1.IMMUNE SYSTEMSpecific and nonspecific response Humoral immunity

2. IMMUNE SYSTEM Pathogen(disease-causing organism) canbe bacteria, fungus, virus, or multicellular parasite. Pathogen infects animalbecause the internal environment of animal offer a suitable habitat. The animal body is the ideal habitat for the pathogen to grow, reproduce, and medium for transportation to the new environments. 3. Thus, a defense system must be made up in order to ward off the invasion of pathogen into the animal body. Immune system recognizes the pathogen as foreign body and respond by producing immune cells and protein. 4. IMMUNITY Immunity is defined as an ability of the body to resistinvasion of pathogen or disease. A study of how the immune system of animal works iscalled immunology. Immunity are divided into nonspecific immunity andspecific immunity. 5. Pathogens(microorganismsand viruses) INNATE IMMUNITYBarrier defenses:Recognition of traits Skinshared by broad rangesMucous membranesof pathogens, using a Secretionssmall set of receptorsInternal defenses:Phagocytic cells Rapid response Antimicrobial proteinsInflammatory responseNatural killer cellsACQUIRED IMMUNITYHumoral response:Recognition of traitsAntibodies defend againstspecific to particular infection in body fluids.pathogens, using a vastarray of receptors Cell-mediated response: Cytotoxic lymphocytes defend Slower response against infection in body cells. 6. NONSPECIFIC IMMUNITY Also known as innate immunity. Present before any exposure to pathogens. Act immediately upon infection. Divided into surface barrier and internal defenses. 7. SURFACE BARRIER Skin is an outer covering of an animal body which act as primary defense system. Possess keratinized epithelial membrane that function as a barrier and prevent the pathogen that swarm on the skin. Keratin is resistant to most weak acids and bases and to bacterial enzymes and toxins. 8. Mucous membranes line all body cavities that open to the exterior; the digestive, respiratory, urinary, and reproductive tracts. Epithelial membranes produce a variety of protective chemicals. 9. The acidity of skin secretions (pH 3 to 5) inhibitsbacterial growth. Sebum contains chemical that aretoxic to bacteria. Vaginal secretion of adult females are very acidic. The stomach mucosa, secretes a concentratedhydrochloric acid solution and protein-digestingenzymes. 10. Saliva, which cleanses the oral cavity and teeth. Lacrimal fluid of eye contains lysozyme, an enzymethat destroys the bacteria. Sticky mucus traps many microorganisms that enterthe digestive and respiratory passageways. Tiny mucus-coated hairs inside the nose traps thepathogen, preventing it from entering the lowerrespiratory passages. 11. INTERNAL DEFENSES:CELLS ANDCHEMICALS Internal defenses involve phagocytic cells, natural killer cells,antimicrobialproteins,and inflammatory response. The inflammatory response enlists macrophages, mast cells, all types of white blood cells, and other chemicals that kill pathogen. The phagocytic cells are the cells that functions in engulfing the pathogen. 12. PHAGOCYTIC CELLS If the pathogens succeed to get through the skin, thenthe phagocytic cells will combat the pathogens. Phagocytic cellsconsistofmonocytes,macrophages, neutrophils and eosinophils. Pathogens are recognized by surface cell receptorswhich are also known as TLR (Toll-like receptors). 13. EXTRACELLULAR LipopolysaccharideFLUIDHelper TLR4 FlagellinproteinWHITEBLOODCELLTLR5 VESICLETLR9 TLR3 Inflammatoryresponsesds RNA 14. Macrophages derived from white blood cells, monocytes which leave and enter the tissues, and develop into macrophages. Neutrophils, the most abundant type of white blood cells. Eosinophils, white blood cells that weakly phagocyte the pathogens. 15. HUMAN LYMPHATIC SYSTEMInterstitial fluid Adenoid TonsilLymphBloodnodescapillarySpleen Tissue Lymphatic cellsvessel Peyers patches (small intestine)AppendixLymphaticvesselsLymphMasses ofnode defensive cells 16. MECHANISM OF PHAGOCYTOSIS Phagocytic cell engulfs the particulate matter. Cytoplasmic extension of phagocyte cell bind to theparticulate matter and pull it into vacuole. Phagosome is formed. Phagosomefuseswith lysosome, forming aphagolysosome. 17. MicrobesPHAGOCYTIC CELLVacuoleLysosomecontainingenzymes 18. NATURAL KILLER CELLS Function in lysing and killing the cancer cells andvirus-infected body cells. Natural killer cells act before the specific immunesystem is activated. Able to detect and eliminate the virus infected cell andcancerous cell (virus infected cell and cancerous celldo not express class I MHC protein). 19. The natural killer cells detect the cell which is lack ofself cell surface receptors (class I MHC protein). Natural killer cells also promote the target cells toundergo apoptosis (programmed cell death). 20. INFLAMMATORY RESPONSE The benefits of inflammatory response:1. Prevent the spread of damaging agents to nearby tissues.2. Disposes of cell debris and pathogen.3. Set the stage for repair (blood clotting). 21. INFLAMMATORY RESPONSE Factors which elicit inflammatory response:1. Physical trauma ( a blow)2. Intense heat3. Irritating chemicals4. Infection by viruses, fungi, and bacteriaThe four cardinal signs of accute inflammation:1. Pain2. Redness3. Heat4. Swelling 22. Tissueinjured Histamine (released bybasophils),chemicalmediators, prostaglandin,complement kinin Vasodilation of Increased Attract neutrophils,arteriolescapillary monocytes, andLocal hyperemiapermeability lymphocytes to(increased blood flow Capillaries leak injured areato injured area fluid (exudate)(chemotaxis)Pus formation 23. Mast cells- key components of inflammatory response., release histamine. Pus- break down tissue, die or dying neutrophils, dead or living pathogen, accumulate in the wound. Hyperemia (congestion of blood)- causes redness and heat of an inflammed region. 24. Inflammation can be divided into local inflammation and systemic inflammation. Fever is an example of systemic inflammation. It is triggered by pyrogens. The high body temperature inhibits the microbial multiplication and enhances body repair. 25. Exudates- fluid containing antibodies and clotting factors. Secretion of exudate causes local edema (swelling) and contributes to the sensation of pain. 26. SplinterChemical MacrophageFluidMast cell signalsCapillaryPhagocytosisRed blood cells Phagocytic cellMajor events in a local inflammatory responses 27. INFLAMMATORY CHEMICALSCHEMICALSOURCEPHYSIOLOGICALEFFECTSHistamine Granules of basophils and mast cells, releasedPromotes vasodilation of localin response to mechanical injury, presence of arterioles, increases permeability ofcertain microorganisms, and chemicals local capillaries, promoting exudatereleased by neutrophils.formation.KininsA plasma protein, kininogen is cleaved by the Same as for histamine, also induceenzyme kallikrein found in plasma, urine, chemotaxis of leukocytes andsaliva, and lysosomes of neutrophils, and other prompt neutrophils to releasetypes of cells, cleavage releases active kininlysosomal enzymes, therebypeptides. enhancing generation of of morekinin, induce pain.ProstaglandinsFatty acidmolecules produced from Sensitize blood vessels to effectsarachidonic acid-found in all cell membranes; of other inflammatory mediators,generated by enzymes of neutrophils,one of the intermediate steps ofbasophils, mast cells and others. prostaglandin generation producesfree radicals, which can causeinflammation; induce pain. 28. ADAPTIVE/ SPECIFIC IMMUNITY Specific; recognizes and respond to specific pathogens or foreign substances. Systemic; Immunity not only involve to the initial infection site. Possess memory; Able to mount stronger attacks on the pathogens which encounter the body previously. 29. Adaptive immunity are dividedinto humoral response and cell-mediated response. Humoralresponse involves the production of antibody. Cell-mediated immunity involves cytotoxic cells. 30. HUMORAL RESPONSE Antibody-mediated immunity. Production of antibodies by lymphocytes. Antibodies present in the bodys humors, or fluids(blood, lymph). Involve antigen recognition, antigen presenting, and Bcell proliferation. 31. B cells undergo maturity (antigen binds to its surface receptor, Tcells nearby)B cells undergo clonalselection (reproduceasexually by mitosis)Plasma cellsAntibodies Long-lived memory cells 32. Humoral (antibody-mediated) immune responseAntigen (1st exposure) StimulatesEngulfed by Gives rise to Antigen-presenting cellB cellHelper T cell Memory Helper T cellsAntigen (2nd exposure)Plasma cellsMemoryB cells SecretedantibodiesDefend against extracellular pathogens 33. Antigen-presentingcellPeptide antigenBacterium Class II MHC moleculeCD4 TCR (T cell receptor) HumoralCytokines Helper T cellimmunity Cell-mediated(secretion ofimmunityantibodies by (attack onplasma cells infected cells)B cellCytotoxic T cell 34. LYMPHOCYTES (B CELLS AND T CELLS) B cells and T cells are lymphocytes. Involve in the humoral immune response. B cells are originated from the bone marrow. T cells are also originated from the bone marrow but itmigrated to the thymus. 35. ANTIGEN Antigens are foreign substances which elicits adaptiveimmune response. Antigens are either natural or synthetic. Nonself; antigens are normally not parts of the body. Most antigens are large and complex molecules. 36. To elicit adaptive immunity, antigen recognition mustoccur. Antigen recognition- the B cell and T cell bind to theantigen. The antigen binding- via antigen receptor whichattached to the surface of B cell and T cell plasmamembranes. 37. B CELL RECEPTORAntigen-Antigen-binding sitebindingDisulfidesite bridge V V Variable regions Light C CConstant chainregionsTransmembraneregionPlasma Heavy chains membrane B cell(a) B cell receptor 38. T CELL RECEPTORAntigen-bindingsite Variable regions V VConstantregionsC CTransmembraneregionPlasmamembraneDisulfide bridgeCytoplasm of T cellT cell (b) T cell receptor 39. B CELLS ANTIGEN RECEPTORSY-shaped.Consist four polypeptide chains. Two identical light chainsand two identical heavy chains.Have constant region (C) and variable region (V).When the antigen receptors bind to an antigen, B cellactivation occurs. 40. The antigen receptor bind to the epitope. Epitope- Also known as antigenic determinant, asmall, accesible portion of an antigen that binds to anantigen receptor. 41. An antigen possesses several different epitopes. All the antigen receptors which are located at a singlelymphocyte only bind to the same epitope. When the antigen bind to the antigen receptor, B cellactivates and give rise to plasma cells. Plasma cells produce antibodies. 42. Epitopes(antigenicdeterminants)Antigen-binding sites AntigenAntibody A Antibody C CC C C Antibody B 43. ANTIBODIES Also known as immunoglobulins. Similar structure with B cell antigen receptors, but antibodies do not attach to the surface cell membranes. 44. ANTIBODY CLASSES Antibodies are divided into five major classes. Polyclonal antibodies- products of many differentclones of B cells following exposure to a microbialagent. Monoclonal antibodies- prepared a single clone of Bcells grown in culture. 45. Class of Immuno- Distribution Functionglobulin (Antibody IgM First Ig classPromotes neutraliza-(pentamer) produced aftertion and cross- initial exposure to linking of antigens; antigen; then its very effective in concentration incomplement system the blood activationdeclines IgGPromotes(monomer)Most abundant Ig opsoniz class in blood;a- also present intion, tissue fluidsneutralization,and cross-linkingof crosses placenta,antigens; less thus conferringeffec- passive immunity on fetusactivationtive inofIgAPresent in Provides localizedcomplement(dimer)secretions suchdefense of mucoussystem as tears, saliva,membranes bythan IgM mucus, and cross-linking and breast milkneutralization ofantigens Triggers release from IgE Present in bloodmast cells and(monomer)at low concen-basophils of hista- trationsmine and other chemicals that cause allergic reactionsIgD (monomer)PresentActs as antigenprimarireceptor in thely antigen-on surface of stimulatB cells that have ednot been proliferation andexposdifferentiation ofed B cells (clonalto antigensselection 46. Class of Immuno-Distribution Functionglobulin (Antibody) IgM First Ig classPromotes neutraliza-(pentamer) produced aftertion and cross- initial exposure to linking of antigens; antigen; then its very effective in concentration incomplement system the blood declinesactivation J chain 47. Class of Immuno-DistributionFunctionglobulin (Antibody)IgG (monomer)Most abundant Ig Promotes opsoniza-class in blood;tion, neutralization,also present inand cross-linking oftissue fluidsantigens; less effec- tive in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus 48. Class of Immuno- DistributionFunction globulin (Antibody)IgA(dimer)Present inProvides localized secretions such defense of mucous as tears, saliva, membranes by mucus, andcross-linking and J chain breast milk neutralization of antigens Presence in breast milk confersSecretorypassive immunitycomponenton nursing infant 49. Class of Immuno-globulin (Antibody)DistributionFunctionIgEPresent in blood Triggers release from (monomer)at low concen- mast cells andtrations basophils of hista- mine and other chemicals that cause allergic reactions 50. Class of Immuno- DistributionFunction globulin (Antibody) IgD Present primarily Acts as antigen(monomer)on surface of receptor in the B cells that have antigen-stimulated not been exposedproliferation and to antigens differentiation of B cells (clonal selection)Trans-membraneregion 51. ANTIBODY TARGETS ANDFUNCTIONS Neutralization- antibodies block specific sites on viruses or bacterial exotoxins (toxin chemicals secreted by bacteria). The virus or exotoxin cannot bind to the receptors on tissue cells to cause injury. 52. Agglutination- Antibodies bind to the antigenic determinant on more on one antigen at a time. Forming antigen-antibody complexes which causes clumping of the foreign cells. 53. Precipitation- Soluble molucles are cross-linked into large complexes that settle out of solution. 54. Complement fixation and activation- Antibodies bind to cells, cause the antibodies to change its shapes. The antibodies expose the transmembrane regions. Complement fixation into the antigenic cells surface is triggered, followed by the cell lysis. 55. Viral neutralization OpsonizationActivation of complement system and pore formation BacteriumComplement proteinsVirusFormation ofmembraneattack complexMacrophageFlow of waterand ions PoreForeigncell 56. ANTIGEN RECOGNITION B cell antigen receptors bind to the epitopes of antigens. T cell antigen receptor bind to the fragments of antigens that are presented on the surface of host cells. 57. MHC Major Histocompatibility Complex molecule. Encodesa group of glycoproteins called MHC proteins. MHC proteins are divided into two groups, Class I MHC proteins and Class II MHC proteins. 58. Class I MHC proteinClass II MHC proteinFound on virtually all body cells. Found only on certain cells that acts on immune system.Involves in the cell-mediatedInvolves in the humoral immunity.immunity. 59. RECOGNITION OF PROTEIN ANTIGENS BY T CELLS The antigen is engulf by the cell. The antigen is cleaved by host cells enzyme into antigen fragment. Antigen fragment binds to MHC molecule. Antigen fragment-MHC complex is brought to the surface of the cell. T cell recognizes the antigen fragment-MHC complex. 60. THE ROLE OF THE MHC Bind to antigen fragment. Transport the antigen fragment to the surface of thecell. Lead to antigen presentation, the display of theantigen fragment on the cell surface. 61. HELPER T CELLS Activates the adaptive immune response. Antigen fragment is presented by class MHC proteins on the host cell. The host cell which displays the antigen fragment is called antigen-presenting cell. 62. In the cell mediated immunity, the Class I MHCprotein formed a complex with the antigen fragment. In the humoral immunity, the antigen fragment forms acomplex with the Class II MHC protein. 63. Top view: binding surface exposed to antigen receptors AntigenClass I MHC Antigenmolecule Plasma membrane of infected cell 64. Antigen-Infected cellMicrobe presenting1. cellAntigen Antigenfragmentassociates with AntigenMHC fragmentClass I MHC moleculmoleculee Class II T cellMHC receptormolecule 2. TcellT cell recognizereceptor s combinati a) Cytotoxic T cell on b) Helper T cell 65. B CELL AND T CELL DEVELOPMENT The antigen presenting leads to B cell and T cellactivation. B cellisactivated(stimulated to undergodifferentiation). B cell proliferates to form clones. The clonesbear thesameantigen-specificreceptors, similar to the activated B lymphocyte cell. 66. Some cells from the clones form effector cells.The effector cells which form from the B cells are plasma cells. 67. T cell is activated and proliferates to form clones.Some of the clones become effector cells. The effector cells which arise from T cells are dividedinto helper T cells and cytotoxic T cells. 68. CLONAL SELECTION The proliferation of B cells is the example of clonalselection process. B cells form clones, a group of cell which are identicalto the original cell. 69. MONOCLONAL ANTIBODY Providing passive immunity. Are made by fusing tumor cells and B lymphocytes. The resulting cell are called hybridomas. Hybridomas proliferates in culture, and produce asingle type of antibody. Used to diagnose pregnancy, sexually transmitteddiseases, hepatitis and rabies. 70. CELL MEDIATED IMMUNITY Involve the cytotoxic T cells. Cytotoxic cells- destroy any cells in the body thatharbor anything foreign. 71. Released cytotoxic T cell Cytotoxic T cellPerforin CD8 Dying target cellClass I Granzymes MHCPoremolecule TCRTarge tcell The killing action of cytotoxic T cells 72. CYTOTOXIC T CELL T cells which undergo proliferation will form effectorcells. The effector cells are helper T cells and cytotoxic Tcells. The surface of the cytotoxic T cells have glycoproteins called CD8 (different from the helper T cells whichpossess CD4). All body cells display class I MHC antigens, so allinfected cells or abnormal cells can be destroyed bycytotoxic T cells. 73. Humoral (antibody-mediated) immune responseCell-mediated immune responseAntigen (1st exposure) StimulatesEngulfed byGives rise toAntigen- presenting cell B cell Helper T cell Cytotoxic T cell Overview Memory Helper T cellsof acquired/ adaptiveAntigen (2nd exposure)Plasma cellsMemory B cells MemoryActiveimmuneCytotoxic T cells Cytotoxic T cells systemSecreted antibodiesDefend against extracellular pathogens by binding to antigens,Defend against intracellular pathogensthereby neutralizing pathogens or making them better targetsand cancer by binding to and lysing thefor phagocytes and complement proteins .infected cells or cancer cells .