Erin C. Amerman Florida State College at Jacksonville

Erin C. Amerman Florida State College at Jacksonville
Lecture Presentation by L’Tanya Patton at Alvin Community College © 2016 Pearson Education, Inc.

Module 20.1 Structure and Function of the Lymphatic System
© 2016 Pearson Education, Inc.

Introduction to the Immune and Lymphatic Systems
Immune and lymphatic systems function together in what is broadly called immunity: set of diverse processes that protect body from both cellular injury and disease-causing cells and molecules known as pathogens: Immune system works to defend body against internal and external threats Contains no organs or tissues but instead consists of cells and proteins located in blood and tissues of other systems, including lymphatic system Includes formed elements known as leukocytes, or white blood cells (WBCs), and immune proteins located in plasma © 2016 Pearson Education, Inc.

Introduction to the Immune and Lymphatic Systems
Lymphatic system – group of organs and tissues that not only works with immune system but also participates in a number of functions such as fluid homeostasis; consists of two main components (Figure 20.1): Lymphatic vessels are a system of blind-ended tubes Lymphatic tissue and organs – includes clusters of lymphoid follicles such as tonsils, as well as lymph nodes, spleen, and thymus © 2016 Pearson Education, Inc.

Functions of the Lymphatic System
Lymphatic system basic functions: Regulation of interstitial fluid volume – net filtration pressure in blood capillaries favors filtration, meaning that water is lost from plasma to interstitial fluid: Fluid lost from plasma is about 2–4 liters per day; must be returned to circulation, or both blood volume and blood pressure will drop too low to maintain homeostasis © 2016 Pearson Education, Inc.

Regulation of interstitial fluid volume (continued): Lymphatic vessels pick up excess fluid in extracellular space, transport it through body, and deliver it back to cardiovascular system When the fluid exits extracellular space and enters lymphatic vessels, it is known as lymph; interstitial fluid and lymph are similar in composition © 2016 Pearson Education, Inc.

Absorption of dietary fats – breakdown products of fats in diet are too large to pass between endothelial cells of blood capillaries: Dietary fats instead enter small lymphatic vessels in small intestine Travel through lymphatic vessels and are delivered to blood with lymph © 2016 Pearson Education, Inc.

Immune functions – lymphatic system plays an important role in immune system; lymphoid organs filter pathogens from lymph and blood; also house several types of leukocytes, and play a role in their maturation © 2016 Pearson Education, Inc.

Lymphatic Vessels and Lymph Circulation
Lymph is collected in vessels called lymph- collecting vessels which merge to form larger vessels, lymph trunks (Figures 20.2, 20.3) Nine lymph trunks drain lymph from specific body regions (Figure 20.2a): Lumbar trunks receive lymph from lower limbs and pelvic area; jugular trunks receive lymph from head and neck Intestinal trunk receives fat-containing lymph from small lymphatic vessels in small intestine Bronchomediastinal trunks receive lymph from thoracic cavity; subclavian trunks receive lymph from upper limbs © 2016 Pearson Education, Inc.

Intestinal trunk and lumbar trunks all drain into a large, swollen vessel called cisterna chyli Cisterna chyli and other lymph trunks drain into one of two lymph ducts Cisterna chyli and trunks from left side of body drain into thoracic duct; drains all of lower body and left side of upper body Thoracic duct, largest lymphatic duct, runs along anterior vertebral column and drains into junction of left internal jugular and left subclavian veins (Figure 20.2b) © 2016 Pearson Education, Inc.

Lymphatic vessels make up a low-pressure circuit because there is no main pump to drive lymph through vessels, and most of them are transporting lymph against gravity: Valves prevent lymph from flowing backward Like deeper veins, often found lodged between muscles, where contracting muscles massage lymph up toward heart Lymph flow through vessels is driven in part by contractions of smooth muscle found in walls of lymph-collecting vessels © 2016 Pearson Education, Inc.

Lymphatic vessels begin in tissues with tiny lymphatic capillaries; form a weblike network that surrounds blood capillary beds although lymphatic capillaries differ both structurally and functionally from blood capillaries: Specialized lymphatic capillaries known as lacteals collect fat in the small intestine Lymphatic capillaries are blind-ended, which makes lymphatic vasculature a one-way system that only moves lymph away from tissues Blood capillaries, of course, form a two-way system that moves blood both toward and away from tissues © 2016 Pearson Education, Inc.

Cells of lymphatic capillary walls are not tightly joined, and instead are able to flap open and closed (Figure 20.3b) Fluid that leaks from blood capillaries increases interstitial fluid pressure; forces lymphatic endothelial cells apart and allows large volumes of fluid to enter lymphatic capillaries When pressure in interstitial fluid decreases, endothelial cells flap shut; plays a crucial role in precise control of amount of fluid between cells These vessels are also leaky enough to allow cells such as macrophages and other immune cells to enter lymph © 2016 Pearson Education, Inc.

Along pathway of lymphatic vessels are clusters of lymphoid organs called lymph nodes Pathogens such as bacteria and cancer cells in interstitial fluid have an easier time entering lymphatic capillaries than blood capillaries Lymph nodes limit spread of pathogens through body by acting as filters, trapping pathogens and preventing them from traveling elsewhere © 2016 Pearson Education, Inc.

Lymphedema Role of lymphatic system in regulating volume of interstitial fluid becomes readily apparent in lymphedema Edema (swelling) is an accumulation of excess interstitial fluid; many conditions can cause mild to moderate edema, including trauma, vascular disease, and heart failure However, edema seen with lymphedema is typically severe and can be disfiguring © 2016 Pearson Education, Inc.

Lymphedema Lymphedema is generally due to removal of lymphatic vessels during surgery or blockage of vessels from pathogens such as parasites Both conditions prevent lymphatic vessels from transporting excess interstitial fluid back to cardiovascular system; fluid therefore accumulates in tissues of affected body part, causing it to enlarge Photo shows a case of lymphedema in arm of a breast cancer patient resulting from surgical removal of lymph nodes © 2016 Pearson Education, Inc.

Lymphoid Tissues and Organs
Predominant tissue type of lymphatic system is a type of loose connective tissue called reticular tissue; contains specialized cells and thin reticular fibers; interweave to form “nets” that trap disease-causing pathogens; example of Structure-Function Core Principle (Figures 20.4–20.9) Lymphatic reticular tissue is typically called lymphoid tissue; found in lymphoid organs and also as independent clusters that have varying degrees of organization © 2016 Pearson Education, Inc.

Lymphoid organs house leukocytes (Figure 20.4): Macrophages – mature monocytes that are very active phagocytes B and T lymphocytes – agranulocytes with diverse immune functions Dendritic cells – immune cells with spiny processes resembling dendrites of neurons; derived from bone marrow while others originate from connective tissue Reticular cells – particularly abundant in organs such as spleen and lymph nodes; produce reticular fibers composed of a specialized, thin type of collagen protein © 2016 Pearson Education, Inc.

Mucosa-associated lymphatic tissue (MALT) – loosely organized clusters of lymphoid tissue that protects mucous membranes, which are exposed to a large number of pathogens (Figures 20.5, 20.6): MALT protect oral and nasal cavities; found scattered throughout gastrointestinal tract, respiratory passages, and, to a limited extent, genitourinary tract Much of MALT in body consists of loosely organized clusters of B and T cells that lack a connective tissue capsule © 2016 Pearson Education, Inc.

Specialized MALT is found in three locations in gastrointestinal tract: Tonsils – located around oral and nasal cavities Peyer’s patches (aggregated lymphoid nodules) – located in last portion of small intestine (called ileum) Appendix – protrudes from large intestine © 2016 Pearson Education, Inc.

Three main tonsils (Figure 20.5): Pharyngeal tonsil (adenoid) – located in posterior nasal cavity (nasopharynx) Palatine tonsils – in posterolateral oral cavity Lingual tonsil – at base of tongue © 2016 Pearson Education, Inc.

Epithelium lining tonsils indents deeply in several locations, forming tonsillar crypts that trap bacteria and debris Tonsil location puts them into contact with a large number of potential pathogens; as a result, commonly become inflamed, a condition known as tonsillitis © 2016 Pearson Education, Inc.

Peyer’s patches are also exposed to a large number of potential pathogens because of their location; allows them to defend against any bacteria that have escaped from large intestine (Figure 20.6) Appendix – blind-ended, worm-shaped tube that juts from large intestine; defends body from bacteria in large intestine, specifically those that could be pathogenic © 2016 Pearson Education, Inc.

Lymph nodes – small, vaguely bean-shaped clusters of lymphatic tissue located along lymphatic vessels throughout body (Figure 20.7): Specific clusters of lymph nodes include: axillary lymph nodes in axillae, cervical lymph nodes in neck, inguinal lymph nodes in groin, and mesenteric lymph nodes in abdominal cavity Lymph nodes have an external connective tissue capsule that surrounds a network of reticular fibers filled with macrophages, lymphocytes, and dendritic cells Interior of a node is divided into two main regions: outer cortex and inner medulla © 2016 Pearson Education, Inc.

Cortex consists of lymphoid follicles divided by inward extensions of capsule, called trabeculae Between cortex and medulla is a zone composed primarily of T cells, while medulla contains fewer leukocytes than cortex, it does contain mature B cells Lymph flows into node through multiple small lymphatic vessels (afferent lymphatic vessels) then percolates through reticular network, where pathogens in lymph become trapped in reticular “net” © 2016 Pearson Education, Inc.

Trapped pathogens then encounter leukocytes and dendritic cells, which eliminate these threats Lymph that has been “cleaned” of pathogens drains out through efferent lymphatic vessels on other side of node at hilum Lymph nodes trap approximately 90% of pathogens in lymph; prevents these pathogens from being delivered to blood, where they could easily spread to other tissues and organs © 2016 Pearson Education, Inc.

Spleen – largest lymphoid organ in body; located on lateral side of left upper quadrant of abdominopelvic cavity (Figure 20.8): Purplish-brown organ about size of a large bar of soap; internal structure consists of a network of reticular fibers made by reticular cells Two distinct histological regions are found in reticular network: red pulp, which contains macrophages that destroy old erythrocytes, and white pulp, which filters pathogens from blood and contains leukocytes and dendritic cells © 2016 Pearson Education, Inc.

Thymus – small, encapsulated organ in superior mediastinum; consists of two lobes; doesn’t trap pathogens (Figure 20.9): Secretes hormones that enable it to carry out its primary function: generating a population of functional T cells capable of protecting body from pathogens Large and very active in infants and children, reaching its maximum size in individuals about 12–14 years old © 2016 Pearson Education, Inc.

After this point, it begins to atrophy and thymic tissue is gradually replaced with fat as its T cell production declines By age 65, rate of T cell production falls to about 2% of rate at which an infant produces T cells Adult thymus consists of subunits called thymic lobules (thymic corpuscles); visible externally as “lumps” on surface of thymus © 2016 Pearson Education, Inc.

Each lobule contains two regions: an outer cortex and an inner medulla Cortex contains densely packed T cells Medulla contains fewer of these cells, and is thought instead to be mostly site of destruction of certain populations of T cells that could react to body’s own cells There are no lymphoid follicles in thymus because it lacks B cells © 2016 Pearson Education, Inc.

Module 20.2 Overview of the Immune System

Introduction Combined components of immune system offer three lines of defense against pathogens: First line of defense – includes cutaneous and mucous membranes that act as surface barriers to block entry of pathogens into body Second line of defense – includes responses of cells and proteins that make up innate immunity Third line of defense – includes responses of cells and proteins of adaptive immunity © 2016 Pearson Education, Inc.

Types of Immunity Immunity is classified according to way it responds to different pathogens or forms of cellular injury: Innate, or nonspecific, immunity responds to all pathogens or classes of pathogen in same way Innate immune system consists of antimicrobial proteins and certain cells that respond quickly; dominant response to pathogens for first 12 hours after exposure Cells and proteins exist in bloodstream, even in absence of a stimulus © 2016 Pearson Education, Inc.

Types of Immunity Components of adaptive, or specific, immunity respond individually to unique glycoprotein markers called antigens; present on all cells and most biological molecules, including our own cells; identify a cell or molecule as belonging to a specific group © 2016 Pearson Education, Inc.

Types of Immunity There are two “arms” of adaptive immune system:
First arm is cell-mediated immunity; brought about by two types of T cells Second arm is antibody-mediated immunity (humoral immunity); carried out by B cells and proteins they produce, called antibodies © 2016 Pearson Education, Inc.

Types of Immunity Adaptive immunity responds more slowly than innate immunity because one must be exposed to a specific antigen for response to be initiated Hence name acquired immunity, as it takes 3–5 days to mount a response, but after this point, it is dominant response © 2016 Pearson Education, Inc.

Types of Immunity Adaptive immunity has the capacity for immunological memory, in which exposure to an antigen is “remembered” by specific lymphocytes and antibodies This allows a more rapid and efficient response on subsequent exposures Innate immunity lacks capacity for immunological memory and will respond in same way with repeat exposure to a pathogen © 2016 Pearson Education, Inc.

Types of Immunity Adaptive immunity and innate immunity are not independently functioning arms of the immune system; each type of immunity relies on other, and response to a pathogen involves a highly integrated series of events within both parts of immune system © 2016 Pearson Education, Inc.

Surface Barriers Surface barriers – first line of defense against any potential threat to body is coverings of body surfaces; skin and mucous membranes, and certain products they secrete: Both skin and mucosae provide a continuous physical barrier to block entry of potential pathogens into body Skin is relatively resistant to mechanical stresses because of its several layers of epithelial cells filled with hard protein keratin Sebaceous glands in skin secrete sebum, or oil, which has a slightly acidic pH that deters growth of most pathogenic organisms © 2016 Pearson Education, Inc.

Surface Barriers Mucous membranes line all passageways in body that open to outside, including respiratory, gastrointestinal, and genitourinary tracts These epithelia lack keratin; less resistant to mechanical abrasion Also secrete products that discourage pathogen invasion, namely, sticky substance mucus Mucus traps pathogens and other debris and also protects underlying cells from chemical and mechanical trauma Mucous membranes of stomach secrete acid, which kills ingested pathogens © 2016 Pearson Education, Inc.

How Pathogens Can Evade Surface Barriers
Pathogens have evolved multiple mechanisms to evade defenses provided by surface barriers and facilitate their invasion of our bodies; following are three examples of such pathogens: Certain bacterial species, notably Clostridium perfringens, produce enzymes called collagenases, which catalyze reactions that degrade collagen; destroy collagen in basement membrane and dermis; allows access to deeper tissues such as skeletal muscle, eventually resulting in massive tissue death; as bacteria destroy tissues, they produce large quantities of gas, leading to the common name of gas gangrene © 2016 Pearson Education, Inc.

Pathogens (continued) To make matters worse, C. perfringens also produces enzymes that catalyze destruction of neutrophils, making immune system much less able to respond to invasion © 2016 Pearson Education, Inc.

Pathogenic organisms that come into contact with mucosae are generally ingested by local macrophages, minimizing risk of infection Some fungi are quite resistant to phagocytosis; for example, fungal yeast cells that cause disease blastomycosis have very thick walls that are difficult for phagocytes to ingest Still other fungal species, such as those producing respiratory diseases cryptococcosis and histoplasmosis, actually survive inside macrophages © 2016 Pearson Education, Inc.

Makes fungi invisible to immune system, and macrophages spread disease as they travel through blood and lymph to different tissues Secretions produced by surface barriers are generally slightly to very acidic, which deters or kills most pathogens Certain pathogens tolerate an acidic pH; for example, poliovirus is able to survive highly acidic environment of stomach when it is ingested, allowing it to replicate in digestive tract and potentially invade rest of body © 2016 Pearson Education, Inc.

Overview of Cells and Proteins of Innate and Adaptive Immune Systems
Cells and proteins of innate and adaptive immune systems produce response of second and third lines of defense: Main cells of immune system are different types of leukocytes: Agranulocytes (B and T lymphocytes and monocytes) lack cytoplasmic granules; and granulocytes (neutrophils, eosinophils, and basophils) contain cytoplasmic granules Many cells of innate immunity can function as cells that “eat” foreign or damaged cells—although neutrophils and macrophages are most active phagocytes © 2016 Pearson Education, Inc.

Other types of leukocytes also function in immunity: Natural killer (NK) cells, located in blood and spleen, function primarily in innate immunity Dendritic cells, located in many lymphoid organs; part of innate immune response, but their main role is to activate T cells of adaptive immunity © 2016 Pearson Education, Inc.

Other main components of immune system are groups of different types of proteins: Antibodies – proteins produced by B lymphocytes that function in adaptive immunity Complement system – functions in innate immunity Cytokines – diverse group of proteins secreted by cells of both innate and adaptive immunity; have a variety of effects, including regulating development and activity of immune cells © 2016 Pearson Education, Inc.

How the Lymphatic and Immune Systems Work Together
Lymphatic and immune systems are closely connected both structurally and functionally: Lymphoid organs and tissues provide a residence for cells of the immune system; B cells, T cells, and macrophages frequently take up residence in lymphoid organs such as lymph nodes, MALT, and spleen Lymphoid organs and tissues trap pathogens for immune system; fine networks of reticular fibers in lymphoid tissues form “nets” that trap pathogens so that leukocytes may interact with them more easily © 2016 Pearson Education, Inc.

How the Lymphatic and Immune Systems Work Together
Lymphoid organs activate cells of immune system; lymphoid organs house cells such as dendritic cells, which play a crucial role in activating B and T cells; thymus is required for selection of a functional population of T cells Lymphatic system plays a greater role in adaptive immunity than in innate immunity, although lymphoid organs do house cells of innate immunity, such as macrophages © 2016 Pearson Education, Inc.

Module 20.3 Innate Immunity: Internal Defenses

Innate Immunity: Internal Defenses
Rapid response of innate immunity consists of two main components: a group of antimicrobial molecules, and several types of cells Cells of innate immunity – Pathogens that are able to bypass body’s surface barriers next meet second line of defense: cells and proteins of innate immunity; cells of innate immunity are divided into two broad types: phagocytic cells and nonphagocytic cells © 2016 Pearson Education, Inc.

Cells of Innate Immunity
Phagocytes – phagocytic cells include macrophages, neutrophils, and eosinophils; process by which cells ingest particles and other cells is called phagocytosis Certain granulocytes and agranulocytes can function as phagocytes Agranulocytes known as monocytes exit bloodstream and take up residence in various tissues where they develop into macrophages © 2016 Pearson Education, Inc.

Macrophages are activated by a variety of stimuli, including certain molecules present on pathogens, chemicals secreted by damaged cells, and signals from cells of adaptive immunity Activated local macrophages are generally first cells to respond to a cellular injury, where they ingest other cells and cellular debris Macrophages kill pathogens they have ingested with chemicals, including hydrogen peroxide and hypochlorous acid (active component in bleach) © 2016 Pearson Education, Inc.

Macrophages also have cytotoxic effects, meaning that they can secrete these substances onto pathogens that are too large to ingest Macrophages function as antigen-presenting cells, which are cells that display portions of pathogens (antigens) they ingest on their plasma membranes T cells become activated by these antigens and in turn secrete substances that increase activity of macrophages, in an example of a positive feedback loop © 2016 Pearson Education, Inc.

Neutrophils – most numerous granulocyte; highly effective phagocytes that kill their ingested pathogens with chemicals such as hydrogen peroxide, hypochlorous acid, and lysozyme Can ingest many types of cells, but are particularly effective at destroying bacterial pathogens Release cytotoxic contents of their granules onto large pathogens to damage their plasma membranes Generally reside in blood and must be recruited to damaged tissues by chemical signals © 2016 Pearson Education, Inc.

Eosinophils – phagocytes that can migrate from blood to tissues where they are needed Primarily involved in responses to parasitic pathogens Cover parasites and release contents of their granules Chemicals from granules damage parasite and either destroy it or make it easier for other immune cells to destroy © 2016 Pearson Education, Inc.

Other cells of innate immunity; nonphagocytic cells include NK cells, dendritic cells, and basophils: NK cells have the remarkable ability to recognize cancerous cells and cells infected with certain viruses in spite of fact they cannot recognize specific antigens Also cytotoxic, releasing substances that destroy their target cells. Secrete an antimicrobial cytokine that activates macrophages and enhances phagocytosis © 2016 Pearson Education, Inc.

Dendritic cells – function as antigen-presenting cells; substances they ingest are presented to T cells (and, to a lesser extent, B cells), which are then activated Basophils – rare granulocytes whose granules contain chemicals that mediate inflammation (inflammatory mediators) Located primarily in blood, although a related type of cell (mast cells) are located in mucous membranes Like regular basophils, mast cells contain granules with chemicals that trigger inflammation; particularly involved in allergic responses © 2016 Pearson Education, Inc.

Antimicrobial Proteins
In addition to these cell types, innate immune response is mediated by a variety of plasma antimicrobial proteins, including complement proteins and several types of cytokines (Figure 20.10): Complement – group of molecules collectively known as complement system consists of 20 or more plasma proteins that are produced primarily by liver (Figure ): Complement proteins are designated with a “C” and a number; play a critical role in both innate and adaptive immunity © 2016 Pearson Education, Inc.

Complement (continued): Circulate primarily in their inactive forms; must be activated by a complex cascade of events mediated by enzymes Two main series of enzymatic reactions, or pathways, activate complement proteins: classical and alternative pathways Classical pathway – begins when inactive complement proteins bind to antibodies bound to antigen Alternative pathway – begins when inactive complement proteins encounter foreign cells such as bacteria © 2016 Pearson Education, Inc.

Complement (continued): Two pathways converge at cleavage of an inactive complement protein called C3 into its active form C3b, which in turn cleaves inactive protein C5 into its active component C5b © 2016 Pearson Education, Inc.

Activated complement proteins lead to following main effects (Figure 20.10): Cell lysis – some complement proteins are able to lyse, or “pop”, plasma membranes of pathogens, leading to their destruction; mediated by C5b C5b binds to surface of a pathogen and provides a docking site for several other activated complement proteins; together these complement proteins form a structure collectively known as membrane attack complex, or MAC MAC inserts itself into plasma membrane of target cell, creating a pore that causes it to lyse © 2016 Pearson Education, Inc.

Enhanced inflammation – inflammatory response is a nonspecific response to cellular injury; several complement proteins enhance this response by triggering basophils and mast cells to release chemicals that mediate inflammation Neutralize viruses – C3b and components of membrane attack complex bind to certain viruses and neutralize them, or block them from infecting host cells © 2016 Pearson Education, Inc.

Enhancing phagocytosis – C3b acts as an opsonin by binding to pathogens; opsonization makes phagocytes bind more strongly to a pathogen and enhances phagocytosis Clearance of immune complexes: C3b binds to immune complexes (clusters of antigens bound to antibodies) and triggers their phagocytosis; clears complexes from circulation, which is critical to preventing these complexes from lodging in different tissues around body © 2016 Pearson Education, Inc.

Cytokines – proteins produced by several types of immune cells; enhance immune response in some way; several cytokines that are involved in innate immunity include the following: Tumor necrosis factor – cytokine secreted primarily by activated macrophages in response to certain bacteria and other pathogens; attracts phagocytes to area of infection, increases phagocytes activity, and stimulates phagocytes to release additional cytokines © 2016 Pearson Education, Inc.

Cytokines (continued): Interferons – cytokines produced by macrophages, dendritic cells, NK cells, and cells of adaptive immunity; produced in response to infection with intracellular agents such as viruses or intracellular bacteria; primary action is to inhibit viral replication inside host cells © 2016 Pearson Education, Inc.

Interleukins (29 cytokines known to date) – produced mainly by various leukocytes; stimulate production of neutrophils by bone marrow, stimulate NK cells, trigger production of interferons, and activate T cells Many cytokines (like TNF) induce “flu-like” symptoms; including fever, chills, and aches (aches are due to stimulation of inflammation) © 2016 Pearson Education, Inc.

The Inflammatory Response
Inflammatory response – innate response that occurs when a cell is damaged by anything, including trauma, bacterial or viral invasion, toxins, heat, or chemicals; two basic stages to inflammatory response (Figures , 20.12): Damaged cells release inflammatory mediators that cause local changes in damaged tissue Phagocytes arrive at area and clean up damaged tissue © 2016 Pearson Education, Inc.

Part 1: Release of inflammatory mediators and cardinal signs of inflammation (Figure 20.11): Tissue damage initiates inflammatory response as damaged cells and local mast cells release inflammatory mediators Inflammatory mediators can include histamine, serotonin, cytokines, bradykinin, prostaglandins, and leukotrienes Activated complement proteins trigger release of inflammatory mediators from cells such as basophils and mast cells, and act as inflammatory mediators themselves Injured area becomes red and swollen, feels warm to touch, and hurts © 2016 Pearson Education, Inc.

Cardinal signs of inflammation include four signs (redness, heat, swelling (edema), and pain) (Figure ): Vasodilation – occurs due to inflammatory mediators such as histamine and bradykinin Relax smooth muscle in arterioles supplying damaged tissue; allows blood to flow through vessels more freely to injured tissues, and area becomes congested with blood (hyperemia) Accounts for redness and heat accompanying inflammation as blood is warmer than surface body temperature © 2016 Pearson Education, Inc.

Increased capillary permeability – occurs as inflammatory mediators increase “leakiness” of local capillary beds Allows protein-rich fluid to leak from blood vessels into tissue spaces; leads to cardinal sign of swelling Proteins in fluid include clotting proteins such as fibrinogen, complement proteins, and proteins needed for tissue repair © 2016 Pearson Education, Inc.

Occurrence of pain – several inflammatory mediators, particularly bradykinin and prostaglandins, trigger action potentials in peripheral processes of sensory neurons, which leads to pain; serves numerous protective functions: Lets us know when our tissues are being damaged to avoid further damage Causes a temporary loss of function; both of which allows body to begin to repair damage. Recruitment of other cells – inflammatory mediators recruit leukocytes to damaged tissue (chemotaxis) particularly macrophages and neutrophils while complement proteins are simultaneously being activated © 2016 Pearson Education, Inc.

Part 2: Phagocyte response – arrival and activation of phagocytes is divided into stages that are based on which phagocytes enter area and processes occurring there (Figure 20.12): Local macrophages (“first responders”) are activated within minutes of cellular injury; enlarge and begin to phagocytize pathogens and damaged cells; only phagocytes present within first hour or so of inflammatory response; perform critical function of containing invading pathogens © 2016 Pearson Education, Inc.

Neutrophils migrate (chemotaxis) to damaged tissue and phagocytize bacteria and cellular debris Inflammatory mediators and activated complement proteins attract neutrophils and enable them to leave blood and enter tissue; make capillary endothelium in damaged area “sticky”, and neutrophils adhere to capillary wall (process called margination) © 2016 Pearson Education, Inc.

Inflammatory mediators increase capillary permeability; provides space between endothelial cells for neutrophils to squeeze through into damaged tissue (known as diapedesis); destroy bacteria and other cellular debris Bone marrow releases stored neutrophils into blood; leads to a rapid rise in level of circulating neutrophils © 2016 Pearson Education, Inc.

Monocytes migrate to tissue (chemotaxis) and become macrophages; phagocytize pathogens and cellular debris Bone marrow increases production of leukocytes, leading to leukocytosis; cytokines produced by activated phagocytes act on cells in bone marrow to increase production of neutrophils and monocytes over next 3–4 days Leads to an elevated number of circulating leukocytes, a condition called leukocytosis; commonly referred to as a “high white cell count” © 2016 Pearson Education, Inc.

Elevated numbers of leukocytes allow damaged area to be cleared and any pathogens removed so that cells such as fibroblasts can begin process of healing Accumulation of dead leukocytes, dead tissue cells, and fluid leads to a whitish mixture known as pus (a wound filled with pus is called purulent) © 2016 Pearson Education, Inc.

Anti-inflammatory Medications
Pain is one of more unpleasant effects of inflammatory response; fortunately, many medications have been developed to reduce inflammation and accompanying pain by blocking production of prostaglandins Prostaglandins and related leukotrienes are derived from a fatty acid called arachidonic acid that is present in nearly all cell membranes; when cell is damaged or triggered in some other way, enzyme phospholipase A2 catalyzes a reaction that cleaves arachidonic acid © 2016 Pearson Education, Inc.

Products of this reaction may be acted on by two broad classes of enzymes: cyclooxygenases, which produce prostaglandins, and lipooxygenases which produce leukotrienes First, and largest, group of medications consists of nonsteroidal anti-inflammatories (NSAIDs); work by inhibiting cyclooxygenase enzyme and preventing formation of prostaglandins; example of a common medication available over counter is ibuprofen © 2016 Pearson Education, Inc.

Corticosteroids make up a second group of medications Mimic actions of hormone cortisol; inhibits formation of both prostaglandins and leukotrienes; leads to a wider- ranging and more potent anti-inflammatory effect Generally used for conditions with more severe inflammation or inflammation due primarily to leukotrienes (such as allergy-related inflammation) Examples of common corticosteroids include cortisone and prednisone © 2016 Pearson Education, Inc.

Fever Fever is defined simply as a body temperature above normal range, which is generally between 36 and 38° C (or 97–99° F) An individual with a fever is referred to as febrile From a clinical perspective, fever is a critical warning sign of inflammatory processes occurring somewhere in body © 2016 Pearson Education, Inc.

Fever Fever is an innate response to cellular injury; initiated when chemicals called pyrogens are released from damaged cells or certain bacteria Pyrogens act on hypothalamus; regulates many aspects of homeostasis Hypothalamus normally functions as body’s thermostat; maintains body temperature within normal range through a series of negative feedback loops; example of Feedback Loops Core Principle © 2016 Pearson Education, Inc.

Fever Pyrogens cause hypothalamic thermostat to reset to a higher range Hypothalamus interprets normal body temperature as being too low, which triggers negative feedback loop; elicits sensation of cold, or having “chills,” when a fever occurs Hypothalamus triggers responses that elevate body temperature to new, higher range; includes familiar sign of shivering; increased muscle activity that generates heat to bring body temperature to new set point © 2016 Pearson Education, Inc.

Fever Fevers may be alleviated, or “break”; results from hypothalamus being reset to normal temperature range; causes hypothalamus to sense febrile temperature as being too high; triggers negative feedback mechanisms to lower body’s temperature Mechanisms include sweating and dilation of blood vessels serving skin, which makes skin appear red or flushed © 2016 Pearson Education, Inc.

Module 20.4 Adaptive Immunity: Cell-Mediated Immunity

Introduction to Adaptive Immunity
Cell-mediated immunity is first arm of adaptive immune system Cell-mediated immunity involves different classes of T cells, including: helper T (TH) cells, or CD4 cells, and cytotoxic T (TC) cells, or CD8 cells (Note that “CD” stands for cluster of differentiation) These cells respond primarily to cells infected with intracellular pathogens (viruses and intracellular bacteria), cancer cells, and foreign cells such as those from a transplanted organ © 2016 Pearson Education, Inc.

T Cell Response to Antigen Exposure
T cells are formed in bone marrow, but they leave bone marrow and migrate to thymus to mature (Figures 20.13– 20.17): T cells undergo gene rearrangements that lead to a huge variety of genetically distinct T cells Each population of T cells that can respond to a specific antigen is known as a clone There are millions of different clones in immune system, but only a few cells of each clone exist in body at any given time © 2016 Pearson Education, Inc.

Some T cell clones are capable of recognizing and responding to pathogens, whereas others are not; thymus “screens” these cells and mediates destruction of those clones that cannot recognize antigens Thymus ensures that an individual is immunocompetent, or able to mount a normal response to foreign antigens © 2016 Pearson Education, Inc.

Other T cell clones, known as self-reactive T cells, recognize your own cells as foreign and would attack your cells if released into circulation Self-reactive T cells are destroyed, ensuring self tolerance; prevents T cells from attacking self cells T cells that survive thymus screening are released into circulation when they mature; known as naïve T cells because they have not yet encountered their specific antigens © 2016 Pearson Education, Inc.

Only certain antigens, called immunogens, are capable of generating a response from immune system Antigens present on your own cells, called self antigens, are not immunogens in your body Haptens are very small antigens that are immunogenic only if they are attached to a protein carrier T cell receptors are found on surface of every T cell; receptor must bind a specific antigen before cell can become activated Unique portion of antigen to which receptor binds is known as its antigenic determinant © 2016 Pearson Education, Inc.

T cells can only interact with pieces of antigen bound to glycoproteins called major histocompatibility complex (MHC) molecules (Figure 20.14): Name comes from fact that MHC molecules are major determinants of compatibility among tissue and organ donors and recipients MHC molecules are found on nearly all nucleated cells except erythrocytes; make blood products considerably easier to donate than other organs and tissues MHC molecules serve as “docking sites” for specific components of antigens that are then displayed to T cells © 2016 Pearson Education, Inc.

There are two types of MHC molecules: Class I MHC molecules – found on surface of plasma membrane on nearly all nucleated cells Present endogenous antigens, or those synthesized inside cell Cytotoxic T (TC) cells generally interact only with class I MHC molecules Class II MHC molecules are found only on surfaces of antigen-presenting cells Helper T (TH) cells generally interact with class II MHC molecules Class II MHC molecules present exogenous antigens, or those cell takes in by phagocytosis © 2016 Pearson Education, Inc.

Exogenous antigens originate outside cell and must be taken into cell by phagocytosis; endogenous antigens are those that originate inside cell An endogenous antigen is either a foreign antigen present on a pathogen that lives inside your cell, such as an intracellular bacterium, or a foreign or self antigen encoded by your DNA; includes normal self antigens, foreign cancer antigens made by mutated DNA, and foreign viral antigens (when a virus infects cell, it inserts its genetic material into DNA and triggers synthesis of its proteins, including antigens) © 2016 Pearson Education, Inc.

Concept Boost: Why Do We Need Both Class I and Class II MHC Molecules?
Answer lies in differing functions of TH and TC cells; as you’ve discovered, TH cells are activated by antigen- presenting cells (APCs) bearing portions of antigen on their class II MHC molecules, as shown here: APCs are not diseased themselves; rather, they function as a warning system that alerts TH cells to a problem somewhere in body; TH cells then stimulate other parts of innate and adaptive defenses to combat threat © 2016 Pearson Education, Inc.

Concept Boost: Why Do We Need Both Class I and Class II MHC Molecules?
Compare this to what happens with a TC cell; TC cell is activated by a diseased cell bearing an antigen on a class I MHC molecule, as shown here: When this occurs, activated TC cell lyses (kills) diseased cell, which is its target If TC cells were also able to bind and recognize class II MHC molecules, they would end up killing APCs, not diseased cells, which would be detrimental to immune function and whole body © 2016 Pearson Education, Inc.

Basic steps by which a class I MHC molecule processes and displays an endogenous antigen are (Figure 20.14a): Cell synthesizes either a self antigen or a foreign antigen; note that some foreign endogenous antigens are not synthesized by cell, such as those from intracellular bacteria Antigen is broken down by enzymes in cytosol An antigen fragment containing antigenic determinant is transported into rough endoplasmic reticulum (RER); coupled with a class I MHC molecule in RER membrane MHC-antigen complex leaves RER by a vesicle and is inserted into cell’s plasma membrane © 2016 Pearson Education, Inc.

Basic steps of how exogenous antigens are displayed by class II MHC molecules are (Figure 20.14b): Cell phagocytoses a pathogen Phagocytic vesicle fuses with a lysosome; pathogen is degraded and its antigens are fragmented Lysosome fuses with a vesicle from RER that contains class II MHC molecules, and an antigen fragment binds to MHC molecule MHC-antigen complex is inserted into cell’s plasma membrane © 2016 Pearson Education, Inc.

Both processes end up with same result: portions of antigens displayed on plasma membrane attached to MHC molecules; these MHC-antigen complexes then interact with and activate T cells © 2016 Pearson Education, Inc.

T cell activation consists of following steps (Figure 20.15): Cells display antigen fragments on their MHC molecules, and MHC-antigen complex binds to receptor of a specific TH or TC cell clone Process of T cell activation begins with a cell processing and displaying antigen fragments on its MHC molecules; then presents antigen to a particular T cell clone, which is specific for its individual MHC-antigen complex When T cell receptor recognizes and binds this complex, multiple changes are triggered inside T cell and process of activation begins; known as clonal selection © 2016 Pearson Education, Inc.

TH or TC cell binds a co-stimulator and becomes activated Full T cell activation requires interaction of T cell with other molecules on antigen-presenting cells called co-stimulators T cell receptors normally have low affinity for their MHC- antigen complexes; protective mechanism that prevents unnecessary T cell activation © 2016 Pearson Education, Inc.

Activated TH or TC cell clone proliferates and differentiates into effector cells (those that cause immediate effects) and memory T cells (responsible for cell-mediated immunological memory) Memory cells respond more quickly and efficiently to subsequent exposures to an antigen; do not need a co- stimulator © 2016 Pearson Education, Inc.

Effects of T Cells TH and TC cells have very different roles, although they do interact and depend on one another to function properly (Figures 20.16, 20.17): Role of TH cells – helper T cells have no phagocytic or cytotoxic abilities; TH cells exert their effects through secretion of cytokines that activate and enhance various components of immune response In this way, they “help” immune response, hence their common name © 2016 Pearson Education, Inc.

Effects of T Cells TH cells are required for normal function of all components of immune system, including innate, antibody-mediated, and cell-mediated immunity; some of main functions of TH cells include: Innate immunity: stimulation of macrophages TH cells secrete cytokine interleukin-3, which stimulates macrophages to become more efficient phagocytes Also causes macrophages to produce interleukin-12, which stimulates TH cells to generate more interleukin-3 in a positive example of Feedback Loops Core Principle © 2016 Pearson Education, Inc.

Effects of T Cells Figure 20.16 Effects of TH cells.

Effects of T Cells Adaptive cell-mediated immunity: activation of TC cells TH cells secrete cytokine interleukin-2 (IL-2); required to activate TC cells In absence of TH cells and IL-2, most TC cells fail to activate and become unresponsive to antigen Figure Effects of TH cells. © 2016 Pearson Education, Inc.

Effects of T Cells Adaptive antibody-mediated immunity: stimulation of B cells TH cells directly bind to B cells and stimulate them to proliferate and differentiate Also secrete various interleukins that stimulate B cell proliferation and increase antibody production Figure Effects of TH cells. © 2016 Pearson Education, Inc.

Effects of T Cells Figure 20.16 Effects of TH cells.

Effects of T Cells Role of TC cells – primary function of cytotoxic T cells is to kill other cells, specifically those with foreign antigens bound to class I MHC molecules (Figure 20.17): Can detect abnormalities in any cell type with a nucleus; critical for detection of cancer cells, foreign cells, and cells infected with intracellular pathogens such as viruses and bacteria Activated in same way as TH cells, with addition that they require IL-2 from TH cells in order to activate fully; protective mechanism prevents abnormal TC cell activation © 2016 Pearson Education, Inc.

Effects of T Cells An activated TC cell binds its target cell, after which it releases a protein called perforin Perforin forms pores in, or perforates, target cell’s plasma membrane; TC cell then releases enzymes that can now enter target cell’s cytosol These enzymes catalyze reactions that degrade target cell proteins and eventually lead to fragmentation of target cell’s DNA and its death © 2016 Pearson Education, Inc.

Effects of T Cells TC cells also bind to proteins on plasma membrane of target cells; induce process of apoptosis (programmed cell death) When target cell begins to degrade, TC cell detaches and searches for a new target cell © 2016 Pearson Education, Inc.

Effects of T Cells Figure 20.17 Function of TC cells.

Organ and Tissue Transplantation and Rejection
Four basic kinds of tissue and organ transplants (grafts): Autografts – involve tissue transplanted from one site to another in same individual Examples of autografts include skin grafts, in which skin is removed from one part of body and placed on another part to repair skin damaged by trauma such as burns Autografts result in no response from TC cells because antigens bound to class I MHC molecules are not recognized as foreign © 2016 Pearson Education, Inc.

Isografts – involve organs and tissues transplanted between two genetically identical individuals; like autografts these result in no response from TC cells because antigens bound to class I MHC molecules are not recognized as foreign Allografts – most common type of grafts; involve organs and tissues transplanted between two nonidentical individuals of same species © 2016 Pearson Education, Inc.

Both allografts and xenografts contain antigens that organ recipient’s immune system recognizes as foreign; leads to a reaction from immune system that, if left untreated, results in rejection of organ or tissue A rejected organ or tissue first fails to function properly, and then its cells die as TC cells destroy them, a condition known as necrosis Rejection can lead to death of transplant recipient from organ failure and from blood clots and other complications of necrotic tissue © 2016 Pearson Education, Inc.

Graft rejection is something that must be prevented; done in two ways: Ensuring that allograft antigens are as similar as possible to recipient’s antigens; determined through a process that screens antigens most likely to cause rejection—those associated with MHC molecules, which are encoded on genes called human leukocyte antigen (HLA) genes Suppressing immune response with medications; known as immunosuppressive therapy © 2016 Pearson Education, Inc.

Module 20.5 Adaptive Immunity: Antibody-Mediated Immunity

Introduction Antibody-mediated immunity involves B cells and proteins secreted by B cells, called antibodies B cells have B cell receptors that bind to specific antigens A group of B cells that bind to a specific antigen is known as a clone Antibodies secreted by a B cell clone bind to same antigen as B cell receptor © 2016 Pearson Education, Inc.

Introduction Antibody-mediated immune responses have three basic phases: First phase – B cell clone recognizes its specific antigen; triggers it to change and secrete antibodies Second phase – begins when antibody level in blood rises dramatically; antibodies (immunoglobulins or gamma globulins) are directly responsible for actions that lead to destruction of antigens to which they bind Third phase – persistence of a population of B cells called memory B cells; react much more rapidly and efficiently if antigen is encountered again © 2016 Pearson Education, Inc.

B Cell Activation, Clonal Selection, and Differentiation
First phase of antibody immune response (Figures 20.18, ): B cells develop and mature within bone marrow from lymphoid cell line; billions of B cells are produced each day (Figure ): Only about 10% of these cells finish their maturation process because B cell clones that recognize self antigens (self-reactive B cells) are destroyed Prevents development of autoimmunity, in which B cells recognize self antigens as foreign and produce autoantibodies that bind self antigens © 2016 Pearson Education, Inc.

B cell clones that complete maturation enter circulation and eventually take up residence in lymphoid organs such as spleen and lymph nodes When antigens enter body, they are captured in these lymphoid organs B cells that are not exposed to their specific antigens within a few days to a few weeks die © 2016 Pearson Education, Inc.

Naïve B cells that do encounter their antigens become activated by following process (Figure ): B cell clone binds its antigen and is activated; clonal selection is process when an antigen binds to a B cell receptor on surface of a specific B cell clone (said to be sensitized) © 2016 Pearson Education, Inc.

Naïve B (continued): Sensitized B cell processes antigen and presents it on its class II MHC molecules; B cell then binds to a TH cell to become fully activated; starts a series of events inside cell that triggers transcription of antibody genes and multiple other changes that activate B cell Two cells interacting and influencing one another is an example of Cell-Cell Communication Core Principle © 2016 Pearson Education, Inc.

B cell divides repeatedly; resulting cells differentiate into: Plasma cells – secrete antibodies Memory B cells – long-lived cells that do not secrete antibodies but will respond to antigens upon a second exposure Dendritic cells and other APCs continue to expose plasma cells and other B cells to antigen, and in response they keep proliferating, differentiating, and actively secreting antibodies © 2016 Pearson Education, Inc.

Antibodies and Their Effects
Second phase of antibody-mediated immune response involves antibodies and their effects Study of antibodies is called serology, which examines structure and functions of antibodies as well as their applications to medicine and research (Figures 20.20–20.22) © 2016 Pearson Education, Inc.

Structural features and classes of antibodies (Figures 20.20, 20.21): Basic subunit of an antibody is a Y-shaped molecule formed from four peptide chains, two heavy (H) and two light (L) chains Each of these chains has two types of regions: Constant (C) region – relatively similar among antibody classes; responsible for many of antibodies’ effects Variable (V) region – unique sequence of amino acids responsible for antigen recognition and binding © 2016 Pearson Education, Inc.

An antibody has V regions at tips of two arms of molecule, so basic subunit of an antibody has two antigen-binding sites, one on each arm A single antibody subunit is a monomer that can be combined with other subunits to form larger structures such as a dimer (two subunits), or a pentamer (five subunits) © 2016 Pearson Education, Inc.

There are five basic classes of antibody; grouped according to structure of their C regions (Figure 20.22) Each antibody is named with two-letter abbreviation “Ig,” which stands for “immunoglobulin,” followed by a letter that designates its class This gives us types IgG, IgA, IgM, IgE, and IgD; remember with mnemonic GAMED: IgG – most prevalent antibody in body; consists of a single subunit; only antibody able to cross from blood of a pregnant woman to her developing fetus through a structure called placenta © 2016 Pearson Education, Inc.

IgA – usually a dimer, consisting of two Y-shaped subunits; gives this antibody four antigen-binding sites; present in secretions from skin, mucous membranes, and exocrine glands (i.e., tears, saliva, sweat, and breast milk) IgM – largest antibody; pentamer, which consists of five subunits in a starlike arrangement, for a total of 10 antigen- binding sites; generally first antibody secreted by plasma cells when body is invaded by a pathogen; also exists as a single subunit embedded in B cell plasma membrane, where it functions as a B cell receptor © 2016 Pearson Education, Inc.

IgE – single-subunit antibody; generally present in very low amounts in body’s fluids Binds to two types of antigen: antigens associated with parasitic pathogens such as tapeworms, and environmental antigens known as allergens, which are linked with inflammatory reactions (allergies) Bind to mast cells in mucous membranes, and when they come into contact with their specific antigens, trigger mast cells to release contents of their granules (degranulation) Mast cell granules contain inflammatory mediators such as histamine; initiate a localized inflammatory response; responsible for common allergy symptoms such as a runny nose and watery eyes © 2016 Pearson Education, Inc.

IgD – unique because it is only antibody not secreted by B cells in significant amounts; its single subunit is located on surface of B cells, where it acts as an antigen receptor that helps activate B cells in a similar manner to IgM Antibodies in a particular class feature similar C regions, but each antibody has a unique V region that determines its ability to recognize and bind a certain antigen © 2016 Pearson Education, Inc.

Functions of secreted antibodies – actions of antibodies are based on their ability to bind antigens, which leads to multiple effects on pathogens; basic effects of secreted antibodies include (Figure 20.21): Agglutination and precipitation Antibodies can bind to antigens on more than one cell; creates a clump of cells that are cross-linked by their attachment to antibodies; known as agglutination Precipitation – similar to agglutination; involves soluble antigens (proteins and other biological molecules) instead of whole cells © 2016 Pearson Education, Inc.

Both agglutination and precipitation decrease solubility of antigen-antibody complexes; make it easier for phagocytes to ingest complex IgM is most potent agglutinating and precipitating antibody due to its 10 antigen-binding sites Opsonization – involves molecules such as complement and IgG antibodies; able to coat pathogens and bind and activate phagocytes, which greatly enhances phagocytosis © 2016 Pearson Education, Inc.

Neutralization – antibodies bind to harmful bacterial toxins, viral proteins, and animal venoms to prevent them from interacting with our cells; most neutralizing antibodies are either IgG or IgA Complement activation – IgM and IgG bind to and activate complement proteins of innate immunity; particularly important in defense against cellular pathogens such as bacteria; partly responsible for our reaction to foreign cells like donated erythrocytes © 2016 Pearson Education, Inc.

Stimulation of inflammation – IgE directly triggers inflammation by initiating release of inflammatory mediators from mast cells and basophils; antibodies also trigger inflammation indirectly through their activation of complement Most antibodies don’t directly “kill” pathogens; either render pathogens less harmful or facilitate their destruction by phagocytes or complement © 2016 Pearson Education, Inc.

Immunological Memory Memory B cells are responsible for antibody-mediated immunological memory, which allows B cells to respond more efficiently when antigen is encountered a second time; phase three of immune response (Figure 20.23, Table 20.1) © 2016 Pearson Education, Inc.

Immunological Memory Upon first exposure to an antigen, a B cell clone specific for that antigen recognizes it, proliferates, and differentiates into plasma and memory B cells, and plasma cells begin to secrete antibodies; response is called primary immune response (Table 20.1): Effective, but slow—there is an initial 4- to 5-day lag phase as the B cells proliferate, differentiate into plasma cells and memory cells, and begin to secrete antibodies Antibody levels peak about 7–14 days after antigen is encountered; it is during lag phase that you generally feel “sick” © 2016 Pearson Education, Inc.

Immunological Memory Future exposure to same antigen results in activation of memory B cell formed during primary immune response When these memory B cells encounter antigen for which they are specific, secondary immune response begins; lasts longer than primary response Has a shorter lag phase (about 1–3 days), and its antibody levels peak more rapidly (3–5 days) and reach a peak 100–1000 times larger © 2016 Pearson Education, Inc.

Immunological Memory Major antibody involved in secondary response is IgG, whereas it’s IgM in primary response Antibodies secreted in secondary immune response are more effective—they bind more tightly (have a higher affinity for their antigens) Key differences between two responses are summarized in Table 20.1 © 2016 Pearson Education, Inc.

Immunological Memory A vaccination, also known as an immunization, involves exposing an individual to an antigen to elicit a primary immune response and generate memory cells Then if individual is exposed to antigen a second time, a secondary immune response will occur and symptoms will be minimal © 2016 Pearson Education, Inc.

Immunological Memory Subunit vaccines – with certain pathogens, only a portion of pathogen that causes disease is required to develop immunity For example, bacteria responsible for tetanus and diphtheria secrete disease-causing toxins Vaccinations called toxoids contain inactivated toxins from these bacteria; induce immune system to produce antibodies to toxins © 2016 Pearson Education, Inc.

Immunological Memory There are two types of antibody-mediated immunity; active and passive (Figure 20.23) Active immunity So named because body’s cells actively respond to an antigen, may be received naturally through exposure to an antigen via infection or via a vaccination Results in production of memory cells and large numbers of antibodies and is, therefore, relatively long-lasting, ranging from years to a lifetime Length of time during which active immunity lasts depends on several factors, particularly extent of exposure © 2016 Pearson Education, Inc.

Immunological Memory Passive immunity
Occurs when preformed antibodies are passed from one organism to another; may be naturally acquired as when IgG of a pregnant woman crosses from her blood into that of her fetus, or artificially acquired, from an injection with preformed antibodies Lasts only amount of time that antibodies stay in bloodstream, which is about three months on average © 2016 Pearson Education, Inc.

The Myth of Vaccines and Autism
If you do an Internet search for “vaccines and autism” you will receive hundreds of thousands of hits, many of which claim that vaccines cause autism (a developmental disorder) Concern about a possible link between vaccinations and autism arose when it was noticed that many children first started showing symptoms of autism around time of childhood vaccinations; thought was that perhaps thimerosal, a mercury-containing preservative found in most vaccines, was culprit (certain forms of mercury are known to cause brain damage) © 2016 Pearson Education, Inc.

One major problem with this hypothesis: form of mercury that causes brain damage is methylmercury, but thimerosal contains ethylmercury Nonetheless, independent researchers across globe have examined thimerosal, but no link between thimerosal and autism has ever been found Thimerosal was removed from vaccines in Denmark in 1992, and autism rate actually increased by a small amount; although no evidence supports idea that thimerosal is harmful, United States removed thimerosal from most vaccines in 2001 as a result of public concerns © 2016 Pearson Education, Inc.

Researchers have also explored other potential links between vaccinations and autism, but results have been same: No link can be established Unfortunately, many people continue to staunchly advocate that vaccines are root cause of autism, even with an absolute lack of evidence Concern among well-meaning parents led to a decline in number of individuals who receive vaccinations; consequence of decreased vaccination rates is an increase in number of cases of potentially lethal diseases, such as measles, whooping cough, and meningitis; raises serious public health concerns © 2016 Pearson Education, Inc.

The Big Picture of the Immune Response to the Common Cold
Figure The Big Picture of the Immune Response to the Common Cold. © 2016 Pearson Education, Inc.

The Big Picture of the Immune Response to a Bacterial Infection
Figure The Big Picture of the Immune Response to a Bacterial Infection. © 2016 Pearson Education, Inc.

The Big Picture of the Immune Response to Cancer Cells
Figure The Big Picture of the Immune Response to Cancer Cells. © 2016 Pearson Education, Inc.

Complete Blood Count with Differential
One of first laboratory tests ordered when a patient is admitted to hospital is a complete blood count (CBC); component of CBC is leukocyte count, which can indicate if inflammation is present somewhere in body Unfortunately, inflammation is nonspecific and an elevated leukocyte count tells little about cause of inflammation For this reason, a differential, which measures relative prevalence of different types of leukocytes in blood, is ordered along with CBC © 2016 Pearson Education, Inc.

Complete Blood Count with Differential
A differential can give a great deal of information: If infection is caused by bacteria, neutrophils tend to be selectively elevated because of their extensive role in eradication of bacteria Viral pathogens tend to induce primarily a lymphocyte- dominant response, so numbers of lymphocytes in blood would likely be elevated with a viral infection Finally, inflammation due to parasites or allergies usually causes an elevated level of eosinophils in blood © 2016 Pearson Education, Inc.

Module 20.7 Disorders of the Immune System

Introduction Disorders of immune system take three forms:
Hypersensitivity disorders cause immune system to overreact, which can damage tissues Immunodeficiency disorders occur when one or more components of immune system fail Immune system may treat self antigens as foreign and attack body’s own tissues in an autoimmune disorder © 2016 Pearson Education, Inc.

Hypersensitivity Disorders
Hypersensitivity disorders include those disorders in which immune system’s response causes tissue damage; four types of hypersensitivity disorders (numbered I–IV) are classified according to exact immune components causing hypersensitivity (Figure 20.27) © 2016 Pearson Education, Inc.

Type I: Immediate hypersensitivity – most common type; known commonly as allergies and accompanying disorders as allergic disorders (Figure 20.27): Occur when an individual reacts to a foreign antigen, (an allergen); includes pollen, dust mites, pet dander, peanuts, shellfish, and bee venom First exposure to an allergen – allergen binds a B cell which triggers B cell differentiation into plasma cells that secrete antibodies © 2016 Pearson Education, Inc.

Plasma cells secrete IgE instead of IgG or IgM – first exposure generates a primary immune response, which results in formation of IgE molecules that bind to mast cells and basophils; considered to be sensitized Subsequent exposures to identical allergens in a sensitized individual result in a rapid response (occurs within a few minutes) This rapid response occurs when allergens bind to IgE molecules on sensitized mast cells or basophils forming cross-links © 2016 Pearson Education, Inc.

Cross-links cause cells to release inflammatory mediators (degranulation): histamine, leukotrienes, and prostaglandins These molecules trigger vasodilation, increased capillary permeability, and smooth muscle spasm; lead to symptoms of variable severity Local reactions, such as those in nasal cavity, produce common symptoms of runny nose and itchy eyes © 2016 Pearson Education, Inc.

Allergen exposure may also result in a skin rash; small areas of skin appear red and elevated, known as hives, or urticaria More potent reactions occur in patients with asthma (allergic respiratory disease), in which allergen exposure severely limits ability to breathe by triggering inflammation, smooth muscle spasm, and excess mucus secretion in respiratory passages © 2016 Pearson Education, Inc.

Anaphylactic shock – most dramatic immediate hypersensitivity reaction; involves a systemic release of histamine and other inflammatory mediators; mediators are responsible for life-threatening events: Severe spasm of smooth muscle of respiratory tract Systemic vasodilation, which causes blood pressure to drop and decreases blood flow to all organs, including brain Increased capillary permeability in all of body’s capillaries; further lowers blood pressure and causes body-wide swelling as there is a massive loss of fluid to tissue spaces and lungs © 2016 Pearson Education, Inc.

Anaphylactic shock is easily fatal if not treated immediately; generally consists of an injection of epinephrine, which causes relaxation of smooth muscle of airways and systemic vasoconstriction Patients with a known risk for anaphylactic shock should carry an epinephrine “pen” with them that allows self- administration of epinephrine in case of exposure to allergen and other inflammatory mediators © 2016 Pearson Education, Inc.

Treatments for Allergies
Given enormous number of people who suffer from allergic disorders, market for medications that treat allergies is huge; most medications available over counter are antihistamines (medications that block cells’ receptors for histamine); prevents pro-inflammatory effects of histamine molecules and limits symptoms experienced by allergy sufferers Unfortunately, histamine is also involved in a variety of other processes, both as a hormone and as a neurotransmitter © 2016 Pearson Education, Inc.

Leads to most common side effect: drowsiness; some are so sedating they are used more as sleep aids than as allergy treatments; newer antihistamines have been modified so they are less able to cross blood-brain barrier, and are therefore somewhat less sedating Other classes of anti-allergy medications and treatments include: Antileukotriene agents block enzyme that produces leukotrienes; inhibits many aspects of allergic inflammatory response © 2016 Pearson Education, Inc.

Corticosteroids block synthesis of leukotrienes and prostaglandins; potent inhibitors of allergic inflammation; commonly used for related allergic disorders such as asthma Allergen immunotherapy, commonly known as “allergy shots”, involves administration of allergen in increasing doses, with aim of inducing tolerance to allergen and a diminished IgE response © 2016 Pearson Education, Inc.

Type II: Antibody-mediated hypersensitivity – antibodies produced by immune response to foreign antigens also bind to self antigens These reactions occur when foreign antigens bind to normal self antigens, when donor erythrocytes infused into another individual are mismatched using the ABO/Rh antigen groups, or when self- reactive B cells are not destroyed in bone marrow, which leads to autoimmunity © 2016 Pearson Education, Inc.

Type II: Antibody-mediated hypersensitivity (continued): First possibility occurs in a reaction caused by penicillin, which can bind to erythrocytes in certain individuals; alters erythrocyte antigens and causes them to be recognized as foreign; activated B cells secrete antibodies that lead to complement activation and complement-mediated lysis of erythrocytes © 2016 Pearson Education, Inc.

Type III: Immune complex–mediated hypersensitivity reactions are mediated by immune complexes or clusters of soluble antigens (those not attached to cell surface) bound to antibodies Immune complexes are generally cleared by phagocytes, but some are difficult for macrophages to ingest and become deposited in various places in body, including capillary beds in kidneys, blood vessel walls, synovial membrane of joints, and choroid plexus in brain © 2016 Pearson Education, Inc.

Type III: Immune complex–mediated hypersensitivity (continued): Once deposited in these organs and tissues, unphagocytized immune complexes initiate an inflammatory reaction, which attracts neutrophils and causes damage to affected tissues © 2016 Pearson Education, Inc.

Type IV: Delayed-type hypersensitivity (DTH) is unique in that it is mediated by T cells rather than antibodies TH cells recognize antigens bound to MHC molecules as foreign and mediate their destruction by activating and recruiting macrophages and in some cases TC cells Reaction generally takes 2–3 days to manifest, hence its name; TH cells must be sensitized by an initial exposure, and reaction occurs with subsequent exposures © 2016 Pearson Education, Inc.

Contact dermatitis is a common DTH reaction in which skin comes into contact with an allergen such as oils in poison ivy or poison oak, certain metals, or other chemicals that form complexes with skin proteins; result in a rash that is itchy and occasionally painful Other forms of DTH are caused by intracellular pathogens that are not easily cleared by immune response; one such pathogen is bacterium Mycobacterium tuberculosis; causes respiratory infection tuberculosis © 2016 Pearson Education, Inc.

The Tuberculin Skin Test
We can take advantage of DTH reaction to determine whether a person has been exposed to bacterium that causes tuberculosis Mantoux test, also known as PPD test (for purified protein derivative), involves injection of a small amount of a protein derived from cell wall of Mycobacterium tuberculosis bacterium just underneath skin © 2016 Pearson Education, Inc.

The Tuberculin Skin Test
Mantoux test (continued): If individual has been exposed to tuberculosis, he or she will have sensitized T cells and will mount a DTH response; leads to an area of induration—a hard, swollen area caused by infiltration of macrophages and subsequent cellular destruction A person who has not been previously exposed to tuberculosis antigens will have no area of induration because he or she will lack sensitized T cells © 2016 Pearson Education, Inc.

Immunodeficiency Disorders
Immunodeficiency disorders are caused by a decrease in function of one or more components of immune system; there are two basic types of immunodeficiency disorders: Primary immunodeficiencies – genetic or developmental in nature Secondary immunodeficiencies – acquired through infection, trauma, cancer, or certain medications (Figure 20.28) © 2016 Pearson Education, Inc.

Primary immunodeficiency disorders may impair either innate or adaptive immunity; most common dysfunctions of innate immunity involve deficient complement proteins or abnormalities in phagocytes Individuals with defective phagocytes and complement proteins are at much higher risk for bacterial infections and parasitic infections Common dysfunctions of adaptive immunity include hypogammaglobulinemias; characterized by a decrease in one or more types of antibodies © 2016 Pearson Education, Inc.

Another common form of primary immunodeficiency involving adaptive immunity is a cluster of disorders referred to as severe combined immunodeficiency, or SCID Different forms of SCID are caused by failures of lymphoid cell lines in bone marrow; affect B cells, NK cells, and T cells to varying degrees Share common features, including low circulating levels of lymphocytes, failure of thymus to develop, and failure of cell-mediated immunity © 2016 Pearson Education, Inc.

Secondary immunodeficiency disorders – have multiple forms, many of which are induced artificially to combat cancers originating in bone marrow or to prevent transplant rejection (Figure 20.28): Cancers of immune cells and lymphoid organs that depress immune response in some way also cause secondary immunodeficiency Most common cause of secondary immunodeficiency by far is virally induced disease acquired immunodeficiency syndrome, or AIDS © 2016 Pearson Education, Inc.

AIDS is caused by human immunodeficiency virus 1 (HIV-1); spread through contact with infected blood, semen, vaginal fluid, or breast milk; HIV-1 preferentially binds and interacts with cells displaying CD4 molecules (Figure 20.28): Virus’ affinity for CD4 molecules is due to a glycoprotein on virus’ surface that fits into CD4 molecule like a key fits into a lock After an HIV-1 virion (viral particle), has bound to a CD4 molecule, it interacts with other cell surface molecules that allow it to gain entry into host cell © 2016 Pearson Education, Inc.

HIV-1 is a retrovirus; means that it contains an RNA genome and reproduces with help of an enzyme called reverse transcriptase Reverse transcriptase catalyzes reverse process of normal transcription—instead of transcribing DNA into RNA, this enzyme catalyzes transcription of viral RNA into DNA DNA copy of viral genome is then inserted into host DNA, where it triggers production of viral RNA and proteins; infected cell eventually lyses, and new virions are released to infect new cells © 2016 Pearson Education, Inc.

Progression of HIV-1 infection can be divided into three phases, although course may vary from one individual to another Acute phase lasts about three months; characterized by a sharp decline in TH cells and a sharp rise in HIV-1 virions; patients may exhibit flu-like symptoms during this phase, although condition often goes unnoticed © 2016 Pearson Education, Inc.

Chronic phase begins with production of antibodies to HIV-1 virions, an initial slight recovery in number of TH cells, and a decline in number of HIV-1 virions; may last eight or more years in untreated individuals, during which many patients show few to no signs of HIV-1 infection It is during final phase when an individual is said to have AIDS; characterized by progressively declining numbers of TH cells and progressively increasing numbers of HIV-1 virions; without treatment, duration of final phase is generally no more than three years © 2016 Pearson Education, Inc.

Signs and symptoms of AIDS are due largely to destruction of TH cells; TH cells are required for almost all parts of innate and adaptive immune responses to function properly; for this reason: Loss of TH cells causes entire adaptive immune response to fail (some innate responses remain), which leads to recurrent infections, particularly with agents that are opportunistic (not generally pathogenic in immunocompetent patients) Other consequences of AIDS include cancers such as Kaposi’s sarcoma, which affects blood vessels and leads to purple-red skin lesions © 2016 Pearson Education, Inc.

Currently, there are a number of drug therapies for HIV-1; three main mechanisms by which most drugs work: Some drugs inhibit enzyme reverse transcriptase, or inhibit viral enzymes needed to synthesize mature virions, while other drugs block entry of HIV-1 into its target cells Drugs are typically administered in combination as a “cocktail” to inhibit as many aspects of viral replication cycle as possible © 2016 Pearson Education, Inc.

Autoimmune Disorders Autoimmune disorders occur when populations of self-reactive T cells or B cells that secrete antibodies bind to self antigens (called autoantibodies); many situations could lead to development of autoimmunity © 2016 Pearson Education, Inc.

Autoimmune Disorders Some of these situations include:
Release of self antigens not previously encountered by T cells; can lead to autoimmune disorder, multiple sclerosis: Some antigens are sequestered, meaning that they are not exposed to developing T cells Infection or trauma might release a sequestered protein and its antigens into circulation, activating T cells specific for this antigen © 2016 Pearson Education, Inc.

Autoimmune Disorders Foreign antigens mimic self antigens; this mechanism can lead to autoimmune disorder, rheumatic fever: Certain viral and bacterial antigens closely resemble normal self antigens Normally, T cells specific for these antigens do not attack self cells because of lack of co-stimulatory signals If an individual comes into contact with these pathogens, co-stimulatory signals may activate these T cells, which then attack self cells © 2016 Pearson Education, Inc.

Autoimmune Disorders Cells may inappropriately express class II MHC molecules An inappropriately expressed class II MHC molecule activates T cells and triggers an immune response to these normal self antigens This appears to be case with type 1 diabetes mellitus, in which immune system destroys insulin-producing cells of pancreas © 2016 Pearson Education, Inc.

Autoimmune Disorders Certain pathogens nonspecifically activate B cells Many pathogens can induce production of cytokines that nonspecifically activate B cells, resulting in production of autoantibodies Proposed mechanism behind disease systemic lupus erythematosus; infection with a certain virus is followed by production of antibodies to proteins in DNA, erythrocytes, platelets, and leukocytes © 2016 Pearson Education, Inc.

Erin C. Amerman Florida State College at Jacksonville

Similar presentations

Presentation on theme: "Erin C. Amerman Florida State College at Jacksonville"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Erin C. Amerman Florida State College at Jacksonville

Similar presentations

Presentation on theme: "Erin C. Amerman Florida State College at Jacksonville"— Presentation transcript:

Similar presentations

About project

Feedback