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Immune response

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  • 1.
    • The Immune Response
    • Immunity : “Free from burden”. Ability of an organism to recognize and defend itself against specific pathogens or antigens.
    • Immune Response : Third line of defense. Involves production of antibodies and generation of specialized lymphocytes against specific antigens.
    • Antigen : Molecules from a pathogen or foreign organism that provoke a specific immune response.
  • 2. The Immune System is the Third Line of Defense Against Infection
  • 3.
    • Innate or Genetic Immunity : Immunity an organism is born with.
      • Genetically determined.
      • May be due to lack of receptors or other molecules required for infection.
        • Innate human immunity to canine distemper.
        • Immunity of mice to poliovirus.
    • Acquired Immunity :Immunity that an organism develops during lifetime.
      • Not genetically determined.
      • May be acquired naturally or artificially.
        • Development of immunity to measles in response to infection or vaccination.
  • 4.
    • Types of Acquired Immunity
    • I. Naturally Acquired Immunity : Obtained in the course of daily life.
      • A. Naturally Acquired Active Immunity :
      • Antigens or pathogens enter body naturally.
      • Body generates an immune response to antigens.
      • Immunity may be lifelong (chickenpox or mumps) or temporary (influenza or intestinal infections).
      • B. Naturally Acquired Passive Immunity :
      • Antibodies pass from mother to fetus via placenta or breast feeding ( colostrum ).
      • No immune response to antigens.
      • Immunity is usually short-lived (weeks to months).
      • Protection until child’s immune system develops.
  • 5.
    • Types of Acquired Immunity (Continued)
    • II. Artificially Acquired Immunity : Obtained by receiving a vaccine or immune serum.
      • 1. Artificially Acquired Active Immunity :
      • Antigens are introduced in vaccines ( immunization ).
      • Body generates an immune response to antigens.
      • Immunity can be lifelong (oral polio vaccine) or temporary (tetanus toxoid).
      • 2. Artificially Acquired Passive Immunity :
      • Preformed antibodies ( antiserum ) are introduced into body by injection.
        • Snake antivenom injection from horses or rabbits.
      • Immunity is short lived (half life three weeks).
      • Host immune system does not respond to antigens.
  • 6.
    • Serum : Fluid that remains after blood has clotted and cells have been removed.
    • Antiserum : Serum containing antibodies to a specific antigen(s). Obtained from injecting an animal (horse, rabbit, goat) with antigen (snake venom, botulism or diphtheria toxin).
    • Serology : The study of reactions between antibodies and antigens.
    • Gamma Globulins : Fraction of serum that contains most of the antibodies.
    • Serum Sickness : Disease caused by multiple injections of antiserum. Immune response to foreign proteins. May cause fever, kidney problems, and joint pain. Rare today.
  • 7. ANATOMY OF THE IMMUNE SYSTEM
    • The immune system is localized in several parts of the body
      • immune cells develop in the primary organs - bone marrow and thymus (yellow)
      • immune responses occur in the secondary organs (blue)
  • 8. ANATOMY OF THE IMMUNE SYSTEM
    • Thymus – glandular organ near the heart – where T cells learn their jobs
    • Bone marrow – blood-producing tissue located inside certain bones
      • blood stem cells give rise to all of the different types of blood cells
    • Spleen – serves as a filter for the blood
      • removes old and damaged red blood cells
      • removes infectious agents and uses them to activate cells called lymphocytes
    • Lymph nodes – small organs that filter out dead cells, antigens, and other “stuff” to present to lymphocytes
    • Lymphatic vessels – collect fluid (lymph) that has “leaked” out from the blood into the tissues and returns it to circulation
  • 9. Antibodies are Produced by B Lymphocytes
  • 10. Antibodies are Proteins that Recognize Specific Antigens
  • 11.
    • Antigens
    • Most are proteins or large polysaccharides from a foreign organism.
      • Microbes : Capsules, cell walls, toxins, viral capsids, flagella, etc.
      • Nonmicrobes : Pollen, egg white , red blood cell surface molecules, serum proteins, and surface molecules from transplanted tissue.
    • Lipids and nucleic acids are only antigenic when combined with proteins or polysaccharides.
    • Molecular weight of 10,000 or higher.
      • Hapten : Small foreign molecule that is not antigenic. Must be coupled to a carrier molecule to be antigenic. Once antibodies are formed they will recognize hapten.
  • 12.
    • Antigens
    • Epitope :
    • Small part of an antigen that interacts with an antibody.
    • Any given antigen may have several epitopes.
    • Each epitope is recognized by a different antibody.
  • 13.
    • Antibodies
    • Proteins that recognize and bind to a particular antigen with very high specificity .
    • Made in response to exposure to the antigen.
    • One virus or microbe may have several antigenic determinant sites , to which different antibodies may bind.
    • Each antibody has at least two identical sites that bind antigen: Antigen binding sites .
    • Valence of an antibody : Number of antigen binding sites. Most are bivalent .
    • Belong to a group of serum proteins called immunoglobulins (Igs).
  • 14.
    • How Do B Cells Produce Antibodies?
      • B cells develop from stem cells in the bone marrow of adults (liver of fetuses).
      • After maturation B cells migrate to lymphoid organs (lymph node or spleen).
      • Clonal Selection : When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cells , which actively secrete antibodies.
      • Each B cell produces antibodies that will recognize only one antigenic determinant.
  • 15.
    • Apoptosis
      • Programmed cell death (“Falling away”).
      • Human body makes 100 million lymphocytes every day. If an equivalent number doesn’t die, will develop leukemia.
      • B cells that do not encounter stimulating antigen will self-destruct and send signals to phagocytes to dispose of their remains.
      • Many virus infected cells will undergo apoptosis, to help prevent spread of the infection.
  • 16. Consequences of Antibody Binding
  • 17.
    • Protection Against Invading Pathogens
      • 1. First Line of Defense : Non-specific natural barriers which restrict entry of pathogen.
      • Examples : Skin and mucous membranes.
      • 2. Second Line of Defense : Innate non-specific immune defenses provide rapid local response to pathogen after it has entered host.
      • Examples : Fever, phagocytes (macrophages and neutrophils), inflammation , and interferon.
      • 3. Third line of defense: Antigen - specific immune responses, specifically target and attack invaders that get past first two lines of defense.
      • Examples : Antibodies and lymphocytes.
  • 18.
    • First Line of Defense:
        • Skin and Mucous Membranes
    • I. Mechanical Defenses
      • 1. Skin has two Layers:
      • A. Epidermis : Thin outer layer of epithelial tissue.
      • Contains Langerhans cells, dead cells, and keratin (waterproof).
      • B. Dermis : Thick inner layer of connective tissue.
      • Infections are rare in intact skin. Exceptions:
        • Hookworms can penetrate intact skin
        • Dermatophytes: “Skin loving” fungi
  • 19. Intact Skin is an Effective Barrier Against Most Pathogens
  • 20.
      • I. Mechanical Defenses
      • 2. Mucous Membranes : Line gastrointestinal, genitourinary, and respiratory tracts.
      • Two layers: Outer epithelial and inner connective layer.
      • Epithelial layer secretes mucus which maintains moist surfaces.
      • Although they inhibit microbial entry, they offer less protection than skin.
      • Several microorganisms are capable of penetrating mucous membranes:
        • Papillomavirus
        • Treponema pallidum
        • E nteroinvasive E. coli
        • Entamoeba histolytica
  • 21.
      • I. Mechanical Defenses
      • 3. Lacrimal apparatus : Continual washing and blinking prevents microbes from settling on the eye surface.
      • 4. Saliva : Washes microbes from teeth and mouth mucous membranes.
      • 5. Mucus : Thick secretion that traps many microbes.
      • 6. Nose Hair : Coated with mucus filter dust, pollen, and microbes.
      • 7. Ciliary Escalator : Cilia on mucous membranes of lower respiratory tract move upwards towards throat at 1-3 cm/hour.
  • 22.
      • I. Mechanical Defenses
      • 8. Coughing and sneezing : Expel foreign objects.
      • 9. Epiglottis : Covers larynx during swallowing.
      • 10. Urination : Cleanses urethra.
      • 11. Vaginal Secretions : Remove microbes from genital tract.
  • 23.
    • B. Chemical Defenses:
      • Sebum : Oily substance produced by sebaceous glands that forms a protective layer over skin. Contains unsaturated fatty acids which inhibit growth of certain pathogenic bacteria and fungi.
      • pH : Low, skin pH usually between 3 and 5. Caused by lactic acid and fatty acids.
      • Perspiration : Produced by sweat glands. Contains lysozyme and acids.
      • Lysozyme : Enzyme that breaks down gram-positive cell walls. Found in nasal secretions, saliva, and tears.
  • 24.
    • B. Chemical Defenses (Continued)
      • Gastric Juice : Mixture of hydrochloric acid, enzymes, and mucus. pH between 1.2 to 3 kills many microbes and destroys most toxins. Many enteric bacteria are protected by food particles.
        • Helicobacter pylori neutralizes stomach acid and can grow in the stomach, causing gastritis and ulcers.
      • Transferrins : Iron-binding proteins in blood which inhibit bacterial growth by reducing available iron.
  • 25.
    • II. Second Line of Defense
      • 1. Phagocytosis :
      • Derived from the Greek words “Eat and cell”.
      • Phagocytosis is carried out by white blood cells: macrophages, neutrophils, and occasionally eosinophils.
      • Neutrophils predominate early in infection.
      • Wandering macrophages : Originate from monocytes that leave blood and enter infected tissue, and develop into phagocytic cells.
      • Fixed Macrophages (Histiocytes): Located in liver, nervous system, lungs, lymph nodes, bone marrow, and several other tissues.
  • 26. Phagocytic Cells: Macrophages (Monocytes), Neutrophils, and Eosinophils (Macrophages)
  • 27. Process of Phagocytosis
  • 28.
    • Inflammation
    • Triggered by tissue damage due to infection, heat, wound, etc.
    • Four Major Symptoms of Inflammation:
    • 1. Redness
    • 2. Pain
    • 3. Heat
    • 4. Swelling
    • May also observe:
    • 5. Loss of function
  • 29.
    • Functions of Inflammation
    • 1. Destroy and remove pathogens
    • 2. If destruction is not possible, to limit effects by confining the pathogen and its products.
    • 3. Repair and replace tissue damaged by pathogen and its products.
  • 30.
      • Stages of Inflammation
      • 1. Vasodilation : Increase in diameter of blood vessels.
      • Triggered by chemicals released by damaged cells: histamine, kinins, prostaglandins, and leukotrienes.
      • 2. Phagocyte Migration and Margination : Margination is the process in which phagocytes stick to lining of blood vessels.
      • Diapedesis (Emigration) : Phagocytes squeeze between endothelial cells of blood vessels and enter surrounding tissue.
  • 31. Process of Inflammation
  • 32.
      • Stages of Inflammation (Continued)
      • Phagocytes are attracted to site of infection through chemotaxis.
      • Phagocytes destroy microbes, as well as dead and damaged host cells.
      • 3. Tissue Repair : Dead and damaged cells are replaced.
  • 33.
      • Antimicrobial Substances :
      • I. Complement System : Large group of serum proteins that participate in the lysis of foreign cells, inflammation, and phagocytosis.
      • Two mechanisms of complement activation:
      • 1. Classical Pathway : Initiated by an immune reaction of antibodies .
      • 2. Alternative Pathway : Initiated by direct interaction of complement proteins with microbial polysaccharides .
      • Both pathways cleave a complement protein called C3, which triggers a series of events .
  • 34. Both Classical and Alternative Complement Pathways Trigger the Cleavage of C3
  • 35.
      • II. Interferons: Antiviral proteins that interfere with viral multiplication.
      • Small proteins (15,000 to 30,000 kDa)
      • Heat stable and resistant to low pH
      • Important in acute and short term infections.
      • Have no effect on infected cells.
      • Host specific, but not virus specific .
      • Interferon alpha and beta: Produced by virus infected cells and diffuse to neighboring cells. Cause uninfected cells to produce antiviral proteins (AVPs).
      • Interferon gamma: Produced by lymphocytes. Causes neutrophils to kill bacteria.
  • 36. Natural killer cells (NK cells)
    • instead of attacking the invaders, they attack the body’s own cells that have become infected by viruses
    • they also attack potential cancer cells, often before they form tumors
    • they bind to cells using an antibody “bridge”, then kill it by secreting a chemical (perforin) that makes holes in the cell membrane of the target cell. With enough holes, the cell will die, because water rushing inside the cell will induce osmotic swelling, and an influx of calcium may trigger apoptosis.
  • 37. Mast cells
    • are found in tissues like the skin, near blood vessels.
    • are activated after antigen binds to a specific type of antibody called IgE that is attached to receptors on the mast cell.
    • activated mast cells release substances that contribute to inflammation, such as histamine.
    • mast cells are important in allergic responses but are also part of the innate immune response, helping to protect from infection.
  • 38. Structures of the Immune System
    • Unlike other body systems, Immune System is NOT contained within a single set of organs or vessels
    • Action depends on structures from lymphatic, cardiovascular, and Integumentary systems
    • Works primarily through antigen-antibody reaction
  • 39. Organs of The Immune System The organs of the immune system are stationed throughout the body. They are known as lymphoid organs because they are concerned with the growth, development, and deployment of lymphocytes white blood cells that are key operatives of the immune system.
  • 40. Functions of the Lymph System
    • lymph/o
    • drain fluid from tissue spaces and return to it to the blood
    • transport materials (nutrients, hormones and oxygen) to body cells
    • carry away waste products to the blood
    • transport lipids away from digestive system
    • control of infection
  • 41.
    • The lymphatic system
      • Plays an active role in defending the body from pathogens
    Adenoid Tonsil Lymph nodes Spleen Peyer’s patches (small intestine) Appendix Lymphatic vessels Masses of lymphocytes and macrophages Tissue cells Lymphatic vessel Blood capillary Lymphatic capillary Interstitial fluid Lymph node Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries. 1 Figure 43.5 Fluid inside the lymphatic capillaries, called lymph, flows through lymphatic vessels throughout the body. 2 Within lymph nodes, microbes and foreign particles present in the circulating lymph encounter macro- phages, dendritic cells, and lymphocytes, which carry out various defensive actions. 3 Lymphatic vessels return lymph to the blood via two large ducts that drain into veins near the shoulders. 4
  • 42. Lymph System
    • Lymph originates in blood plasma
    • Interstitial fluid
    • cleans and nourishes body tissues
    • collects cellular debris, bacteria
    • return to blood or lymph capillaries
  • 43.  
  • 44. Lymphoid organs
    • Peripheral – remove and destroy antigens in the blood and lymph
      • Tonsils
      • Lymph nodes
      • Spleen
      • Intestinal lymphoid tissues
    • Central – site of maturation of cells
      • Thymus
      • Bone marrow
  • 45. Lymphatic System
    • Major structures
      • lymph vessels
      • lymph nodes
      • lymph fluid
      • tonsils
    • Also
      • spleen
      • thymus
  • 46. Lymph capillaries
    • Closed-ended vessels
    • Lined by endothelium
    • 1-way flaps into capillary
      • Allows passage of tissue fluid, large proteins, bacteria, viruses, cancer cells, cell debris
  • 47. Lymph capillaries
    • Found in all areas of blood capillaries except:
      • Bone, teeth, bone marrow, CNS
    • Lacteals – lymph capillaries in villi of small intestine transports fat (chyle) [compare with blood capillaries]
  • 48. Lymphatic Vessels
    • Lymphatic Collecting Vessels
      • Receive lymph from lymphatic capillaries
      • Have the same 3 tunics as veins, but:
        • Are thinner, have more internal valves, and anastomose more
    • Lymphatic Trunks
      • Formed from the union of the largest of the lymphatic collecting vessels
      • Drain large areas of the body
  • 49. Lymphatic Vessels
    • Lymphatic Ducts
      • 2 vessels that receive lymph from lymphatic trunks
        • Right Lymphatic Duct
          • Drains lymph from the right upper arm and the right side of the head and the thorax
          • Empties into the vascular system at the junction of the right internal jugular vein and right subclavian vein
        • Thoracic Duct
          • Drains lymph from the left upper arm, left side of the head and thorax, and digestive organs, pelvis, and legs
          • Much larger
          • Empties into the vascular system at the junction of the left internal jugular vein and left subclavian vein
  • 50. Lymph Nodes
    • located in lymph vessels
    • small round or oval structures (filters)
    • depositories for cellular debris
    • bacteria and debris phagocytized
  • 51. Lymph Nodes
    • inside are masses of tissue which contain WBCs (lymphocytes)
    • almost always grouped 2 or 3 to 100
    • invading cells destroyed in nodes and often swell as an indicator of the disease process
  • 52.  
  • 53. Lymph Node Function
    • Multiple afferent lymphatic vessels enter a lymph at its hilus - the indented region on the concave side
    • Lymph percolates thru the node and it is scrutinized by macrophages and lymphocytes ready to mount an immune response
    • Lymph leaves via a few efferent lymphatic vessels
    • Lymph usually has to pass thru several nodes before it is “clean”
  • 54.  
  • 55. Lymph ducts
    • Thoracic (L) lymphatic duct
      • Drains ¾ of lymph
      • L head, neck, thorax, upper extremity
      • R&L abdomen, lower extremities
    • Right lymph duct
      • R head, neck, thorax, upper extremity
    • Ducts drain into subclavian veins
    20.6a
  • 56. Spleen
    • Largest lymphoid organ. About the size of a fist.
    • Location:
      • Left side of the abdominal cavity, just beneath the diaphragm and curling around the anterior stomach
    • Served by the splenic artery and vein which enter at its hilus
    • Surrounded by a fibrous CT capsule with inward extending trabeculae
  • 57.
    • Functions include:
      • Extracting old & defective RBCs and removal of debris and foreign matter from blood
      • Storage of blood platelets and iron
    • Internal structure consists of:
      • White Pulp
        • Smaller portion
        • Islands of lymphocytes and reticular fibers
      • Red Pulp
        • Venous sinuses and splenic cords (regions of reticular fibers and macrophages)
  • 58. Spleen
    • Functional tissue:
    • White pulp
      • Lymphocytes around central arteries
      • Immune response to antigens
      • Produces both B & T lymphocytes
  • 59. Spleen
    • Red pulp
      • Splenic cords
        • Lymphocytes
        • Reticular fibers
        • Macrophages
        • Cleanse blood
        • Remove old rbcs
  • 60. Tonsils
    • masses of lymph tissue designed to filter tissue fluid, not lymph
    • located beneath certain areas of moist epithelium exposed to outside and hence to contamination
    • any or all may become so loaded with bacteria that the pathogens gain dominance
    • should not be removed unless absolutely necessary.
  • 61. Tonsils
    • Form a ring of lymphoid tissue around the entrance to the pharynx
    • 3 main sets:
      • Palatine
        • Located on either side of the posterior oral cavity
        • Largest and infected most often
      • Lingual
        • Lie at the base of the tongue
      • Pharyngeal
        • Found in the posterior wall of the nasopharynx
        • Called adenoids when infected
  • 62. Tonsils
    • Aggregations of lymphocytes and lymph nodules
    • MALT – mucosa associated lympoid tissue
    20.12
  • 63. Thymus
    • Found in inferior neck and anterior thorax
    • Secretes hormones that allow T lymphocyte maturation
    • Prominent in newborns, it increases in size throughout childhood. In adolescence, it begins to atrophy and is fatty/ fibrotic in adults.
    • Only lymphoid organ that does not fight antigens
  • 64. Thymus
    • lymphatic tissue
    • mediastinum
    • primary role: changes lymphocytes to T cells for cellular immunity
  • 65. Features of Immune System
    • Self/Non self recognition
    • Immunological specificity
      • B and T cells zero in on certain kinds of pathogens; response is pathogen specific
    • Diversity
    • Immunological memory
      • Immune system recognizes and reacts swiftly to a pathogen it has “seen”
  • 66. Cells and tissues of the immune system
    • Pluripotential hematopoietic stem cells
    • Located within the bone marrow, fetal liver and yolk sac of the fetus
    • Stem cells differentiate into 2 types of “committed” stem cells
      • produce platelets, erythrocytes (red blood cells), monocytes or granulocytes.
      • produces cells of the lymphoid line only
  • 67.  
  • 68. Cells and Tissues of the Immune System
    • Cells of the immune system are found within the blood, body tissues, thymus, spleen, liver, lymph nodes and body areas exposed to the external environment.
    • These organs comprise the reticuloendothelial system (RES).
  • 69. Lymphocyte Activation
  • 70. B Cell Formation
    • Derived from stem cells in bone marrow
    • Acquire unique antigen-binding receptors in marrow
    • Receptors interact with just one antigen
    • Exposure to that antigen causes clonal selection
      • Division of cells specific for that antigen
  • 71. T Lymphocytes (T cells)
    • Derived from stem cells in the bone marrow.
    • Leave bone marrow and travel to the thymus to mature
    • Approximately 75 to 80% of lymphocytes are T cells.
    • Important in recognizing foreign material that is fixed in the tissues of cells.
  • 72. T Lymphocytes (T cells)
    • Play an important role in regulating the production of antibodies by B cells
      • Helper T cell
      • Suppressor T cell
      • Killer or Killer T cells
    • T cells have surface proteins known as cluster determinants (CDs)
      • Helper T cells are CD4 positive cells enhance and promote the action of other immune cells.
      • Suppressor T cells are CD8 positive and have suppressive or cytotoxic effects
  • 73. Composition of Human Blood
  • 74.
    • Cellular Elements of Blood
    • Cell Type # Cells/mm 3 Function
    • Erythrocytes (RBC) 4.8-5.4 million Transport O 2 and CO 2
    • Leukocytes (WBC) 5000-9000 Various
    • A. Granulocytes:
    • 1. Neutrophils (70% of WBC) Phagocytosis
    • 2. Basophils (1%) Produce histamine
    • 3. Eosinophils (4%) Toxins against parasites some phagocytosis
    • B. Monocytes/Macrophages (5%) Phagocytosis
    • C. Lymphocytes (20%) Antibody production (B cells)
    • Cell mediated immunity (T cells)
    • Platelets 300,000 Blood clotting
  • 75. Blood
    • hem /o and hemat /o
    • plasma - 55%
    • formed elements - 45%
    • serum - plasma without clotting proteins
  • 76. Blood Cells
    • RBC - erythrocytes - erythropoiesis
    • WBC - leukocytes - leukopoiesis
    • Platelets - thrombocytes - thrombopoiesis
  • 77. Erythrocytes
    • erythr/o - red
    • cyte - cell
    • Hemoglobin - blood protein transports oxygen
    • Reticulocyte - immature erythrocyte
    • RBCs produced by red bone marrow
  • 78. Leukocytes
    • leuk /o - white
    • Protect the body against invasion
    • Pass through capillary walls
  • 79.
    • Granulocytes
      • neutrophils (phagocytosis)
      • eosinophils (allergies)
      • basophils (promote inflammation)
    • Agranulocytes
      • lymphocytes (production of circulating antibodies)
      • monocytes (macrophages)
    • Collection of dead and living bacteria and leukocytes called pus, abscess .
  • 80. Lymphocytes
    • T cells or T Lymphocytes
      • mature in thymus gland
      • Cell mediated immunity
    • B cells or B Lymphocytes
      • mature in bone marrow
      • antibody-mediated immunity
  • 81. Thrombocytes
    • smallest formed element
    • made in bone marrow
    • essential to blood coagulation
    • If injury, blood comes in contact with any tissue other than the lining of the vessels, platelets stick together, form plug, seals wound. Chemicals released, series of reactions, formation of clot.
  • 82. Plasma
    • plasma
      • 92% water
      • 8% plasma proteins
        • albumin
        • globulin
        • fibrinogen
    • serum - plasma without clotting proteins or fibrinogen
  • 83. Functions of the Immune System
    • To protect the entire body from a variety of harmful substances
      • pathogenic microorganisms
      • allergens
      • toxins
      • malignant cells