1.IMMUNITY AND IMMUNE SYSTEM PREPARED BY: ASOGWA INNOCENT KINGSLEY ( ) -508SUBMITED TO: DR.

2. IMMUNITY Is the state of having sufficient biologicaldefenses to avoid infection, disease, or other unwanted biological invasion. It is the capability of the body to resist harmful microbes from entering it. Immunity involves both specific and nonspecific components 3. IMMUNE SYSTEM is a system of biological structures and processes within anorganism that protects against disease. To function properly, an immune system must detect a wide variety of agents, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. The immune system recognizes foreign bodies and responds with the production of immune cells and proteins Barriers help an organism to defend itself from the many dangerous pathogens it may encounter 4. BARRIER DEFENSES Barrier defenses include the skin and mucousmembranes of the respiratory, urinary, and reproductive tracts Mucus traps and allows for the removal of microbes Many body fluids including saliva, mucus, and tears are hostile to microbes The low pH of skin and the digestive system prevents growth of microbes 5. CLASSIFICATION 6. Pathogens (microorganisms and viruses)INNATE IMMUNITY Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Rapid responseACQUIRED IMMUNITY Recognition of traits specific to particular pathogens, using a vast array of receptors Slower responseBarrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. 7. INNATE IMMUNITY nonspecific immunity is the natural resistances with which a person is born. It provides resistances through several physical, chemical and cellular approaches. Microbes first encounter the epithelial layers, physical barriers that line skin and mucous membranes. Subsequent general defenses include secreted chemical signals (cytokines), antimicrobial substances, fever, and phagocytic activity associated with the inflammatory responses. The phagocytes express cell surface receptors that can bind and respond to common molecular patterns expressed on the surface of invading microbes. Through these approaches, innate immunity can prevent the colonization, entry and spread of microbes. 8. A white blood cell engulfs a microbe, then fuseswith a lysosome to destroy the microbe There are different types of phagocytic cells: Neutrophils engulf and destroy microbes Macrophages are part of the lymphatic system and are found throughout the body Eosinophils discharge destructive enzymes Dendritic cells stimulate development of acquired immunity 9. ANTIMICROBIAL PEPTIDES AND PROTEINS Peptides and proteins function in innate defenseby attacking microbes directly or impeding their reproduction Interferon proteins provide innate defense against viruses and help activate macrophages About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation 10. Fig. 43-7Interstitial fluid Adenoid TonsilBlood capillaryLymph nodes SpleenTissue cellsLymphatic vesselPeyers patches (small intestine) AppendixLymphatic vesselsLymph nodeMasses of defensive cells 11. Inflammatory Responses Following an injury, mast cells release histamine,which promotes changes in blood vessels; this is part of the inflammatory response These changes increase local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation 12. Fig. 43-8-3PathogenSplinterChemical Macrophage signals Mast cell CapillaryRed blood cells Phagocytic cellFluid Phagocytosis 13. CLASSIFICATION 14. ACQUIRED IMMUNITY Adaptive immunity /Specific sub-divided into two major types depending on how theimmunity was introduced: Naturally acquired immunity occurs through contact with a disease causing agent, when the contact was not deliberate Artificially acquired immunity develops only through deliberate actions such as vaccination.N/B: Memory cells are only produced in active immunity. Protection for active immunity is permanent whereas in passive immunity it is only temporary. Antigens are only encountered in active immunity. Active immunity takes several weeks to become active but passive is immediate. 15. NATURAL ACQUIRED IMMUNITY Subdivided into: Naturally acquired active immunity: occurs when a person isexposed to a live pathogen, and develops a primary immune response, which leads to immunological memory. This type of immunity is natural because it is not induced by deliberate exposure. Many disorders of immune system function can affect the formation of active immunity such as immunodeficiency (both acquired and congenital forms) and immunosuppression. Naturally acquired passive immunity: Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus by its mother during pregnancy through placenta. IgG is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies. 16. ARTIFICIAL ACQUIRED IMMUNITY Artificially acquired active immunity: can be induced by avaccine, a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease. Artificially acquired passive immunity: is a short-term immunization induced by the transfer of antibodies, which can be administered in several forms; as human or animal blood plasma, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, and in the form of monoclonal antibodies (MAb). Passive transfer is used prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia. It is also used in the treatment of several types of acute infection, and to treat poisoning. Immunity derived from passive immunization lasts for only a short period of time, and there is also a potential risk for hypersensitivity reactions, and serum sickness, especially from gamma globulin of non-human origin. 17. IN ACQUIRED IMMUNITY, LYMPHOCYTE RECEPTORS PROVIDE PATHOGEN-SPECIFIC RECOGNITION White blood cells called lymphocytes recognize and respond to antigens, foreign molecules Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells Lymphocytes contribute to immunological memory, an enhanced response to a foreign molecule encountered previously Cytokines are secreted by macrophages and dendritic cells to recruit and activate lymphocytes The acquired immune system has three important properties: Receptor diversity A lack of reactivity against host cells Immunological memory 18. ACQUIRED IMMUNITY: AN OVERVIEW B cells and T cells have receptor proteins that can bind toforeign molecules Each individual lymphocyte is specialized to recognize a specific type of molecule All antigen receptors on a single lymphocyte recognize the same epitope, or antigenic determinant, on an antigen B cells give rise to plasma cells, which secrete proteins called antibodies or immunoglobulins 19. Fig. 43-9Antigenbinding siteAntigenbinding siteAntigenbinding site Disulfide bridgeVariable regionsLight chainCCVVConstant regionsCCTransmembrane region Plasma membrane chain chainDisulfide bridge T cellHeavy chainsB cell (a)B cell receptorCytoplasm of B cellCytoplasm of T cell(b)T cell receptor 20. Fig. 43-10Antigenbinding sites Antigen-binding sitesAntibody A Antigen Antibody CCC Antibody BEpitopes (antigenic determinants) 21. THE ANTIGEN RECEPTORS OF B CELLS B cell receptors bind to specific, intact antigens The B cell receptor consists of two identical heavy chains andtwo identical light chains The tips of the chains form a constant (C) region, and each chain contains a variable (V) region, so named because its amino acid sequence varies extensively from one B cell to another Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane 22. THE ANTIGEN RECEPTORS OF T CELLS Each T cell receptor consists of two different polypeptide chains The tips of the chain form a variable (V) region; the rest is a constant (C) region T cells can bind to an antigen that is free or on the surface of a pathogen T cells bind to antigen fragments presented on a host cell These antigen fragments are bound to cell-surface proteins called MHC molecules MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex 23. THE ROLE OF THE MHC In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation A nearby T cell can then detect the antigen fragment displayed on the cells surface Depending on their source, peptide antigens are handled by different classes of MHC molecules: Class I MHC molecules are found on almost all nucleated cells of the body They display peptide antigens to cytotoxic T cells Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells Dendritic cells, macrophages, and B cells are antigen-presenting cells that display antigens to cytotoxic T cells and helper T cells 24. Fig. 43-12Infected cellMicrobeAntigenpresenting cell1 Antigen associates with MHC moleculeAntigen fragmentAntigen fragment1 1Class I MHC molecule T cell receptor(a)22Cytotoxic T cellClass II MHC molecule T cell receptor2 T cell recognizes combination(b)Helper T cell 25. AMPLIFYING LYMPHOCYTES BY CLONAL SELECTION In the body there are few lymphocytes with antigen receptorsfor any particular epitope The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly This proliferation of lymphocytes is called clonal selection Two types of clones are produced: - short-lived activated effector cells and - long-lived memory cells 26. Fig. 43-14Antigen molecules B cells that differ in antigen specificityAntigen receptorAntibody moleculesClone of memory cellsClone of plasma cells 27. IMMUNE RESPONSE The first exposure to a specific antigen represents theprimary immune response During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms In the secondary immune response, memory cells facilitate a faster, more efficient response 28. Fig. 43-15Antibody concentration (arbitrary units)Primary immune response to antigen A produces antibodies to A.Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B.104 103 Antibodies to A102Antibodies to B101 10007Exposure to antigen A1421283542Exposure to antigens A and B Time (days)4956 29. ACQUIRED IMMUNITY DEFENDS AGAINST INFECTION OF BODY CELLS AND FLUIDS Acquired immunity has two branches:-the humoral immune response and - the cell-mediated immune response Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells Helper T cells aid both responses 30. Fig. 43-16 Humoral (antibody-mediated) immune responseCell-mediated immune response KeyAntigen (1st exposure)+Engulfed byGives rise toAntigenpresenting cell+Stimulates++B cellHelper T cell+Cytotoxic T cell+Memory Helper T cells+++Antigen (2nd exposure) Plasma cellsMemory B cells+Memory Cytotoxic T cellsActive Cytotoxic T cellsSecreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins.Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells. 31. Fig. 43-16aHumoral (antibody-mediated) immune responseKey +Antigen (1st exposure) Stimulates Gives rise toEngulfed byAntigenpresenting cell++ B cellHelper T cell+Memory Helper T cells+ Plasma cells+ Antigen (2nd exposure)Memory B cellsSecreted antibodies Defend against extracellular pathogens+ 32. Fig. 43-16bCell-mediated immune response Key +Antigen (1st exposure) Engulfed by Antigenpresenting cellStimulates Gives rise to++ Helper T cellCytotoxic T cell+Memory Helper T cells+ + Antigen (2nd exposure) +Active Cytotoxic T cellsMemory Cytotoxic T cellsDefend against intracellular pathogens 33. T HELPER CELLS: A RESPONSE TO NEARLY ALL ANTIGENS A surface protein called CD4 binds the class II MHCmolecule This binding keeps the helper T cell joined to the antigenpresenting cell while activation occurs Activated helper T cells secrete cytokines that stimulate other lymphocytes 34. Fig. 43-17Antigenpresenting cellPeptide antigenBacterium Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Humoral immunity (secretion of antibodies by plasma cells)Cytokines+ B cell+++ Cytotoxic T cellCell-mediated immunity (attack on infected cells) 35. CYTOTOXIC T CELLS: A RESPONSE TO INFECTED CELLS Cytotoxic T cells are the effector cells in cell-mediatedimmune response Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer The activated cytotoxic T cell secretes proteins that destroy the infected target cell 36. Fig. 43-18-3Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8TCRClass I MHC moleculeTarget cellDying target cell PorePeptide antigen 37. B CELLS: A RESPONSE TO EXTRACELLULAR PATHOGENS The humoral response is characterized by secretion ofantibodies by B cells Activation of B cells is aided by cytokines and antigen binding to helper T cells Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity 38. Fig. 43-19Antigen-presenting cellBacterium Peptide antigenB cellClass II MHC molecule TCRClone of plasma cells+ CD4CytokinesSecreted antibody moleculesEndoplasmic reticulum of plasma cellHelper T cellActivated helper T cellClone of memory B cells2 m 39. ANTIBODY CLASSES The five major classes of antibodies, or immunoglobulins,differ in distribution and function Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen Monoclonal antibodies are prepared from a single clone of B cells grown in culture 40. Fig. 43-20aClass of Immunoglobulin (Antibody) IgM (pentamer)J chainDistributionFirst Ig class produced after initial exposure to antigen; then its concentration in the blood declinesFunctionPromotes neutralization and crosslinking of antigens; very effective in complement system activation 41. Fig. 43-20bClass of Immunoglobulin (Antibody) IgG (monomer)DistributionMost abundant Ig class in blood; also present in tissue fluidsFunctionPromotes opsonization, neutralization, and cross-linking of antigens; less effective in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus 42. Fig. 43-20cClass of Immunoglobulin (Antibody)IgA (dimer) J chainSecretory componentDistribution Present in secretions such as tears, saliva, mucus, and breast milkFunction Provides localized defense of mucous membranes by cross-linking and neutralization of antigens Presence in breast milk confers passive immunity on nursing infant 43. Fig. 43-20dClass of Immunoglobulin (Antibody) IgE (monomer)Distribution Present in blood at low concentrationsFunction Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions 44. Fig. 43-20eClass of Immunoglobulin (Antibody) IgD (monomer)Transmembrane regionDistributionPresent primarily on surface of B cells that have not been exposed to antigensFunctionActs as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) 45. THE ROLE OF ANTIBODIES IN IMMUNITY Neutralization occurs when a pathogen can no longer infecta host because it is bound to an antibody Opsonization occurs when antibodies bound to antigens increase phagocytosis Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis 46. Fig. 43-21Viral neutralizationOpsonizationActivation of complement system and pore formationBacteriumComplement proteins Virus Formation of membrane attack complex Flow of water and ionsMacrophagePoreForeign cell 47. 1. 2. 3. 4.5. 6.7. 8. 9.You should now be able to:Distinguish between innate and acquired immunity Name and describe four types of phagocytic cells Describe the inflammation response Distinguish between the following pairs of terms: antigens and antibodies; antigen and epitope; B lymphocytes and T lymphocytes; antibodies and B cell receptors; primary and secondary immune responses; humoral and cell-mediated response; active and passive immunity Explain how B lymphocytes and T lymphocytes recognize specific antigens 6. Describe clonal selection and distinguish between effector cells and memory cells Describe the cellular basis for immunological memory Explain how a single antigen can provoke a robust humoral response Compare the processes of neutralization and opsonization