Immunity Overview of Defense Mechanisms Defense

Immunity

Overview of Defense Mechanisms • Defense mechanisms include – Barriers • Skin, stomach acid, tears, vomiting – Nonspecific defense mechanisms • Phagocytosis, inflammation – Specific defense mechanisms • Immune response – antibodies – T cells

Pathogens Cause Disease • Disease-causing agents include – Living organisms • Bacteria • Fungi • Parasites – Nonliving infectious “particles” • Viruses • Prions

Bacteria • Characteristics – Simple (no organelles) – Single-celled – Small • Infections – Pneumonia, tonsillitis, tuberculosis, botulism, toxic shock syndrome, syphilis, Lyme disease, etc. • Generally treated with antibiotics

Viruses • Extremely small, much smaller than bacteria • Not alive – No cells – Unable to reproduce outside of a host cell – No metabolic activity • Structure – Contain DNA or RNA – Surrounded by protein coat • Diseases – AIDS, hepatitis, encephalitis, rabies, influenza, colds, warts, chicken pox

Prions • Infectious proteins • Normal brain proteins not folded correctly • Misfolding becomes self-propagating – fills and disables cell with protein debris • Resist cooking, freezing, drying • Diseases – Bovine spongiform encephalitis (BSE, “mad cow disease”) – Creutzfeldt-Jakob disease (CJD)

Determining Health Risk • Transmissibility – Ease of passage between people • Mode of transmission – Respiratory, fecal–oral, body fluids • Virulence – How much damage is caused by infection

Lymphatic System • Functions – Maintenance of blood volume in cardiovascular system – Transport of fats and fat-soluble material from digestive system – Filtration of foreign material to defend against infection

Lymphatic System: Components • Lymphatic vessels transport lymph • Lymph nodes cleanse lymph • Spleen cleanses blood • Thymus gland facilitates maturation of T lymphocytes • Tonsils and adenoids protect throat

Keeping Pathogens Out: The First Line of Defense • Skin • Tears and saliva – contain lysozyme (antibacterial enzyme) • Ear wax – entraps microorganisms • Mucus – entraps microorganisms • Stomach – highly acidic, inhibits microorganisms • Vagina – slightly acidic, inhibits some microorganisms • Vomiting, urination, and defecation – remove microorganisms • Resident bacteria – outcompete pathogens

Nonspecific Defenses • Phagocytic cells: WBCs engulf invading pathogens – Neutrophils, macrophages, eosinophils • Inflammation – Redness, warmth, swelling, pain • Natural killer cells: type of lymphocyte; attacks tumor cells and virus-infected cells • Complement proteins: lyse invading bacteria • Interferons: antiviral proteins • Fever response

1 2 Activated complement proteins form complexes of proteins that create holes in the bacterial cell wall. 3 Water and salts diffuse into the bacterium through the holes. The bacterium swells and eventually bursts. Water and salts Complement proteins Bacterium Cell wall of bacteria Photomicrograph of an intact bacterium A bacterium after lysis by activated complement proteins Figure 9. 8

Specific Defense Mechanisms (The Immune Response) • Characteristics – Recognizes/targets specific pathogens or foreign substances – Has “memory” • “remembers” initial exposure • responds more quickly and aggressively on subsequent exposures • Able to distinguish between – Self cells and foreign invaders – Healthy cells and abnormal (tumor) cells

Immune Response Targets Antigens • Antigen: substance that triggers immune response – On outer surface of invading cell or virus – MHC (major histocompatibility complex) proteins • Self-antigens on human cell surfaces • Enable immune system to distinguish “self” from “nonself”

Lymphocytes • B lymphocytes: Antibody-mediated immunity – Antibodies: bind and neutralize specific antigens – Active against viruses and bacteria • T lymphocytes: Cell-mediated immunity – Directly attack foreign cells – Coordinate immune response – Active against parasites, viruses, fungi, intracellular bacteria, cancer cells, cells with “nonself” MHC

Antibody-Mediated Immunity • B cells activated when they recognize an antigen • Divide into two cell types – Memory cells – store information for future responses – Plasma cells – actively secrete antibodies, which will bind to antigen

T Cells: Cell-Mediated Immunity • T cells – Originate in bone marrow – Mature in thymus • Types of T cells – CD 4 T cells – Helper T cells and Memory T cells – CD 8 T cells – Cytotoxic T cells

T Cells: Cell-Mediated Immunity • Helper T cells – Activate other immune system cells – Are target of HIV infection • Cytotoxic T cells – Attack and destroy abnormal (tumor or viral-infected) cells and foreign cells • Memory T cells – Reactivate during later exposures

Immune Memory Creates Immunity • Primary immune response – Occurs on first exposure to antigen – Characteristics • Lag time of 3– 6 days for antibody production • Peak at 10– 12 days • Secondary immune response – Occurs on second and subsequent exposure to antigen – Characteristics • Lag time in hours • Peak in days

Primary immune response Secondary immune response Antibody concentration (units/ml) 100 10 1 0 7 14 1 st exposure 21 28 0 7 14 21 28 35 42 2 nd exposure Time (days after exposure) Figure 9. 16

Immunization • Active immunization – Intentionally expose to a form of antigen that doesn’t produce disease – Also known as vaccination • Passive immunization – Administer protective antibodies to an individual – Passed from mother to baby

Antibiotics Combat Bacteria • Antibiotics kill bacteria or inhibit their growth • Antibiotics are selectively toxic for bacteria – Target features unique to prokarotes • Antibiotics are not effective against viruses – Cold, flu, etc

Tissue Rejection: A Medical Challenge • Tissue rejection – recipient’s immune system attacks transplanted tissue/organ • To minimize risk of rejection – Must match ABO and other blood group antigens and MHC antigens – 75% MHC match is essential – Immunosuppressive drugs – Prevent patient’s immune system from attacking transplanted tissue

Allergies • Allergies - Inappropriate response to an allergen – Allergen: any substance (antigen) that causes an allergic reaction • • Pollen Bee venom Foods (nuts, seafood) Oil from poison ivy plant • Treatment of allergies – Antihistamines – Epinephrine injection – Allergy shots

Autoimmune Disorders • Inability of immune system to distinguish “self” from “nonself” • Autoantibodies and cytotoxic T cells target body’s own tissues • Examples – Lupus erythematosis (LE or lupus) • Inflamed connective tissue – Rheumatoid arthritis • Inflamed synovial membrane

Immune Deficiency: AIDS • AIDS: Acquired Immune Deficiency Syndrome • Caused by infection with HIV (Human Immunodeficiency Virus) • HIV targets helper T cells • Transmission via body fluids (blood, semen, breast milk, vaginal secretions)

Retrovirus Single-stranded DNA made from RNA template Double-stranded DNA Viral coat Viral RNA Nucleus Proteins Core of virus Figure 9. 21

AIDS Develops Slowly: Phase I • Phase I – May last a few weeks to a few years – Brief period of flu-like symptoms • • • Swollen lymph nodes Chills Fever Fatigue Body aches – Most people don’t exhibit recognizable symptoms – Virus is multiplying, antibodies are made but are ineffective for complete virus removal

AIDS Develops Slowly: Phase II • Phase II – Occurs within 6 months to 10 years – Opportunistic infections present – Helper T cells affected, numbers are decreasing – If untreated, 95% will progress to next phase (AIDS)

AIDS Develops Slowly: Phase III (AIDS) • Phase III: Clinical AIDS – Helper T cells fall below 200 cells/mm 3 – Opportunistic infections and cancers present • • • Tuberculosis Pneumonia Meningitis Encephalitis Kaposi’s sarcoma Non-Hodgkins lymphoma – If untreated, nearly always fatal

Phase III Concentration of helper T cells in blood (cells per mm 3) 900 800 700 The time of transition from Phase II to Phase III is highly variable between individuals. 600 500 T cells 400 Antibodies 300 200 100 0 HIV in blood 0 1 2 3 4 Years after infection 5 6 7 Figure 9. 22

The AIDS Epidemic: A Global Health Issue • Worldwide – More than 33 million infected with HIV – 25 million dead, so far – Most infections in sub-Saharan Africa – Increasing spread in Asia and India • United States – Just over 1 million infected with HIV – 20, 000 deaths/year

Risky Behaviors Increase Your Chances of Getting AIDS • Males (3/4 of new cases) – Sex with other men – Sharing needles during intravenous drug use – Heterosexual sex with HIV-infected female • Females (1/4 of new cases) – Sex with HIV-infected male – Sharing needles during intravenous drug use

Table 9. 3

Sex Can Be Safer • • Abstinence Reduce number of sexual partners Choose sexual partners with low-risk behavior Avoid high-risk sexual practices – Anal-genital sex is a high-risk practice • Use latex or polyurethane condoms or barriers • GET TESTED

New Treatments Offer Hope • HIV Drugs – Reverse transcriptase inhibitors: AZT – Protease inhibitors: ritonavir, saquinavir – Maraviroc: new drug • Blocks entry of HIV into T cells – Early treatment may delay or prevent clinical AIDS • Vaccine – Under development and testing – Challenge: Virus mutates rapidly

80 AIDS Deaths (thousands) 60 40 20 0 1992 1994 1996 1998 2000 2002 2004 2006 2008 Year a) Estimated number of deaths due to HIV/AIDS, 1990 -2007. Living with AIDS (millions) 1. 5 1. 0 0. 5 0 1992 1994 1996 1998 2000 2002 2004 Year b) Estimated number of people living with HIV/AIDS, 1990 -2007. Figure 9. 23