Chapter 43 – Body’s Defenses What is Immunity? Immunity • Immunity – The ability of the body to fight infection and/or foreign invaders by producing antibodies or killing infected cells. • Immune System – The system in the body responsible for maintaining homeostasis by recognizing harmful from nonharmful organisms and produces an appropriate response. Foreign Invaders • Called Pathogens – Viruses, bacteria or other living thing that causes disease/immune response. • Antigens – Toxins that pathogens produce that cause harm to an organism. • Antibodies – Proteins produced by your immune system that attack antigens and fight disease Parts of the Immune System • Blood - White Blood Cells in particular. • Lymph nodes • Thymus Gland – Produces T Lymphocytes • Bone Marrow – Produces B Lymphocytes Lines of Defense How does the body fight infection/foreign invaders? The Body’s THREE lines of Defense First Line of Defense – The Skin • Provides Physical and Chemical barriers • Physical – hard to penetrate, made of indigestible keratin • Chemical – tears, sweat Second Line of Defense – Nonspecific Immune Response These are defenses the body uses no matter what the invader may be. These defenses include: – Phagocytosis – done by Macrophages – Natural Cell Killers – Inflammation - caused by release of Histamine from leukocytes – Fever – caused by histamines. The fever (high temp) kills invaders by denaturing their proteins. Phagocytic and Natural Killer Cells (Non specific 2nd line of defense) • Neutrophils 60-70% WBCs; engulf and destroy microbes at infected tissue • Monocytes 5% WBCs; develop into…. • Macrophages enzymatically destroy microbes • Eosinophils 1.5% WBCs; destroy large parasitic invaders (blood flukes) • Natural killer (NK) cells destroy virus-infected body cells & abnormal cells The Inflammatory Response (Non specific 2nd line of defense) • Tissue injury; release of chemical signals~ • histamine (basophils/mast cells): causes Step 2..• prostaglandins: increases blood flow & vessel permeability, allows fluid and blood cells to get to injury • Dilation and increased permeability of capillary~ • chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs • Phagocytosis of pathogens~ • fever & pyrogens: leukocyte-released molecules increase body temperature Antimicrobial proteins (Non specific 2nd line of defense) • Complement – chemical warfare of the immune systems, triggers series of reactions that “blow up” pathogens • Interferons – secreted by virus infected cells, many forms, may help with some cancers Third Line of Defense – Specific Immune Response This is a specific response to a specific pathogen/antigen. • The response involves the creation of Antibodies. Antibodies • Y-shaped protein molecule. • Made up of variable and constant regions. • Made up of Heavy and Light chains. • Produced by B-Lymphocytes • Function: Recognize antigens, bind to and deactivate them. – Note: Variable region recognizes the anitgens. How an antibody operates/works? Specific Immunity • Lymphocytes provide specificity and diversity •derived from pluripotent stem cells • B Cells (mature in bone marrow) • T Cells (mature in thymus) • Antigen: a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms) • Antibodies: antigen-binding immunoglobulin, produced by B cells, binds to target • Antigen receptors: plasma membrane receptors on b and T cells that recognize antigens Clonal selection • Clonal selection: antigen-driven cloning of lymphocytes – antigen “chooses” which lymphocytes get replicated • “Each antigen, by binding to specific receptors, selectively activates a tiny fraction of cells from the body’s diverse pool of lymphocytes; this relatively small number of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to eliminating the antigen.” • Effector cells: short-lived cells that combat the antigen • Memory cells: long-lived cells that bear receptors for the antigen Cellular Immunity .vs. Antibody Immunity • Carried out by T-Cells • Infected cells are killed by Cytotoxic T –Cells. • Carried out by B-cells • Antibodies are produced and dumped into blood stream. • Antibodies bind to antigens and deactivate them. Immune Response Summary Primary .vs. Secondary Immune Response • Primary Immune Response – This is a response to an invader the First time the invader infects the body. • No measurable immune response for first few days. • Next 10 – 15 days antibody production grows steadily • Secondary Immune Response – A more rapid response to an invader the 2nd time it invades the body. • Antibody production increases dramatically and in a much shorter time period.. Primary .vs. Secondary Immune Response Induction of Immune Responses • Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen • Plasma cells: antibody-producing effector B-cells • Secondary immune response: immune response if the individual is exposed to the same antigen at some later time, immunological memory (memory cells), quicker and stronger response than primary (usually don’t get chickenpox more than once) Self/Nonself Recognition • Self-tolerance: capacity to distinguish self from non-self • Major Histocompatability Complex (MHC): body cell surface antigens coded by a family of genes • Class I MHC molecules: found on all nucleated cells • Class II MHC molecules: found on macrophages, B cells, and activated T cells Self/Nonself Recognition • Antigen presentation: process by which an MHC molecule “presents’ an intracellular protein to an antigen receptor on a nearby T cell, tells immune system that an invader is present • Cytotoxic T cells (TC): bind to protein fragments displayed on class I MHC molecules • Helper T cells (TH): bind to proteins displayed by class II MHC molecules • Autoimmune diseases: failure of self-tolerance; multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus Passive .vs. Active Immunity • Active Immunity This is immunity where the body is “actively” producing antibodies to fight infection. Ex: You have a throat infection and you are actively creating antibodies to fight it. Vaccination: An injection of a weakened strain of an infectious microbe (pathogen) that causes the body to undergo active immunity (produce antibodies). • Passive Immunity This is immunity where antibodies are given to a person from the blood of another person or animal. This immunity only lasts for a short period of time. ex: Breastfeeding mothers pass antibodies to their children through the milk. Vaccination A preparation containing antigenic material: • Whole live microorganism • Dead microorganism • Attenuated (harmless) microorganism • Toxoid (harmless form of toxin) • Preparation of harmless ags Vaccination • Injection into vein or muscle • Oral Smallpox Symptoms • Red spots containing transparent fluid all over body. • Spots fill with pus • Eyelids swell and become glued together Smallpox Mortality • 12-30% died • Survivors often left blind and disfigured with scabs. Smallpox Eradication programme • Started by WHO in 1956 • Aimed to rid world of smallpox by 1977 • Involved vaccination and surveillance • Over 80% of populations at risk of the disease were vaccinated • After any reported case everyone in the household and 30 surrounding households vaccinated – RING VACCINATION Smallpox Eradication programme • Last case of smallpox reported in Somalia in 1977 • World declared free of smallpox in 1980 Measles • Caused by an airborne virus • 9th leading cause of death worldwide • Causes rash and fever • Can have fatal complications • Passive immunity from mothers in infants under 8 months • Now quite a rare disease in developed countries due to vaccination Measles • Transmitted easily in overcrowded, insanitary conditions • Mainly affects malnourished infants with vitamin A deficiencies • Responsible for many cases of childhood blindness and can cause severe brain damage • Herd immunity of 93-95% needed to prevent transmission within a population. Autoimmune Disease • Autoimmune diseases are diseases where the immune system begins to attack itself. – Ex: • Rheumatoid Arthritis – crippling disease of the joints. • Lupus – disease of blood and organs. • Multiple Sclerosis – disease of nervous system • Cause(s): unknown • Cures/Treatments: No known cures. Usually treated with drugs. Allergies Allergy - An exaggerated response by the immune system to an allergen. Allergen: a normally harmless substance that causes an allergic reaction. ex: dust, pollen, mould, food, insect stings Types of Allergic reactions There are two types of allergic reactions. a. Immediate – occurs within seconds and normally lasts for about 30 mins. b. Delayed – takes longer to react and can last for a much longer time. What happens during an allergic reaction? • During an allergic reaction antibodies cause histamines to be released from certain cells. Histamines cause: a. Swelling of tissues b. Release of fluids (runny noses and eyes) c. muscle spasms (some cases) Anaphylaxis or anaphylactic shock: This is the sudden and severe allergic reaction to a substance that can cause death. Treatments for Allergies • Avoidance of material – especially food. • Epinephrine – “epi – pen” • Antihistamines -- benadryl Types of immune responses • Humoral immunity • B cell activation • Production of antibodies • Defend against bacteria, toxins, and viruses free in the lymph and blood plasma • Cell-mediated immunity • T cell activation • Binds to and/or lyses cells • Defend against cells infected with bacteria, viruses, fungi, protozoa, and parasites; nonself interaction Helper T lymphocytes • Function in both humoral & cell-mediated immunity • Stimulated by antigen presenting cells (phagocytes that have engulfed an infectious agent) • T cell surface protein CD4 enhances activation • Cytokines secreted (stimulate other lymphocytes): a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells b) interleukin-1 (IL-1): activates helper T cell to produce IL-2 Cell-mediated: cytotoxic T cells • Destroy cells infected by intracellular pathogens and cancer cells • Class I MHC molecules (nucleated body cells) expose foreign proteins • Activity enhanced by CD8 surface protein present on most cytotoxic T cells (similar to CD4 and class II MHC) • TC cell releases perforin, a protein that forms pores in the target cell membrane; cell lysis and pathogen exposure to circulating antibodies Humoral response: B cells • Stimulated by T-dependent antigens (helped by TH cells) • Helper T cell (CD4 protein) • Activated T cell secretes IL-2 (cytokines) that activate B cell • B cell differentiates into memory and plasma cells (antibodies) Antibody Structure & Function • Epitope: region on antigen surface recognized by antibodies • 2 heavy chains and 2 light chains joined by disulfide bridges • Antigen-binding site (variable region) • Constant region determines which class of antibody it is 5 classes of Immunoglobins • IgM: 1st to circulate; indicates infection; too large to cross placenta • IgG: most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement • IgA: produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, breast milk and perspiration • IgD: do not activate complement and cannot cross placenta; found on surfaces of B cells; probably help differentiation of B cells into plasma and memory cells • IgE: very large; small quantity; releases histamines-allergic reaction Antibody-mediated Antigen Disposal • Neutralization (opsonization): antibody binds to and blocks antigen activity • Agglutination: antigen clumping • Precipitation: cross-linking of soluble antigens • Complement fixation: activation of 20 serum proteins, through cascading action, lyse viruses and pathogenic cells Immunity in Health & Disease • Active immunity/natural: conferred immunity by recovering from disease • Active immunity/artificial: immunization and vaccination; produces a primary response • Passive immunity: transfer of immunity from one individual to another • natural: mother to fetus via placenta; or mother to infanct via breast milk • artificial: rabies antibodies • ABO blood groups (antigen presence) • Rh factor (blood cell antigen); Rh- mother vs. an Rh+ fetus (inherited from father) Abnormal immune function • Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine • Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus • Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.