Chapter 22. Immunity

Transcription

1 Chapter 22 Immunity

2 Body Defenses-Immunity The Lympha6c System and Body Defenses Body defenses provide resistance to fight infec6on, illness, and disease Two categories of defenses 1. Innate (nonspecific) defenses 2. Adap5ve (specific) defenses

3 22-2 Structures of Body Defenses Innate (Nonspecific) Defenses Always work the same way Against any type of invading agent Nonspecific resistance Adap5ve (Specific) Defenses Protect against specific pathogens Depend on ac6vi6es of lymphocytes Specific resistance (immunity) Develops afer exposure to environmental hazards

4 22-3 Nonspecific Defenses Seven Major Categories of Innate (Nonspecific) Defenses 1. Physical barriers 2. Phagocytes 3. Immunological surveillance 4. Interferons 5. Complement 6. Inflammatory response 7. Fever

5 22-3 Nonspecific Defenses Physical Barriers Keep hazardous materials outside the body Phagocytes AVack and remove dangerous microorganisms Immunological Surveillance Constantly monitors normal 6ssues With natural killer cells (NK cells)

6 Interferons 22-3 Nonspecific Defenses Chemical messengers that trigger produc6on of an6viral proteins in normal cells An6viral proteins Do not kill viruses Block replica6on in cell Complement System of circula6ng proteins Assists an6bodies in destruc6on of pathogens

7 22-3 Nonspecific Defenses Inflammatory Response Localized, 6ssue-level response that tends to limit spread of injury or infec6on Fever A high body temperature Increases body metabolism Accelerates defenses Inhibits some viruses and bacteria

8 Figure Innate Defenses (Part 1 of 2) Innate Defenses Physical barriers keep hazardous organisms and materials outside the body. Duct of eccrine sweat gland Hair Secre6ons Epithelium Phagocytes engulf pathogens and cell debris. Fixed macrophage Neutrophil Free macrophage Eosinophil Monocyte Immunological surveillance is the destruc6on of abnormal cells by NK cells in peripheral 6ssues. Interferons are chemical messengers that coordinate the defenses against viral infec6ons. Natural killer cell Interferons released by ac6vated lymphocytes, macrophages, or virus-infected cells Lysed abnormal cell

9 Figure Innate Defenses (Part 2 of 2) Innate Defenses Complement system consists of circula6ng proteins that assist an6bodies in the destruc6on of pathogens. Inflammatory response is a localized, 6ssue-level response that tends to limit the spread of an injury or infec6on. Fever is an eleva6on of body temperature that accelerates 6ssue metabolism and the ac6vity of defenses. Complement Mast cell 1. Blood flow increased 2. Phagocytes ac6vated 3. Capillary permeability increased 4. Complement ac6vated 5. Clo^ng reac6on walls off region 6. Regional temperature increased 7. Adap6ve defenses ac6vated Body temperature rises above 37.2ºC in response to pyrogens Lysed pathogen

10 22-3 Nonspecific Defenses Physical Barriers Outer layer of skin Hair Epithelial layers of internal passageways Secre6ons that flush away materials Sweat glands, mucus, and urine Secre6ons that kill or inhibit microorganisms Enzymes, an6bodies, and stomach acid

11 22-3 Nonspecific Defenses Two Classes of Phagocytes 1. Microphages Neutrophils and eosinophils Leave the bloodstream Enter peripheral 6ssues to fight infec6ons

12 22-3 Nonspecific Defenses Two Classes of Phagocytes 2. Macrophages Large phagocy6c cells derived from monocytes Distributed throughout body Make up monocyte macrophage system (re6culoendothelial system)

13 22-3 Nonspecific Defenses Ac6vated Macrophages Respond to pathogens in several ways Engulf pathogen and destroy it with lysosomal enzymes Bind to pathogen so other cells can destroy it Destroy pathogen by releasing toxic chemicals into inters66al fluid

14 22-3 Nonspecific Defenses Two Types of Macrophages 1. Fixed macrophages Also called his6ocytes Stay in specific 6ssues or organs For example, dermis and bone marrow 2. Free macrophages Also called wandering macrophages Travel throughout body

15 22-3 Nonspecific Defenses Special His6ocytes Microglia found in central nervous system Kupffer cells found in liver sinusoids Free Macrophages Special free macrophages Alveolar macrophages (phagocy6c dust cells)

16 22-3 Nonspecific Defenses Movement and Phagocytosis All macrophages: Move through capillary walls (emigra6on) Are avracted or repelled by chemicals in surrounding fluids (chemotaxis) Phagocytosis begins: When phagocyte avaches to target (adhesion) And surrounds it with a vesicle

17 22-3 Nonspecific Defenses Immunological Surveillance Is carried out by natural killer (NK) cells Ac6vated NK Cells 1. Iden6fy and avach to abnormal cell (nonselec6ve) 2. Golgi apparatus in NK cell forms perforin vesicles 3. Vesicles release proteins called perforins (exocytosis) 4. Perforins lyse abnormal plasma membrane Also avack cancer cells and cells infected with viruses

18 Figure How Natural Killer Cells Kill Cellular Targets (Step 1) Recogni6on and Adhesion NK cell Golgi apparatus Abnormal cell

19 Figure How Natural Killer Cells Kill Cellular Targets (Step 2) Realignment of Golgi apparatus

20 Figure How Natural Killer Cells Kill Cellular Targets (Step 3) Secre6on of Perforin Perforin molecules Pores formed by perforin complex NK cell Abnormal cell

21 Figure How Natural Killer Cells Kill Cellular Targets (Step 4) Lysis of Abnormal Cell

22 22-3 Nonspecific Defenses Immunological Surveillance Cancer cells With tumor-specific an5gens Are iden6fied as abnormal by NK cells Some cancer cells avoid NK cells (immunological escape)

23 22-3 Nonspecific Defenses Immunological Surveillance Viral infec6ons Cells infected with viruses Present abnormal proteins on plasma membranes Allow NK cells to iden6fy and destroy them

24 Interferons 22-3 Nonspecific Defenses Proteins (cytokines) released by ac6vated lymphocytes and macrophages Cytokines Chemical messengers released by 6ssue cells To coordinate local ac6vi6es To act as hormones to affect whole body

25 22-3 Nonspecific Defenses Three Types of Interferons 1. Alpha-interferons Produced by leukocytes S6mulate NK cells 2. Beta-interferons Secreted by fibrocytes Slow inflamma6on 3. Gamma-interferons Secreted by T cells and NK cells S6mulate macrophage ac6vity

26 Figure Interferons Alpha (α)-interferons are produced by cells infected with viruses. They avract and s6mulate NK cells and enhance resistance to viral infec6on. Beta (β)-interferons, secreted by fibroblasts, slow inflamma6on in a damaged area. Gamma (γ)-interferons, secreted by T cells and NK cells, s6mulate macrophage ac6vity.

27 22-3 Nonspecific Defenses Complement Plasma contains 11 special complement (C) proteins That form complement system and complement an6body ac6on Complement ac6va6on Complements work together in cascades Two pathways ac6vate the complement system 1. Classical pathway 2. Alterna5ve pathway

28 22-3 Nonspecific Defenses Complement Ac6va6on: The Classical Pathway Fast method C1 binds to: An6body molecule avached to an6gen (bacterium) Bound protein acts as enzyme Catalyzes chain reac6on

29 Figure Pathways of Complement Ac5va5on (Part 2 of 3) Classical Pathway The most rapid and effec6ve ac6va6on of the complement system occurs through the classical pathway. An6body Binding and C1 AVachment An6body binding C3b AVachment (alternate pathway) C3b An6bodies Bacterial cell wall Ac6va6on and Cascade C4 C2 C3 C3b AVachment (classical pathway) C1 C3b C3b C1 avachment The avached C1 protein then acts as an enzyme, catalyzing a series of reac6ons involving other complement proteins. The classical pathway ends with the conversion of an inac6ve C3 to an ac6vated C3b that avaches to the cell wall.

30 22-3 Nonspecific Defenses Complement Ac6va6on: The Alterna6ve Pathway Slow method exposed to an6gen Factor P (properdin) Factor B Factor D Interact in plasma

31 Figure Pathways of Complement Ac5va5on (Part 1 of 3) Alterna6ve Pathway The alterna6ve pathway is important in the defense against bacteria, some parasites, and virus-infected cells. Properdin Factor B Factor D Bacterial cell wall C3 C3b The alterna6ve pathway begins when several complement proteins, notably properdin, interact in the plasma. This interac6on can be triggered by exposure to foreign materials, such as the capsule of a bacterium. The end result is the avachment of an ac6vated C3b protein to the bacterial cell wall.

32 22-3 Nonspecific Defenses Complement Ac6va6on Both pathways end with: Conversion of inac6ve complement protein C3 To ac6ve form C3b ANIMATION Immunity: Complement

33 22-3 Nonspecific Defenses Effects of Complement Ac6va6on Pore forma6on Destruc6on of target plasma membranes Five complement proteins join to form membrane asack complex (MAC) Enhancement of phagocytosis by opsoniza5on Complements working with an6bodies (opsonins) Histamine release Increases the degree of local inflamma6on and blood flow

34 22-3 Nonspecific Defenses Inflamma5on Also called inflammatory response A localized response Triggered by any s6mulus that kills cells or injures 6ssue

35 22-3 Nonspecific Defenses Cardinal Signs and Symptoms Swelling (tumor) Redness (rubor) Heat (calor) Pain (dolor)

36 22-3 Nonspecific Defenses Three Effects of Inflamma6on 1. Temporary repair and barrier against pathogens 2. Retards spread of pathogens into surrounding areas 3. Mobiliza6on of local and systemic defenses And facilita6on of repairs (regenera6on)

37 Figure Inflamma5on and the Steps in Tissue Repair (Part 1 of 2) Tissue Damage Chemical change in inters66al fluid Mast Cell Ac6va6on Release of histamine and heparin from mast cells

38 Figure Inflamma5on and the Steps in Tissue Repair (Part 2 of 2) Redness, Swelling, Warmth, and Pain Phagocyte AVrac6on AVrac6on of phagocytes, especially neutrophils Dila6on of blood vessels, increased blood flow, increased vessel permeability Clot forma6on (temporary repair) Release of cytokines Removal of debris by neutrophils and macrophages; s6mula6on of fibroblasts Ac6va6on of specific defenses Tissue Repair Pathogen removal, clot erosion, scar 6ssue forma6on

39 22-3 Nonspecific Defenses Products of Inflamma6on Necrosis Pus Local 6ssue destruc6on in area of injury Mixture of debris and necro6c 6ssue Abscess Pus accumulated in an enclosed space

40 Fever 22-3 Nonspecific Defenses A maintained body temperature above 37 C (99 F) Pyrogens Any material that causes the hypothalamus to raise body temperature Circula6ng pathogens, toxins, or an6body complexes Endogenous pyrogens or interleukin-1 (IL-1) Pyrogen released by ac6ve macrophages A cytokine ANIMATION Immunity: Nonspecific Defenses

41 22-4 Specific Defenses Adap6ve (Specific) Defenses Specific resistance (immunity) Responds to specific an6gens With coordinated ac6on of T cells and B cells

42 Specific Defenses T Cells 22-4 Specific Defenses Provide cell-mediated immunity Defend against abnormal cells and pathogens inside cells B Cells Provide an5body-mediated immunity Defend against an6gens and pathogens in body fluids

43 22-4 Specific Defenses Forms of Immunity 1. Innate Present at birth 2. Adap5ve AFer birth 3. Ac5ve An6bodies develop afer exposure to an6gen 4. Passive An6bodies are transferred from another source

44 Ac5ve Immunity 22-4 Specific Defenses Naturally acquired Through environmental exposure to pathogens Ar5ficially induced Through vaccines containing pathogens

45 22-4 Specific Defenses Passive Immunity Naturally acquired An6bodies acquired from the mother Ar5ficially induced By an injec6on of an6bodies

46 Figure Forms of Immunity Immunity Response to threats on an individualized basis Adap6ve Immunity Adap6ve immunity is not present at birth; you acquire immunity to a specific an6gen only when you have been exposed to that an6gen or receive an6bodies from another source. Ac6ve Immunity Develops in response to an6gen exposure Passive Immunity Produced by transfer of an6bodies from another source Innate Immunity Gene6cally determined-no prior exposure or an6body produc6on involved Naturally acquired ac6ve immunity Ar6ficially induced ac6ve immunity Naturally acquired passive immunity Ar6ficially induced passive immunity Develops afer exposure to an6gens in environment Develops afer administra6on of an an6gen to prevent disease Conferred by transfer of maternal an6bodies across placenta or in breast milk Conferred by administra6on of an6bodies to combat infec6on

47 22-4 Specific Defenses Four Proper6es of Immunity 1. Specificity Each T or B cell responds only to a specific an6gen and ignores all others 2. Versa5lity The body produces many types of lymphocytes Each fights a different type of an6gen Ac6ve lymphocyte clones itself to fight specific an6gen

48 22-4 Specific Defenses Four Proper6es of Immunity 3. Memory Some ac6ve lymphocytes (memory cells): 4. Tolerance Stay in circula6on Provide immunity against new exposure Immune system ignores normal an6gens (selfan6gens)

49 22-4 Specific Defenses An Introduc6on to the Immune Response Two main divisions 1. Cell-mediated immunity (T cells) 2. An6body-mediated immunity (B cells)

50 Figure An Overview of the Immune Response Cell-Mediated Immunity Direct Physical and Chemical AVack Adap6ve Defenses An6gen presenta6on triggers specific defenses, or an immune response. Phagocytes ac6vated T cells ac6vated Ac6vated T cells find the pathogens and avack them through phagocytosis or the release of chemical toxins. Communica6on and feedback Destruc6on of an6gens An6body-Mediated Immunity AVack by Circula6ng An6bodies Ac6vated B cells give rise to cells that produce an6bodies.

51 22-5 T Cells and Immunity Four Major Types of T Cells 1. Cytotoxic T cells (also called T C cells) AVack cells infected by viruses Responsible for cell-mediated immunity 2. Memory T cells Clone more of themselves in response to remembered an6gen 3. Helper T cells (also called T H cells) S6mulate func6on of T cells and B cells 4. Suppressor T cells (also called T S cells) Inhibit func6on of T cells and B cells

52 22-5 T Cells and Immunity An5gen Presenta5on T cells only recognize an6gens that are bound to glycoproteins in plasma membranes MHC Proteins The membrane glycoproteins that bind to an6gens Gene6cally coded in chromosome 6 The major histocompa5bility complex (MHC) Differs among individuals

53 22-5 T Cells and Immunity Two Classes of MHC Proteins Class I Found in membranes of all nucleated cells Class II Found in membranes of an5gen-presen5ng cells (APCs) Found in lymphocytes

54 22-5 T Cells and Immunity Class I MHC Proteins Pick up small pep6des in cell and carry them to the surface T cells ignore normal pep6des Abnormal pep6des or viral proteins ac6vate T cells to destroy cell

55 Figure 22-18a An5gens and MHC Proteins Plasma membrane An6gen presenta6on by Class I MHC proteins is triggered by viral or bacterial infec6on of a body cell. Viral or bacterial pathogen The abnormal pep6des are displayed by Class I MHC proteins on the plasma membrane. The infec6on results in the appearance of abnormal pep6des in the cytoplasm. The abnormal pep6des are incorporated into Class I MHC proteins as they are synthesized at the endoplasmic re6culum. Endoplasmic re6culum Nucleus Transport vesicle AFer export to the Golgi apparatus, the MHC proteins reach the plasma membrane within transport vesicles. Infected cell

56 22-5 T Cells and Immunity Class II MHC Proteins An6genic Fragments From an5genic processing of pathogens Bind to Class II proteins Inserted in plasma membrane to s6mulate T cells An5gen-Presen5ng Cells (APCs) Responsible for ac6va6ng T cells against foreign cells and proteins

57 Figure 22-18b An5gens and MHC Proteins Phagocy6c APCs engulf the extracellular pathogens. Plasma membrane An6genic fragments are displayed by Class II MHC proteins on the plasma membrane. An6genic fragments are bound to Class II MHC proteins. Lysosomal ac6on produces an6genic fragments. The endoplasmic re6culum produces Class II MHC proteins. Lysosome Phagocy6c an6gen-presen6ng cell Nucleus Endoplasmic re6culum

58 22-5 T Cells and Immunity Phagocy6c APCs 1. Free and fixed macrophages In connec6ve 6ssues 2. Kupffer cells Of the liver 3. Microglia In the CNS

59 22-5 T Cells and Immunity Non-phagocy6c APCs Langerhans cells In the skin Dendri6c cells In lymph nodes and spleen

60 22-5 T Cells and Immunity An5gen Recogni5on Inac6ve T cell receptors Recognize Class I or Class II MHC proteins Recognize a specific an6gen Binding occurs when MHC protein matches an6gen

61 CD Markers 22-5 T Cells and Immunity Also called cluster of differen6a6on markers In T cell membranes Molecular mechanism of an6gen recogni6on More than 70 types Designated by an iden6fying number CD3 Receptor Complex Found in all T cells

62 22-5 T Cells and Immunity Two Important CD Markers 1. CD8 Markers Found on cytotoxic T cells and suppressor T cells Respond to an6gens on Class I MHC proteins 2. CD4 Markers Found on helper T cells Respond to an6gens on Class II MHC proteins CD8 or CD4 Markers Bind to CD3 receptor complex Prepare cell for ac6va6on

63 22-5 T Cells and Immunity Cos6mula6on For T cell to be ac6vated, it must be cos6mulated By binding to s6mula6ng cell at second site Which confirms the first signal

64 22-5 T Cells and Immunity Ac6va6on of CD8 T Cells Ac6vated by exposure to an6gens on MHC proteins One responds quickly Producing cytotoxic T cells and memory T cells The other responds slowly Producing suppressor T cells

65 22-5 T Cells and Immunity Cytotoxic T Cells Seek out and immediately destroy target cells 1. Release perforin To destroy an6genic plasma membrane 2. Secrete poisonous lymphotoxin To destroy target cell 3. Ac6vate genes in target cell That cause cell to die

66 Figure An5gen Recogni5on by and Ac5va5on of Cytotoxic T Cells (Steps 1-3) An6gen Recogni6on An6gen recogni6on occurs when a CD8 T cell encounters an appropriate an6gen on the surface of another cell, bound to a Class I MHC protein. Ac6va6on and Cell Division An6gen recogni6on results in T cell ac6va6on and cell division, producing ac6ve T C cells and memory T C cells. Infected cell Inac6ve CD8 T cell Ac6ve T C cell Viral or bacterial an6gen Memory T C cells (inac6ve) Cos6mula6on CD8 protein Class I MHC Cos6mula6on ac6vates CD8 T cell T cell receptor Before ac6va6on can occur, a T cell must be chemically or physically s6mulated by the abnormal target cell. Infected cell An6gen CD8 T cell

67 Figure An5gen Recogni5on by and Ac5va5on of Cytotoxic T Cells (Steps 4) Destruc6on of Target Cells The ac6ve T C cell destroys the an6gen-bearing cell. It may use several different mechanisms to kill the target cell. Lysed cell Perforin release Destruc6on of plasma membrane Cytokine release S6mula6on of apoptosis Lymphotoxin release Disrup6on of cell metabolism

68 22-5 T Cells and Immunity Memory T C Cells Produced with cytotoxic T cells Stay in circula6on Immediately form cytotoxic T cells if same an6gen appears again

69 22-5 T Cells and Immunity Suppressor T Cells Secrete suppression factors Inhibit responses of T and B cells Act aler ini6al immune response Limit immune reac6on to single s6mulus

70 22-5 T Cells and Immunity Ac6va6on of CD4 T cells Ac6ve helper T cells (T H cells) Secrete cytokines Memory helper (T H) cells Remain in reserve

71 Figure An5gen Recogni5on and Ac5va5on of Helper T Cells (Part 1 of 2) An6gen Recogni6on by CD4 T Cell Foreign an6gen An6gen-presen6ng cell (APC) Class II MHC APC An6gen T cell receptor Cos6mula6on T H cell CD4 protein Inac6ve CD4 (T H ) cell

72 Figure An5gen Recogni5on and Ac5va5on of Helper T Cells (Part 2 of 2) CD4 T Cell Ac6va6on and Cell Division Memory T H cells (inac6ve) Ac6ve T H cells Ac6ve helper T cells secrete cytokines that s6mulate both cell-mediated and an6body-mediated immunity. Cytokines Cytokines Cytokines

73 22-5 T Cells and Immunity Four Func6ons of Cytokines 1. S6mulate T cell divisions Produce memory T H cells Accelerate cytotoxic T cell matura6on 2. AVract and s6mulate macrophages 3. AVract and s6mulate ac6vity of cytotoxic T cells 4. Promote ac6va6on of B cells

74 Figure 22-21a A Summary of the Pathways of T Cell Ac5va5on Ac6va6on by Class I MHC proteins An6gen bound to Class I MHC protein Indicates that the cell is infected or otherwise abnormal CD8 T Cells Cytotoxic T Cells AVack and destroy infected and abnormal cells displaying an6gen Memory T C Cells Await reappearance of the an6gen Suppressor T Cells Control or moderate immune response by T cells and B cells

75 Figure 22-21b A Summary of the Pathways of T Cell Ac5va5on Ac6va6on by Class II MHC proteins An6gen bound to Class II MHC protein Indicates presence of pathogens, toxins, or foreign proteins CD4 T Cells Helper T Cells S6mulate immune response by T cells and B cells Memory T H Cells Await reappearance of the an6gen

76 B Cells 22-6 B Cells and Immunity Responsible for an6body-mediated immunity AVack an6gens by producing specific an6bodies Millions of popula6ons, each with different an6body molecules

77 22-6 B Cells and Immunity B Cell Sensi6za6on Corresponding an6gens in inters66al fluids bind to B cell receptors B cell prepares for ac6va6on Prepara6on process is sensi5za5on During sensi6za6on, an6gens are: Taken into the B cell Processed Reappear on surface, bound to Class II MHC protein

78 Figure The Sensi5za5on and Ac5va5on of B Cells (Step 1) Sensi6za6on An6gens Class II MHC An6bodies Inac6ve B cell An6gens bound to an6body molecules An6gen binding Sensi6zed B cell

79 22-6 B Cells and Immunity Helper T Cells Sensi6zed B cell is prepared for ac6va6on but needs helper T cell ac6vated by same an6gen B Cell Ac6va6on Helper T cell binds to MHC complex Secretes cytokines that promote B cell ac6va6on and division

80 Figure The Sensi5za5on and Ac5va5on of B Cells (Step 2) Ac6va6on Class II MHC T cell receptor An6gen B cell T cell Cytokine cos6mula6on Helper T cell Sensi6zed B cell

81 22-6 B Cells and Immunity B Cell Division Ac6vated B cell divides into: Plasma cells Memory B cells

82 Figure The Sensi5za5on and Ac5va5on of B Cells (Step 3) Division and Differen6a6on ANTIBODY PRODUCTION Plasma cells Ac6vated B cells Memory B cells (inac6ve)

83 Plasma Cells 22-6 B Cells and Immunity Synthesize and secrete an6bodies into inters66al fluid Memory B Cells Like memory T cells, remain in reserve to respond to next infec6on

84 22-6 B Cells and Immunity An6body Structure Two parallel pairs of polypep6de chains One pair of heavy chains One pair of light chains Each chain contains: Constant segments Variable segments

85 22-6 B Cells and Immunity Five Heavy-Chain Constant Segments Determine five types of an6bodies 1. IgG 2. IgE 3. IgD 4. IgM 5. IgA

86 22-6 B Cells and Immunity Variable Segments of Light and Heavy Chains Determine specificity of an6body molecule Binding Sites Free 6ps of two variable segments Form an5gen binding sites of an6body molecule Which bind to an5genic determinant sites of an6gen molecule An6gen An6body Complex An an6body bound to an an6gen

87 22-6 B Cells and Immunity The An5gen An5body Complex A Complete An5gen Has two an5genic determinant sites Binds to both an6gen-binding sites of variable segments of an6body B Cell Sensi6za6on Exposure to a complete an6gen leads to: B cell sensi6za6on Immune response

88 22-6 B Cells and Immunity Hapten (Par6al An6gens) Must avach to a carrier molecule to act as a complete an6gen Dangers of Haptens An6bodies produced will avack both hapten and carrier molecule If carrier is normal : An6body avacks normal cells For example, penicillin allergy

89 Figure 22-23a An5body Structure and Func5on An6gen binding site Heavy chain An6gen binding site Variable segment Disulfide bond Light chain Constant segments of light and heavy chains Complement binding site Site of binding to macrophages A diagramma6c view of the structure of an an6body.

90 Figure 22-23b An5body Structure and Func5on An6gen binding site Light chain Heavy chain A computer-generated image of a typical an6body.

91 Figure 22-23c An5body Structure and Func5on An6genic determinant sites An6gen An6bodies An6bodies bind to por6ons of an an6gen called an6genic determinant sites, or epitopes.

92 Figure 22-23d An5body Structure and Func5on Complete an6gen Hapten Carrier molecule An6body molecules can bind a hapten (par6al an6gen) once it has become a complete an6gen by combining with a carrier molecule.

93 22-6 B Cells and Immunity Five Classes of An6bodies Also called immunoglobulins (Igs) IgG, IgD, IgE, IgM, IgA Are found in body fluids Are determined by constant segments Have no effect on an6body specificity

94 22-6 B Cells and Immunity Five Classes of An6bodies IgG is the largest and most diverse class of an6bodies 80 percent of all an6bodies IgG an6bodies are responsible for resistance against many viruses, bacteria, and bacterial toxins Can cross the placenta, and maternal IgG provides passive immunity to fetus during embryological development An6-Rh an6bodies produced by Rh-nega6ve mothers are also IgG an6bodies and produce hemoly6c disease of the newborn

95 22-6 B Cells and Immunity Five Classes of An6bodies IgE avaches as an individual molecule to the exposed surfaces of basophils and mast cells When an an6gen is bound by IgE molecules: The cell is s6mulated to release histamine and other chemicals that accelerate inflamma6on in the immediate area IgE is also important in the allergic response

96 22-6 B Cells and Immunity Five Classes of An6bodies IgD is an individual molecule on the surfaces of B cells, where it can bind an6gens in the extracellular fluid Binding can play a role in the sensi6za6on of the B cell involved

97 22-6 B Cells and Immunity Five Classes of An6bodies IgM is the first class of an6body secreted afer an an6gen is encountered IgM concentra6on declines as IgG produc6on accelerates Plasma cells secrete individual IgM molecules, but it polymerizes and circulates as a five-an6body starburst The an6-a and an6-b an6bodies responsible for the agglu6na6on of incompa6ble blood types are IgM an6bodies IgM an6bodies may also avack bacteria that are insensi6ve to IgG

98 22-6 B Cells and Immunity Five Classes of An6bodies IgA is found primarily in glandular secre6ons such as mucus, tears, saliva, and semen AVack pathogens before they gain access to internal 6ssues IgA an6bodies circulate in blood as individual molecules or in pairs Epithelial cells absorb them from blood and avach a secretory piece, which confers solubility, before secre6ng IgA molecules onto the epithelial surface

99 Table 22-1 Classes of An5bodies (Part 1 of 2)

100 Table 22-1 Classes of An5bodies (Part 2 of 2) Secretory piece

101 22-6 B Cells and Immunity Seven Func6ons of An6gen An6body Complexes 1. Neutraliza5on of an6gen binding sites 2. Precipita5on and agglu5na5on - forma6on of immune complex 3. Ac6va6on of complement 4. AVrac6on of phagocytes 5. Opsoniza6on increasing phagocyte efficiency 6. S6mula6on of inflamma6on 7. Preven6on of bacterial and viral adhesion

102 22-6 B Cells and Immunity Primary and Secondary Responses to An6gen Exposure Occur in both cell-mediated and an6bodymediated immunity First exposure Produces ini6al primary response Next exposure Triggers secondary response More extensive and prolonged Memory cells already primed

103 22-6 B Cells and Immunity The Primary Response Takes 6me to develop An6gens ac6vate B cells Plasma cells differen6ate An5body 5ter (level) slowly rises

104 22-6 B Cells and Immunity The Primary Response Peak response IgM Can take two weeks to develop Declines rapidly Is produced faster than IgG Is less effec6ve

105 Figure 22-24a The Primary and Secondary Responses in An5body-Mediated Immunity An6body concentra6on in serum PRIMARY RESPONSE IgM IgG Time (weeks)

106 22-6 B Cells and Immunity The Secondary Response Ac6vates memory B cells At lower an6gen concentra6ons than original B cells Secrete an6bodies in massive quan66es

107 Figure 22-24b The Primary and Secondary Responses in An5body-Mediated Immunity SECONDARY RESPONSE IgG IgM Time (weeks)

108 22-6 B Cells and Immunity Effects of Memory B Cell Ac6va6on IgG IgM Rises very high and very quickly Can remain elevated for extended 6me Produc6on is also quicker Slightly extended

109 22-6 B Cells and Immunity Combined Responses to Bacterial Infec6on Neutrophils and NK cells begin killing bacteria Cytokines draw phagocytes to area An6gen presenta6on ac6vates: Helper T cells Cytotoxic T cells B cells ac6vate and differen6ate Plasma cells increase an6body levels

110 Figure The Course of the Body s Response to a Bacterial Infec5on Neutrophils Macrophages Plasma cells Number of ac6ve immune cells Natural killer cells Cytotoxic T cells An6body 6ter Time (weeks)

111 22-6 B Cells and Immunity Combined Responses to Viral Infec6on Similar to bacterial infec6on But cytotoxic T cells and NK cells are ac6vated by contact with virus-infected cells

112 Figure 22-27a Defenses against Bacterial and Viral Pathogens BACTERIA Phagocytosis by macrophages and APCs An6gen presenta6on Ac6va6on of cytotoxic T cells Ac6va6on of helper T cells Ac6va6on of B cells Destruc6on of bacteria by cell lysis or phagocytosis An6body produc6on by plasma cells Opsoniza6on and phagocyte avrac6on Forma6on of an6gen-an6body complexes Defenses against bacteria involve phagocytosis and an6gen presenta6on by APCs.

113 Figure 22-27b Defenses against Bacterial and Viral Pathogens VIRUSES Infec6on of 6ssue cells Infec6on of or uptake by APCs Release of interferons Appearance of an6gen in plasma membrane An6gen presenta6on Increased resistance to viral infec6on and spread S6mula6on of NK cells Ac6va6on of cytotoxic T cells Ac6va6on of helper T cells Destruc6on of virus-infected cells Ac6va6on of B cells Destruc6on of viruses or preven6on of virus entry into cells An6body produc6on by plasma cells Defenses against viruses involves direct contact with virus-infected cells and an6gen presenta6on by APCs.

114 22-7 Immune System Development Immune System Development Fetus can produce immune response (has immunological competence) AFer exposure to an6gen At about three to four months

115 22-7 Immune System Development Development of Immunological Competence Fetal thymus cells migrate to 6ssues that form T cells Liver and bone marrow produce B cells Four month fetus produces IgM an6bodies

116 22-7 Immune System Development Before Birth Maternal IgG an6bodies Pass through placenta Provide passive immunity to fetus AFer Birth Mother s milk provides IgA an6bodies While passive immunity is lost

117 22-7 Immune System Development Normal Resistance Infant produces IgG an6bodies through exposure to an6gens An6body, B cell, and T cell levels slowly rise to adult levels About age 12

118 22-7 Immune System Development Cytokines of the Immune System Chemical messengers involved in cellular immunity Hormones and paracrine-like glycoproteins Examples of cytokines:» Interferons» Interleukins» Tumor necrosis factors (TNFs)

119 22-7 Immune System Development Interleukins Func6ons include: 1. Increasing T cell sensi6vity to an6gens exposed on macrophage membranes 2. S6mula6ng B cell ac6vity, plasma cell forma6on and an6body produc6on

120 22-7 Immune System Development Interleukins Func6ons include: 3. Enhancing nonspecific defenses S6mula6on of inflamma6on Forma6on of scar 6ssue by fibroblasts Eleva6on of body temperature via the preop6c nucleus of the hypothalamus S6mula6on of mast cell forma6on Promo6on of adrenocor6cotroic hormone (ACTH) secre6on by the anterior lobe of the pituitary gland 4. Modera6ng the immune response Some interleukins help suppress immune func6on and shorten the immune response

121 22-7 Immune System Development Interleukins IL-1 and IL2, are important in s6mula6ng and maintaining the immune response When released by ac6vated macrophages and lymphocytes, these cytokines s6mulate the ac6vi6es of other immune cells and of the secre6ng cell Result is a posi6ve feedback loop that helps to recruit addi6onal immune cells

122 22-7 Immune System Development Three Types of Interferons 1. Alpha-interferons Produced by leukocytes S6mulate NK cells 2. Beta-interferons Secreted by fibrocytes Slow inflamma6on 3. Gamma-interferons Secreted by T cells and NK cells S6mulate macrophage ac6vity

123 Figure Interferons Alpha (α)-interferons are produced by cells infected with viruses. They avract and s6mulate NK cells and enhance resistance to viral infec6on. Beta (β)-interferons, secreted by fibroblasts, slow inflamma6on in a damaged area. Gamma (γ)-interferons, secreted by T cells and NK cells, s6mulate macrophage ac6vity.

124 22-7 Immune System Development Tumor Necrosis Factors (TNFs) TNFs slow the growth of a tumor and kill sensi6ve tumor cells Ac6vated macrophages secrete one type of TNF and carry the molecules in their plasma membranes Cytotoxic T cells produce a different type of TNF In addi6on to their effects on tumor cells: TNFs s6mulate granular leukocyte produc6on, promote eosinophil ac6vity, cause fever, and increase T cell sensi6vity to interleukins

125 22-7 Immune System Development Phagocyte-Ac5va5ng Chemicals Several cytokines coordinate immune defenses by adjus6ng the ac6vi6es of phagocy6c cells Include factors that avract free macrophages and microphages and prevent their premature departure from the site of an injury Colony-S5mula5ng Factors Factors are produced by ac6ve T cells, cells of the monocyte-macrophage group, endothelial cells, and fibrocytes CSFs s6mulate the produc6on of blood cells in red bone marrow and lymphocytes in lymphoid 6ssues

126 22-7 Immune System Development Cytokines are OFen Classified According to their Origins Lymphokines are produced by lymphocytes Monokines are secreted by ac6ve macrophages and other an6gen-presen6ng cells These terms are misleading, because lymphocytes and macrophages may secrete the same cytokines Cells involved in adap6ve defenses and 6ssue repair can also secrete cytokines

127 22-7 Immune System Development Immune Disorders Autoimmune disorders Immunodeficiency disease Allergies

128 22-7 Immune System Development Autoimmune Disorders A malfunc6on of system that recognizes and ignores normal an6gens Ac6vated B cells make autoan5bodies against body cells Examples: Thyroidi6s Rheumatoid arthri6s Insulin-dependent diabetes mellitus (IDDM)

129 22-7 Immune System Development Immunodeficiency Diseases Result from: Problems with embryological development of lymphoid 6ssues Can result in severe combined immunodeficiency disease (SCID) Viral infec6ons such as HIV Can result in AIDS Immunosuppressive drugs or radia6on treatments Can lead to complete immunological failure

130 22-7 Immune System Development Allergies Inappropriate or excessive immune responses to an6gens Allergens An6gens that trigger allergic reac6ons

131 22-7 Immune System Development Four Categories of Allergic Reac6ons 1. Immediate hypersensi6vity Type I 2. Cytotoxic reac6ons Type II 3. Immune complex disorders Type III 4. Delayed hypersensi6vity Type IV

132 22-7 Immune System Development Type I Allergy Also called immediate hypersensi5vity A rapid and severe response to the presence of an an6gen Most commonly recognized type of allergy Includes allergic rhini6s (environmental allergies)

133 22-7 Immune System Development Type I Allergy Sensi6za6on leads to: Produc6on of large quan66es of IgE an6bodies distributed throughout the body Second exposure leads to: Massive inflamma6on of affected 6ssues

134 22-7 Immune System Development Type I Allergy Severity of reac6on depends on: Individual sensi6vity Loca6ons involved Allergens (an6gens that trigger reac6on) in bloodstream may cause anaphylaxis

135 22-7 Immune System Development Anaphylaxis Can be fatal Affects cells throughout body Changes capillary permeability Produces swelling (hives) on skin Smooth muscles of respiratory system contract Make breathing difficult Peripheral vasodilata6on Can cause circulatory collapse (anaphylac5c shock)

136 Figure The Mechanism of Anaphylaxis (Part 1 of 2) First Exposure Allergen fragment Allergens Macrophage T H cell ac6va6on B cell sensi6za6on and ac6va6on Plasma cell IgE an6bodies

137 Figure The Mechanism of Anaphylaxis (Part 2 of 2) Subsequent Exposure Allergen IgE Granules Massive s6mula6on of mast cells and basophils Sensi6za6on of mast cells and basophils Release of histamines, leukotrienes, and other chemicals that cause pain and inflamma6on Capillary dila6on, increased capillary permeability, airway constric6on, mucus secre6on, pain and itching

138 22-7 Immune System Development An5histamines Drugs that block histamine released by mast cells Can relieve mild symptoms of immediate hypersensi6vity Benadryl

139 22-7 Immune System Development Stress and the Immune Response Glucocor6coids Secreted to limit immune response Long-term secre6on (chronic stress) Inhibits immune response Lowers resistance to disease

140 22-7 Immune System Development & Integra6on Func6ons of Glucocor6coids Depression of the inflammatory response Reduc6on in abundance and ac6vity of phagocytes Inhibi6on of interleukin secre6on Nervous and Endocrine Systems Interact with thymic hormones Adjust sensi6vity of immune response

141 22-8 Effects of Aging on the Immune System Immune System Diminishes with Age Increasing vulnerability to infec6ons and cancer Four Effects of Aging 1. Thymic hormone produc6on is greatly reduced 2. T cells become less responsive to an6gens 3. Fewer T cells reduces responsiveness of B cells 4. Immune surveillance against tumor cells declines