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Transcript
Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Fig. 12-CO, p. 406 Immunity • Body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells • Immune system activities – Defends against invading pathogens – Removes “worn-out” cells and tissue damaged by trauma – Identifies and destroys abnormal or mutant cells that have originated in the body – Mounts inappropriate immune responses that lead either to allergies or to autoimmune diseases Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immunity • Major targets of immune system – Bacteria • Non-nucleated, single-celled microorganisms • Primarily cause tissue damage and cause disease by releasing enzymes or toxins – Viruses • Consists of either DNA or RNA enclosed by a protein coat • Cannot carry out metabolism or reproduce without invading a host cell • Virulent forms of both bacteria and viruses can cause disease Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Leukocytes • • Effectors of the immune system Five types – Neutrophils • Highly mobile phagocytes that engulf and destroy unwanted materials – Eosinophils • Secrete chemicals that fight parasites • Involved in allergic reactions – Basophils • Release histamine and heparin • Involved in allergic reactions – Monocytes • Transformed into macrophages (tissue-bound phagocytic specialists) – Lymphocytes • Β lymphocytes (β cells) – Transformed into plasma cells that secrete antibodies • T lymphocytes (T cells) – Responsible for cell-mediated immunity Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Lymphocytes • Mainly produced from lymphoid colonies in lymphoid tissues • Lymphoid tissues – Tissues that produce, store, or process lymphocytes – Include • • • • • • • • Bone marrow Lymph nodes Spleen Thymus Tonsils Adenoids Appendix Peyer’s patches (GALT) – Gut associated lymphatic tissue Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Table 12-1, p. 409 • Innate (nonspecific) vs. Adaptive (specific) Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immune Responses • Innate immune system – Nonspecific – Responses work immediately when body is exposed to threatening agent – Nonselectively defend against foreign invaders – First line of defense – Rapid but limited responses – Neutrophils, macrophages, several plasma proteins are important in innate defense Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immune Responses • Adaptive or acquired immune system – Specifically targets foreign material to which body has already been exposed – Body has taken time to prepare to attack – Ultimate weapon against most pathogens – Responses are mediated by β and T lymphocytes – Formation of memory cells allows system to react more swiftly against specific invaders in the future Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity • Defenses include the following – Inflammation – Interferon – Natural killer cells – Complement system Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity • Inflammation – Nonspecific response to tissue injury – Ultimate goal is to bring phagocytes and plasma proteins to invaded or injured area • Isolate, destroy, or inactivate the invaders • Remove debris • Prepare for subsequent healing and repair Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Bacterial invasion or tissue damage Release of histamine by mast cells Local arteriolar vasodilation Increased local capillary permeability Increased blood delivery to injured tissue Local accumulation of fluid Redness Heat Increase in crucial plasma proteins, such as clotting factors, in tissue Swelling Pain Increase in phagocytes in tissue Defense against foreign invader; tissue repair Phagocytic secretions Systemic responses, such as fever Fig. 12-2, p. 411 Innate Immunity • Inflammation – Inflammatory response is similar no matter what the triggering event • • • • • • • • • Defense by resident tissue macrophages Localized vasodilation Increased capillary permeability Localized edema Walling-off the inflamed area Emigration of leukocytes Leukocyte proliferation Marking of bacteria for destruction by opsonins Leukocytic destruction of bacteria Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity (Inflammatory Response) Phagocyte-Secreted Chemicals Chemical Secreted by Function Nitric oxide (NO) Macrophages Toxic to nearby microorganisms Lactoferrin Neutrophils Protein that binds with iron, making it unavailable for use by invading bacteria Histamine Mast cells Induces local vasodilation and increases capillary permeability Kallikrein Neutrophils Converts specific plasma proteins precursors produced by liver into activated kinins Endogenous pyrogen (EP) Macrophages Induces development of fever Leukocyte endogenous mediator (LEM) Macrophages Decreases the plasma concentration of iron by altering iron metabolism within the liver, spleen and other tissues; also stimulates synthesis and release of neutrophils by the bone marrow Acute phase proteins Liver upon stimulation by LEM Play role in inflammatory process, tissue repair, and immune cell activities C-reactive protein Liver Specific acute phase protein that is clinically used as a blood-borne marker of inflammation Interleukin 1 (IL-1) Macrophages Enhances proliferation and differentiation of β and T lymphocytes Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity (Tissue Repair) • Tissue repair can be perfect – Cell division replaces lost cells with same kind of cells • In nonregenerative tissue (nerve and muscle) – Lost cells are replaced with scar tissue • Drugs that suppress with inflammatory process – Nonsteroidal anti-inflammatory drugs (NSAIDs) • Aspirin • Ibuprofen – Glucocorticoids • Suppress almost all aspects of inflammatory process • Reduce body’s ability to resist infection Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity • Interferon – Transiently inhibits multiplication of viruses in most cells – Triggers the production of virus-blocking enzymes by potential host cells – Released nonspecifically from any cell infected by a virus – Provides general, rapid defense until more specific but slower-responding immune mechanisms can begin – Enhances macrophage phagocytic activity, stimulates production of antibodies, boosts the power of killer cells – Exerts anticancer effects Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity Mechanism of Action of Interferon in Preventing Viral Replication Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity • Natural killer (NK) cells – Naturally occurring lymphocyte-like cells – Nonspecifically destroy virus-infected cells and cancer cells – Mode of action • Directly lyse cell membranes upon first exposure to these cells Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity • Complement system – Nonspecific response – Primary mechanism activated by antibodies to kill foreign cells – Also activated by exposure to carbohydrate chains present on surfaces of microorganisms but not on human cells – Forms membrane attack complexes that punch holes in victim cells – Composed of plasma proteins that are produced by the liver and circulate in inactive form Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity • Complement system – Cascade sequence of events • C1 is activated → activates C2 → activates C3 → activates C4 → activates C5 • Components C5 through C9 assemble into large, doughnut-shaped protein complex (membrane attack complex – MAC) – Embeds itself in surface membrane of nearby microorganisms – Resulting hole makes membrane leaky – Victim cell swells and bursts – Means of killing microbes without killing them Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Innate Immunity Membrane Attack Complex (MAC) Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Fig. 12-10, p. 420 Innate Immunity • Several proteins in complement cascade additionally augment inflammatory process by – Serving as chemotaxins – Acting as opsonins – Promoting vasodilation and increased vascular permeability – Stimulating release of histamine from mast cells – Activating kinins Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Adaptive Immunity • Two classes of adaptive immunity – Antibody-mediated or humoral immunity • Involves production of antibodies by β lymphocyte derivatives known as plasma cells – Cell-mediated immunity • Involves production of activated T lymphocytes – Directly attack unwanted cells Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Adaptive Immunity Origins of β and T Cells Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Adaptive Immunity • Antigen – Large, foreign, unique molecule – Induces an immune response against itself – In general, the more complex a molecule is, the greater its antigenicity • Antibody – Complex proteins made in B and T cells that bind to an antigen in a specific (adaptive) manner Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning β Lymphocytes: Antibody-Mediated Immunity • Each lymphocyte has surface receptors for binding with one particular type of possible antigens • Antigens stimulate β cells to convert into plasma cells that produce antibodies • On binding with processed and presented antigen – Most β cells differentiate into active plasma cells – Other β cells become dormant Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Plasma Cells • • • Produce antibodies that can combine with a specific kind of antigen All antibodies eventually enter blood where they are known as gamma globulins or immunoglobulins Antibody (Immunoglobulin) subclasses – IgM • Serves as the β cell surface receptor for antigen attachment • Secreted in early stages of plasma cell response – IgG • Most abundant immunoglobulin in blood • Produced in large amounts when body is exposed to same antigen – IgE • Helps protect against parasitic worms • Antibody mediator for common allergic responses – IgA • Found in secretions of digestive, respiratory, and genitourinary systems; also in milk and tears – IgD • Present on surface of many β cells • Function is uncertain Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Antibodies • Y-shaped molecules • Composed of four interlinked polypeptide chains – Two long, heavy chains and two short, light chains • Properties of tail portion determine functional properties of the antibody • Identical antigen-binding fragments (Fab) at tip of each arm (unique for each different antibody) • Tail (constant region) regions within each subclass are identical Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Antibodies • Can physically hinder antigens • By neutralization, they prevent harmful chemicals from interacting with susceptible cells • Can bind to foreign cells by agglutination • Enhance activity of other defense systems by – Activating complement system – Enhancing phagocytosis – Stimulating killer (K) cells Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Fig. 12-10a, p. 420 B cell specific to antigen Different B cell clones Antigens Rough endoplasmic Plasma cells reticulum Memory cells Antibodies Fig. 12-11, p. 421 Β Lymphocytes • Activated β-cell clones multiply and differentiate into – Plasma cells • Produce and secrete IgG antibodies • Antibody combines with an antigen, marking it for destruction • During initial contact with microbial antigen, antibody response is delayed and plasma cells are formed • Peak is reached in a couple of weeks by primary response • After peak, antibody concentration decreases – Memory cells • Small percentage of β lymphocytes become memory cells • Remain dormant • Upon reexposure to same antigen, they are more ready for immediate action than the original lymphocytes of the clone • Secondary response is quicker, more potent, and longerlasting – Can be induced by disease or vaccination Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Primary and Secondary Immune Responses Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning First exposure to a pathogen’s antigens Natural exposure to virulent, antigenic pathogen Virulent portion Exposure to nonvirulent, antigenic pathogen through vaccination Antigenic portion No virulence Combat Disease Specific B cell clone Specific B cell clone No disease Plasma cells Memory cells (long-term immunity) Memory cells (long-term immunity) Plasma cells Antibodies (slow, weak primary response) Antibodies (not needed) Subsequent exposure to same virulent pathogen Plasma cells Plasma cells Combat Combat Antibodies (swift, strong secondary response) No disease Antibodies (swift, strong secondary response) Fig. 12-13, p. 423 Active and Passive Immunity • Active immunity – “self-generated” – Results from exposure to an antigen • Passive immunity – “borrowed immunity” – Results from transfer of preformed antibodies – Can provide immediate protection or bolster resistance – Example of passive immunity is transfer of IgG antibodies from mother to fetus Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Antigen Presentation • Lymphocytes respond only to antigens presented to them by antigen-presenting cells – Macrophages can be antigen-presenting cells • Cluster around appropriate β-cell clone • Phagocytosis occurs, processing the raw antigen intracellularly and presenting the processed antigen, exposing it to the outer surface of the macrophage’s plasma membrane • As macrophage engulfs and ingests microbe, it digests the microbe into antigenic peptides • Antigenic peptides bind to a MHC molecule which transports the bound antigen to the cell surface where it is presented to passing lymphocytes • Antigen-presenting macrophages secrete interleukin – Enhances differentiation and proliferation of now-activated βcell clone Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning T Lymphocytes • Carry out cell-mediated immunity • Do not secrete antibodies – directly bind to targets • Killer T cells release chemicals that destroy targeted cells • Clonal and antigen specific – acquire receptors in the thymus • T cells are activated for foreign attack only when it is on the surface of a cell that carries foreign and self antigens • Learn to recognize foreign antigens only in combination with a person’s own tissue antigens • A few days are required before T cells are activated to launch a cell-mediated attack Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning T Lymphocytes • Two main types of T cells – CD8 cells (cytotoxic, or killer T cells) • Destroy host cells harboring anything foreign – CD4 cells (mostly helper T cells) • Modulate activities of other immune cells • Secrete chemicals that amplify the activity of other immune cells – Β-cell growth factor – T-cell growth factor (interleukin 2) – Macrophage-migration inhibition factor Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Invading bacteria Macrophages secrete interleukin 1, which enhances B cell proliferation and antibody secretion Macrophages “process and present” bacterial antigen to B and T lymphocyte clones specific to the antigen Interleukin 1 Antibodies enhance phagocytosis by coating the bacteria and serving as opsonins Macrophage B cell Helper T cell Activated helper T cell B cell growth factor Helper T cells secrete B cell growth factor that enhances B cell proliferation and antibody secretion Plasma cell Plasma cells secrete antibodies that bind with the antigenic bacteria Antibodies Fig. 12-15, p. 427 Fig. 12-17, p. 430 Mechanism of Killing by Killer Cells Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Fig. 12-20, p. 435 Fig. 12-23, p. 437 Cytotoxic T cell T cell receptor Foreign antigen MHC self-antigen Invaded cell Fig. 12-19, p. 434 Innate and Adaptive Responses to Bacterial Infection Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Β versus T Lymphocytes Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immune System Tolerance • Tolerance refers to preventing the immune system from attacking the person’s own tissues • Mechanisms involved in tolerance – Clonal deletion – Clonal anergy – Receptor editing – Inhibition by regulatory T cells – Immunological ignorance – Immune privilege Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Autoimmune Diseases • Arise from loss of tolerance to self-antigens • Examples of causes – Exposure of normally inaccessible self-antigens sometimes induces an immune attack against these antigens – Normal self-antigens may be modified by factors such as drugs, environmental chemicals, viruses, or genetic mutations so that they are no longer recognized and tolerated by the immune system. – Exposure of the immune system to a foreign antigen structurally identical to a self-antigen – May be related to pregnancy, arising from lingering fetal cells in the mother’s body after the pregnancy Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Self-antigens • Plasma membrane-bound glycoproteins called MHC molecules • Synthesis is directed by group of genes called major histocompatibility complex (MHC) • Exact pattern of MHC molecules varies from one individual to another Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immune Surveillance • Process by which T cells recognize and destroy newly arisen, potentially cancerous tumor cells • Tumor – Clone of cells identical to original mutated cell • Benign tumor – Does not infiltrate surrounding tissues • Malignant tumor – Invasive and cancerous – Cells tend to metastasize – May spread throughout body and cannot be removed surgically • Untreated cancer is eventually fatal • Most genetic mutations do not lead to cancer Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immune Surveillance Against Cancer Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immune Diseases • Due to abnormal functioning of the immune system • Two general ways – Immunodeficiency diseases • Too little immune response • Examples – severe combined immunodeficiency – AIDS – Inappropriate immune attacks • Too much or mistargeted immune response • Categories of inappropriate attacks – Autoimmune responses – Immune complex diseases – Allergies Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Allergy • Acquisition of an inappropriate specific immune reactivity (hypersensitivity) to a normally harmless environmental substance • Offending agent is known as an allergen • Categories of allergic responses – Immediate hypersensitivity – Delayed hypersensitivity Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Fig. 12-24, p. 440 Comparison of Immediate and Delayed Hypersensitivity Reactions Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Immediate Hypersensitivity • Chemical mediators – Histamine – Slow-reactive substance of anaphylaxis (SRS-A) – Eosinophil chemotactic factor • Symptoms – Vary depending on site, allergen, and mediators involved • Hay fever • Asthma • Hives Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning External Defenses • Most obvious external defense is the skin, or integument • Consists of two layers – Epidermis • Outer, vascular, keratinized layer – Dermis • Inner, connective tissue layer Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Anatomy of the Skin Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Epidermis • Four cell types – Melanocytes • Produce melanin which protects the skin by absorbing harmful UV radiation – Keratinocyes • Produce keratin that forms outer protective layer of skin • Discourages bacteria and other harmful environmental agents from entering body • Prevents loss of water and other valuable body substances • Secrete interleukin 1 – Langerhans cells • Function in specific immunity by presenting antigen to helper T cells – Granstein cells • Suppress skin-activated immune responses Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Dermis • Contains – Blood vessels • Nourish the skin • Play role in regulating body temperature – Sensory nerve endings • Provide information about the external environment – Several exocrine glands and hair follicles • Sebaceous glands – Produce sebum – Oily substance that softens and waterproofs the skin • Sweat glands – Produce sweat which helps cool the body Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Additional Defenses • Additional protective measures guard against entry of potential pathogens through internal cavities that communicate directly with the external environment – Digestive system • • • • Antimicrobial salivary enzyme Destructive acidic gastric secretions Gut-associated lymphoid tissue Harmless resident colonic secretions – Genitourinary system • Destructive acidic and particle-entrapping mucus secretions Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Additional Defenses – Respiratory system • Alveolar macrophage activity • Secretion of sticky mucus that traps debris which is swept out by ciliary action • Nasal hairs filter out large inspired particles • Reflex cough and sneeze mechanisms expel irritant materials from trachea and nose • Tonsils and adenoids defend immunologically Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Blood Groups • Form of passive immunity • ABO blood types are named for presence of antigens on surface of erythrocytes – Type A has A antigens and anti-B antibodies – Type B has B antigens and anti-A antibodies – Type AB has both A and B antigens and no antibodies related to the ABO system – Type O does not have A or B surface antigens and both anti-A and anti-B antibodies • Transfusion reaction occurs when blood of incompatible type is given • Blood type O is the universal donor • Blood type AB is the universal recipient Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Transfusion Reaction Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Other Blood Group Systems • Rh factor – Rh-positive individual has Rh factor – Rh-negative individual lacks Rh factor – Erythroblastosis fetalis (hemolytic disease of the newborn) • Occurs when Rh-negative mother develops antibodies against the erythrocytes of an Rh-positive fetus • Approximately 12 other minor human erythrocyte antigen systems Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Chapter 12 The Body Defenses Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning