OBJECTIVES 5 BIO

Define the complement system, and describe how it is activated.

One of the most important antimicrobial groups of substances of innate immunity is the complement system. It is composed of at least 30 plasma proteins that make up approximately 10% of the blood serum proteins. These proteins are collectively referred to as complement. The name is derived from how they complement, or work along with, antibodies (proteins produced by differentiated B-lymphocytes, which are described in section 22.8). Individual complement proteins are generally identified with the letter "C" followed by a number (e.g., C1, C2). The liver continuously synthesizes and releases inactive complement proteins into the blood. Once in the blood, inactive complement proteins are activated by an enzyme cascade. (Recall that a similar process of an enzyme cascade of inactive proteins produced by the liver is also involved in blood clotting; see section 18.4c.) ♦ How it is activated. - Activation of complement occurs following entry of a pathogen into the body. Two of the major means of activation include the classical pathway, in which a complement protein binds to an antibody that has previously attached to a foreign substance (e.g., a portion of a bacterium); and the alternative pathway, in which surface polysaccharides of certain bacterial and fungal cell walls bind directly with a complement protein. Note that antibody is required for the activation by the classical pathway, but not for activation by the alternative pathway. Following its activation, the complement system mediates several important defense mechanisms, and it is especially potent against bacterial infections (figure 22.5).

Name the two categories of lymphatic tissue and organs, and identify components of the body that belong to each category.

These tissues and organs include red bone marrow, the thymus, lymph nodes, the spleen, tonsils, lymphatic nodules, and MALT (mucosa-associated lymphatic tissue) ♦ Table 21.1 Lymphatic Structures Component

Compare and contrast blood pressure and blood pressure gradients in the arteries, capillaries, and veins.

♦ Arterial Blood Pressure Blood flow is pulsing, or pulsatile, in arteries as a consequence of the ventricles contracting and relaxing. The highest blood pressure generated in arteries is during ventricular systole when the artery is maximally stretched; this value is recorded as the systolic pressure. The lowest pressure is during ventricular diastole when the artery recoils no further; this value is recorded as the diastolic pressure. Arterial blood pressure is expressed as a ratio, in which the numerator (upper number) is the systolic pressure and the denominator (lower number) is the diastolic pressure. The average adult has a blood pressure of 120/80 mm Hg, but blood pressure can vary greatly among individuals. Two values can be calculated from systolic pressure and diastolic pressure: pulse pressure and mean arterial pressure. Pulse PressurePulse pressure is the additional pressure placed on the arteries from when the heart is resting (diastolic blood pressure) to when the heart is contracting (systolic blood pressure). Pulse pressure can be calculated by taking the difference between the systolic and the diastolic blood pressure. So, for an individual with a blood pressure of 120/80 mm Hg, the pulse pressure would be 40 mm Hg (120 mm Hg − 80 mm Hg = 40 mm Hg). Pulse pressure is significant because it is a measure of the elasticity and recoil of arteries. Healthy elastic arteries expand and recoil easily, assisting in the movement of blood through the cardiovascular system. However, as vessels age or become diseased (e.g., with atherosclerosis), arteries lose their elasticity and expand and recoil less readily, making it more difficult for the heart to pump blood. Thus, although temporary changes in pulse pressure are associated with increased cardiac output, such as would occur during exercise, permanent changes in pulse pressure may be an indication of unhealthy arteries. ♦ Capillary Blood Pressure By the time the blood reaches the capillaries, fluctuations between systolic and diastolic blood pressure disappear, so the pulse pressure disappears. Blood flow is smooth and even as it enters the capillaries. Capillary blood pressure must be sufficient for exchange of substances between the blood and surrounding tissue, but not be so high that it would damage the relatively fragile capillaries. Blood pressure on the arterial end of the capillary is about 40 mm Hg and drops quickly (along the approximately 1-millimeter length of a capillary) to below 20 mm Hg on the venous end of the capillary. These blood pressure values are used to determine net filtration pressure for capillary exchange as previously described in section 20.3. Recall that the relatively high blood pressure on the arteriole end of the capillary accounts for filtration, and the relatively low blood pressure on the venous end allows for reabsorption as colloid osmotic pressure pulls fluids back into the blood. ♦ Venous Blood Pressure The movement of blood from the capillaries back to the heart via the veins is called venous return. Blood pressure in the venules and veins is not pulsatile because the blood is far removed from (and thus not influenced by) the pumping action of the heart. Therefore, veins also have no demonstrable pulse pressure. Blood pressure is 20 mm Hg in the venules and almost 0 mm Hg by the time blood travels through the inferior vena cava to the right atrium of the heart. Thus, the pressure gradient in the veins is only 20 mm Hg. This relatively small blood pressure gradient is generally insufficient to move blood through the veins under given conditions without assistance, such as when an individual is standing. Thus, venous return must be facilitated by valves within veins and two "pumps"—the skeletal muscle pump and the respiratory pump

Explain the process of formation of MHC class I molecules in nucleated cells and MHC class II molecules in professional antigen- presenting cells.

♦ MHC class I molecules are glycoproteins; they are genetically determined and are unique to each individual (see Clinical View: "Organ Transplants and MHC Molecules"). MHC class I molecules are continuously synthesized by the rough endoplasmic reticulum (RER), inserted into the ER, shipped within and modified by the endomembrane system (see section 4.6a), and then embedded within the plasma membrane for the purposes of displaying peptide fragments of endogenous proteins (proteins within the cell). This process is referred to as the endogenous pathway (figure 22.11a). A significant event occurs during the synthesis and transport of MHC class I molecules to the cell surface involving the endogenous pathway: Peptide fragments in the cell randomly bind with the MHC class I molecules. This occurs within the RER. These peptide fragments in uninfected, healthy cells are simply partially degraded proteins of the cell and are considered "self." Consequently, in uninfected, healthy cells MHC class I molecules are displaying self-antigens on their surface. These self-antigens are ignored or tolerated by the immune system cells. However, if the cell is infected, the antigens presented are foreign antigens (figure 22.11b). Proteins of an intracellular infectious agent (e.g., viral particle) are cleaved by a proteasome in the cytosol into peptide fragments of 3 to 15 amino acids; these degraded peptide fragments of the infectious agent are considered "nonself." The peptide fragments of the infectious agent that are in the cytosol are shipped into the RER, where the peptide fragments combine with MHC class I molecules within the RER. Through the endomembrane system, the MHC class I molecules carrying the foreign antigens are shipped to the plasma membrane where they are displayed at the cell surface. We will see that the display of foreign antigens with an MHC class I molecule provides the means of communicating specifically with cytotoxic T-lymphocytes and will result in the destruction of these infected cells. ♦ The MHC class II molecule, like the MHC class I molecule, is a glycoprotein continuously synthesized by the rough endoplasmic reticulum (RER), modified by the endomembrane system, and then embedded within the plasma membrane (figure 22.12). However, antigens are presented with MHC molecules only after an APC engulfs exogenous antigens (pathogens, cellular debris, or other potentially harmful substances located outside of cells). The process involving proteins that are engulfed from outside of a cell is referred to as the exogenous pathway. Recall from section 22.3b that cells of innate immunity, including dendritic cells and macrophages, recognize microbes through pattern recognition receptors (e.g., toll-like receptors) that are displayed on their cell surface. Exogenous antigen, through the process of endocytosis, is brought into the cell. A phagosome (vesicle) is formed. The phagosome containing foreign antigen merges with a lysosome to form a phagolysosome, where the substance is digested into peptide fragments. The vesicle containing peptide fragments (antigens) then merges with vesicles containing newly synthesized MHC class II molecules. The peptide fragments are then "loaded" into the MHC class II molecules. These vesicles in turn then merge with the plasma membrane of the APC, with exogenous antigen now displayed bound to MHC class II molecules. This display of foreign antigen with an MHC class II molecule provides the means of communicating specifically with helper T-lymphocytes. Degraded components of the engulfed exogenous antigen are also removed from the cell by exocytosis. A similar process occurs by APCs to display antigen with MHC class I molecules. However, this display of foreign antigen with an MHC class I molecule provides the means of communicating specifically with cytotoxic T-lymphocytes. In either case, the communication between the APCs and T-lymphocyte will trigger their activation (as described in detail in section 22.6).

Describe the location and general function of red bone marrow.

♦ Red bone marrow is located within trabeculae in selected portions of spongy bone within the skeleton. In adults, these include the flat bones of the skull, the vertebrae, the ribs, the sternum, the ossa coxae, and proximal epiphyses of each humerus and femur (see section 7.2d). ♦ Formation of all formed elements; site of B-lymphocyte maturation

Discuss the location and anatomic structure of lymphatic capillaries.

♦ The lymph vessel network begins with lymphatic capillaries, which are the smallest lymph vessels (figure 21.2). Lymphatic capillaries are microscopic, closed-ended vessels that absorb interstitial fluid. They are interspersed throughout areolar connective tissue among blood capillary networks, except those within the red bone marrow, spleen, and the central nervous system. Note that lymphatic capillaries are absent within avascular tissues such as epithelia and cartilage. ♦ A lymphatic capillary resembles the anatomic structure of a blood capillary in that its wall is composed of an endothelium (figure 21.2b). However, lymphatic capillaries are typically larger in diameter than blood capillaries, lack a basement membrane, and have overlapping endothelial cells. These overlapping endothelial cells act as one-way flaps to allow fluid to enter the lymphatic capillary, but prevent its loss. Anchoring filaments help hold these endothelial cells to the nearby structures. Lymphatic capillaries located within the gastrointestinal (GI) tract, called lacteals (lak′tē-ăl; lactis = milk), allow for the absorption of lipid-soluble substances from the GI tract, a concept detailed in section 26.4c.

Describe the six types of cells that function in innate immunity.

♦ neutrophils, macrophages, dendritic cells, basophils, mast cells, NK cells, and eosinophils -Neutrophils, macrophages, and dendritic cells engulf unwanted substances such as infectious agents and cellular debris through phagocytosis (see section 4.3c). What follows phagocytosis is dependent upon the cell type. Both neutrophils and macrophages function to destroy infectious agents through a process that involves a lysosome and a respiratory burst (figure 22.3a). The vesicle containing the unwanted substance (a phagosome) merges with a lysosome to form a phagolysosome. Within the phagolysosome, digestive enzymes contributed from the lysosome chemically digest the unwanted substances. Destruction of microbes and viruses is facilitated by the production of reactive oxygen-containing molecules, such as nitric oxide, hydrogen peroxide, and superoxide; the release of these molecules is called a respiratory burst (or oxidative burst). Degraded residues of the engulfed substance are then released from the cell by exocytosis. -Dendritic cells function to destroy infectious agents and then present fragments of the microbe on its cell surface to T-lymphocytes—a process called antigen presentation, which is necessary for initiating adaptive immunity (see sections 6.1a and 22.4c). This role of antigen presentation is shared with macrophages. (This role for macrophages is not depicted in figure 22.3a.) -Basophils and mast cells are both proinflammatory chemical-secreting cells (figure 22.3b). Recall that basophils circulate in the blood, and mast cells reside in connective tissue of the skin, mucosal linings, and various internal organs. Substances secreted by basophils and mast cells increase fluid movement from the blood to an injured tissue. They also serve as chemotactic chemicals, which are chemicals that attract immune cells as part of the inflammatory response (see section 22.3d). Basophils and mast cells release granules during the inflammatory response. These granules contain various substances including histamine, which increases both vasodilation and capillary permeability, and heparin, an anticoagulant. They also release eicosanoids (ī′kō-să-noydz; ecosa = twenty; eidos = form) from their plasma membrane (see section 17.3b), which increase inflammation. -NK (natural killer) cells destroy a wide variety of unwanted cells, including virus-infected cells, bacteria-infected cells, tumor cells, and cells of transplanted tissue (figure 22.3c). NK cells are formed in the bone marrow, circulate in the blood, and accumulate in secondary lymphatic structures of the lymph node, spleen, and tonsils. NK cells patrol the body in an effort to detect unhealthy cells, a process referred to as immune surveillance. NK cells make physical contact with unhealthy cells and destroy them by release of cytotoxic chemicals. These cytotoxic chemicals include perforin, which forms a transmembrane pore in the unwanted cells, and granzymes, which then enter the cell through the transmembrane pore initiating apoptosis. Apoptosis (see section 4.10) is a form of cellular death in which the cell does not lyse, but rather "shrivels"; this helps limit the spread of the infectious agent. -Eosinophils (ē′ō-sin′ō-fil) target parasites (figure 22.3d). Mechanisms of destruction include degranulation and release of enzymes and other substances (e.g., reactive oxygen-containing compounds, neurotoxins) that are lethal to the parasite. Like NK cells, eosinophils can release proteins that form a transmembrane pore to destroy cells of the multicellular organism. Eosinophils also participate in the immune response associated with allergy and asthma (see Clinical View: "Hypersensitivities" in section 22.9c) and engage in phagocytosis of antigen-antibody complexes (see section 22.8b). Cells of the innate immune system are able to recognize foreign microbes because they possess pattern recognition receptors (e.g., toll-like receptors or TLRs) on their cell surface. These receptors bind to common molecular patterns (or motifs) of microbes including those of bacteria and viruses. TLRs are actually a class (or family) of receptors, with each class recognizing a specific microbial component.

Define inflammation, and describe the basic steps involved.

♦Inflammation, or the inflammatory response, is an immediate, local, nonspecific event that occurs in vascularized tissue against a great variety of injury-causing stimuli. Inflammation occurs, for example, in response to a scratch of your skin, a bee sting, overuse of a body structure (e.g., pitching arm), or from proteolytic enzymes released by fungi. This physiologic process is the major effector response of innate immunity and is successful in helping to eliminate most infectious agents and other unwanted substances from the body! Steps: Inflammation involves several steps (figure 22.6). ♦The first step is the release of various chemicals. Damaged cells of injured tissue, basophils, dendritic cells, macrophages, mast cells, and infectious organisms release numerous chemicals, including histamine, leukotrienes, prostaglandins, interleukins, TNFs, and chemotactic factors. Table 22.4 lists various chemicals of inflammation, describes their function, and identifies their source. ♦The second step encompasses vascular changes. Released chemicals cause a variety of responses in local blood vessels, including vasodilation, increase in capillary permeability, and stimulation of the capillary endothelium to provide molecules for leukocyte adhesion (cell-adhesion molecules, or CAMs). ♦The third step involves the recruitment of leukocytes. Leukocytes make their way from the blood to the infected tissue through the following processes: -Margination is the process by which CAMs on leukocytes adhere to CAMs on the endothelial cells of capillaries within the injured tissue. The result is similar to "cellular Velcro." Neutrophils are generally the first to arrive and are short-lived, followed later by the longer-lived macrophages. -Diapedesis (dī′ă-pĕ-dē-sis) is the process by which cells exit the blood by "squeezing out" between vessel wall cells, usually in the postcapillary venules, and then migrate to the site of infection (see section 18.3c). -Chemotaxis is migration of cells along a chemical gradient (see section 18.3c). Chemicals released from damaged cells, dead cells, or invading pathogens diffuse outward and form a chemical gradient that attracts immune cells. Recruited cells also participate in the inflammatory response through the release of specific cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), that stimulate leukopoiesis within red bone marrow (see section 18.3a). This helps account for the increase in leukocyte count that occurs during an active infection. Macrophages may also release pyrogens, such as interleukin 1 (IL-1), that induce a fever (see section 22.3e). ♦Delivery of plasma proteins also occurs as shown in the fourth step. Selective plasma proteins are brought into the injured or infected site, including immunoglobulins (described in section 22.8), complement (just described), clotting proteins, and kinins. Clotting proteins lead to formation of a clot that walls off microbes and prevents them from spreading into blood and other tissues (see section 18.4c). However, some bacterial species can dissolve clots. Kinins (kī′nin) are produced from kininogens, which are inactive plasma proteins produced by the liver (and released into and transported by the blood) and locally by numerous other cells. Kinins, including bradykinin, are activated by tissue injury and have similar effects to histamine; they increase capillary permeability and the production of CAMs by the capillary endothelium. Kinins also stimulate sensory pain receptors and are the most significant stimulus for causing the pain associated with inflammation.

Name the five types of lymphatic trunks and the regions of the body from which they drain lymph

♦Jugular trunks drain lymph from both the head and neck. ♦Subclavian trunks remove lymph from the upper limbs, breasts, and superficial thoracic wall. ♦Bronchomediastinal trunks drain lymph from deep thoracic structures. ♦Intestinal trunks drain lymph from most abdominal structures. ♦Lumbar trunks remove lymph from the lower limbs, abdominopelvic wall, and pelvic organs.

List the types of leukocytes of the immune system, and describe where they may be found.

-are formed in red bone marrow include : ♦ granulocytes: neutrophils,eosinophils, and basophils) ♦ monocytes: that become macrophages or dendritic cells when they exit blood vessels and take up residence in the tissues ♦ three types of lymphocytes, which include T-lymphocytes (or T-cells), B-lymphocytes (or B-cells), and NK (natural killer) cells. ♦ found in body tissues (as opposed to in the blood). The primary locations that house immune cells include lymphatic tissue, select organs, epithelial layers of the skin and mucosal membranes, and connective tissues of the body ♦ Lymphatic tissue. T-lymphocytes, B-lymphocytes, macrophages, dendritic cells, and NK cells are housed in secondary lymphatic structures of lymph nodes, the spleen, tonsils, MALT (mucosa-associated lymphatic tissue), and lymphatic nodules ♦ Select organs. Macrophages are also housed in other organs; some are specifically named based on their location, such as alveolar macrophages of the lungs and microglia of the brain. Macrophages may be permanent residents, referred to as fixed macrophages, or migrate through tissues and are called wandering macrophages. ♦ Epithelial layers of the skin and mucosal membranes. Dendritic cells are located in the skin and mucosal membranes, and are typically derived from monocytes. These cells in the epidermis of the skin are more specifically called epidermal dendritic cells. Dendritic cells engulf pathogens in the skin and mucosal membranes and subsequently migrate to a lymph node through lymph vessels that drain the tissue ♦ Connective tissue. Mast cells (cells similar to basophils) are located within the connective tissue throughout the body, typically in close proximity to small blood vessels. They are especially abundant in the dermis of the skin and the mucosal linings of the respiratory, digestive, urinary, and reproductive tracts. However, they are also housed in connective tissue of organs, such as the endomysium that ensheathes muscle fibers

Define fever, and describe how it occurs.

A fever may accompany the inflammatory response. A fever is defined as an abnormal elevation of body temperature (pyrexia) of at least 1°C (1.8°F) from the typically accepted core body temperature of 37°C (98.6°F). It results from release of fever-inducing molecules called pyrogens (e.g., IL-1, IL-6, TNF-α) that are released from either infectious agents (e.g., bacterial toxins) or immune cells in response to infection, trauma, drug reactions, and brain tumors. Events of Fever Pyrogens are released and circulate in the blood; they target the hypothalamus (see section 13.4c) and cause release of prostaglandin E2 (PGE2). It raises the temperature set point of the hypothalamus from the normal 37°C. The following stages of a fever occur in response: onset, stadium, and defervescence. (Keep in mind that these stages can be cyclical until the pathogen is eliminated or at least brought under control.) During the onset of a fever, the hypothalamus stimulates blood vessels in the dermis of the skin to vasoconstrict to decrease heat loss through the skin, and a person shivers to increase heat production through muscle contraction (see section 1.5b). Consequently, body temperature rises. The person may experience chills during this stage, which leads to the shivering. The period of time where the elevated temperature is maintained is referred to as stadium. The metabolic rate increases to promote physiologic processes involved in eliminating the harmful substance. The liver and spleen bind zinc and iron (minerals needed by microbes) to slow microbial reproduction. Defervescence (def′ĕr-ves′ents) occurs when the temperature returns to its normal set point. This happens when the hypothalamus is no longer stimulated by pyrogens, prostaglandin release decreases, and the temperature set point reverts to its normal value. The hypothalamus then stimulates the mechanisms to release heat from the body, including vasodilation of blood vessels in the skin and sweating. The person may appear flushed and the skin warm to the touch. An increase in fluid intake should occur during a fever to prevent dehydration caused by an increased loss of body fluid.

Define immunologic memory and explain how it occurs.

Activation of adaptive immunity requires direct physical contact between a lymphocyte and an antigen. On the first exposure to an antigen (the antigen challenge), limited numbers of helper T-lymphocytes, cytotoxic T-lymphocytes, and B-lymphocytes recognize the antigen (about 1 in 100,000 to 1,000,000). Generally a lag time occurs between the body's initial exposure to the antigen and the physical contact with lymphocytes required to develop an immune response. The antigen challenge, however, causes the formation of memory cells in response to the activation of T-lymphocytes and B-lymphocytes, as described in earlier sections. These long-lived lymphocytes represent an "army" of thousands against specific antigens and are responsible for immunologic memory. On subsequent exposures to an antigen, these vast number of memory cells make contact with the antigen more rapidly and produce a more powerful response, which is referred to as the secondary response, memory response, or anamnestic (an′am-nes′tik; an = not, amnesia = forgetfulness) response. On each subsequent exposure to a specific pathogen, the pathogen is typically eliminated even before disease symptoms develop. For example, a person who develops measles will not develop measles again, even if reexposed to that virus. The virus is eliminated by activated memory T-lymphocytes, memory B-lymphocytes, and antibodies before it causes harm. This feature of immunologic memory makes adaptive immunity a highly potent protector. Vaccines are typically effective in developing memory, and a secondary response is seen on exposure to the substance vaccinated against (see Clinical View: "Vaccinations").

Explain the lymphatic system's role at the capillary bed.

Although net filtration occurs at the arterial end of a capillary and net reabsorption at its venous end, not all of the fluid is reabsorbed at the venous end of the capillary. The capillary typically reabsorbs only about 85% of the fluid that has passed into the interstitial fluid. What happens to the excess 15% of fluid that wasn't reabsorbed? Another body system, the lymphatic system, is responsible for picking up this excess fluid and returning it to the blood. Lymph vessels reabsorb this excess fluid, filter it, and return it to the venous circulation (see section 21.1). The lymphatic system is described in detail in chapter 21.

Describe the features of an antigen, and explain what is meant by antigenic determinant.

An antigen is usually a protein or a large polysaccharide (see section 2.7). Examples of antigens include parts of infectious agents such as the protein capsid of viruses, cell wall of bacteria or fungi, and bacterial toxins. Tumor cells also contain antigens. In the case of cancerous cells, mutations occur that generally result in the production of unique (abnormal) proteins designated as tumor antigens. ♦Lymphocytes normally have contact with only a portion of the antigen. The specific site on the antigen molecule that is recognized by components of the immune system is referred to as the antigenic determinant, or epitope. Each type of antigenic determinant has a different shape, and a pathogenic organism can have numerous different antigenic determinants. Figure 22.9 shows an antigen and several antigenic determinants.

Describe the general structure of an immunoglobulin molecule, including its two functional regions.

An immunoglobulin molecule is a Y-shaped, soluble protein composed of four polypeptide chains: two identical heavy chains and two identical light chains, with flexibility at the hinge region of the two heavy chains. These four polypeptide chains are held together by disulfide bonds to form an antibody monomer (i.e., a single Y-shaped protein). Two important functional regions of the antibody monomer are the variable regions and the constant region. ♦Variable Regions The variable regions located at the ends of the "arms" of the antibody contain the antigen-binding site, which attach to a specific antigenic determinant of an antigen. Most antibodies have two antigen-binding sites, which allow each antibody to bind to two antigenic determinants. The variable region binds the antigen through weak intermolecular forces, including hydrogen bonds, ionic bonds, and hydrophobic interactions (see section 2.3d). ♦Constant Region The constant region contains the Fc region, which is the portion of the antibody that determines the biological functions of the antibody. The constant region is the same or nearly the same in structure for antibody molecules of a given class; there are five major classes of immunoglobulins: IgG, IgM, IgA, IgD, and IgE. These classes are described in greater detail in section 22.8c.

Describe the function of plasma cells in the effector response of B-lymphocytes.

Antibodies are the effectors of humoral immunity. Antibodies are formed primarily by plasma cells (although limited amounts are produced by B-lymphocytes). Plasma cells typically remain in the lymph nodes, continuing to synthesize and release antibodies. Antibodies circulate throughout the body in the lymph and blood, ultimately coming in contact with antigen at the site of infection. Plasma cells, over their life span of about 5 days, produce hundreds of millions of antibodies against the specific antigen. The circulating blood concentration of antibody against a specific antigen is referred to as the antibody titer. This can be a measure of immune response. The details of antibody structure and function are described next.

Name the veins that return blood from the systemic circulation to the right atrium of the heart.

Blood is returned to the right atrium of the heart by three vessels: the superior vena cava, the inferior vena cava, and the coronary sinus (figure 20.19b). The veins that drain the head, neck, upper limbs, and thoracic and abdominal walls from each side of the body merge to form the left and right brachiocephalic veins. The two brachiocephalic veins merge to form the superior vena cava. The veins that drain blood inferior to the diaphragm merge to collectively form the inferior vena cava. The inferior vena cava is responsible for transporting venous blood toward the heart from the lower limbs, pelvis and perineum, and abdominal structures. It lies to the right side of the descending abdominal aorta and extends through an opening (caval opening) in the diaphragm.

List the functions of the antigen-binding site and Fc region of antibodies, and briefly describe how each occurs.

Antibody (Ab) functions to "tie up" the antigen (Ag) until it can be eliminated. (a) Three functions of antibodies involve the binding of the antigen-binding site to an antigen to cause neutralization, agglutination, or precipitation. (b) Three other functions first require the binding of antibody to an antigen; the Fc region of the antibody projects externally. The Fc region can then bind complement, bind to phagocytic cells to enhance phagocytosis of the unwanted cell, or bind to NK cells to trigger apoptosis of the unwanted cell. ♦Neutralization. An antibody physically covers an antigenic determinant of a pathogen to make it ineffective in establishing an infection or causing harm. For example, neutralization occurs when an antibody covers the region of a virus used to bind to a cell receptor, preventing entry of the virus into a cell. A similar process neutralizes toxins. Agglutination. Antibody cross-links antigens of foreign cells, causing them to agglutinate or "clump." This is especially effective against bacterial cells and mismatched erythrocytes in a blood transfusion (see section 18.3b). Precipitation. Antibody can cross-link soluble, circulating antigens such as viral particles (not whole cells) to form an antigen-antibody complex. These complexes become insoluble and precipitate out of body fluids. The precipitated complexes are then engulfed and eliminated by phagocytic cells such as macrophages. -Complement fixation. The Fc region of certain classes of antibodies (IgG and IgM) can bind specific complement proteins to cause activation of complement by the classical pathway. The functions of complement are described in section 22.3c and include opsonization, increasing inflammation, inducing cytolysis, and elimination of immune complexes. -Opsonization. The Fc region of certain classes of antibodies (e.g., IgG) can also cause opsonization (making it more likely that a target is "seen" by phagocytic calls). Phagocytic cells such as neutrophils and macrophages have receptors for the Fc region of certain antibody classes. The phagocytic receptors bind in a "zipperlike" fashion to the Fc region of the antibodies to engulf both the antigen and antibody. -Activation of NK cells. The Fc region of certain classes of antibodies (IgG) bind to specific receptors on NK cells (much like phagocytes). This induces NK cells to destroy abnormal cells by the release of cytotoxic chemicals that cause apoptosis of the cell. This process is called antibody-dependent cell-mediated cytotoxicity (ADCC).

Describe antigen-presenting cells, and list cells that serve this function.

Antigen presentation is the display of antigen on a cell's plasma membrane surface. This is a necessary process performed by other cells so that T-lymphocytes can recognize an antigen. Generally, two categories of cells present antigen to T-lymphocytes: all nucleated cells of the body (i.e., all cells except erythrocytes) and a category of cells called antigen-presenting cells. The term antigen-presenting cell (APC) is used to describe any immune cell that functions specifically to communicate the presence of antigen to both helper T-lymphocytes and cytotoxic T-lymphocytes. Dendritic cells, macrophages, and B-lymphocytes function as APCs. Antigen presentation requires the physical attachment of antigen to a specialized transmembrane protein called MHC. MHC is an abbreviation for major histocompatibility (his′tō-kom-pat′i-bil′i-tē; histo = tissue) complex. This name refers to the group of genes that code for MHC molecules embedded within plasma membranes. There are two primary categories of MHC molecules: MHC class I molecules and MHC class II molecules. All nucleated cells present antigen with MHC class I molecules, whereas APCs display antigen with both MHC class I molecules and with MHC class II molecules (a molecule displayed only by APCs).

Name the arteries and veins associated with the head and neck structures.

Arterial supply to the head and neck comes from the branches of the aortic arch. Venous drainage of the head and neck is through the jugular veins, which then drain into the brachiocephalic veins. We discuss the arterial supply first. ♦ Arterial Supply Most of the blood to the head and neck is supplied by the common carotid arteries (figure 20.20a). The common carotid arteries travel parallel immediately lateral to either side of the trachea. At the superior border of the thyroid cartilage of the larynx, each artery divides into an external carotid artery that supplies structures external to the skull, and an internal carotid artery that supplies internal skull structures. Recall that the carotid sinus, a receptor that helps regulate blood pressure, is within the internal carotid artery near its bifurcation from the common carotid artery (see section 19.5b). Additional blood to the head and neck comes from the vertebral artery, thyrocervical (thy′rō-ser′vi-kal) trunk, and costocervical (kos′tō-ser′vi-kal) trunk. These are all branches of the subclavian artery. External CarotidThe external carotid artery supplies blood to several branches that include the superior thyroid artery, ascending pharyngeal (fă-rin′jē-ăl; pharynx = throat) artery, lingual (lin′gwăl) artery, facial artery, occipital artery, and posterior auricular artery. Thereafter, the external carotid artery divides into the maxillary artery and the superficial temporal artery. The specific regions supplied by these arteries are listed in figure 20.20a. Internal CarotidThe internal carotid artery branches only after it enters the skull through the carotid canal. Once inside the skull, it forms multiple branches, including the anterior and middle cerebral arteries, which supply the brain, and the ophthalmic (op-thal′mik; ophthalmos = eye) arteries, which supply the eyes and some of the surrounding structures (figure 20.20b). Vertebral ArteriesThe vertebral arteries emerge from the subclavian arteries and travel through the transverse foramina of the cervical vertebrae before entering the skull through the foramen magnum, where they merge to form the basilar (bas′i-lăr; basis = base) artery.The basilar artery travels immediately anterior to the pons and extends many branches prior to subdividing into the posterior cerebral arteries, which supply the posterior portion of the cerebrum. Cerebral Arterial CircleThe cerebral arterial circle (circle of Willis) is an important arterial anastomosis around the sella turcica (inset, figure 20.20b). The circle is formed from posterior cerebral arteries, posterior communicating arteries (branches of the posterior cerebral arteries), internal carotid arteries, anterior cerebral arteries, and an anterior communicating artery (which connects the two anterior cerebral arteries). This arterial circle equalizes blood pressure in the brain and can provide collateral channels should one vessel become blocked ♦ Venous Drainage Three primary pairs of veins drain the neck and head (figure 20.21). On each side of the head is a vertebral vein and an external jugular vein, both of which empty into the subclavian vein. The third vein is an internal jugular vein, which joins with the subclavian vein to form the brachiocephalic vein. The external jugular primarily drains superficial head and neck structures, while the internal jugular drains blood from the cranial cavity. The right and left brachiocephalic veins join to form the superior vena cava

Explain the distinguishing features of the tunics found in arteries, capillaries, and veins.

Arteries and veins that supply the same body region and tend to lie next to one another are called companion vessels. Figure 20.2 is a histologic image of a companion artery and vein. Compared to their venous companions, arteries have a thicker tunica media, a narrower lumen, and more elastic and collagen fibers. These differences mean that arterial walls can spring back to shape, and are more resilient and resistant to changes in blood pressure than are veins. In addition, an artery remains patent (open) even without blood in it. In contrast, veins have a thicker tunica externa, a wider lumen, and less elastic and collagen fibers than a companion artery. The wall of a vein is typically collapsed if no blood is in the vessel. The characteristics of arteries and veins are summarized in table 20.1.

Explain how a tissue autoregulates local blood flow based on metabolic needs.

Autoregulation is the process by which a tissue itself regulates or controls its local blood flow in response to its changing metabolic needs. The initial stimulus typically is inadequate perfusion due to increased metabolic activity of the tissue. If the tissue is not receiving adequate blood perfusion, then the oxygen and nutrient levels decline, while there is an increase in carbon dioxide, lactate, hydrogen ion (H+), and potassium ion (K+) levels. These altered levels act as local vasodilators, and as a result additional blood enters the capillaries serving the tissue. As perfusion increases in the tissue and these levels adjust back to homeostatic values, the vessels constrict. Thus, there is a negative feedback loop between elevated levels of these molecules and the degree of vasodilation.

Describe how both helper T-lymphocytes and cytotoxic T-lymphocytes are activated.

Both types of T-lymphocytes must undergo activation before they can carry out immune system functions. Activation of both types of T-lymphocytes requires two signals; however, the specific process differs between the two types. ♦Activation of Helper T-Lymphocytes The specifics of activation of helper T-lymphocytes is shown in figure 22.16b. The first signal is direct physical contact between the MHC class II molecule of an antigen-presenting cell (APC) and the TCR of a helper T-lymphocyte. Exogenous antigen previously engulfed by an APC is presented on its surface with MHC class II molecules (as described in section 22.4c). The APC is either housed in the secondary lymphatic structure (e.g., macrophage) or migrates there from the skin (e.g., dendritic cells) to make contact with the helper T-lymphocyte. A helper T-lymphocyte binds to the APC to inspect the antigen: The specific TCR of a T-lymphocyte binds with the peptide fragment presented with an MHC class II molecule of the APC. This interaction is stabilized by the CD4 molecule of the helper T-lymphocyte binding to other regions of the MHC class II molecule. If the TCR does not recognize the presented antigen, it disengages from the APC. If it does recognize the antigen, contact between the two cells lasts several hours. The second signal takes place when other receptors of the APC (e.g., B7) interact with receptors of the helper T-lymphocyte (e.g., CD28). Ultimately, helper T-lymphocytes are induced to synthesize and release the cytokine interleukin 2 (IL-2), which occurs within about 24 hours. IL-2 acts as an autocrine hormone to further stimulate the helper T-lymphocyte from which it was released. T-lymphocytes are activated and proliferate to form a "clone" of helper T-lymphocytes (T-lymphocytes that possess TCRs that bind that specific antigen). Some of the cells produced are activated helper T-lymphocytes that continue to produce IL-2, and some are memory helper T-lymphocytes, cells available for subsequent encounters with the specific antigen. (Note that lack of second signal is thought to result in helper T-lymphocytes becoming Tregs. Recall that Tregs can also be formed in the thymus when CD4+ cells bind self-antigen with moderate affinity.) ♦Activation of Cytotoxic T-Lymphocytes The first signal for a cytotoxic T-lymphocyte is similar to the first stimulation for a naive helper T-lymphocyte (figure 22.16a). However, direct physical contact is made between the TCR of a cytotoxic T-lymphocyte and a peptide fragment presented with an MHC class I molecule of either an APC or an infected cell. This interaction is stabilized by the CD8 of the cytotoxic T-lymphocyte binding to other regions of the MHC class I molecule. The second signal is the binding of IL-2 that is released from helper T-lymphocytes. IL-2 acts as a paracrine hormone to stimulate the cytotoxic T-lymphocyte. IL-2 is required for cytotoxic T-lymphocytes to become fully activated. (Note that only APCs [e.g., dendritic cells] are able to activate naive cytotoxic T-lymphocytes—that is, when cytotoxic T-lymphocytes are first exposed to the antigen they recognize.) Upon activation, cytotoxic T-lymphocytes proliferate and differentiate into clones, some becoming activated cytotoxic T-lymphocytes, and others developing into memory cytotoxic T-lymphocytes that are activated upon reexposure to the same antigen.

Describe the general anatomic structure and function of capillaries.

Capillaries are the smallest blood vessels. They connect arterioles to venules (the smallest veins). The average capillary is approximately 1 mm in length with a diameter of 8 to 10 micrometers, just slightly larger than the diameter of a single erythrocyte. The narrow vessel diameter means erythrocytes must travel in single file (termed rouleau) through each capillary (see section 18.3b). Capillaries consist solely of an endothelial layer (of simple squamous cells) resting on a basement membrane. ♦ function: -he narrow vessel diameter and the thin wall are optimal for exchange of substances between blood and body tissues. ♦ Types of Capillaries Capillaries are differentiated based on their relative degree of permeability and include continuous capillaries, fenestrated capillaries, and sinusoids (table 20.2).

Define cytokines, and describe their similarities to hormones.

Cytokines are small, soluble proteins produced by cells of both the innate and adaptive immune system to regulate and facilitate immune system activity. These soluble proteins: (1) serve as a means of communication between the cells; (2) control the development and behavior of effector cells of immunity; (3) regulate the inflammatory response of innate immunity; and (4) function as weapons to destroy cells. Cytokines have also recently been shown to influence other, non-immune cells such as those of the nervous system. A cytokine is released from one cell and binds to a specific receptor of a target cell, where its action is similar to that of a hormone. Cytokines can act on the cell that released it (autocrine stimulation), local neighboring cells (paracrine stimulation), or circulate in the blood to cause systemic effects (endocrine stimulation). To prevent continuous stimulation, cytokines have a short half-life

Explain why the processes of T-lymphocytes are collectively called the cell-mediated branch of adaptive immunity.

If the cytotoxic T-lymphocyte recognizes the antigen presented by the infected cell (with MHC class I molecules), it destroys the cell by releasing granules containing the cytotoxic chemicals perforin and granzymes (the same substances released from NK cells described in section 22.3b). Perforin forms a channel in the target plasma membrane that increases the cell's permeability; granzymes enter the cell through the perforin channels. Granzymes induce cell death by apoptosis, which helps to limit spread of the infectious agent. It is because the immune response of T-lymphocytes is effective against antigens associated with cells that it is referred to as cell-mediated immunity.

Compare the activation of B-lymphocytes with that of T-lymphocytes.

Immunocompetent but naive B-lymphocytes are also activated by a specific antigen in secondary lymphatic structures. As with T-lymphocytes, two signals are required. However, B-lymphocytes do not require antigen to be presented by other nonlymphocyte cells. B-lymphocytes recognize and respond to antigens outside of cells, such as antigens of viral particles, bacteria, bacterial toxins, or yeast spores. The first signal occurs when intact antigen binds to the BCR, and the antigen cross-links BCRs (figure 22.16c). The stimulated B-lymphocyte engulfs, processes, and presents the antigen to the helper T-lymphocyte that recognizes that antigen. (This is similar to the action of other APCs.) The second signal occurs when an activated helper T-lymphocyte releases IL-4 to stimulate the B-lymphocyte. Activation of B-lymphocytes causes the B-lymphocytes to proliferate and differentiate. Most of the activated B-lymphocytes differentiate into plasma cells that produce antibodies, and the remainder become memory B-lymphocytes that are activated upon reexposure of the same antigen. Memory B-lymphocytes differ from plasma cells in some respects: (1) The memory B-lymphocytes retain their BCRs, and (2) memory B-lymphocytes have a much longer life span (months to years) than plasma cells (typically 5 to 7 days). Note that B-lymphocytes can be stimulated by antigen without direct contact between a B-lymphocyte and helper T-lymphocyte under certain conditions. However, the production of memory B-lymphocytes and the various forms of antibodies (described in section 22.8) requires helper T-lymphocyte participation during B-lymphocyte activation. Observe figure 22.16 and notice the central role that helper T-lymphocytes play in activating both cytotoxic T-lymphocytes (cell-mediated branch of immunity) and B-lymphocytes (humoral branch of immunity).

List the cardinal signs of inflammation, and explain why each occurs.

Inflammation is accompanied by certain cardinal signs that may include the following: ♦Redness, due to increased blood flow Heat, due to increased blood flow and increased metabolic activity within the area ♦Swelling, resulting from increase in fluid loss from capillaries into the interstitial space Page 861 ♦Pain, which is caused by stimulation of pain receptors from compression due to accumulation of interstitial fluid, and chemical irritation by kinins, prostaglandins, and substances released by microbes ♦Loss of function (which may occur in more severe cases of inflammation due to pain and swelling) The inflammatory response typically lasts no longer than 8 to 10 days under normal conditions. The ending of the normal acute inflammatory response (the process just described) is necessary to prevent the unwanted detrimental effects of chronic inflammation

Describe the anatomic components associated with regulating blood pressure through shortterm mechanisms.

Short-term regulation of blood pressure occurs through autonomic reflexes involving nuclei within the medulla oblongata (see section 13.5c). These reflexes adjust blood pressure quickly, such as occurs when you arise from a sitting to a standing position, by altering cardiac output, resistance, or both. We first describe the anatomic structures involved in the autonomic reflexes and then discuss how they function to maintain a normal blood pressure. Please refer to figure 20.14 as you read through this section.

Explain the general function of interferons.

Interferons (IFNs) are a category of cytokines that include (1) IFN-α and IFN-β produced by leukocytes and virus-infected cells and (2) IFN-γ produced by T-lymphocytes and NK cells. IFNs serve as a nonspecific defense mechanism against the spread of any viral infection. A virus-infected cell, although "doomed" because either the virus or the immune cells will destroy it, helps prevent further spread of the virus by releasing IFNs. Following their release, IFNs function as follows ♦ function: -IFN-α and IFN-β bind to receptors of neighboring cells, preventing them from becoming infected by triggering synthesis of enzymes that both destroy viral RNA or DNA and inhibit synthesis of viral proteins. IFN-α and IFN-β also stimulate NK cells to destroy virus-infected cells. -IFN-γ is released from NK cells to stimulate macrophages to also destroy virus-infected cells.

Explain how an unhealthy cell is destroyed by cytotoxic T-lymphocytes.

Like helper T-lymphocytes, activated and memory cytotoxic T-lymphocytes also leave the secondary lymphatic structure after several days and migrate to the site of infection in the body's tissue. Cytotoxic T-lymphocytes destroy infected cells that display the antigen. The effector response of cytotoxic T-lymphocytes is initiated when physical contact is made between a cytotoxic T-lymphocyte and the specific foreign antigen displayed on an unhealthy or foreign cell (e.g., a virus-infected cell, bacteria-infected cell, tumor cell, or foreign transplanted cell) (figure 22.17b). If the cytotoxic T-lymphocyte recognizes the antigen presented by the infected cell (with MHC class I molecules), it destroys the cell by releasing granules containing the cytotoxic chemicals perforin and granzymes (the same substances released from NK cells described in section 22.3b). Perforin forms a channel in the target plasma membrane that increases the cell's permeability; granzymes enter the cell through the perforin channels. Granzymes induce cell death by apoptosis, which helps to limit spread of the infectious agent. It is because the immune response of T-lymphocytes is effective against antigens associated with cells that it is referred to as cell-mediated immunity.

Describe how local blood flow is altered by tissue damage and as part of the body's defense.

Local blood flow is also regulated when vasoactive chemicals are released from damaged tissue, leukocytes, and platelets in response to tissue damage or as part of the body's defense. This process is referred to as inflammation and is discussed in detail in section 22.3d. For example, histamine and bradykinin are released in response to a trauma, allergic reaction, infection, or even exercise. These chemicals cause vasodilation by either directly stimulating arterioles or indirectly by stimulating endothelial cells of the vessel to release nitric oxide. Nitric oxide is a very powerful, but short-lived, vasodilator. Other vasoactive substances, such as prostaglandins and thromboxanes, which are local hormones released with tissue injury, can cause vasoconstriction (see description of local hormones in section 17.3b). Recall from section 18.4a that if endothelial cells are damaged, they release an array of chemicals that are powerful vasoconstrictors to help prevent blood loss from the damaged vessel. Systemic hormones also alter blood flow, and their effects are described in section 20.6b. See table 20.3 for a list of vasodilators and vasoconstrictors.

Describe the regions that are drained by the right lymphatic duct and by the thoracic duct.

Lymphatic Ducts Lymphatic trunks drain into the largest lymph vessels called lymphatic ducts. There are two lymphatic ducts: the right lymphatic duct and the thoracic duct. Both of these convey lymph back into the venous blood circulation. Right Lymphatic DuctThe right lymphatic duct is located near the right clavicle. It receives lymph from the lymphatic trunks that drain the following areas: (1) the right side of the head and neck, (2) the right upper limb, and (3) the right side of the thorax. It returns the lymph into the junction of the right subclavian vein and the right internal jugular vein. Thus, the right lymphatic duct drains lymph from the upper right quadrant of the body. Thoracic DuctThe larger of the two lymphatic ducts is the thoracic duct. It has a length of about 37.5 to 45 centimeters (15 to 18 inches) and extends from the diaphragm to the junction of the left subclavian and left jugular veins. The thoracic duct drains lymph from the remaining areas of the body (left side of head and neck, left upper limb, left thorax, all of the abdomen, and both lower limbs). At the base of the thoracic duct and anterior to the L2 vertebra is a rounded, saclike structure called the cisterna chyli (sis-ter′nă kī′lī). The cisterna chyli gets its name from the milky, lipid-rich lymph called chyle (kīl; chylos = juice) it receives from vessels that drain the small intestine of the gastrointestinal (GI) tract. Both left and right intestinal and lumbar trunks drain into the cisterna chyli. The thoracic duct extends superiorly from the cisterna chyli and lies directly anterior to the vertebral bodies. It passes through the aortic opening of the diaphragm then ascends to the left of the vertebral body midline.

Explain the function of lymph nodes.

Lymphocytes housed within the lymph node also come into contact with foreign substances. An immune response may be initiated after this contact, during which lymphocytes undergo cellular division, especially in the germinal centers. Some of these new lymphocytes remain within the lymph node, whereas others are transported within the lymph and then enter into the blood, to ultimately reach areas of infections (see section 22.6). When a person has an infection, often some lymph nodes are swollen and tender to the touch. This is a condition erroneously termed swollen glands. These enlarged nodes are a sign that lymphocytes are proliferating and attempting to fight an infection. Swollen superficial lymph nodes, such as those in the neck and axilla, can generally be palpated (felt).

Calculate pulse pressure and mean arterial pressure (MAP) in the arteries.

Mean Arterial PressureMean arterial pressure (MAP) is the average (or mean) measure of the blood pressure forces on the arteries. Because diastolic pressure usually lasts slightly longer than systolic pressure, MAP is not simply an average of these two pressures. Rather, MAP may be estimated as follows: So for a person with average blood pressure of 120/80 mm Hg, his or her MAP would be approximately 93 mm Hg (80 + 40/3 = 93). Mean arterial pressure is clinically significant because it provides a numerical value for how well body tissues and organs are perfused. A MAP of 70 to 110 mm Hg typically indicates good perfusion. A MAP lower than 60 mm Hg may indicate insufficient blood flow, and a very high MAP could indicate the delivery of too large of blood flow to body tissues with the possibility of causing edema (swelling) in the tissues (see Clinical View: "Cerebral Edema").

Identify features of the pulmonary circulation that distinguish it from systemic circulation.

Pulmonary arteries have less elastic connective tissue and wider lumens than systemic arteries. Compared to the systemic circulation, pulmonary vessels are relatively short, because the lungs are close to the heart. As a result, blood pressure is lower throughout the pulmonary circulation in comparison to the systemic circulation. The pressure changes associated with the pulmonary circulation are as follows: Blood leaves the right ventricle with a systolic pressure of about 15 to 25 mm Hg, depending upon whether the body is resting or active. Blood pressure drops as the blood passes through the pulmonary trunk and right and left pulmonary arteries, reaching an overall pressure of about 10 mm Hg in the pulmonary capillaries of the alveoli. This lower pressure means that the blood moves more slowly in pulmonary capillaries than in systemic capillaries, facilitating gas exchange within the lungs. Blood exits the pulmonary capillaries into progressively larger veins that become the pulmonary veins; blood pressure is almost 0 mm Hg as these veins empty into the left atrium.

Define resistance, and explain how it is influenced by blood viscosity, vessel length, and vessel radius.

Resistance also influences total blood flow. Resistance is defined as the amount of friction the blood experiences as it is transported through the blood vessels. Blood flow is always opposed by resistance. This friction is due to the contact between blood and the blood vessel wall. The term peripheral resistance is typically used when discussing the resistance of blood in the blood vessels (as opposed to the resistance of blood in the heart). Several factors affect peripheral resistance, including blood viscosity, blood vessel length, and the size of the lumen of blood vessels (as indicated by vessel radius). ♦ Vessel Length Increasing vessel length increases resistance, because the longer the vessel, the greater the friction the fluid experiences as it travels through the vessel. Consequently, shorter vessels offer less resistance than longer vessels with comparable diameters. Normally, vessel length in a person remains relatively constant. However, if one gains a large amount of weight, the body must produce miles of additional vessel length by angiogenesis for blood to be transported through the extra fat. Thus, vessel resistance increases if one gains weight, and decreases if someone loses a lot of weight (because those vessels are no longer needed and regress). ♦ Vessel Radius Blood viscosity and vessel length remain relatively constant in a typical healthy individual. The major way resistance may be regulated is by altering vessel lumen radius (and thus changing the vessel diameter.) How specifically does vessel radius influence resistance? Blood tends to flow fastest in the center of the vessel lumen, while blood near the sides of the vessels slows, because it encounters resistance from the nearby vessel wall. This difference in flow rate within a blood vessel (or in any conduit) is called laminar flow. You can see evidence of laminar flow by studying a river: The water flow near the banks or edges of the river is a bit slower or sluggish, while the water flow near the center of the river is quite fast in comparison. So, if vessel diameter increases, relatively less blood flows near the edges and overall blood flow increases. In contrast, if vessel radius decreases, relatively more blood flows near the edges and overall blood flow decreases. The relationship between blood flow and the radius of blood vessel lumen may be stated as follows (where the symbol ∝ means "is proportional to"): where F = flow and r = radius of the lumen of a vessel (The radius is 1/2 the diameter of the lumen.). This mathematical expression reflects that flow is directly proportional to the fourth power of a radius. If a vessel vasodilates and its radius increases from 1 millimeter (mm) to 2 mm, the overall change in flow is 16 times greater: If r = 1 mm, then r4 = 1, and F = 1 mm per second; and when r = 2 mm, then r4 = 16, and F = 16 mm per second. In contrast, if a vessel vasoconstricts and its radius decreases from 2 mm to 1 mm, the overall change in flow is 16 times less

Describe receptors of both T-lymphocytes and B-lymphocytes.

T-lymphocytes and B-lymphocytes differ from other immune cells because each lymphocyte has a unique receptor complex, which are composed of several different and separate proteins. There are typically about 100,000 receptor complexes per cell. A receptor complex will bind one specific antigen. The antigen receptor (which is a portion of a receptor complex) of a T-lymphocyte is referred to as the TCR (or T-cell receptor), and the antigen receptor of a B-lymphocyte is called a BCR (or B-cell receptor) (figure 22.10). The initial contact made between a BCR or TCR of a lymphocyte and the antigen it recognizes is different in B-lymphocytes and T-lymphocytes. B-lymphocytes can make direct contact with an antigen. In contrast, T-lymphocytes must first have the antigen processed and presented in the plasma membrane of another type of cell. T-lymphocytes simply are not able to recognize the antigen without this preliminary step. T-lymphocytes have additional receptor molecules (called coreceptors) that facilitate T-lymphocyte physical interaction with a cell presenting antigen. One significant category of coreceptors is the CD molecules. In fact, the two major types of T-lymphocytes—helper T-lymphocytes and cytotoxic T-lymphocytes—can be distinguished based on the specific CD protein associated with the TCR (figure 22.10a). The plasma membranes of helper T-lymphocytes contain the CD4 protein, and the plasma membranes of cytotoxic T-lymphocytes contain the CD8 protein.

Explain how T-lymphocytes mature.

T-lymphocytes originate in red bone marrow and then migrate to the thymus to complete their maturation. (The "T" of T-lymphocytes reflects the role of the thymus in its maturation.) Millions of pre-T-lymphocytes migrate from the red bone marrow to the thymus; they possess a unique TCR receptor and initially both the CD4 and CD8 proteins (referred to as "double positive"). These cells are immature T-lymphocytes with a TCR that was produced randomly through "gene shuffling," a concept beyond the scope of this text. Each T-lymphocyte must have its TCR "tested" to determine not only whether it is able to bind to the MHC molecule with presented antigen, but also whether it binds only to antigen that is foreign or "nonself." This testing results in T-lymphocyte selection.

List the arteries that carry blood away from the left ventricle of the heart to the major areas of the body

The ascending aorta curves toward the left side of the body and becomes the aortic arch (also called the arch of the aorta). Recall that the aortic bodies for regulating blood pressure are within the tunica externa of the aortic arch. Three main arterial branches emerge from the aortic arch: The brachiocephalic (brā-kē-ō-se-fal′ik) trunk, which bifurcates into the right common carotid (ka-rot′id) artery, supplying arterial blood to right side of the head and neck, and the right subclavian (sŭb-klā′vē-an; sub = beneath + clavicle) artery, supplying the right upper limb and some thoracic structures The left common carotid artery, supplying the left side of the head and neck The left subclavian artery, supplying the left upper limb and some thoracic structures Page 810 The aortic arch curves and projects inferiorly as the descending thoracic aorta, several branches of which supply the thoracic wall and internal organs. As this artery extends inferiorly through the aortic opening (hiatus) in the diaphragm, it is renamed the descending abdominal aorta, where it supplies the abdominal wall and internal organs. At the level of the fourth lumbar vertebra, the descending abdominal aorta bifurcates into left and right common iliac (il′ē-ak; ileum = groin) arteries. Each of these arteries further divides into an internal iliac artery (to supply pelvic and perineal structures) and an external iliac artery (to supply the lower limb).

Explain how fluid enters lymphatic capillaries.

The driving force to move fluid into the lymphatic capillaries is an increase in hydrostatic pressure within the interstitial space. Interstitial hydrostatic pressure rises as additional fluid is filtered from the blood capillaries (see section 20.3b). An increase in pressure at the margins of the lymphatic capillary endothelial cells "pushes" interstitial fluid into the lymphatic capillary lumen. The higher the interstitial fluid pressure, the greater the amount of fluid that enters the lymphatic capillary. The anchoring filaments extending between lymphatic capillary cells and the surrounding tissue prevent the collapse of the lymphatic capillaries as pressure exerted by the interstitial fluid increases. The pressure exerted by lymph after it enters the lymphatic capillary forces the endothelial cells of these vessels to close. Thus, lymph becomes "trapped" within the lymphatic vessel and cannot be released back into the interstitial space. Lymph is then transported through a network of increasingly larger vessels that include (in order) lymphatic capillaries, lymphatic vessels, lymphatic trunks, and lymphatic ducts.

Explain the function of the hepatic portal system.

The hepatic portal system provides the means for the liver to process blood that has passed through the blood vessels of the digestive organs before it is returned to the heart and redistributed throughout the body. This blood is nutrient-rich, deoxygenated, and may potentially contain harmful substances (e.g., alcohol, toxins) that were absorbed from the digestive organs. The hepatic portal system allows for the most efficient route for handling these absorbed substances. The hepatic portal system also receives products of erythrocyte destruction from the spleen, so that the liver can recycle some of these components.

Describe the structure and general function of the thymus.

The thymus (thī′mŭs) is a bilobed organ that is located in the superior mediastinum and functions in T-lymphocyte maturation (figure 21.5). In infants and young children, the thymus is quite large and extends into the anterior mediastinum as well. The thymus continues to grow until puberty, when it reaches a maximum weight of 30 to 50 grams. Cells within the thymus begin to regress after it reaches this size. Thereafter, much of the thymic tissue is replaced by adipose connective tissue. ♦ function The thymus in a child, consists of two fused thymic lobes, each surrounded by a connective tissue capsule. Fibrous extensions of the capsule, called trabeculae (tră-bek′ū-lē), or septa, subdivide the thymic lobes into lobules. Each lobule is arranged into an outer cortex and inner medulla. Both parts are composed primarily of epithelial tissue infiltrated with T-lymphocytes in varying stages of maturation. The cortex contains immature T-lymphocytes (pre-T-lymphocytes) and the medulla contains mature T-lymphocytes. The epithelial cells secrete thymic hormones (e.g., thymulin) that participate in the maturation of T-lymphocytes (see section 17.10c). Because the thymus contains both lymphatic cells and epithelial tissue, it is described as a lymphoepithelial organ. The details of T-lymphocyte maturation are described in section 22.5.

Identify the main groups of tonsils and their location and function.

Tonsils (ton′sillz; tonsilla = a stake) are secondary lymphatic structures that are not completely surrounded by a connective tissue capsule. They are found in the pharynx (throat) and oral cavity. A pharyngeal tonsil is found in the posterior wall of the nasopharynx; when this tonsil becomes enlarged, it is called adenoids (ad′ĕ-noydz; aden = gland). Palatine tonsils are in the posterolateral region of the oral cavity, and lingual tonsils are along the posterior one-third of the tongue (figure 21.8). Tonsils help protect against foreign substances that may be either inhaled or ingested. Invaginated outer edges called tonsillar crypts increase the tonsil's surface area to help trap material. Lymphatic nodules, some containing germinal centers, are housed with the tonsils.

Explain the process of diffusion and vesicular transport between capillaries and tissues

Within systemic capillaries, substances such as oxygen, hormones, and nutrients move by diffusion (see section 4.3a) from their relatively high concentration in the blood into the interstitial fluid and then into the tissue cells, where the concentration of these materials is lower. Conversely, carbon dioxide and waste products diffuse from the higher concentration in the tissue cells to the lower concentration in the blood. Very small solutes (e.g., O2, CO2, glucose, ions) and fluids may diffuse via the endothelial cells or intercellular clefts, while larger solutes, such as small proteins, must pass through the fenestrations in fenestrated capillaries or gaps in sinusoids. Vesicular transport occurs when endothelial cells use pinocytosis (see section 4.3c) to form fluid-filled vesicles, which are then transported to the other side of the cell and released by exocytosis. Substances can be moved either from the blood into the interstitial fluid or from the interstitial fluid into the blood. Solutes such as certain hormones (e.g., insulin) and fatty acids are transported across the endothelial cells by this method.

Trace the route of blood from the gastrointestinal tract to the inferior vena cava.

Within the hepatic portal system, blood from the digestive organs drains into three main venous branches: The splenic vein, a horizontally positioned vein The inferior mesenteric vein, a vertically positioned vein The superior mesenteric vein, another vertically positioned vein on the right side of the body Blood from all three of these drain into the hepatic portal vein, which drains blood to the liver. Some small veins, such as the left and right gastric veins, drain directly into the hepatic portal vein. The venous blood in the hepatic portal vein flows through the sinusoids of the liver. In these sinusoids, the venous blood mixes with arterial oxygenated blood entering the liver via the hepatic arteries. Thus, deoxygenated but high-nutrient-filled blood from digestive organs and oxygenated blood from the hepatic artery flow within the liver sinusoids. Blood leaves the liver through hepatic veins that merge with the inferior vena cava.

Contrast the effects of aldosterone, antidiuretic hormone, and angiotensin II on blood pressure with those of atrial natriuretic peptide.

♦ Aldosterone is released from the adrenal cortex in response to several stimuli, including angiotensin II. Aldosterone increases the absorption of sodium ion (Na+) and water in the kidney, decreasing their loss in the urine; this helps maintain blood volume and blood pressure. ♦ Antidiuretic hormone (ADH) is released from the posterior pituitary in response to nerve signals from the hypothalamus (see section 17.7b). The hypothalamus stimulates the posterior pituitary following either detection of increased concentration of blood (typically correlated with low blood volume) or stimulation of the hypothalamus by angiotensin II. ADH increases the absorption of water in the kidney, decreasing its loss in the urine; this helps maintain blood volume and blood pressure. ADH also stimulates the thirst center so there is fluid intake, and blood volume increases. During extreme cases of low blood volume, such as might occur with hemorrhaging, extensive release of ADH occurs, which causes vasoconstriction. This vasoconstriction increases peripheral resistance and blood pressure. This is why ADH is also referred to as vasopressin. ♦ Renin-Angiotensin System The renin-angiotensin system "straddles" short-term neural regulation and long-term hormonal regulation because the synthesis of the angiotensin II is initiated by the nervous system (short-term mechanisms), and angiotensin II causes the release of other hormones (long-term mechanisms). The liver produces a plasma protein called angiotensinogen (an inactive hormone) and continuously releases it into the blood. The kidney releases the enzyme renin into the blood in response to either low blood pressure or stimulation by the sympathetic division (figure 20.15). Within the blood, renin converts angiotensinogen into angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE), an enzyme associated with the capillary endothelium. ACE is found in very high concentrations on the pulmonary capillary endothelium, so most (but not all) angiotensin conversion occurs in the lungs. Having most of the ACE enzyme in pulmonary capillary endothelium helps ensure that sufficient angiotensin I is converted to angiotensin II. This is because all blood moves through the pulmonary circulation to be oxygenated, so contact between angiotensin I and ACE is maximized. Angiotensin II has several important effects: It is a powerful vasoconstrictor—much more powerful than comparable hormones, such as norepinephrine—and thus it increases peripheral resistance and raises blood pressure to a greater extent. Angiotensin II stimulates the thirst center; fluid intake increases blood volume, which increases blood pressure. Angiotensin II also regulates blood volume by direct action in the kidneys to decrease urine formation, and by indirect action through stimulating the release of other hormones (aldosterone and antidiuretic hormone). A decrease in urine formation results in less fluid lost from the blood; this helps maintain blood volume and thus blood pressure. **** In summary, angiotensin II, aldosterone, and ADH decrease urine output to help maintain blood volume and blood pressure. Angiotensin II and ADH (in high doses) increase peripheral resistance and blood pressure, and further increase blood pressure if there is fluid intake.

Define blood pressure and a blood pressure gradient.

♦ Blood pressure is the force per unit area that blood exerts against the inside wall of a vessel (as described earlier in the section on bulk flow). ♦ A blood pressure gradient is the change in blood pressure from one end of a blood vessel to its other end. A blood pressure gradient exists in the vasculature because blood pressure is highest in the arteries as the heart rhythmically contracts, and it is lowest in the veins. Blood pressure gradients are both clinically and physiologically significant because they are the driving force that propels blood through the vessels. Please refer to figure 20.11 as you read through this section.

Explain the processes of bulk flow, filtration, and reabsorption

♦ Bulk flow refers to the movement of large amounts of fluids and their dissolved substances in one direction down a pressure gradient. ♦ Filtration, a process that occurs on the arterial end of a capillary, is the movement of fluid by bulk flow out of the blood through the openings in the capillaries (e.g., intercellular clefts, fenestrations). During this process, fluids and small, dissolved solutes flow through easily, while large solutes are generally blocked. In contrast, reabsorption occurs on the venous end of a capillary. ♦ Reabsorption is the movement of fluid by bulk flow in the opposite direction, back into the blood (figure 20.10).

Name the three major arteries that branch from the descending aorta to supply the gastrointestinal tract, and list their major branches.

♦ Celiac TrunkThe celiac trunk: is located immediately inferior to the aortic opening (hiatus) of the diaphragm. Three branches emerge from this arterial trunk (figure 20.24): (1) the left gastric artery, (2) the splenic artery, and (3) the common hepatic artery. The common hepatic artery divides into the hepatic artery proper and the gastroduodenal (gas′trō-dū′ō-dē′năl) artery. ♦ Superior Mesenteric ArteryThe superior mesenteric (mez-en-ter′īk; mesos = middle, enteron = intestine) artery is located immediately inferior to the celiac trunk. Its branches include 18-20 intestinal arteries, the middle colic artery, the right colic artery, and the ileocolic (il′ē-ō-kol-ik) artery. ♦ Inferior Mesenteric ArteryThe inferior mesenteric artery emerges approximately 5 centimeters superior to bifurcation of the aorta at about the level of the L3 vertebra. Its branches include the left colic artery, the sigmoid arteries, and the superior rectal (rek′tăl; rectus = straight) artery. The specific regions that each arterial branch supplies blood to are included in figure 20.24.

Compare the anatomic structure, function, and location of continuous capillaries, fenestrated capillaries, and sinusoids

♦ Continuous capillaries are the most common type of capillary. The endothelial cells form a complete, continuous lining around the lumen that rests on a complete basement membrane. Tight junctions (see section 4.6d) secure endothelial cells to one another; however, they do not form a complete "seal." The gaps between the endothelial cells are called intercellular clefts. Materials can move into or out of the blood either through endothelial cells by membrane transport processes (e.g., diffusion, pinocytosis; see section 4.3), or between endothelial cells through intercellular clefts by diffusion and bulk flow (see section 20.3). The size of intercellular clefts prevents movement of large substances, including formed elements and plasma proteins, while allowing the movement of fluid containing small substances (smaller than about 5 nanometers), such as glucose, amino acids, and ions. Continuous capillaries are found, for example, in muscle, the skin, lungs, and central nervous system. ♦Fenestrated (fen′es-trā′ted; fenestra = window) capillaries are also composed of a complete, continuous lining of endothelial cells, and a complete basement membrane. However, small regions of the endothelial cells (typically 10 to 100 nanometers in diameter) are extremely thin; these thin areas are called fenestrations (or pores). Fenestrations are small enough to prevent formed elements from passing through the wall, yet large enough to allow movement of some smaller plasma proteins. Fenestrated capillaries are seen where a great deal of fluid transport between the blood and interstitial tissue occurs. Examples of structures that contain fenestrated capillaries include the small intestine for the absorption of nutrients, the ciliary process of the eye in the production of aqueous humor, choroid plexus of the brain in the production of cerebrospinal fluid, most of the endocrine glands to facilitate the absorption of hormones into the blood, and the kidney for the filtering of blood. ♦Sinusoids (si′nŭ-soyd; sinus = cavity, eidos = appearance), or discontinuous capillaries, have an incomplete lining of the endothelial cells with large openings or gaps, and the basement membrane is either discontinuous or absent. These openings allow for transport of large substances (formed elements, large plasma proteins), as well as plasma between the blood and tissues. Sinusoids are found in red bone marrow for entrance of formed elements into the circulation, the liver and spleen for removing aged erythrocytes from circulation, and some endocrine glands (e.g., anterior pituitary, parathyroid glands) for facilitating the movement of hormone molecules into the blood. A common feature of structures with sinusoids is their reddish color.

Compare total blood flow and distribution at rest and during exercise.

♦ During exercise, there is both an increase in total blood flow due to a faster and stronger heartbeat and because blood is removed from the "reservoirs" of the veins to the active circulation. There is also a redistribution of blood. Both of these changes help ensure that the most metabolically active tissues are receiving adequate blood flow to meet the needs of the tissue cells. Figure 20.17 provides an example in which blood flow changes from 5.25 L/min (5250 mL/min) at rest to 17.5 L/min (17,500 mL/min) during exercise. The following increases in blood flow to specific regions or organs can be noted: --- Blood flow to the coronary vessels of the heart increases approximately three-fold (from 250 mL/min to 750 mL/min), a change that helps to ensure that sufficient oxygen reaches the cardiac muscle within the heart wall. ---Skeletal muscle blood flow increases an amazing 11-fold (from 1100 mL/min to 12,500 mL/min)—which is approximately 70% of the total cardiac output—a change needed to meet the high metabolic demands experienced by skeletal muscle during exercise. ---The percentage of blood flow to the skin increases to almost five times its resting level (from 400 mL/min to 1900 mL/min) to dissipate heat. ♦ In contrast, relatively less total blood flow is distributed to the abdominal organs slowing digestive processes; less is transported to the kidneys, which decreases urine output to maintain blood volume and blood pressure. Smaller amounts reach other structures that are not as metabolically active during exercise.

List the functions of the spleen.

♦ Function The spleen functions to filter blood (not lymph). As blood enters the spleen and flows through the central arteries, the white pulp monitors the blood for foreign materials, bacteria, and other potentially harmful substances. After passing through a central artery, blood travels through sinusoids of red pulp. As blood moves through the sinusoids, macrophages lining the sinusoids phagocytize bacteria and foreign debris from the blood, as well as both old and defective erythrocytes and platelets. Thus, the general flow of blood through the spleen is the splenic artery, the central artery (of white pulp), the splenic sinusoid (of red pulp), venules (that drain sinusoids), and ultimately the splenic vein (figure 21.7c). In summary, the spleen serves several functions, including: (1) phagocytosis of bacteria and other foreign materials in the blood as part of the body's defense (red and white pulp); (2) phagocytosis of old, defective erythrocytes and platelets from circulating blood (red pulp); and (3) acting as a blood reservoir and storage site for both erythrocytes and platelets (red pulp). Red pulp of the spleen serves as a blood reservoir, including a storage site for both erythrocytes and platelets (about 30% of all platelets are stored in the spleen). In situations where more erythrocytes and platelets are needed, such as during hemorrhage, these stored formed elements reenter the blood (see section 18.3d).

Explain the mechanisms that move lymph through lymphatic vessels, trunks, and ducts.

♦ Lymphatic capillaries merge to form larger structures that are called lymphatic vessels (figure 21.1). Superficial lymphatic vessels are generally positioned adjacent to the superficial veins of the body; in contrast, deep lymphatic vessels are next to deep arteries and veins. Lymphatic vessels resemble small veins because both contain all three vessel tunics (intima, media, and externa) and have valves within their lumen. Valves are required to prevent lymph from pooling in these vessels and help prevent lymph backflow because the lymphatic vessel network is a low-pressure system, These valves are especially important in areas where lymph flow is against the direction of gravity, such as in the lower limbs. ♦ The lymphatic system lacks a pump. It relies on several mechanisms to move lymph through its vessels: (1) contraction of nearby skeletal muscles in the limbs (skeletal muscle pump) and the respiratory pump in the torso (as described in section 20.5a), (2) the pulsatile movement of blood in nearby arteries, and (3) rhythmic contraction of smooth muscle in walls of larger lymph vessels (trunks and ducts). ♦ Some lymphatic vessels connect directly to lymphatic organs called lymph nodes. Foreign or pathogenic material is filtered as lymph passes through lymph nodes. They are arranged in a series along lymph vessels, are described in more detail in section 21.4a.

Compare and contrast hydrostatic pressure and colloid osmotic pressure in the capillaries.

♦ Hydrostatic pressure (HP) is the physical force exerted by a fluid on a structure. For example, blood hydrostatic pressure (HPb) (or simply blood pressure) is the force exerted per unit area by the blood as it presses against the vessel wall. Blood hydrostatic pressure promotes filtration from the capillary. The interstitial fluid also has its own hydrostatic pressure, called interstitial fluid hydrostatic pressure (HPif), which is the force of the interstitial fluid on the external surface of the blood vessel. For most tissues, the interstitial fluid hydrostatic pressure is very small and for simplicity's sake is assumed to be close to zero. Thus, for our discussion, the main hydrostatic pressure is the blood hydrostatic pressure, which pushes materials out of the capillary. ♦ Colloid Osmotic Pressure The other main force regulating filtration and reabsorption is osmotic pressure, which refers to the "pull" of water into an area by osmosis due to the higher relative concentration of solutes. Colloid osmotic pressure (COP) refers to the pull of water back into a tissue by the tissue's concentration of proteins (colloid). The blood colloid osmotic pressure (COPb) is the force that draws fluid back into the blood due to the proteins in blood, such as albumin. Blood colloid osmotic pressure opposes hydrostatic pressure, and thus promotes reabsorption. Clinicians also use the term oncotic (onkosis = swelling) pressure to describe the blood colloid osmotic pressure. An interstitial fluid colloid osmotic pressure (COPif) also exists, but its value is relatively low because few proteins are present in the interstitial fluid. COPif may range from 0 to 5 mm Hg. By knowing the specific values for the hydrostatic and osmotic pressures, the direction of bulk flow can be determined through the calculation of net filtration pressure

Compare and contrast innate and adaptive immunity.

♦ Innate Immunity ( non-specific immunity) Some defense mechanisms of the immune system serve to protect us against numerous different substances, and because we are born with these defenses, this type of immunity is referred to as innate immunity (or nonspecific immunity). Innate immunity includes the barriers of the skin and mucosal membranes that prevent entry, as well as nonspecific cellular and molecular internal defenses. The structures and mechanisms associated with innate immunity do not require previous exposure to a foreign substance, and they respond immediately to any potentially harmful agent. ♦ Adaptive Immunity ♦ acquired immunity involves specific T-lymphocytes and B-lymphocytes, which respond to different foreign substances (or antigens) to which we are exposed during our lifetime. For example, one lymphocyte may respond to the virus that causes chickenpox, but this same lymphocyte does not respond if it encounters the bacterium that causes strep throat. Lymphocytes provide a powerful means of eliminating foreign substances. However, although the process begins immediately, adaptive immunity typically takes several days to be effective. In the past, the immune system was defined as the functional system composed only of lymphocytes and their response to specific foreign substances. That is, the immune system was synonymous with adaptive immunity. The definition of the immune system has since changed because of a greater understanding of the interdependency of adaptive immunity and innate immunity, and it now includes the structures and processes of both. Although we consider these two components of immunity separately, you will see that innate and adaptive immunity work together to defend the body

Describe the structure of lymph nodes.

♦ Lymph nodes are small, round or oval encapsulated structures, which are located along the pathways of lymph vessels where they serve as the main lymphatic organ. Lymph nodes function in the filtering of lymph and removal of unwanted substances. ♦ Lymph nodes vary in both their size (from 1 to 25 millimeters) and their number (estimated between 500 and 700 throughout the entire body). Lymph nodes are located both superficially and deep within the body and typically occur in clusters that receive lymph from selected body regions. Some examples of clustered lymph nodes include the cervical lymph nodes that receive lymph from the head and neck; the axillary lymph nodes in the armpit that receive lymph from the breast, axilla, and upper limb; and inguinal lymph nodes in the groin that receive lymph from the lower limb and pelvis (see figure 21.1). In addition to clusters, lymph nodes are found individually distributed throughout the body. ♦ Numerous afferent lymphatic vessels bring lymph into a lymph node (figure 21.6). There is typically only one efferent lymphatic vessel, which originates at the involuted portion of the lymph node called the hilum (hī′lŭm), or hilus. Lymph is drained via the efferent lymphatic vessel from this region of the lymph node. ♦ The capsule of a lymph node is composed of dense irregular connective tissue that both encapsulates the node and sends internal extensions into it that are called trabeculae. They subdivide the node into compartments. The connective tissue provides a pathway through which blood vessels and nerves may enter the lymph node. The lymph node regions deep to the capsule are subdivided into an outer cortex and an inner medulla. The cortex is composed in part of multiple lymphatic nodules. Each lymphatic nodule within the lymph node is composed of reticular fibers, which support an inner germinal center that houses both proliferating B-lymphocytes and some macrophages. The germinal center is surrounded by an outer region called a mantle zone, which contains T-lymphocytes, macrophages, and dendritic cells (described in section 22.2a). The medulla differs because it has strands of connective tissue fibers that support B-lymphocytes, T-lymphocytes, and macrophages. These structures are called medullary cords. ♦ Both the cortex and medulla of a lymph node also contain tiny open channels called lymphatic sinuses (cortical sinuses and medullary sinuses, respectively). These spaces are lined with macrophages.

Describe lymph and its contents.

♦ Lymph originates as interstitial fluid surrounding tissue cells; it moves passively into the lymphatic capillaries due to a hydrostatic pressure gradient. Lymphatic capillaries merge to form larger lymph vessels. ♦Characteristics of Lymph Approximately 15% of the fluid that enters the interstitial space surrounding the cells is not reabsorbed back into the blood capillaries during capillary exchange (see section 20.3d). This interstitial fluid amounts to about 3 liters daily and is normally absorbed into lymphatic capillaries. Once inside the lymph vessels, the interstitial fluid is called lymph (limf; lympha = clear spring water). The components of lymph include water, dissolved solutes (e.g., ions), a small amount of protein (approximately 100 to 200 grams that leaked into the interstitial space during capillary exchange), sometimes foreign material that includes both cell debris and pathogens, and perhaps metastasized cancer cells (see Clinical View: "Metastasis").

Describe the four major means by which complement participates in innate immunity.

♦Opsonization (op′sŏn-ī-zā′shŭn) is the binding of a protein (in this case, complement) to a portion of bacteria or other cell type that enhances phagocytosis. The binding protein is called an opsonin (op′sŏ-nin). The binding of complement makes it more likely that a substance is identified and engulfed by a phagocytic cell (e.g., macrophage). ♦Inflammation. Complement increases the inflammatory response through the activation of mast cells and basophils and by attracting neutrophils and macrophages (see section 22.3d). ♦Cytolysis. Various complement components (e.g., C5-C9) trigger direct killing of a target by forming a protein channel in the plasma membrane of a target cell called a membrane attack complex (MAC). The MAC protein channel compromises the cell's integrity, allowing an influx of fluid that causes lysis of the cell. ♦Elimination of immune complexes. Complement links immune (antigen-antibody) complexes to erythrocytes so they may be transported to the liver and spleen. Erythrocytes are stripped of these complexes by macrophages within these organs, and the erythrocytes then continue circulating in the blood.

Compare and contrast the superficial venous drainage and the deep venous drainage of the lower limb.

♦ Superficial Venous DrainageOn the dorsum of the foot, a dorsal venous arch drains into the great saphenous (să-fē′nŭs) vein and the small saphenous vein. The great saphenous vein originates in the medial ankle and extends adjacent to the medial surface of the entire lower limb before it drains into the femoral vein. The small saphenous vein extends adjacent to the lateral ankle and then travels along the posterior calf, before draining into the popliteal vein. These superficial veins have perforating branches that connect to the deeper veins. If the valves in these veins (or the perforating branches) become incompetent, varicose veins develop. (See Clinical View: "Varicose Veins" in section 20.5a). ♦ Deep Venous DrainageThe digital veins and deep veins of the foot drain into pairs of medial and lateral plantar veins. These veins and a pair of fibular veins drain into a pair of posterior tibial veins. On the dorsum of the foot and ankle, deep veins drain into a pair of anterior tibial veins, which traverse alongside the anterior tibial artery. The anterior and posterior tibial veins merge to form a popliteal vein that curves to the anterior portion of the thigh and is renamed the femoral vein. Once this vein passes superior to the inguinal ligament, it is renamed as the external iliac vein. The external and internal iliac veins merge in the pelvis, forming the common iliac vein. Left and right common iliac veins then merge to form the inferior vena cava.

Compare and contrast the superficial venous drainage and the deep venous drainage of the upper limb.

♦ Superficial Venous DrainageOn the dorsum of the hand, a dorsal venous network (or arch) of veins drains into both the medially located basilic (ba-sil′ik) vein and the laterally located cephalic (se-fal′ik) vein. These veins drain into the axillary vein, and they also have perforating branches that allow them to connect to the deeper veins. In the cubital region, an obliquely positioned median cubital vein connects the cephalic and basilic veins. The median cubital vein is a common site for venipuncture, in which a vein is punctured with a hollow needle to draw blood or inject fluids and medications. All of these superficial veins are highly variable among individuals and have multiple superficial tributaries draining into them. ♦ Deep Venous DrainageThe digital veins and deep and superficial palmar venous arches drain into pairs of radial veins and ulnar veins that run parallel to arteries of the same name. At the level of the cubital fossa, the radial and ulnar veins merge to form a pair of brachial veins that travel with the brachial artery. Brachial veins and the basilic vein merge to form the axillary vein. ♦ Superior to the lateral border of the first rib, the axillary vein is renamed the subclavian vein (see figure 20.19b). When the subclavian vein and internal jugular veins of the neck merge, they form the brachiocephalic vein. As we have seen, the left and right brachiocephalic veins form the superior vena cava

Describe the physical, chemical, and biological barriers to entry of harmful agents into the body

♦ Table 22.3 The epithelial tissues of the epidermis and connective tissue of the dermis of the skin provide a physical barrier that very few microbes can penetrate, if the skin is intact. The cells of the skin also release a number of antimicrobial substances, including sebum, lysozyme, defensins, and dermicidin. Additionally, nonpathogenic microorganisms, termed the normal flora, reside on the skin and help prevent the growth of pathogenic microorganisms. Mucosal membranes that line the openings of the body produce mucin that when hydrated forms mucus and also release lysozyme, defensins, and immunoglobulin A (IgA). In addition, harmless bacteria also live in the linings of the various tracts of the body and suppress the growth of other potentially more virulent types. The various mechanisms used by the skin, mucosal membranes, and other structures to help prevent entry are summarized in table 22.3.

Explain the mechanisms that help overcome the small pressure gradient in veins to return blood to the heart

♦ The skeletal muscle pump assists the movement of blood primarily within the limbs. As skeletal muscles contract, veins are squeezed to help propel the blood toward the heart, and valves prevent blood backflow. When skeletal muscles are more active—for example, when a person is walking—blood is pumped more quickly and efficiently toward the heart by the skeletal muscle pump. Conversely, extended inactivity leads to blood pooling in the leg veins, which increases an individual's risk for development of deep vein thrombosis (see Clinical View: "Deep Vein Thrombosis"). ♦ The respiratory pump assists the movement of blood within the thoracic cavity. The diaphragm contracts and flattens as we inspire (inhale). Intra-abdominal pressure increases and places pressure on the vessels within the abdominal cavity. Concomitantly, thoracic cavity volume increases and intrathoracic pressure decreases. Blood is propelled from the vessels in the abdominopelvic cavity into the vessels in the thoracic cavity. When we expire (exhale), the diaphragm relaxes and returns to its dome shape. Thoracic cavity volume decreases and intrathoracic pressure increases, which places pressure on vessels within the thoracic cavity. Blood moves from the vessels in the thoracic cavity back into the heart. In addition, intra-abdominal pressure decreases, allowing blood to move from the lower limbs into the abdominal vessels. When breathing rate increases—for example, when a person is exercising—blood is moved more quickly back to the heart by the respiratory pump.

Compare and contrast a vasodilator and a vasoconstrictor.

♦ Vasodilators are substances that cause smooth muscle relaxation, which results in both vasodilation of arterioles and opening of precapillary sphincters. Consequently, blood flow increases into a capillary bed. ♦ Vasoconstrictors are substances that cause smooth muscle contraction, which results in both arterioles vasoconstricting and precapillary sphincters closing. Thus, blood flow decreases into a capillary bed (see figure 20.5).

Describe the three tunics common to most vessels.

♦ three tunics are the tunica intima, tunica media, and tunica externa -Tunica intima The innermost layer of a blood vessel wall is the tunica intima (tū′ni-kă in′tim-mă; intimus = inmost), or tunica interna. It is composed of an endothelium (a simple squamous epithelium, see section 5.1c) that faces the blood vessel lumen and a thin subendothelial layer of areolar connective tissue. The endothelium both provides a smooth surface as the blood moves through the lumen of the blood vessel and releases substances (e.g., nitric oxide, endothelin) to regulate contraction and relaxation of smooth muscle within the tunica media. Recall that the endothelium is continuous with the endocardium, which is the inner lining of the heart (see section 19.3b). -tunica media is the middle layer of the vessel wall. It is composed predominantly of circularly arranged layers of smooth muscle cells that are supported by elastic fibers. Contraction of smooth muscle in the tunica media results in vasoconstriction, or narrowing of the blood vessel lumen; relaxation of the smooth muscle causes vasodilation (vā′sō-dī-lā′shŭn), or widening of the blood vessel lumen. -tunica externa, or tunica adventitia, is the outermost layer of the blood vessel wall. It is composed of areolar connective tissue that contains elastic and collagen fibers. The tunica externa helps anchor the vessel to other structures. Very large blood vessels require their own blood supply to the tunica externa in the form of a network of small arteries called the vasa vasorum (vā′să vā-sŏr′ŭm; vessels of vessels). The vasa vasorum extend through the tunica externa.

Define active immunity and passive immunity.

♦Active immunity results from a direct encounter with a pathogen or foreign substance that results in the production of memory cells and can be obtained either naturally or artificially. Naturally acquired active immunity occurs when an individual is directly exposed to the antigen of an infectious agent. Artificially acquired active immunity takes place when the exposure occurs through a vaccine. In both cases, memory cells against that specific antigen are formed. ♦ passive immunity: is obtained from another individual or animal, and it can also be obtained naturally or artificially. Naturally acquired passive immunity occurs from the transfer of antibodies from the mother to the fetus across the placenta (IgG) or to the baby in the mother's breast milk (IgA, IgM, and IgG). In contrast, when serum containing antibodies against a specific antigen is transferred from one individual to another, this process is referred to as artificially acquired passive immunity. For example, serum containing antibodies against the toxins associated with tetanus and botulism, can be transferred to an individual who is at risk from one of these toxins. Antibodies to a poisonous snake venom (antivenom) can also be transferred to an individual who has been bitten by that species of snake. The antibodies neutralize the toxin or venom to prevent it from doing harm until the body is able to eliminate it.

Define antigen presentation.

♦Antigen presentation is the display of antigen on a cell's plasma membrane surface. This is a necessary process performed by other cells so that T-lymphocytes can recognize an antigen. Generally, two categories of cells present antigen to T-lymphocytes: all nucleated cells of the body (i.e., all cells except erythrocytes) and a category of cells called antigen-presenting cells. The term antigen-presenting cell (APC) is used to describe any immune cell that functions specifically to communicate the presence of antigen to both helper T-lymphocytes and cytotoxic T-lymphocytes. Dendritic cells, macrophages, and B-lymphocytes function as APCs.

List the benefits and risks of a fever.

♦Benefits of Fever Fever actually has numerous benefits. A fever inhibits replication of bacteria and viruses, promotes interferon activity, increases activity of adaptive immunity, and accelerates tissue repair. Most recently, it has been demonstrated that a fever also increases CAMs on the endothelium of capillaries in the lymph nodes, resulting in additional immune cells migrating out of the blood and into the lymphatic tissue. Thus, it is not necessary (and may be detrimental) to treat a mild fever. Most physicians now recommend letting a fever "run its course" and give fever-reducing medication only if the fever becomes very high or if the patient is in significant discomfort from the fever. ♦Risks of a High Fever A fever is significant when it is above 100°F. High fevers (103°F in children, and slightly lower in an adult) are potentially dangerous because of the changes in metabolic pathways and denaturation of body proteins (see section 2.8b). Seizures may occur at sustained body temperature above 102°F (although generally they occur at much higher temperatures), irreversible brain damage may occur at body temperatures that are sustained at greater than 106°F, and death is likely when body temperature reaches 109°F.

Explain the effector response of helper T-lymphocytes.

♦Effector Response of Helper T-Lymphocytes Activated and memory helper T-lymphocytes leave the secondary lymphatic structure after several days of exposure to antigen. They migrate to the site of infection, where they continue to release the cytokines to regulate other immune cells (figure 22.17a). Although helper T-lymphocytes were named based on their function in helping activate B-lymphocytes, their contributions are much more encompassing. Helper T-lymphocytes activate cytotoxic T-lymphocytes, as described previously, through the release of cytokines (e.g., IL-2); they also enhance formation and activity of cells of the innate immune system, including macrophages and NK cells. Thus, healthy helper T-lymphocytes play a central role in a normal functioning immune system (see Clinical View: "HIV and AIDS" in section 22.9c).

Discuss the difference between the primary response and the secondary response to antigen exposure.

♦Initial Exposure and the Primary Response The initial exposure to a specific antigen can be in the form of an active infection or a vaccine. The measurable response of antibody production to the first exposure is called the primary response: -Lag or latent phase. There is initially a period of no detectable antibody in the blood. This period may extend 3 to 6 days. Antigen detection, activation, proliferation, and differentiation of lymphocytes, including development of memory lymphocytes, occur during the lag phase. -Production of antibody. Within 1 to 2 weeks, plasma cells produce IgM and then IgG. Antibody titer levels peak and then generally decrease over time. ♦Subsequent Exposures and the Secondary Response Subsequent exposures to an antigen can occur after varying lengths of time following the initial exposure, and the measurable response to subsequent exposure is called the secondary response: -Lag or latent phase. A much shorter lag phase occurs with subsequent exposures to the same antigen. This difference is due to the presence of memory lymphocytes. -Production of antibody. Antibody levels rise more rapidly, with a greater proportion of the IgG class of antibodies. This higher level of IgG production may continue for longer periods, perhaps even years.

Describe the spleen and its location.

♦The spleen (splēn) is the largest lymphatic organ in the human body. It is located in the left upper quadrant of the abdomen, inferior to the diaphragm and adjacent to ribs 9-11 (figure 21.7). This deep red organ lies lateral to the left kidney and posterolateral to the stomach. The spleen can vary considerably in size and weight, but typically is about 12 centimeters (5 inches) long and 7 centimeters (3 inches) wide. ♦The spleen's posterolateral aspect (called the diaphragmatic surface) is convex and rounded; the concave anteromedial border (the visceral surface) contains the hilum (or hilus), where blood vessels and nerves enter and leave the spleen. A splenic (splen′ik) artery delivers blood to the spleen, whereas blood is drained by a splenic vein. The spleen is surrounded by a connective tissue capsule from which trabeculae extend into the organ. The spleen lacks a cortex and medulla. Rather, the trabeculae subdivide the spleen into regions of white pulp and red pulp. White pulp consists of spherical clusters of T-lymphocytes, B-lymphocytes, and macrophages, which surround a central artery ♦The remaining splenic tissue, called red pulp, contains erythrocytes, platelets, macrophages, and B-lymphocytes. The cells in red pulp are housed in reticular connective tissue and form structures called splenic cords (cords of Bilroth). Splenic sinusoids are associated with red pulp. (Recall from section 20.1c that sinusoids are very permeable capillaries that have a discontinuous basal lamina, so blood cells can easily enter and exit across the vessel wall.) The sinusoids drain into small venules that ultimately lead into a splenic vein.

Identify the two major types of lymphocytes.

♦The two major types of lymphocytes are (1) T-lymphocytes (also called T-cells) and (2) B-lymphocytes (also called B-cells). Most formed elements move from the red bone marrow into the blood following hemopoiesis. Unlike the other formed elements, T-lymphocytes must migrate to the thymus to complete their maturation. The functions of both T-lymphocytes and B-lymphocytes are described in detail in chapter 22. The "T" in the name "T-lymphocytes" originates from the requirement of these cells to complete their maturation in the thymus