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introduction to Immunology 1st and 2nd lecture

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introduction to Immunology 1st and 2nd lecture

  1. 1. Introduction to ImmunologyIntroduction to Immunology Lecture 1Lecture 1stst Dr. Humera Kausar (PhD Molecular Biology)
  2. 2. What is immunology?What is immunology?  Immunology is a branch of biomedicalis a branch of biomedical science that covers the study of allscience that covers the study of all aspects of the immune system in allaspects of the immune system in all organisms. It deals with the physiologicalorganisms. It deals with the physiological functioning of the immune system in statesfunctioning of the immune system in states of both health and diseases.of both health and diseases.  Immunity is the body's ability to fight offImmunity is the body's ability to fight off harmful micro-organisms –PATHOGENS-harmful micro-organisms –PATHOGENS- that invade it, e.g.Fungi, protozoans,that invade it, e.g.Fungi, protozoans, bacteria, and viruses are all potentialbacteria, and viruses are all potential pathogens.pathogens.
  3. 3. Edward Jenner (1749-1823) & The Discovery of Vaccination (1796) “Vaccinia (cowpox)” & “human smallpox”
  4. 4. Eradication of smallpox (1979, WHO)
  5. 5. Other historic events & important findings:Other historic events & important findings:  L. Pasteur (1880s)L. Pasteur (1880s) – Vaccines against cholera, and rabiesVaccines against cholera, and rabies  R. Kock (late 19R. Kock (late 19thth century)century) – Infections caused by microorganismsInfections caused by microorganisms  P. Ehrlich et al. (1890s)P. Ehrlich et al. (1890s) – Serum factors transfer of immunitySerum factors transfer of immunity  Behring & Kitasato (1890s)Behring & Kitasato (1890s) – Antibodies in serum bound to pathogensAntibodies in serum bound to pathogens  Porter & Edelman (1960s)Porter & Edelman (1960s) – Antibody structureAntibody structure  J. Gowans (1960s)J. Gowans (1960s) – Immunological importance of lymphocytesImmunological importance of lymphocytes
  6. 6. Koch’s PostulatesKoch’s Postulates 1.1. Pathogen must be found in the host in everyPathogen must be found in the host in every case.case. 2.2. Pathogen must be isolated from the host andPathogen must be isolated from the host and grown in pure culture.grown in pure culture. 3.3. When placed in a healthy host, pathogenWhen placed in a healthy host, pathogen produced in pure culture must cause theproduced in pure culture must cause the disease in the host.disease in the host. 4.4. Pathogen must be isolated from the new hostPathogen must be isolated from the new host and shown to be the original pathogen.and shown to be the original pathogen.
  7. 7. TheThe immune systemimmune system recognizes, attacks,recognizes, attacks, destroys, and remembers eachdestroys, and remembers each pathogen that enters the body.pathogen that enters the body. The Immune SystemThe Immune System includes all parts of theincludes all parts of the body that help in the recognition andbody that help in the recognition and destruction of foreign materials.  White blooddestruction of foreign materials.  White blood cells, phagocytes and lymphocytes, bonecells, phagocytes and lymphocytes, bone marrow, lymph nodes, tonsils, thymus, andmarrow, lymph nodes, tonsils, thymus, and your spleen are all part of the immuneyour spleen are all part of the immune system.system. Immune system
  8. 8.    Immune system Organ of Immune System Cells Of Immune System
  9. 9. V Organ of Immune System
  10. 10. Cells Of Immune System
  11. 11. Types of ImmunityTypes of Immunity  Innate immunityInnate immunity – ““Innate” because shared by all animalsInnate” because shared by all animals (vertebrates and invertebrates)(vertebrates and invertebrates) – Pre-existingPre-existing – Non-specificNon-specific  Adaptive immunityAdaptive immunity – ResponsiveResponsive – SpecificSpecific
  12. 12. 1313 The immune system protects organisms with layered defenses of increasing specificity  Most simply,Most simply, 1. physical barriers1. physical barriers preventprevent pathogens such as bacteria and viruses frompathogens such as bacteria and viruses from entering the bodyentering the body  If a pathogen breaches these barriers, theIf a pathogen breaches these barriers, the 2. innate2. innate immune systemimmune system provides an immediate, but non-provides an immediate, but non- specific responsespecific response – Innate immune systems are found in all plants and animalsInnate immune systems are found in all plants and animals  If pathogens successfully evade the innate response,If pathogens successfully evade the innate response, vertebrates possess a third layer of protection, thevertebrates possess a third layer of protection, the 3.3. adaptive immune systemadaptive immune system
  13. 13. Overview of the Immune SystemOverview of the Immune System Immune System Innate (Nonspecific) Adaptive (Specific) Cellular Components Humoral Components Cell-Mediated Humoral (Ab)
  14. 14. Innate & adaptive mechanisms work together in a cohesive fashion
  15. 15. Innate ImmunityInnate Immunity  Protection against infection that relies onProtection against infection that relies on mechanisms that exist before infectionmechanisms that exist before infection – First line of defenseFirst line of defense  BarriersBarriers – Skin (epidermis and dermis)Skin (epidermis and dermis) – Mucous membranes: respiratory, GI,Mucous membranes: respiratory, GI, genitourinary tractsgenitourinary tracts – Lacrimal apparatus: tearsLacrimal apparatus: tears – SalivaSaliva  ChemicalChemical – Sebum: acidsSebum: acids – Perspiration: lysozymePerspiration: lysozyme – Gastric juiceGastric juice – UrineUrine
  16. 16. Innate ImmunityInnate Immunity  Protection against infection that relies onProtection against infection that relies on mechanisms that exist before infectionmechanisms that exist before infection – Second line of defenseSecond line of defense  PhagocytosisPhagocytosis  InflammationInflammation  ComplementComplement  IntererronIntererron
  17. 17. First line of defenseFirst line of defense
  18. 18. The SkinThe Skin Serves both as mechanical and Chemical barrier. Microorganisms normally Associated with skin prevent Potential pathogens from Colonizing. Sebaceous glands secrete Fatty acids and lactic acid Which lower the skin pH (pH 4-6). Unbroken skin is a contiguous Barrier.
  19. 19. Mucosal membranesMucosal membranes Mucosal membrane consist of epithelial layerand under lying connective tissue layer. Mm of respiratory tract contains hair like projections called celia.that remove microbes inhaled through the nose and mouth. Mucus secreted by Goblet cells prevent the microbes from associating Too closely with the cells Mucous membrane’s microbicidal activity is owed due to the precence of Lysozyme ,Mucopeptide and Secretary immunoglobulins A. .
  20. 20. Lacrimal apparatus; TearLacrimal apparatus; Tear Lacrimal apparatus is the physiologic system containing the orbital structures for tear production and drainage.
  21. 21. Lacrimal apparatusLacrimal apparatus Tear mechanically remove the foreign partical and also contains, Lysozyme which constantly baths surface of the eye. (also found with egg whites and the female urogenital tract, and saliva) Lysozyme breaks the glycosidic bonds between the NAG and NAM that make up the backbone of peptidoglycan—causing bacteria to lyse.
  22. 22. Saliva Saliva mechanically washes pathogens off your teeth, and reduces the # of pathogens. Saliva contain an antibody called secretory immunoglobulin A, or “SIgA” which coats and protects every tooth from harmful bacteria that may cause decay.
  23. 23. Second line of defenseSecond line of defense
  24. 24. Phagocytosis
  25. 25. Phagocytosis
  26. 26.  Inflamation causescauses  Redness - due to capillary dilation- due to capillary dilation resulting in increased blood flowresulting in increased blood flow  Heat - due to capillary dilation resulting in- due to capillary dilation resulting in increased blood flowincreased blood flow  Swelling – due to passage of plasma– due to passage of plasma from the blood stream into the damagedfrom the blood stream into the damaged tissuetissue  Pain – due mainly to tissue destruction– due mainly to tissue destruction and, to a lesser extent, swelling.and, to a lesser extent, swelling.
  27. 27. Complement system  ~20 different proteins that work together to destroy~20 different proteins that work together to destroy invaders and recruit immune cellsinvaders and recruit immune cells  Activated three different waysActivated three different ways – ““Classical” pathway: by antibodies bound to pathogenClassical” pathway: by antibodies bound to pathogen (vertebrates only)(vertebrates only) – ““Alternative” pathway: by bacterial surfacesAlternative” pathway: by bacterial surfaces – Lectin activation pathway: by binding of mannose-Lectin activation pathway: by binding of mannose- binding lectin (MBL) to yeast, bacteria, parasites orbinding lectin (MBL) to yeast, bacteria, parasites or viruses (e.g., HIV)viruses (e.g., HIV)  Activation of complement system is tightlyActivation of complement system is tightly regulated because end results can be dangerousregulated because end results can be dangerous
  28. 28. InterferonInterferon  Interferons are proteins, immunologist prefer toInterferons are proteins, immunologist prefer to call them cytokinescall them cytokines – They are glycosylatedThey are glycosylated  The name originates from the fact that theyThe name originates from the fact that they interfere with viral infectioninterfere with viral infection  Cells producing IFNsCells producing IFNs – Plasmacytoid DCs (major producers of IFN-Plasmacytoid DCs (major producers of IFN- αα and IFN-and IFN- ββ)) – Fibroblasts and epithelial cellsFibroblasts and epithelial cells – Macrophages and Th1 CellsMacrophages and Th1 Cells
  29. 29. Interferon Antiviral ActivityInterferon Antiviral Activity
  30. 30. Adaptive Immunity: Characteristics  SpecificitySpecificity: directed at specific targets: directed at specific targets  SystemicSystemic: not restricted to initial site of infection /: not restricted to initial site of infection / invasioninvasion  MemoryMemory: after initial exposure & activation, a: after initial exposure & activation, a more rapid & more vigorous response is made tomore rapid & more vigorous response is made to subsequent exposures to pathogenssubsequent exposures to pathogens
  31. 31. Adaptive Defenses: Components  Humoral ImmunityHumoral Immunity:: (antibody mediated immunity)(antibody mediated immunity) provided by antibodies floating free in body fluidsprovided by antibodies floating free in body fluids  Cell mediated immunity:Cell mediated immunity: – lymphocytes directly attack specific invaders bylymphocytes directly attack specific invaders by lysis or indirect attack by initiating inflammationlysis or indirect attack by initiating inflammation and/or activating other lymphocytes &and/or activating other lymphocytes & macrophagesmacrophages
  32. 32. Antigens vs AntibodiesAntigens vs Antibodies  AntigensAntigens areare macromolecules that elicit an immune response in the body and can specifically bind with antibody. The most common antigens are proteins and polysaccharides.  AnAn antibodyantibody is a “Y” shaped proteinis a “Y” shaped protein produced in response to an antigen.produced in response to an antigen.
  33. 33. Antigens vs ImmunogenAntigens vs Immunogen An immunogen refers to a molecule that is capable of eliciting an immune response, whereas an antigen refers to a molecule that is capable of binding to the product of that immune response (Ab). So, an immunogen is necessarily an antigen, but an antigen may not necessarily be an immunogen - The terms immunogen and antigen are often used interchangeably but the later is more common.
  34. 34.  AntigensAntigens can enter the body from the environment.can enter the body from the environment. These includeThese include 1) inhaled macromolecules (e.g., proteins on cat hairs1) inhaled macromolecules (e.g., proteins on cat hairs that can trigger an attack ofthat can trigger an attack of asthmaasthma in susceptiblein susceptible people)people) 2) ingested macromolecules (e.g., shellfish proteins that2) ingested macromolecules (e.g., shellfish proteins that trigger antrigger an allergic responseallergic response in susceptible people)in susceptible people) 3) molecules that are introduced beneath the skin (e.g.,3) molecules that are introduced beneath the skin (e.g., on a splinter or in an injectedon a splinter or in an injected vaccinevaccine)) AntigensAntigens
  35. 35. Properties of AntigenProperties of Antigen 1. Antigenic Determinant 2. Foreignness 3. Complexity 4. Molecular Size 5. Charge 6. Solubility 7. Accessibility 8. Valency
  36. 36. Properties of AntigenProperties of Antigen 1) Antigenic Determinant: A site on an antigen molecule to which an antibody molecule binds. Also called epitope.
  37. 37. Properties of AntigenProperties of Antigen 1. Antigenic Determinant:
  38. 38. Properties of AntigenProperties of Antigen 2. Foreignness An antigen must be foreign or alien to the host with which it makes contact. The greater the phylogenetic difference, the more Foreign something becomes.
  39. 39. Properties of AntigenProperties of Antigen 2) Foreignness a. Autologous antigens are found within the same individual; that is, they are not foreign to that individual. For example, a skin graft from an individual's thigh to his chest is an auto graft, and is not foreign. b. Syngeneic antigens are found in genetically identical individuals (e.g., individuals from an inbred strain of mice of identical twins). A graft between members of an inbred strain is a syngeneic graft or an isograft, and is not foreign. c. Allogeneic antigens (alloantigens) are found in genetically dissimilar members of the same species. For example, a kidney transplant from mother to daughter is called an allograft or a homograft, and it is foreign.
  40. 40. Properties of AntigenProperties of Antigen 3. Complexity Just because a molecule is large, if its a polymer of a single amino acid or sugar it tends to lack immunogenicity. complexity of a molecule increses its immunogenicity
  41. 41. Properties of AntigenProperties of Antigen 4. Molecular Size Molecular weight greater than 10,000 daltons are excellent Antigens Insulin(5700 daltons) and (3600 daltons) are immunogenic BUT Gelatin with molecular weight of 10,000 is poor immunogen.Why? 5. Charge Net surface charge of antigen has no effect. But a significant Property b/c net surface charge of antigen determines the net surface charge of an Antibodies.
  42. 42. Properties of AntigenProperties of Antigen 6. Solubility A chemical compound exhibit a high class of antigenesity if it is highly degradable and soluble. e.g natural antigens. Synthetic polymers fail to initiate an immune response.
  43. 43. Properties of AntigenProperties of Antigen 7. Accessibility More accessible the antigenic determinants to the immune cells more power full immune response will developed.
  44. 44. Properties of AntigenProperties of Antigen 8. Valency The combining capacity of an antigen with specific antigen binding sites of an antibody molecule is the antigenic valency.
  45. 45. Chemical and physical classes ofChemical and physical classes of AntigenAntigen (2) Chemical composition and structure(2) Chemical composition and structure Protein>polysaccharides, nucleic acids, lipidsProtein>polysaccharides, nucleic acids, lipids (Protein containing aromatic amino acid,such as(Protein containing aromatic amino acid,such as tyrosine)tyrosine)other examplesother examples ?? (3) Physical nature(3) Physical nature Polymer > MonomerPolymer > Monomer Cycle molecule >linear moleculeCycle molecule >linear molecule Particulate Ag> soluble AgParticulate Ag> soluble Ag ExamplesExamples??
  46. 46. 1. Haptens are partial antigens. That is: a.Haptens are antigenic: they can react with immune lymphocytes or antibodies. b. However, haptens are not immunogenic: they can not by themselves cause the production of immune lymphocytes or antibodies. HaptensHaptens::
  47. 47. Haptens: 2.Haptens are usually molecules which are too small to be immunogenic. a.Examples? b.if a hapten of coupled to a larger carrier molecule, however, it becomes immunogenic. Immunogens :possess both characteristics Hapten + carrier = complete antigen (immunogens)
  48. 48. SuperantigensSuperantigens Conventional Antigen Monoclonal T cell response Superantigen Polyclonal T cell response • Definition?
  49. 49. SuperantigensSuperantigens ExamplesExamples – Staphylococcal enterotoxinsStaphylococcal enterotoxins – Staphylococcal toxic shock toxinStaphylococcal toxic shock toxin – Staphylococcal exfoliating toxinStaphylococcal exfoliating toxin – Streptococcal pyrogenic exotoxinsStreptococcal pyrogenic exotoxins
  50. 50. TD-Ag (thymus dependent Ag ) TD-AgTD-Ag stimulate B cell to produce Ab withstimulate B cell to produce Ab with thethe help of T cellhelp of T cell  Most of TD-Ag are proteinMost of TD-Ag are protein  Have many kinds of determinantsHave many kinds of determinants  Can induce HI and CMICan induce HI and CMI  Stimulate B cell to produce :Stimulate B cell to produce :IgGIgG, IgM,, IgM, IgAIgA  Have immune memoryHave immune memory  ExamplesExamples – Microbial proteinsMicrobial proteins – Non-self or altered-self proteinsNon-self or altered-self proteins
  51. 51. TI-Ag (thymus independent Ag) TI-AgTI-Ag can stimulate B cells to produce Abcan stimulate B cells to produce Ab withoutwithout thethe help of T cellhelp of T cell  Most are polysaccharideMost are polysaccharide  Have more same or repeat determinantsHave more same or repeat determinants  Only induce B cell to produce IgMOnly induce B cell to produce IgM  Can not induce CMICan not induce CMI  No immune memoryNo immune memory • ExamplesExamples – Pneumococcal polysaccharide, LPSPneumococcal polysaccharide, LPS – FlagellaFlagella
  52. 52. Factors Influencing ImmunogenicityFactors Influencing Immunogenicity Method of AdministrationMethod of Administration  DoseDose  RouteRoute – Subcutaneous > Intravenous > IntragastricSubcutaneous > Intravenous > Intragastric  AdjuvantAdjuvant – Substances that enhance an immuneSubstances that enhance an immune response to an Agresponse to an Ag
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