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Transcript
Lines of Defense and Immunity • 1st line of defense – intact skin – mucous membranes & their secretions • 2nd line of defense – phagocytic white blood cells – inflammation – fever • 3rd line of defense– B & T lymphocytes – antibodies Nonspecific/Innate -complement -interferon Specific/Acquired Formed Elements of Blood Leukocytes Characteristics of Leukocytes • Diapedesis – migration of cells out of blood vessels into the tissues • Chemotaxis – migration in response to specific chemicals at the site of injury or infection Cytokines: Involved in host defenses: Inflammation! Chemokines: chemotactic Surveillance by Leukocytes Plasma Proteins Blood plasma contains: – Clotting factors – Complement – Antibodies – Molecules not related to defense Serum is missing clotting proteins The Lymphatic System 1. 2. 3. Provides an auxiliary route for return of extracellular fluid to the circulatory system Is involved with the inflammatory response Carries out surveillance, recognition, and protection against foreign material GALT: Gut-Associated Lymphatic Tissue The Reticuloendothelial, Circulatory and Lymphatic Systems Lymphatic Fluid • Lymph is a plasma-like liquid carried by lymphatic circulation • Formed when blood components move out of blood vessels into extracellular spaces • Made up of water, dissolved salts, 2-5% proteins • Transports white blood cells, fats, cellular debris & infectious agents (foreign matter) Lymph nodes • Small, encapsulated, bean-shaped organs stationed along lymphatic channels & large blood vessels of the thoracic and abdominal cavities Lines of Defense and Immunity • 1st line of defense – intact skin – mucous membranes & their secretions • 2nd line of defense – phagocytic white blood cells – inflammation – fever • 3rd line of defense– B & T lymphocytes – antibodies Nonspecific/Innate -interferon -complement Specific/Acquired Nonspecific Host Defenses – Innate Immunity • • • Always present Immediately effective No immune memory – work at the same speed each time Four Cardinal Symptoms of Inflammation: 1. Rubor (redness) 2. Calor (an increase in temperature) 3. Tumor (swelling/edema) 4. Dolor (pain) The Wound Response Enter: Fluid and Macrophages (phagocytes!) The Wound Response Contain the Pathogen! Ah, Repair… All Together Now! 1. Rubor (redness) 2. Calor (an increase in temperature) 3. Tumor (swelling/edema) 4. Dolor (pain) Phagocytes and Their Activities Phagocytes = eating cells – Neutrophils (PMNs) are present in the highest numbers in blood – Macrophages (“big eaters”) in the tissues encounter the pathogen first • Secrete cytokines ---> inflammation, systemic responses (e.g. fever) 1. 2. 3. To survey tissue compartments & discover microbes, particulate matter & dead or injured cells To infest and eliminate these materials To extract immunogenic information from foreign matter Interferon • Small protein produced by certain cells – Alpha (α) interferon- leukocytes – Beta (β) interferon – fibroblasts & epithelial cells – Gamma (γ) interferon – T cells • Produced in response to viruses, RNA, immune products, and various antigens • Bind to cell surfaces and induce expression of antiviral proteins • Inhibit expression of cancer genes (γ) Mechanism of α and β Action Lines of Defense and Immunity • 1st line of defense – intact skin – mucous membranes & their secretions • 2nd line of defense – phagocytic white blood cells – inflammation – fever • 3rd line of defense– B & T lymphocytes – antibodies Nonspecific/Innate -interferon -complement Specific/Acquired Lines of Defense and Immunity • 1st line of defense – intact skin – mucous membranes & their secretions • 2nd line of defense – phagocytic white blood cells – inflammation – fever • 3rd line of defense– B & T lymphocytes – antibodies Nonspecific/Innate -interferon -complement Specific/Acquired The Complement System • • • • Consists of 26 blood proteins that work in concert to destroy bacteria and viruses Complement proteins are activated by cleavage Classical pathway Alternative pathway General Functions of the Complement System: 1. 2. 3. Enhance phagocytosis by phagocytes (opsonization) Directly lyse microbes, bacteria, and enveloped viruses Generate peptide fragments that regulate inflammation and immune responses The Complement System Activation of the Classical Pathway: Membrane Attack Complexes (MACs) • • Amplification by enzyme activity Highly regulated so our cells don’t lyse Summary of Nonspecific Defenses The Acquisition of Specific Immunity and Its Applications (Chapter 15) Genetic and Acquired Defenses • • • Some hosts are genetically immune to the diseases of other hosts. Some pathogens have great specificity Some genetic differences exist in susceptibility Lines of Defense and Immunity • 1st line of defense – intact skin – mucous membranes & their secretions • 2nd line of defense – phagocytic white blood cells – inflammation – fever • 3rd line of defense– B & T lymphocytes – antibodies Nonspecific/Innate -interferon -complement Specific/Acquired Acquired/Adaptive Immunity • • • • Specific resistance to certain pathogens (antigens) Discriminates foreignness (danger) Slow starting – needs nonspecific defenses to be engaged Immune memory – faster response on repeat exposure Formed Elements of Blood Leukocytes Specific Immunities • B and T lymphocytes B-Cell and T-Cell Development • Directed by bone marrow sites that harbor cells, which nurture the lymphocyte stem cells & provide hormonal signals • Millions of distinct B cells develop & home to specific sites in the lymph nodes, spleen, and GALT where they come into contact with antigens throughout life B and T Lymphocytes B and T Cells have receptors that recognize (bind) antigens specific to individual pathogens Specific Immunities • B and T lymphocytes Antigens & Antibodies • Antigens are foreign to host – Proteins and large polysaccharides • Antibodies are host proteins that bind specifically to an epitope on an antigen • Each antigen has many epitopes = antibody-binding sites Antigens & Antibodies The Hapten-Carrier Phenomenon Haptens: Small molecules that are too small (by themselves) to elicit an immune response Examples: industrial/household/environmental chemicals metals small drug compounds hydralazine (blood pressure lowering drug) can cause drug-induced lupus erythematosus Antigens & Antibodies Antigen with four epitopes Activation of the Humoral Response Antigen-Antibody Reactions • • • • Opsonization Neutralization Agglutination Complement fixation Nature of Antibodies • • • • • Immunoglobulins (Ig) A large Y-shaped protein (IgG = Immunoglobulin class G) Consists of 4 polypeptide chains (two heavy chains, two light chains) Contains 2 identical fragments (Fab) with ends that bind to specific antigen Fc binds to self through disulfide bridge Immunoglobulins • • • Immunoglobulin genes lie on 3 different chromosomes Undifferentiated lymphocyte has 150 different genes for the variable region of light chains & 250 for the variable region and diversity region of the heavy chain During development, genetic recombination causes only the selected V and D genes to be active in the mature cell. Take home message: Billions and billions of distinct antibodies can be produced! Different Classes of Antibodies Antibodies are Receptors in the Plasma Membrane of B-Cells • Each B cell has a uniquely specific receptor (a membrane-bound antibody!) • B cells with certain receptors are produced randomly in the bone marrow So, Where Do All These Different B Cells Come From? Clonal Selection Theory • Lymphocytes use 500 genes to produce a tremendous variety of specific receptors (Abs!) • Undifferentiated lymphocytes (stem cells) undergo genetic mutations & recombinations while they proliferate in the embryo forming a billion different clones with the ability to react with a tremendous variety of antigens. Clonal Selection Theory - continued • Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system. • Each genetically different type of lymphocyte expresses a single specificity. • First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte and causes it to expand into a clone of cells that can react to that antigen. Clonal Selection Theory - continued Clonal Deletion Apoptosis/Programmed Cell Death Leads to Immune Tolerance Activation of the Humoral Response Antigen-Antibody Reactions • • • • Opsonization Neutralization Agglutination Complement fixation Primary and Secondary Immune Responses to an Antigen • Primary response – after first exposure to an antigen immune system produces IgM and a gradual increase in antibody titer (amount of substance in a body fluid) • Secondary response –after second contact with the same antigen, immune system produces a more rapid, stronger response due to memory cells