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Transcript
Altered Spring 09 Immune Responses 1 Immunity “a truly amazing constellation of responses to attacks from outside the body” • A state of resistance to an agent (the pathogen) that normally produces an infection – microorganisms such as bacteria and viruses – Parasites – fungus – Cancer (rids body of altered cells) • Also recognizes self from non-self – Cells – Tissue – Organs 2 Self/non-self recognition • Achieved by having every cell display a marker based on the major histocompatibility complex (MHC). • Any cell not displaying this marker is treated as non-self and attacked. • The process is so effective that undigested proteins are treated as antigens. 3 Normal Immune Response • Three functions – Defense • Specialized cells and structures against invasions by microorganisms • Prevents development of infection by attacking foreign antigens and pathogens – Homeostasis • Maintains healthy internal environment • Damaged or old cellular substances are digested and removed primarily by the spleen – Surveillance • Identifies mutations that continually arise in body but are normally recognized as foreign cell and destroyed 4 Anatomy of the Immune System Immunity is responsiveness to foreign substances • Comprised of cells and molecules with specialized roles • Defends against invasion and infection • Major components – – – – – Bone marrow (WBCs leukocytes) Lymphoid tissue (nodes) Thymus Spleen Tonsils 5 6 Bone Marrow • Production site of WBC – Lymphocytes • generated from stem cells (Undifferentiated cells) • B lymphocytes (B cells) – Mature in bone marrow – Enter Circulation (“B” “Blood”) – 10%-20% • T lymphocytes – Move from bone marrow to (t)hymus (“tissue”) to mature into several kinds of cells capable of different functions – 60%-70% 7 White Blood Cell Action • Participate in both natural and acquired – Granulocytes (granular leukocytes) • Fight invasion by mediator release that engulfs foreign bodies and toxins – Histamine – Bradykinin – Prostaglandins 8 Granulocytes – Neutrophils • First to arrive at the scene of inflammation – Eosinophils and Basophils • increase in number during allergic reactions and stress response – Monocytes and macrophages • Engulfs, ingests, destroys – Lymphocytes • B cells and T cells • Plays major roles in humoral and cell medicated immune responses 9 Lymphoid Organs • Central (primary) – Thymus gland –Differentiation and maturation of T lymphocytes –Essential for cell-mediated immune response –Gland is large in childhood –Shrinks to be collection of reticular fibers 10 The human lymphoid system has the following Secondary Organs: • Peripheral (lymph nodes)at or near possible portals of entry for pathogens: • adenoids, tonsils, spleen (located at the upper left of the abdomen), • lymph nodes (along the lymphatic vessels with concentrations in the neck, armpits, abdomen, and groin) • Peyer's patches (within the intestines) • The appendix. 11 Lymphoid Organs – Tonsils (adenoids)- Associated lymphoid tissues – Gut- Associated lymphoid tissues – Genital- Associated lymphoid tissues – Bronchial- Associated lymphoid tissues – Skin-Associated lymphoid tissues 12 Lymphoid Tissues • Lymph nodes distributed throughout body • Connected by lymph channels and capillaries • Removes foreign material before entering bloodstream • Lymph nodes serve as immune cell proliferation 13 Lymphoid Organs – Spleen (composed of red & white pulp) • • • • • • • Red-destruction / recycling material White-T and B lymphocytes Filters foreign substances from blood Red pulp-erythrocytes Macrophages line pulp and sinuses Major site of blood-borne antigens If removed, can predispose to life-threatening septicemia 14 Types of Immunity • Classified as: – Natural (innate) • • • • Non-specific response to foreign invasion Not produced by an immune response Exists in a person without prior contact with an antigen Usually species specific – Acquired • Active • Passive 15 Physical and Chemical Barriers • Human body protects itself from invasion by foreign substances (microorganisms) • Complex defense system • Nonspecific protection mechanisms – Skin – Cilia – Coughing and Sneezing 16 Physical and Chemical Barriers • Chemical barriers – Enzymes in tears – Saliva enzymes – Gastric acid secretions – Mucus – Sebaceous and sweat – Phagocytosis by some WBCs 17 Inflammatory Response • Major function of the natural (non-specific or innate) immune system • Chemical mediators assist to: – minimize blood loss – wall off invading organism – Activate phagocytes – Promote formation of fibrous scar tissue – Regenerate injured tissue 18 Inflammatory Response • Dysfunction when immune component are inactivated or when they remain active long after their effects are beneficial 19 Immunodeficiencies • Immune components – Inactivation – Impairment • Disorders of inflammatory component – Asthma – “Allergies” – Arthritis Persistent inflammatory responses “foreign rather than self” 20 Types of Immunity • Active Acquired – Results from invasion – Development of subsequent antibodies and sensitized lymphocytes – With each reinvasion, response to fight off invader is more rapid and vigorous – Results from disease or through inoculation of less virulent antigen – Takes time to develop but long-lasting 21 Types of Immunity • Passive Acquired – Implies the host receives antibodies to an antigen rather than synthesizing them – May take place naturally through transfer of immunoglobulins (mommy-baby) – Artificial occurs through injection with gammaglobulin – Short lived (host didn’t make it) – Does not retain memory cells for the antigen 22 Humoral Immunity • Immunoglobulins – – – – – Composed of amino acids Essential component in humoral response IgG- only one that crosses placenta, secondary immunity IgA- lines Mucous membranes, protects body surfaces IgM- primary immune response, antibodies to ABO blood antigens – IgD- plasma, assists in differentiation of B-lymphocytes – IgE- plasma, causes symptoms of allergic reactions, assists in defense of parasitic infections 23 Cell- mediated Immunity • Cytokines – Immune response involves complex interactions of T-cells, B-cells, monocytes, and neutrophils - depends on Cytokines – Acts as messenger between the cell types – Instruct cells to alter their proliferation, differentiation, secretion, or activity – 60 different ones – Can have detrimental effects in inflammation, autoimmunity, and infection 24 Cell- mediated Immunity • Macrophages – Cytokines attract and activate macrophages in area for immune response – Macrophages secrete cytokines which modulate response – They release lysosomal enzymes that damage surrounding tissue 25 Haptens • low molecular weight substances that by themselves are harmless, however, they can form complexes with larger molecules called carriers that are antigenic • Once antibodies produced, future exposure to hapten alone can elicit immune response • Common Haptens – – – – Dust Dander Drugs Industrial chemicals • Immune responses to haptens are basis for many common allergies 26 Cell- mediated Immunity • Immune responses that are initiated through specific antigen recognition by T cells • T lymphocytes – T-cytotoxic • Attacks antigen on cell membrane and “pours” cytolytic substance on it – T-helper • Positive signal, humoral antibody response, cellmediated immunity – T-suppressor • Decreases amount of T-helper cells 27 T helper Cells • Maximizes capabilities of immune system • They have NO cytotoxic or phagocytic activity, they do not kill • Make the antibodies recognize the antigen by tagging them (cytokines) and get T cells and B cells activated to attack antigen and or initiate inflammatory response • helps signal other cells (like phagocytes) to do their jobs. 28 T-killer cell (cytoxic T cells) • Differentiated T cells • Destroys target cells only when specifically activated by helper T cells. • Recognize and lyse target cells bearing a specific foreign antigen, usually by infection with a virus • Also function in defense against cancer cells. Also called cytotoxic T cell, killer T cell. 29 Cell- mediated Immunity • Macrophages • Natural killer cells (NK) – Not T and not B – Large lymphocytes – Do not require prior sensitization for their generation – Involved in the recognition and killing of virusinfected cells, tumor cells, and transplanted grafts – Has significant role in immune surveillance for malignant cells 30 Cellular Responses (T Cells) • • • • • • Transplant rejection Delayed hypersensitivity (tuberculin reaction) Graft vs. host disease Tumor surveillance or destruction Intracellular infections Viral, fungal and parasitic infections 31 Humoral Responses (B cells) • • • • • Bacterial phagocytosis and lysis Anaphylaxis Allergy hay fever and asthma Immune complex disease Bacterial and some viral infections 32 Complement System • Circulating plasma proteins (made in liver, activated when antibody couples with its antigen • Interact sequentially with one another • Cascade of events – Alters cell membranes on which antigen-antibody complex forms – Permits fluid to enter cell – Cell lysis and death – Attracts macrophages and granulocytes to areas of antigenantibody reactions – Devours antibody-coated microbes and releases bacterial agents 33 Complement System • Activation of complement has 3 major physiologic functions – Defending body against bacterial infection – Bridging natural and acquired immunity – Disposing of immune complexes and byproducts of inflammation 34 Complement-mediated Immune Responses Cytolysis Lysis and destruction of cell membranes of body cells or pathogens Iosonization Targeting of antigen to be easily engulfed and digested by macrophages, etc. Chemotaxis Chemical attraction of neutrophils and phagocytic cells to the antigen Anaphylaxis Activation of mast cells and basophils with inflammatory mediator release smooth muscle contraction and increased vascular permeability 35 Genetic Engineering • • • • Evolving technology Involves use of recombinant DNA Combine genes of a second organism Allows for cells and microorganisms to manufacture proteins, monokines and lymphkines • Can alter and enhance immune function • Gene therapy –replace missing or damaged gene 36 Stem Cells • Precursor cell that continually replenishes red and white cells • Immune system restored with implanted refurbished stem cells 37 Immunoregulation • Eliminating the inciting antigen that has stimulated the immune response • When eliminated (as cascade cools down) the response goes back to normal level • Can better control disease by suppressing areas of immune system that are overactive • Boosting those areas that are under-active 38 Immunity • Affected by: – Age – Predisposition – CNS function – Emotional status, Stress – Medications – Trauma – Surgery – Illness 39 Stress and the Immune System • Stress of any type and duration will effect the immune system • Stress causes increased CORTISOL production • Cortisol decreases production of ANTIBODIES and other substances released by leukocytes that stimulate other cells of the immune system 40 Stress and the Immune System • Cortisol production occurs when norepinephrine and epinephrine are released by the SNS (FIGHT or FLIGHT) • The combined effect of these three hormones increases the total number of neutrophils in the circulation 41 Stress and the Immune System • Lymphocyte maturation in the lymph nodes stops because epinephrine decreases blood flow to the lymph nodes as it increases blood flow to the heart, lungs, brain and muscles • These changes in the immune response brought on by stress leave the body less capable of fighting off the effects of injury, disease, and other stress causes 42 Stress Response 43 Renin angiotensin aldosterone mechanism 44 Things That Can Go Wrong With the Immune System • Disorders of the immune system can be broken down into four main categories: • immunodeficiency disorders (primary or acquired) • autoimmune disorders (in which the body's own immune system attacks its own tissue as foreign matter) • allergic disorders (in which the immune system overreacts in response to an antigen) • cancers of the immune system 45 Immunity • The immune response that generates immunity is also responsible in some situations for – Allergies – Delayed hypersensitivity states – Autoimmune disease – And Transplant Rejection. 46