Download - CHAPTER 19 Natural Defenses Against Disease
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Natural Defenses Against Disease
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Nonspecific DefensesTable 18.1
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Animal Defenses Against Pathogens
• most animals have defenses that are non-specific, or innate
– physical barriers
– cellular, chemical, or coordinated defenses
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a septic wound
mastcells
release histamine
and chemotactic
agentsFigure 18.4
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Nonspecific Defenses
• inflammatory response to injury
– activated mast cells release histamine
– blood capillaries dilate & leak
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Nonspecific Defenses
• inflammatory response to injury
– activated mast cells release histamine
– blood capillaries dilate & leak
– complement proteins attract macrophages
– macrophages engulf bacteria & dead cells
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Figure 18.3
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Animal Defenses Against Pathogens
• most animals have defenses that are non-specific, or innate
• vertebrates (and perhaps other groups) possess defenses that are specific, or targeted
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Defensive Cells and Proteins
• non-specific & specific defenses are mediated by
cells & proteins of the bloodstream & lymphatic system
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defensive roles of white blood cellsFigure 18.2
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organs and
vessels of the
lymphatic system
Figure 18.1
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Circulatory & Lymphatic Systems
• defensive cells and molecules circulate in the blood
• some cells and molecules leave the blood and enter the lymphatic system
• cells and molecules of the blood and lymph monitor the body and respond to pathogens
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cell signaling in defense
• defensive responses resemble other cellular responses
– the receptor, toll, binds a fragment of a bacterium or a fungus
– a transduction pathway phosphorylates NF-B
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Figure 18.5
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Targeted Defense: The Immune System
• immune system cells produce several protein types
– antibodies & T cell receptors bind foreign substances
– MHC (HLA) proteins help recognize foreign substances & activate defensive cells
– cytokines alter the behavior of other cells
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Targeted Defense: The Immune System
• attacks antigens that evade the non-specific defenses
• four features of the immune response
– specificity
– ability to respond to great diversity of antigens
– ability to distinguish self from non-self
– memory
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Targeted Defense: The Immune System
• capacity of the immune response
– can respond to millions of different targets
– each cell responds to only one specific target
• targets that elicit a response are antigens
– antigens bear antigenic determinants
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antigens and antigenic determinantsFigure 18.6
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Targeted Defense: The Immune System
• humoral & cellular responses are coordinated
– humoral response
• uses antibodies
–secreted by plasma cells
–target antigens in body fluids
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Targeted Defense: The Immune System
• humoral & cellular responses are coordinated
– cellular response
• uses T cells
–attack body cells
»virus-infected or mutated
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Targeted Defense: The Immune System
• clonal selection
– effector and memory cells are produced as T cell & B cell clones expand
• explains the rapid, specific, and diverse response
• explains immunological memory
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clonal selection:a B cell is “selected”
resulting in a
clone of plasma cells producing
the selected antibody & memory cells
Figure 18.7
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Targeted Defense: The Immune System
• natural & artificial immunity both depend on immunological memory
– vaccination or previous exposure prepares an aggressive anamnestic immune response
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immunological memoryFigure 18.8
the anamnestic response
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Targeted Defense: The Immune System
• natural & artificial immunity both depend on immunological memory
– vaccination or previous exposure prepares an aggressive anamnestic immune response
• memory cells are stimulated without illness
– vaccines use inactive toxins as antigens
• attenuated cells
• cloned proteins
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Table 18.2
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Targeted Defense: The Immune System
• tolerance of self results from clonal deletion of anti-self lymphocytes
– ~90% of B cells are deleted by apoptosis
– loss of tolerance results in autoimmune disease
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Addison's Disease Meniere's MyositisAlopecia Areata Psoriasis DiabetesBehcet's Disease Vitiligo VasculitisRheumatic Fever Fibromyalgia SarcoidosisGoodpasture Syndrome SclerodermaGraft Versus Host Disease Graves' Disease Guillain-Barre Syndrome Multiple SclerosisWegener's Granulomatosis Myasthenia GravisChronic Fatigue Syndrome Pemphigus
VulgarisPrimary Biliary Cirrhosis Ankylosing Spondylitis Antiphospholipid Syndrome (APS)Crohn's Disease and Ulcerative Colitis
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Figure 18.9
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B Cells: The Humoral Immune Response
• activated B cells
– form plasma cells
• synthesize & secrete specific antibodies
• antibodies, or immunoglobulins
– tetramers of four polypeptides
• two light chains & two heavy chains
• each with a constant & a variable region
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components of an immunoglobulinFigure 18.10
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B Cells: The Humoral Immune Response
• variable regions form antigen-binding sites
– determine the antibody’s specificity
• constant region determines destination and function
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B Cells: The Humoral Immune Response• five immunoglobulin classes
– IgM: formed first; membrane receptor on B cells
– IgD: membrane receptor on B cells
– IgG: most abundant class; several functions
– IgE: inflammation & allergic reactions
– IgA: in various body secretions
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five antibody classesFigure 18.3
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B Cells: The Humoral Immune Response
• monoclonal antibodies
– identical & directed against a single antigenic determinant
• hybridomas
– produced by fusing B cells with myeloma cells
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hybridoma production
Figure 18.12
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Figure 18.14
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T Cells: The Cellular Immune Response
• cellular immune response– directed against altered or antigen-infected
cells– TC cells attack & lyse virus-infected or
tumor cells– TH cells activate B cells & guide
development of other T cells and macrophages
– T cell receptors are analogous to immunoglobulins
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atypical T cell
receptorFigure 18.13
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T Cells: The Cellular Immune Response
• the major histocompatibility complex (MHC)
– encodes membrane proteins in macrophages, B cells, or body cells
– MHC proteins
• bind processed antigen
• present it to T cells (displayed on cell surface)
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aClass II
MHC protein presents a processed antigen fragment to a
TH cellFigure 18.15
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antigen presentation & MHC recognitionFigure 18.16
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T Cells: The Cellular Immune Response
• activation of the humoral immune response
– class II MHC molecules
– T cell surface protein CD4
– cytokines
– effector phase results in active plasma cells
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formation of a
B cell clone and
antibodiesFigure 18.17
cytokines
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T Cells: The Cellular Immune Response
• cellular immune response
– class I MHC molecules
– TC cells
– CD8
– cytokines
– activate TC cells with appropriate specificity
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preparation of a
cytotoxic T cell
Figure 18.17
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T Cells: The Cellular Immune Response
• developing T cells are tested in the thymus
– must recognize self MHC molecules
• or fail to develop (anergy)
– must not bind to both self MHC & any of the body’s own antigens
• or die (clonal deletion - apoptosis)
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T Cells: The Cellular Immune Response
• rejection of organ transplants is due to the genetic diversity of MHC molecules
– each individual (or pair of identical twins) has unique MHC proteins
– MHC proteins of one are treated as foreign by the immune system of others
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The Genetic Basis of Antibody Diversity
• several gene families produce the diversity of antibodies & T cell receptors
• antibody heavy-chain genes
– constructed from one each of many V, D, J, & C segments
– V, D, and J segments combine by DNA rearrangement
– transcription & processing yields a mRNA
– other gene families produce light chains
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heavy chain gene segments available for rearrangement
Figure 18.18
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random combinations yield unique chainsFigure 18.19
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heavy chain dimer
produced by recombined
DNAFigure 18.10
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The Genetic Basis of Antibody Diversity
• possible antibodies as a result of these
– millions due to DNA recombinations
– tens to hundreds of thousands due to
• imprecise DNA rearrangements
• mutations
• random addition of terminal bases before DNA’s before are joined
– ~1011 possible different antibodies
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The Genetic Basis of Antibody Diversity
• ~1011 possible different antibodies
– each B cell produces only one antibody
– millions of different B cells monitor blood, lymph, tissues for antigens that “fit”
• millions of different T cells produce unique receptors similarly from a different set of gene families
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The Genetic Basis of Antibody Diversity
• plasma cells produce
– IgM first
– may switch to other classes of antibodies
• same antigen specificity
• different function
– accomplished by switching constant regions
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switching from IgM to
IgG by switching
constant regions
Figure 18.20
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Disorders of the Immune System
• allergies
– overreaction of the immune system to an antigen
• autoimmune diseases
– failure of self-recognition
– antiself B and T cells attack the body’s cells
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inverse relationship betweenviral load & T cell concentration
Figure 18.21
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Disorders of the Immune System
• immune deficiency disorders
– failure of some part of the immune system
• AIDS
–depletion of TH cells
–result of HIV infection
–when certain T cell clones are lost, their target pathogens are able to infect “opportunistically”
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opportunistic infections vs. TH cell countFigure 18.22
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Disorders of the Immune System
• HIV is a retrovirus
– inserts its genome into a chromosome of a macrophage or TH cell
– may lie dormant for years
– when transcription and translation occur, new viruses form
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Disorders of the Immune System
• AIDS treatments
– steps in the reproductive cycle of HIV are possible targets for drugs