Chapter 22 L.O.

Diagram the general interaction of TCR and CD receptors of a T-lymphocyte with antigen associated with the MHC molecules of other cells.

CD4 -Class two CD8- Class one

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. 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

Epithelial layers of the skin and mucosal membranes

Dendritic cells are located in the skin and mucosal membranes, and are typically derived from monocytes. Dendritic cells engulf pathogens in the skin and mucosal membranes and subsequently migrate to a lymph node through lymph vessels that drain the tissue

Tumor necrosis factor (TNF)

Destroys tumor cells; may have other functions as well. Source: T-lymphocytes, macrophages, mast cells, dendritic cells

Cytotoxic T-Lymphocytes

release chemicals that are toxic to cells, resulting in their destruction

Explain how T-lymphocytes mature.

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.

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

Helper T-Lymphocytes- 1. 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. 2. Second Signal: other receptors of the APC interact with receptors of the helper T-lymphocyte. induced to synthesize and release the cytokine interleukin 2 (IL-2), as an autocrine hormone. T-lymphocytes are activated and proliferate to form a "clone" of helper T-lymphocytes. lack of second signal is thought to result in helper T-lymphocytes becoming Tregs

Explain the effector response of helper T-lymphocytes.

Helper T-lymphocytes activate cytotoxic T-lymphocytes, through the release of cytokines; they also enhance formation and activity of cells of the innate immune system, including macrophages and NK cells

exudate

Helps to "wash" the area of injurious agents. Increased fluid, protein, and immune cells leave the capillaries and then enter the interstitial space of the tissue. delivers cells and substances needed to eliminate the injurious agent and promote healing. This increase in fluid movement is due to several factors: Vasodilation, Increased capillary permeability, Loss of plasma protein, which decreases capillary osmotic pressure, resulting in less fluid being retained in the blood and reabsorbed back into the blood during capillary exchange. Pus may form in severe infections. Pus is exudate that contains destroyed pathogens, dead leukocytes, macrophages, and cellular debris.

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

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. 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

Describe the structure, location, and specific function of the five major classes of immunoglobulins. G-MADE

IgG- is the major class of immunoglobulins. It makes up 75-85% of antibody in the blood and is the predominant antibody in the lymph, cerebrospinal fluid, serous fluid, and peritoneal fluid. can participate in all of the functions previously listed for actions of antibodies including the neutralization of toxins. cross the placenta and can be responsible for hemolytic disease of the newborn

IgE

In blood. very low rate of synthesis and is generally formed in response to allergic reactions and to parasitic infections. causes release of histamine and other mediators of inflammation from basophils and mast cells, and it attracts eosinophils

Define inflammation, and discuss the basic steps involved, including the formation of exudate and its role in removing harmful substances.

Inflammation: is an immediate, local, nonspecific event that occurs in vascularized tissue against a great variety of injury-causing stimuli. is the major effector response of innate immunity. Events of inflammation: 1. release of various chemicals (chemo tactic factors) 2. 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). 3. recruitment of leukocytes: -Margination: is the process by which CAMs on leukocytes adhere to CAMs on the endothelial cells of capillaries within the injured tissue. -Diapedesis: 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. -Chemotaxis: is migration of cells along a chemical gradient 4. Delivery of plasma proteins: Kinins are produced from kininogens, which are inactive plasma proteins produced by the liver. also stimulate sensory pain receptors and are the most significant stimulus for causing the pain associated with inflammation.

Compare and contrast the primary features of innate and adaptive immunity.

Innate (nonspecific): we are born with these defenses. includes the barriers of the skin and mucosal membranes that prevent entry, as well as nonspecific cellular and molecular internal defenses. do not require previous exposure to a foreign substance, and they respond immediately to any potentially harmful agent. Adaptive (acquired): involves specific T-lymphocytes and B-lymphocytes, which respond to different foreign substances (or antigens) to which we are exposed during our lifetime. process begins immediately, but typically takes several days to be effective.

B lymphocyte humoral

It is because the immune response of B-lymphocytes is effective against soluble antigens (antigens dissolved in the body's "humors") that it is referred to as humoral immunity.

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

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.

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

Leukocytes are formed in the red bone marrow prior to circulating in the blood. They include (1) the three types of granulocytes (neutrophils, eosinophils, and basophils); (2) monocytes that become macrophages or dendritic cells when they exit blood vessels and take up residence in the tissues; and (3) the three types of lymphocytes, which include T-lymphocytes (or T-cells), B-lymphocytes (or B-cells), and NK (natural killer) cells. Most leukocytes are found in body tissues (as opposed to in the blood).

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.

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

Neutrophils, Macrophages, and Dendritic Cells

Neutrophils, macrophages, and dendritic cells engulf unwanted substances such as infectious agents and cellular debris through phagocytosis. Both neutrophils and macrophages function to destroy infectious agents through a process that involves a lysosome and a respiratory burst. 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 also macrophages.

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

Primary response: measurable response of antibody production to the first exposure. 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. 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.

Interleukin

Regulates immune cells. Source: T-lymphocytes, macrophages, endothelial cells, and other various cells

Antimicrobial proteins

specific types of molecules of the innate immune system that function against microbes. Two of those, interferons and complement

Discuss how haptens stimulate immune responses.

Some substances are too small to function as an antigen alone, but when attached to a carrier molecule in the host, become antigenic and trigger an immune response. An example is the lipid toxin in poison ivy, which penetrates the skin and triggers an immune response after combining with a body protein. Hapten-stimulating immune responses account for hypersensitivity reactions to drugs, such as penicillin, and to chemicals in the environment, such as pollen, animal dander, mold, and snake or bee venom

Colonystimulating factor (CSF)

Stimulates leukopoiesis in bone marrow to increase synthesis of a specific type (colony) of leukocytes. Source: T-lymphocytes, monocytes

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

Describe lymphocyte recirculation and explain its general function.

The "odds" for contact are increased because lymphocytes reside only temporarily in any given secondary lymphatic structure, and after a period of time they exit and then circulate through blood and lymph every several days, makes it more likely it will encounter its antigen.

Define antibody titer.

The circulating blood concentration of antibody against a specific antigen

Eosinophils

target parasites. 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. also participate in the immune response associated with allergy and asthma.

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

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. 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 (Attacks the cell wall of some bacteria), defensins (Form pores in the plasma membrane of microbes, compromising their structural integrity), and immunoglobulin A (IgA)(Binds with a specific foreign substance (antigen).

antigen challenge

The first encounter between an antigen and lymphocyte

Secondary Response

the measurable response to subsequent exposure Lag or latent phase: A much shorter lag phase, 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.

Define immunologic memory and explain how it occurs.

These long-lived lymphocytes represent an "army" of thousands against specific antigens and are responsible for immunologic memory. This feature of immunologic memory makes adaptive immunity a highly potent protector. This feature of immunologic memory makes adaptive immunity a highly potent protector

Interferon (IFN)

Three classes: IFN-α and IFN-β are antiviral agents, and IFN-γ is a pro-inflammatory agent. Source: Leukocytes, fibroblasts

Explain the general function of interferons.

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. serve as a nonspecific defense mechanism against the spread of any viral infection. 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.

IgM

a pentamer (composed of five monomers), Found mostly in blood. not efficient at virus neutralization. most effective at causing agglutination of cells and binding complement. responsible for rejection of mismatched blood transfusions

Explain the additional changes to T-lymphocytes after selection.

a subclass of CD4+ cells is also formed called regulatory T-lymphocytes (Tregs). migrate to the periphery (body structures outside the primary lymphatic structures), where they release inhibitory chemicals that turn off both the cell-mediated immune response and the humoral immune response.

IgD

along with a monomer form of IgM. functions as the antigen-specific B-lymphocyte receptor. It also functions to identify when immature B-lymphocytes may be ready for activation to participate in adaptive immunity.

MHC Class I

are glycoproteins; they are genetically determined and are unique to each individual. continuously synthesized by the rough endoplasmic reticulum (RER), inserted into the ER, shipped within and modified by the endomembrane system. 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. if the cell is infected, the antigens presented are foreign antigens.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.

Basophils and Mast Cells

both proinflammatory chemical-secreting cells. 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. 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 (prevents blood clot). eicosanoids from their plasma membrane which increase inflammation

Define a fever, and describe how it occurs.

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). results from release of fever-inducing molecules called pyrogens (e.g., IL-1, IL-6, TNF-α) Pyrogens are released and circulate in the blood; they target the hypothalamus and cause release of prostaglandin E2 (PGE2)

Natural Killer Cells

destroy a wide variety of unwanted cells, including virus-infected cells, bacteria-infected cells, tumor cells, and cells of transplanted tissue. 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. patrol the body in an effort to detect unhealthy cells, a process referred to as immune surveillance. 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.

Helper T-Lymphocytes

function to coordinate the immune response—helping both cell-mediated immunity and humoral immunity, as well as enhancing certain aspects of innate immunity

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

has a unique receptor complex, which are composed of several different and separate proteins. Will bind to one specific antigen. 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 have additional receptor molecules (called coreceptors) that facilitate T-lymphocyte physical interaction. The plasma membranes of helper T-lymphocytes contain the CD4 protein, and the plasma membranes of cytotoxic T-lymphocytes contain the CD8 protein

Describe the benefits of inflammationh

helping to eliminate pathogens by limiting their spread; destroying infectious agents and removing cellular debris; and producing the conditions for tissue repair and healing.

List the general categories of cytokines.

interleukin (IL), tumor necrosis factor (TNF), colony-stimulating factor (CSF), and interferon (IFN)

humoral immunity (or antibody-mediated immunity)

involving B-lymphocytes that develop into plasma cells to synthesize and release antibodies

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

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. 1. Variable region- 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. binds the antigen through weak intermolecular forces, including hydrogen bonds, ionic bonds, and hydrophobic interactions 2. Constant region- contains the Fc region, which is the portion of the antibody that determines the biological functions of the antibody.

IgA

is a dimer (i.e., composed of two antibody molecules). found in areas exposed to the environment, such as mucosal membranes and tonsils, and it is produced in various secretions, including mucus, saliva, tears, and breast milk. significant role in protecting the respiratory and gastrointestinal tract. helps to prevent pathogens from adhering to epithelial tissue and penetrating underlying tissue through the process of neutralization. especially effective at agglutination.

MHC Class II

is a glycoprotein continuously synthesized by the rough endoplasmic reticulum (RER), modified by the endomembrane system, and then embedded within the plasma membrane. 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). exogenous pathway: proteins that are engulfed from outside of a cell. Exogenous antigen, through the process of endocytosis, is brought into the cell. This display of foreign antigen with an MHC class II molecule provides the means of communicating specifically with helper T-lymphocytes

Define antigen presentation.

is the display of antigen on a cell's plasma membrane surface. necessary process performed by other cells so that T-lymphocytes can recognize an antigen. 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

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

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.

cell-mediated immunity (or cellular immunity)

which differentiate into helper T-lymphocytes and cytotoxic T-lymphocytes

immunocompetent

lymphocytes are "tested" to see whether they are able to bind antigen and respond to it. occurs primarily during development and shortly after birth in primary lymphatic structures

Fc Region. CON, aNAP can help you CONcentrate

1. Complement fixation: bind specific complement proteins to cause activation of complement by the classical pathway. 2. Opsonization: making it more likely that a target is "seen" by phagocytic calls. neutrophils and macrophages have receptors for the Fc region. The phagocytic receptors bind in a "zipperlike" fashion to the Fc region of the antibodies to engulf both the antigen and antibody. 3. Activation of NK cells- antibody-dependent cell-mediated cytotoxicity (ADCC).

Activation of Cytotoxic T-Lymphocytes

1. First signal- CD8 binds with MHC class I molecule of infected cell;TCR interacts with antigen. 2. Second Signal-binding of IL-2 that is released from helper T-lymphocytes (required). acts as a paracrine hormone. proliferate and differentiate into clones

Identify the three significant events that occur in the lifetime of a lymphocyte.

1. Formation of lymphocytes. 2. Activation of lymphocytes 3. Effector response

Stages of fever

1. Onset-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 2. Stadium- period of time where the elevated temperature is maintained 3. Defervescence- when the temperature returns to its normal set point

Describe the four major means by which complement participates in innate immunity (O-ICE)

1. Opsonization: is the binding of a complement to a portion of bacteria or other cell type that enhances phagocytosis. The binding protein is called an opsonin. Antibodies coat bacterium making it easier for macrohpages to engulf it 2. Inflammation: Complement increases the inflammatory response through the activation of mast cells and basophils and by attracting neutrophils and macrophages 3. Cytolysis: Various complement components 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. 4. 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 positive and negative selection of T-lymphocytes.

1. Positive Selection (For)- The TCR embedded in the plasma membrane of a T-lymphocyte must be able to recognize and bind an MHC molecule. This is "tested" by having T-lymphocytes bind with thymic epithelial cells that have MHC molecules. Those T-lymphocytes that can bind MHC survive, and those that cannot are eliminated 2. Negative Selection(Against)- The newly formed T-lymphocyte must also not bind to any self-antigens that are presented within an MHC molecule. This is "tested" by thymic dendritic cells presenting self-antigens with MHC class I and II molecules. If the T-lymphocyte does bind to the self-antigen, then it is destroyed. T-lymphocytes that survive both positive and negative selection can bind an MHC molecule and recognize foreign antigen.

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

1. Redness-due to increased blood flow 2. Heat, due to increased blood flow and increased metabolic activity within the area 3. Swelling- resulting from increase in fluid loss from capillaries into the interstitial space 4. 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 5. Loss of function (which may occur in more severe cases of inflammation due to pain and swelling) lasts 8-10 days

Define the complement system and describe how it is activated

most important antimicrobial groups. 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. 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

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. Passive immunity- is obtained from another individual or animal, and it can also be obtained naturally or artificially. the individual has not had an antigenic challenge and has not produced memory cells

Describe the cells that function in innate immunity.

neutrophils, macrophages, dendritic cells, basophils, mast cells, NK cells, and eosinophils.

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

Antibodies circulate throughout the body in the lymph and blood, ultimately coming in contact with antigen at the site of infection

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

Antigen -binding site (Fap region): 1. Neutralization:An antibody physically covers an antigenic determinant of a pathogen to make it ineffective in establishing an infection or causing harm. 2. Agglutination: Antibody cross-links antigens of foreign cells, causing them to agglutinate or "clump." effective against bacterial cells and mismatched erythrocytes in a blood transfusion. 3. Precipitation: Antibody can cross-link soluble, circulating antigens such as viral particles (not whole cells) to form an antigen-antibody complex. Insoluble. The precipitated complexes are then engulfed and eliminated by phagocytic cells such as macrophages.

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

Antigen presentation requires the physical attachment of antigen to a specialized transmembrane protein called MHC (major histocompatibility complex)- mark cells as self and present antigens. 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

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

B-lymphocytes recognize and respond to antigens outside of cells, such as antigens of viral particles, bacteria, bacterial toxins, or yeast spores. 1. First Signal- intact antigen binds to the BCR, and the antigen cross-links BCRs. The stimulated B-lymphocyte engulfs, processes, and presents the antigen to the helper T-lymphocyte that recognizes that antigen 2. Second Signal- 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

List the benefits and risks of a fever.

Benefits- A fever inhibits replication of bacteria and viruses, promotes interferon activity, increases activity of adaptive immunity, and accelerates tissue repair. Risks- High fevers are potentially dangerous because of the changes in metabolic pathways and denaturation of body proteins. Seizures may occur at sustained body temperature above 102°F. 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.