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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. Defense Systems. Pathogens Lymphatic system Nonspecific defenses First line Second line
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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
Defense Systems • Pathogens • Lymphatic system • Nonspecific defenses • First line • Second line • Specific defenses
Pathogens: Bacteria • single celled, prokaryotic • antibiotics based on differences between prokaryotic and eukaryotic cells • Infections can result in toxins
Viruses • Extremely small • “parasitic DNA” or RNA • Enter cells via endocytosis • Diseases: AIDS, hepatitis, encephalitis, rabies, colds, warts, chicken pox
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
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
Lymphatic System • Functions: • Maintain blood volume in cardiovascular system • Transport of fats from digestive system • Filters out foreign material to defend against infection
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
Lymphatic Vessels Lymph capillaries have flap-like minivalves • Fluid leaks into lymph capillaries • anchored by filaments
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
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
Body Defenses protects against variety of invaders responds immediately Specific for each type of invader Figure 12.6
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
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
Second Line of Defense: Defensive Cells 1. Phagocytes (neutrophils and macrophages) • Engulf foreign material into a vacuole • Eosinophils • Natural killer cells (NK) • lyse and kill cancer cells, virus-infected cells • Secrete perforins that destroy membranes Figure 12.7a
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
Antimicrobial Chemicals • Interferons • proteins secreted by virus-infected cells • bind to surfaces of nearby healthy cells to inhibit virus entry, replication • = alert system
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
Steps in the Inflammatory Response Figure 12.8
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
Defense Mechanisms fever
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
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
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
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
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
Secondary Response • Memory cells are long-lived • 2nd exposure causes a rapid response • Secondary response is stronger and longer lasting Figure 12.13
Antibodies (Immunoglobulins) (Ig) • IgG shown here: • Four amino acid chains linked by disulfide bonds • 2 heavy chains, 2 identical light chains • Specific antigen-binding sites are present Figure 12.15b
Antibody Function • Antibodies inactivate antigens in a number of ways • Complement fixation • Neutralization • Agglutination • Precipitation PRESS TO PLAY ANTIBODY FUNCTION ANIMATION
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
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
Cellular (Cell-Mediated) Immune Response Figure 12.17
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 re-exposure • Suppressor T cells
Summary of the Immune Response Figure 12.19
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
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
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
Allergy Mechanisms Second exposure: antigens bind to IgE, cause release of histamine First exposure: antigen invades body, IgE antibodies produced and bind to mast cells.
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
Self Tolerance Breakdown - How? 1. Inefficient lymphocyte programming • Appearance of self-proteins in the circulation that have not been exposed to the immune system • Cross-reaction of antibodies produced against foreign antigens with self-antigens
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
Time Course of the Progression of AIDS after HIV Infection Figure 9.21
AIDS quilt Figure 10.22x2
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