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The Immune System The Immune System The body’s defense The body’s defense 1. Nonspecific 1. Nonspecific 2. Specific 2. Specific Cell mediated Cell mediated.

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Presentation on theme: "The Immune System The Immune System The body’s defense The body’s defense 1. Nonspecific 1. Nonspecific 2. Specific 2. Specific Cell mediated Cell mediated."— Presentation transcript:

1 The Immune System The Immune System The body’s defense The body’s defense 1. Nonspecific 1. Nonspecific 2. Specific 2. Specific Cell mediated Cell mediated Antibody mediated Antibody mediated The body’s defense The body’s defense 1. Nonspecific 1. Nonspecific 2. Specific 2. Specific Cell mediated Cell mediated Antibody mediated Antibody mediated

2 Three cooperative lines of defense have evolved to counter these threats. Two of these are nonspecific - that is, they do not distinguish one infectious agent from another. Three cooperative lines of defense have evolved to counter these threats. Two of these are nonspecific - that is, they do not distinguish one infectious agent from another.

3 Nonspecific defenses “Nonspecific” = don’t have to recognize an invader to fight it Skin: physical barrier Sweat glands: chemical defense Mucous membranes: Line body openings- physical barrier Secretions: Antimicrobial proteins present in secretions Mucous traps particles Acid in stomach-destroy most except hept.A “Nonspecific” = don’t have to recognize an invader to fight it Skin: physical barrier Sweat glands: chemical defense Mucous membranes: Line body openings- physical barrier Secretions: Antimicrobial proteins present in secretions Mucous traps particles Acid in stomach-destroy most except hept.A

4 Besides being a physical barrier, the skin and mucous membranes chemically destroy pathogens. Secretions from oil and sweat glands give the skin a pH ranging from 3 to 5, acidic enough to kill most microbes. Growth is also inhibited by saliva, tears, and mucous secretions that continually bathe the exposed epithelium. All these secretions contain antimicrobial proteins. One of these, the enzyme lysozyme, digests the cell walls of many bacteria, destroying them. Besides being a physical barrier, the skin and mucous membranes chemically destroy pathogens. Secretions from oil and sweat glands give the skin a pH ranging from 3 to 5, acidic enough to kill most microbes. Growth is also inhibited by saliva, tears, and mucous secretions that continually bathe the exposed epithelium. All these secretions contain antimicrobial proteins. One of these, the enzyme lysozyme, digests the cell walls of many bacteria, destroying them.

5 2ND LINE-Internal Microbes that penetrate the first line of defense face the second line of defense, which depends mainly on phagocytosis, the ingestion of invading organisms by certain types of white cells. Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins. Microbes that penetrate the first line of defense face the second line of defense, which depends mainly on phagocytosis, the ingestion of invading organisms by certain types of white cells. Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins.

6 Second line of defense cells function like roaming patrols 1. Nonspecific defenses of chemicals and cells-Stimulated by cytokinnins 2. Act rapidly with infection 3. Employ negative test that cannot be foiled by copycat foreign cells Second line of defense cells function like roaming patrols 1. Nonspecific defenses of chemicals and cells-Stimulated by cytokinnins 2. Act rapidly with infection 3. Employ negative test that cannot be foiled by copycat foreign cells

7 4. All cells possess major histocompatibility complex (MHC) proteins 5. Different in each individual. Distinguish self from non self. Due to MHC proteins-before birth 1. MHC 1-nucleated cells-body cells 2. MHC II- Nucleated cells-macrophages-B cells- some t cells a. 50 alleles-20 genes b. In autoimmune diseases defensive cells attack body's own tissues c.Autoimmune diseases like arthritis have inflammation without infection 4. All cells possess major histocompatibility complex (MHC) proteins 5. Different in each individual. Distinguish self from non self. Due to MHC proteins-before birth 1. MHC 1-nucleated cells-body cells 2. MHC II- Nucleated cells-macrophages-B cells- some t cells a. 50 alleles-20 genes b. In autoimmune diseases defensive cells attack body's own tissues c.Autoimmune diseases like arthritis have inflammation without infection

8 Major Histocompatibility Complex The basis of “self” Genes for cell surface glycoproteins In humans: human leukocyte antigens (HLA) ENORMOUS variation (polymorphic) 2 Types: Class 1: found on all nucleated cells Class 2 : found on macrophages, B cells, CD4 T cells The basis of “self” Genes for cell surface glycoproteins In humans: human leukocyte antigens (HLA) ENORMOUS variation (polymorphic) 2 Types: Class 1: found on all nucleated cells Class 2 : found on macrophages, B cells, CD4 T cells

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10 Phagocytic and Natural Killer Cells Neutrophils: Most abundant WBC’s Chemotaxic Engulf invaders, then self-destruct Monocytes: Less abundant, but more effective than neutrophils Form macrophages Reach pathogen with pseudopodia Engulf pathogen, fuse it with a lysosome Kill pathogen with toxic oxygen or enzymes Neutrophils: Most abundant WBC’s Chemotaxic Engulf invaders, then self-destruct Monocytes: Less abundant, but more effective than neutrophils Form macrophages Reach pathogen with pseudopodia Engulf pathogen, fuse it with a lysosome Kill pathogen with toxic oxygen or enzymes

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12 More WBC’s Eosinophils: Fight large invaders (ex: parasites) Natural Killer (NK) cells: destroy “self” cells infected with viruses, cancer cells Eosinophils: Fight large invaders (ex: parasites) Natural Killer (NK) cells: destroy “self” cells infected with viruses, cancer cells

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14 The Inflammatory Response Histamine is released by circulating leucocytes called basophils and by mast cells in connective tissue. Histamine triggers both dilation and increased permeability of nearby capillaries. Also discharge prostaglandins and other substances that promote blood flow to the site of injury. Greater clotting capacity, faster repair Initiated by chemical signals From microbe- Chemotactic factor From damaged ‘self’ cells (ex: histamine) Chemokines from damaged cells attract phagocytes Pus = dead phagocytes + fluids Extreme = septic shock Histamine is released by circulating leucocytes called basophils and by mast cells in connective tissue. Histamine triggers both dilation and increased permeability of nearby capillaries. Also discharge prostaglandins and other substances that promote blood flow to the site of injury. Greater clotting capacity, faster repair Initiated by chemical signals From microbe- Chemotactic factor From damaged ‘self’ cells (ex: histamine) Chemokines from damaged cells attract phagocytes Pus = dead phagocytes + fluids Extreme = septic shock

15 The Complement System Antimicrobial proteins ~ 20 serum proteins Function: microbe lysis Antimicrobial proteins ~ 20 serum proteins Function: microbe lysis

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17 Another set of proteins that provide nonspecific defenses are the interferons, which are secreted by virus-infected cells. –While they do not seem to benefit the infected cell, these proteins diffuse to neighboring cells and induce them to produce other chemicals that inhibit viral reproduction. –Interferon limits cell-to-cell spread of viruses, helping to control viral infection. –Because they are nonspecific, interferons produced in response to one virus may confer short-term resistance to unrelated viruses. –One type of interferon activates phagocytes. Another set of proteins that provide nonspecific defenses are the interferons, which are secreted by virus-infected cells. –While they do not seem to benefit the infected cell, these proteins diffuse to neighboring cells and induce them to produce other chemicals that inhibit viral reproduction. –Interferon limits cell-to-cell spread of viruses, helping to control viral infection. –Because they are nonspecific, interferons produced in response to one virus may confer short-term resistance to unrelated viruses. –One type of interferon activates phagocytes.

18 Temperature Response Pyrogens Ex: Interleukin-1 Detected in blood by hypothalamus -- raise in body temp How it works: Speeds cellular reactions Stimulates phagocytosis Stimulates liver/spleen to store Fe Endotherms - may regulate behaviorally Pyrogens Ex: Interleukin-1 Detected in blood by hypothalamus -- raise in body temp How it works: Speeds cellular reactions Stimulates phagocytosis Stimulates liver/spleen to store Fe Endotherms - may regulate behaviorally

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20 Immunity terms Humoral vs Cell mediated Acquired/active vs Passive Lymphocytes: T and B cells, specific Antigen: Foreign molecule (from pathogens, pollen, transplanted tissue, etc.) Antibodies: made by B cells, specific Antigen receptors: on membranes of T & B cells B cells: membrane antibodies T cells: similar, but never secreted Humoral vs Cell mediated Acquired/active vs Passive Lymphocytes: T and B cells, specific Antigen: Foreign molecule (from pathogens, pollen, transplanted tissue, etc.) Antibodies: made by B cells, specific Antigen receptors: on membranes of T & B cells B cells: membrane antibodies T cells: similar, but never secreted

21 T cells TI = inducer TC = cytotoxic killers TH = helpers Activate others TS = suppressor Causes B cells to ignore antigens TI = inducer TC = cytotoxic killers TH = helpers Activate others TS = suppressor Causes B cells to ignore antigens

22 Antigen presentation Antigen binds to MHC within cell MHC molecules bring proteins to surface Antigen binds to MHC within cell MHC molecules bring proteins to surface

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25 Cell mediated response TC cells kill cancer cells, viral infected cells All cells have class 1 MHCs (all susceptible to viral infection) Class 1 MHC captures viral protein MHC + antigen move to cell surface Present to T cytotoxic cell Enhanced by CD8 Active killer cell TC cells kill cancer cells, viral infected cells All cells have class 1 MHCs (all susceptible to viral infection) Class 1 MHC captures viral protein MHC + antigen move to cell surface Present to T cytotoxic cell Enhanced by CD8 Active killer cell

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27 Mechanism T cytotoxic cell releases perforin Forms pores in membrane of target cell Cell lyses, pathogen inside is exposed to circulating antibodies T cytotoxic cell moves on to other cells infected w/ same pathogen T cytotoxic cell releases perforin Forms pores in membrane of target cell Cell lyses, pathogen inside is exposed to circulating antibodies T cytotoxic cell moves on to other cells infected w/ same pathogen

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31 Antibody mediated immunity Aka Humoral immunity, B cells activated, antibody production Ex: macrophage engulfs a bacterium Class 2 MHC picks up bacterial peptide MHC + antigen move to cell surface Presents to T helper cell/releases Il-1 Enhanced by CD4 receptor on T helper cell T cell proliferates Activated T helper cells: secrete cytokines to stimulate other lymphocytes Aka Humoral immunity, B cells activated, antibody production Ex: macrophage engulfs a bacterium Class 2 MHC picks up bacterial peptide MHC + antigen move to cell surface Presents to T helper cell/releases Il-1 Enhanced by CD4 receptor on T helper cell T cell proliferates Activated T helper cells: secrete cytokines to stimulate other lymphocytes

32 Humoral response in detail B cell activation by IL-2, proliferate into plasma and memory cells Plasma cells: secrete antibodies Memory cells: long-lived Some antigens are T-independent Bind to membrane antibodies on B cells Plasma cells made w/ out signal from T cells B cell activation by IL-2, proliferate into plasma and memory cells Plasma cells: secrete antibodies Memory cells: long-lived Some antigens are T-independent Bind to membrane antibodies on B cells Plasma cells made w/ out signal from T cells

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36 Structure of antibodies Globular protein, in plasma, aka: immunoglobulins (Igs) Structure: 4 chains: 2 heavy, 2 light Constant region Variable region Epitope: part of the antigen where antibody binds 5 classes Made in vitro Polyclonal: made from many B cell clones Work on different epitopes of the same antigen Monoclonal: made from one B cell clone All work at the same epitope of the same antigen Globular protein, in plasma, aka: immunoglobulins (Igs) Structure: 4 chains: 2 heavy, 2 light Constant region Variable region Epitope: part of the antigen where antibody binds 5 classes Made in vitro Polyclonal: made from many B cell clones Work on different epitopes of the same antigen Monoclonal: made from one B cell clone All work at the same epitope of the same antigen

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39 How antibodies work Neutralization: Block antigen activity Opsonization: Enhance macrophage attachment/phagocytosis Agglutination: Clumping Complement fixation: can be activated by antibodies or by pathogens Antibodies attach to antigens Complement proteins activate, cause lysis Neutralization: Block antigen activity Opsonization: Enhance macrophage attachment/phagocytosis Agglutination: Clumping Complement fixation: can be activated by antibodies or by pathogens Antibodies attach to antigens Complement proteins activate, cause lysis

40 Active vs. Passive Immunity Active immunity: your own response Natural: from infection Artificial: from vaccinations Passive: antibodies from another individual Ex: across placenta, through breast milk Ex: antivenoms,Rhogam Rhogam: injection given to Rh- mothers after birth of Rh+ child. Destroy fetal cells before her immune system responds to them, develops antibodies Anti Rh antibodies are class IgG - can cross placenta Active immunity: your own response Natural: from infection Artificial: from vaccinations Passive: antibodies from another individual Ex: across placenta, through breast milk Ex: antivenoms,Rhogam Rhogam: injection given to Rh- mothers after birth of Rh+ child. Destroy fetal cells before her immune system responds to them, develops antibodies Anti Rh antibodies are class IgG - can cross placenta

41 Tissue transplantation Blood types: ‘A’ and ‘B’ antigens T-independent humoral response Antibodies don’t cross the placenta Organ transplants Rejection due to MHCs that are too dissimilar Suppress immune system to decrease rejection Bone marrow: graft rejection Blood types: ‘A’ and ‘B’ antigens T-independent humoral response Antibodies don’t cross the placenta Organ transplants Rejection due to MHCs that are too dissimilar Suppress immune system to decrease rejection Bone marrow: graft rejection

42 Overactive/under active Immune Systems Allergies: antigen induces inflammatory response Histamine released from mast cells Anaphylactic shock: severe allergic reaction, may cause death (due to  BP) Epinephrine may counteract Autoimmune diseases: immune system attacks self tissue Lupus, rheumatoid arthritis, MS, type 1 diabetes Allergies: antigen induces inflammatory response Histamine released from mast cells Anaphylactic shock: severe allergic reaction, may cause death (due to  BP) Epinephrine may counteract Autoimmune diseases: immune system attacks self tissue Lupus, rheumatoid arthritis, MS, type 1 diabetes

43 Under active Immune System Immunodeficiency diseases: Severe combine immunodeficiency (SCID) Genetic, need marrow transplant May treat w/ gene therapy Hodgkin’s: damages lymphatic system AIDS Susceptible to opportunistic infections Caused by HIV, 2 strains Infect CD4 cells: requires CD4 receptor and co-receptor Implications for treatment: Chemokines bind to coreceptor - may block entry Defective CD4 receptors prevent infection Immunodeficiency diseases: Severe combine immunodeficiency (SCID) Genetic, need marrow transplant May treat w/ gene therapy Hodgkin’s: damages lymphatic system AIDS Susceptible to opportunistic infections Caused by HIV, 2 strains Infect CD4 cells: requires CD4 receptor and co-receptor Implications for treatment: Chemokines bind to coreceptor - may block entry Defective CD4 receptors prevent infection

44 More on AIDS High mutation rate Test is actually for HIV antibodies T cell count indicates disease progression Drugs only slow the progression, are very expensive million (?) world wide cases 70% in sub-saharan Africa High mutation rate Test is actually for HIV antibodies T cell count indicates disease progression Drugs only slow the progression, are very expensive million (?) world wide cases 70% in sub-saharan Africa


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