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Current Topics Organ transplants - stem cells, xenografts Allergies - more common? More serious? Vaccinations - stricter requirements? Possible epidemics - avian flu, SARS HIV and AIDS Stress Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Defense Systems Pathogens Lymphatic system Nonspecific defenses First line Second line Specific defenses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Pathogens: Bacteria single celled, prokaryotic antibiotics based on differences between prokaryotic and eukaryotic cells Infections can result in toxins Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Viruses Extremely small “parasitic DNA” or RNA Enter cells via endocytosis Diseases: AIDS, hepatitis, encephalitis, rabies, colds, warts, chicken pox Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Prions Infectious proteins Cause folding problems of normal brain proteins Resist cooking, freezing, drying Diseases: bovine spongiform encephalitis (BSE), Creutzfeld-Jakob disease (CJD) Other pathogens: protozoa, fungi, worms Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Determination of Health Risk Transmissibility: how easily passed from person to person Mode of transmission: respiratory, fecal-oral, body fluids Virulence: how much damage caused by infection Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lymphatic System Functions: Maintain blood volume in cardiovascular system Transport of fats from digestive system Filters out foreign material to defend against infection Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lymphatic Characteristics Lymph – from excess tissue fluid lymphatic vessels One way system toward the heart No pump; lymph moved by - milking action of skeletal muscle - smooth muscle in vessel walls - one-way valves Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lymphatic Vessels Lymph capillaries have flap-like minivalves Fluid leaks into lymph capillaries anchored by filaments Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lymph Nodes Defense cells within lymph nodes Macrophages – engulf and destroy foreign substances: bacteria, viruses, cancerous cells, cell debris Lymphocytes – provide immune response to antigens Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lymphatic System: Components Lymph Lymph nodes Spleen: cleanses blood, removes dying red blood cells, helps fight infection Thymus: secretes hormones that cause T lymphocytes to mature Tonsils: protect throat Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Body Defenses protects against variety of invaders Specific for each type of invader responds immediately Figure 12.6 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Surface Membrane Barriers – First Line of Defense Skin - physical and chemical defenses Keratin, dead cells Constant replacement; pathogens also shed pH 5-6 inhibits bacterial growth Antibiotic peptide in sweat Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Surface Membrane Barriers Saliva and lacrimal fluid contain lysozyme Mucus traps microorganisms in digestive and respiratory pathways Stomach mucosa Secretes HCl acid Has proteases Vomiting, defecation, urination Resident bacteria Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Second Line of Defense: Defensive Cells 1. Phagocytes (neutrophils and macrophages) Engulf foreign material into a vacuole 2. Eosinophils 3. Natural killer cells (NK) lyse and kill cancer cells, virus-infected cells Secrete perforins that destroy membranes Figure 12.7a Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antimicrobial Chemicals Complement A group of at least 20 plasma proteins Activated when they attach to cells (complement fixation) Damage foreign cell surfaces Figure 12.10 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antimicrobial Chemicals Interferons proteins secreted by virus-infected cells bind to surfaces of nearby healthy cells to inhibit virus entry, replication = alert system Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Inflammatory Response Triggered when tissues are injured Produces four cardinal signs Redness Heat Swelling Pain Prevents spread of damaging agents Disposes of cell debris and pathogens Sets the stage for repair Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Steps in the Inflammatory Response Figure 12.8 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Fever Abnormally high body temperature Hypothalamus control reset by pyrogens (secreted by WBCs) Fever inhibits release of iron and zinc from liver and spleen (needed by bacteria) Fever speeds tissue repair Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Defense Mechanisms fever Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Specific Defense: The Immune System Antigen-specific – acts against particular foreign substances Systemic – not restricted to the initial infection site Has memory – mounts a stronger attack on “known” pathogens Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antigens (Nonself) Any substance capable of activating the immune system response Examples Foreign proteins, large carbohydrates Haptens - small molecules that bind to our proteins and become antigenic Pollen grains, microorganisms MHC - Major Histocompatibility Complex are cell surface proteins that provide unique “fingerprint” on each person’s cells Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Cells of the Immune System Lymphocytes Originate from hemocytoblasts in red bone marrow B lymphocytes mature in bone marrow Antibody-mediated immunity (humoral) Cells produce chemical defense (antibodies) T lymphocytes mature in thymus gland Cellular immunity - living cells attack invader Mature = become immunocompetent, able to react with antigen Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Cells of the Immune System Lymphocytes Macrophages Arise from monocytes reside in lymphoid organs Consume foreign particles Present antigens on their surface as a signal to B, T cells Release chemicals (monokines) that stimulate immune response Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antibody-Mediated Immune Response B cell with specific receptors binds to its specific antigen binding activates the B cell to divide rapidly, producing a clone Plasma cells secrete antibodies into lymph Memory cells of same clone Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Secondary Response Memory cells are long-lived 2nd exposure causes a rapid response Secondary response is stronger and longer lasting Figure 12.13 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antibodies (Immunoglobulins) (Ig) IgG shown here: Four amino acid chains linked by disulfide bonds 2 heavy chains, 2 identical light chains Specific antigenbinding sites are present Figure 12.15b Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antibody Function Antibodies inactivate antigens in a number of ways Complement fixation Neutralization Agglutination QuickTime™ and a Cinepak decompressor are needed to see this picture. Precipitation PRESS TO PLAY ANTIBODY FUNCTION ANIMATION Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antibody Classes Antibodies of each class have slightly different roles Five major immunoglobulin classes IgM – can fix complement; ABO blood system IgA – found mainly in mucus, mother’s milk IgD – important in activation of B cell IgG – most common; can cross the placental barrier and protect fetus IgE – least frequent; involved in allergies Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Monoclonal Antibodies Antibodies from descendents of a single cell line Examples of uses Diagnosis of pregnancy Treatment after exposure to hepatitis and rabies Targeted drug delivery Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Cellular (Cell-Mediated) Immune Response Figure 12.17 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Cell-Mediated Immune Response T cells: 4 types Helper T cells: stimulate other immune cells Cytotoxic T cells: kill abnormal and foreign cells Memory T cells: reactivate on reexposure Suppressor T cells Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Summary of the Immune Response Figure 12.19 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Active Immunity B cells encounter antigens and produce antibodies Active immunity can be naturally or artificially acquired Passive immunity: use of antibodies made elsewhere Figure 12.14 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Tissue Rejection Transplants: 75%+ match of MHC essential Autografts, isografts Allografts, xenografts improvements in immunosuppressive drugs, better tissue typing, national organ banks New technologies: Stem cells - adult, cord blood, embryogenic Engineered pigs Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Allergies (Hypersensitivity) Abnormal, vigorous immune responses Triggered by IgE Localized: affects only the area exposed Systemic: affects several organ systems Anaphylactic shock – severe, systemic inflammatory response Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms First exposure: antigen invades body, IgE antibodies produced and bind to mast cells. Second exposure: antigens bind to IgE, cause release of histamine Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Autoimmune Diseases The immune system does not distinguish between self and foreign molecules The body produces antibodies and sensitized T lymphocytes that attack its own tissues Multiple sclerosis Myasthenia gravis Juvenile diabetes Rheumatoid arthritis Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Self Tolerance Breakdown - How? 1. Inefficient lymphocyte programming 2. Appearance of self-proteins in the circulation that have not been exposed to the immune system 3. Cross-reaction of antibodies produced against foreign antigens with self-antigens Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings AIDS Pandemic More than 36 million infected with HIV worldwide Increasing spread in Asia and India Outside U.S., most often spread by heterosexual contact Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings HIV is a retrovirus Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Invasion of T cell by HIV Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Time Course of the Progression of AIDS after HIV Infection Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 9.21 AIDS quilt Figure 10.22x2 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Safer Sex Transmission: body fluids, i.e., blood, semen, breast milk, vaginal secretions Abstinence Reduce number of sexual partners Choose sexual partners with low-risk behavior Use latex or polyurethane condoms or barriers GET TESTED Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings