, and other cells also produce peptides called defensins and cathelicidins that destroy bacteria, viruses, and fungi. The effects of these defenses are enhanced by vitamin D (calcitriol), pointing to the benefit of a moderate amount of sunlight exposure for one's resistance to infection. The digestive, respiratory, urinary, and reproductive tracts = protected by mucous membranes. Sticky mucus physically ensnares microbes. Organisms trapped in the respiratory mucus are moved by cilia to the pharynx, swallowed, and destroyed by stomach acid. Microbes are flushed from the upper digestive tract by saliva and from the lower urinary tract by urine. Mucus, tears, and saliva also contain ***lysozyme***, an enzyme that destroys bacteria by dissolving their cell walls. Beneath the epithelia of the skin and mucous membranes is a layer of areolar tissue. Its ground substance contains a giant glycosaminoglycan called hyaluronic acid, which gives it a viscous consistency. It is normally difficult for microbes to migrate through this sticky tissue gel. Some organisms overcome this obstacle, however, by producing an enzyme called hyaluronidase, which breaks it down to a thinner consistency that is more easily penetrated.

The lymphatic trunks converge to form

two collecting ducts The right lymphatic duct is formed by the convergence of the right jugular, subclavian, and bronchomediastinal trunks in the right thoracic cavity. It receives lymphatic drainage from the right arm and right side of the thorax and head and empties into the right subclavian vein. The thoracic duct, on the left, is larger and longer. It begins just below the diaphragm anterior to the vertebral column at the level of the second lumbar vertebra. Here, the two lumbar trunks and the intestinal trunk join and form a prominent sac called the cisterna chyli, named for the large amount of chyle (fatty intestinal lymph) that it collects after a meal. The thoracic duct then passes through the diaphragm with the aorta and ascends the mediastinum adjacent to the vertebral column. As it passes through the thorax, it receives additional lymph from the left bronchomediastinal, left subclavian, and left jugular trunks, then empties into the left subclavian vein. Collectively, this duct therefore drains all of the body below the diaphragm, and the left upper limb and left side of the head, neck, and thorax.