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Chapter 43 The Immune System.

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1 Chapter 43 The Immune System

2 Overview: Reconnaissance, Recognition, and Response
Barriers help an animal to defend itself from the many dangerous pathogens it may encounter The immune system recognizes foreign bodies and responds with the production of immune cells and proteins Two major kinds of defense have evolved: innate immunity and acquired immunity

3 Fig. 43-1 Fig 43.1 How do immune cells of animals recognize foreign cells? For the Cell Biology Video Leukocyte Adhesion and Rolling, go to Animation and Video Files. 1.5 µm

4 Innate immunity is present before any exposure to pathogens and is effective from the time of birth
It involves nonspecific responses to pathogens Innate immunity consists of external barriers plus internal cellular and chemical defenses

5 Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances It involves a very specific response to pathogens

6 Pathogens (microorganisms and viruses)
Fig. 43-2 Pathogens (microorganisms and viruses) INNATE IMMUNITY Barrier defenses: Skin Mucous membranes Secretions Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Rapid response Figure 43.2 Overview of animal immunity ACQUIRED IMMUNITY Humoral response: Antibodies defend against infection in body fluids. Recognition of traits specific to particular pathogens, using a vast array of receptors Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. Slower response

7 Concept 43.1: In innate immunity, recognition and response rely on shared traits of pathogens
Both invertebrates and vertebrates depend on innate immunity to fight infection Vertebrates also develop acquired immune defenses

8 Innate Immunity of Invertebrates
In insects, an exoskeleton made of chitin forms the first barrier to pathogens The digestive system is protected by low pH and lysozyme, an enzyme that digests microbial cell walls Hemocytes circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria

9 Microbes PHAGOCYTIC CELL Vacuole Lysosome containing enzymes Fig. 43-3
Figure 43.3 Phagocytosis

10 Hemocytes also secrete antimicrobial peptides that disrupt the plasma membranes of bacteria

11 Fig. 43-4 Figure 43.4 An inducible innate immune response

12 The immune system recognizes bacteria and fungi by structures on their cell walls
An immune response varies with the class of pathogen encountered

13 Fruit fly survival after infection by N. crassa fungi
Fig. 43-5 RESULTS 100 Wild type 75 Mutant + drosomycin % survival 50 Mutant Mutant + defensin 25 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by N. crassa fungi 100 Wild type Mutant + defensin 75 Figure 43.5 Can a single antimicrobial peptide protect fruit flies against infection? % survival 50 Mutant + drosomycin Mutant 25 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by M. luteus bacteria

14 Fruit fly survival after infection by N. crassa fungi
Fig. 43-5a RESULTS 100 Wild type 75 Mutant + drosomycin % survival 50 Mutant + defensin Mutant 25 Figure 43.5 Can a single antimicrobial peptide protect fruit flies against infection? 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by N. crassa fungi

15 Fruit fly survival after infection by M. luteus bacteria
Fig. 43-5b RESULTS 100 Wild type Mutant + defensin 75 % survival 50 Mutant + drosomycin Mutant 25 Figure 43.5 Can a single antimicrobial peptide protect fruit flies against infection? 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by M. luteus bacteria

16 Innate Immunity of Vertebrates
The immune system of mammals is the best understood of the vertebrates Innate defenses include barrier defenses, phagocytosis, antimicrobial peptides Additional defenses are unique to vertebrates: the inflammatory response and natural killer cells

17 Barrier Defenses Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts Mucus traps and allows for the removal of microbes Many body fluids including saliva, mucus, and tears are hostile to microbes The low pH of skin and the digestive system prevents growth of microbes

18 Cellular Innate Defenses
White blood cells (leukocytes) engulf pathogens in the body Groups of pathogens are recognized by TLR, Toll-like receptors

19 EXTRACELLULAR FLUID Lipopolysaccharide Helper protein Flagellin TLR4
Fig. 43-6 EXTRACELLULAR FLUID Lipopolysaccharide Helper protein Flagellin TLR4 WHITE BLOOD CELL TLR5 VESICLE TLR9 CpG DNA Figure 43.6 TLR signaling Inflammatory responses TLR3 ds RNA

20 There are different types of phagocytic cells:
A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe There are different types of phagocytic cells: Neutrophils engulf and destroy microbes Macrophages are part of the lymphatic system and are found throughout the body Eosinophils discharge destructive enzymes Dendritic cells stimulate development of acquired immunity

21 Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Spleen
Fig. 43-7 Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Spleen Tissue cells Lymphatic vessel Peyer’s patches (small intestine) Appendix Figure 43.7 The human lymphatic system Lymphatic vessels Lymph node Masses of defensive cells

22 Antimicrobial Peptides and Proteins
Peptides and proteins function in innate defense by attacking microbes directly or impeding their reproduction Interferon proteins provide innate defense against viruses and help activate macrophages About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation

23 Inflammatory Responses
Following an injury, mast cells release histamine, which promotes changes in blood vessels; this is part of the inflammatory response These changes increase local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation

24 Pathogen Splinter Chemical signals Macrophage Fluid Mast cell
Fig Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Phagocytosis Figure 43.8 Major events in a local inflammatory response For the Cell Biology Video Chemotaxis of a Neutrophil, go to Animation and Video Files. Red blood cells Phagocytic cell

25 Inflammation can be either local or systemic (throughout the body)
Fever is a systemic inflammatory response triggered by pyrogens released by macrophages, and toxins from pathogens Septic shock is a life-threatening condition caused by an overwhelming inflammatory response

26 Natural Killer Cells All cells in the body (except red blood cells) have a class 1 MHC protein on their surface Cancerous or infected cells no longer express this protein; natural killer (NK) cells attack these damaged cells

27 Innate Immune System Evasion by Pathogens
Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis Tuberculosis (TB) is one such disease and kills more than a million people a year

28 Concept 43.2: In acquired immunity, lymphocyte receptors provide pathogen-specific recognition
White blood cells called lymphocytes recognize and respond to antigens, foreign molecules Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells

29 Lymphocytes contribute to immunological memory, an enhanced response to a foreign molecule encountered previously Cytokines are secreted by macrophages and dendritic cells to recruit and activate lymphocytes

30 Acquired Immunity: An Overview
B cells and T cells have receptor proteins that can bind to foreign molecules Each individual lymphocyte is specialized to recognize a specific type of molecule

31 Antigen Recognition by Lymphocytes
An antigen is any foreign molecule to which a lymphocyte responds A single B cell or T cell has about 100,000 identical antigen receptors

32 Figure 43.9 Antigen receptors on lymphocytes
binding site Antigen- binding site Antigen- binding site V Disulfide bridge V V V Variable regions C V V C Constant regions C C C C Light chain Transmembrane region Plasma membrane Heavy chains  chain  chain Figure 43.9 Antigen receptors on lymphocytes Disulfide bridge B cell Cytoplasm of B cell Cytoplasm of T cell T cell (a) B cell receptor (b) T cell receptor

33 Antigen- binding site Antigen- binding site V Disulfide bridge V V V
Fig. 43-9a Antigen- binding site Antigen- binding site V Disulfide bridge V V V Variable regions C C Constant regions C C Light chain Transmembrane region Figure 43.9 Antigen receptors on lymphocytes Plasma membrane Heavy chains B cell Cytoplasm of B cell (a) B cell receptor

34 Antigen-binding sites
Fig Antigen- binding sites Epitopes (antigenic determinants) Antigen-binding sites Antibody A Antigen V V Antibody C V V C C C C Figure Epitopes (antigenic determinants) Antibody B

35 The Antigen Receptors of B Cells and T Cells
B cell receptors bind to specific, intact antigens The B cell receptor consists of two identical heavy chains and two identical light chains The tips of the chains form a constant (C) region, and each chain contains a variable (V) region, so named because its amino acid sequence varies extensively from one B cell to another

36 Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane

37 Video: T Cell Receptors
Each T cell receptor consists of two different polypeptide chains The tips of the chain form a variable (V) region; the rest is a constant (C) region T cells can bind to an antigen that is free or on the surface of a pathogen Video: T Cell Receptors

38 T cells bind to antigen fragments presented on a host cell
These antigen fragments are bound to cell-surface proteins called MHC molecules MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex

39 The Role of the MHC In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation A nearby T cell can then detect the antigen fragment displayed on the cell’s surface Depending on their source, peptide antigens are handled by different classes of MHC molecules

40 Top view: binding surface exposed to antigen receptors
Fig Top view: binding surface exposed to antigen receptors Antigen Class I MHC molecule Antigen Figure Antigen presentation by an MHC molecule Plasma membrane of infected cell

41 Class I MHC molecules are found on almost all nucleated cells of the body
They display peptide antigens to cytotoxic T cells

42 Infected cell Microbe Antigen- presenting cell 1 Antigen associates
Fig Infected cell Microbe Antigen- presenting cell 1 Antigen associates with MHC molecule Antigen fragment Antigen fragment 1 1 Class I MHC molecule Class II MHC molecule 2 2 T cell receptor T cell receptor 2 T cell recognizes combination Figure The interaction of T cells with antigen-presenting cells (a) Cytotoxic T cell (b) Helper T cell

43 Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells
Dendritic cells, macrophages, and B cells are antigen-presenting cells that display antigens to cytotoxic T cells and helper T cells

44 Lymphocyte Development
The acquired immune system has three important properties: Receptor diversity A lack of reactivity against host cells Immunological memory

45 Generation of Lymphocyte Diversity by Gene Rearrangement
Differences in the variable region account for specificity of antigen receptors The immunoglobulin (Ig) gene encodes one chain of the B cell receptor Many different chains can be produced from the same Ig chain gene by rearrangement of the DNA Rearranged DNA is transcribed and translated and the antigen receptor formed

46 Variable region Constant region
Fig DNA of undifferentiated B cell V37 V38 V39 V40 J1 J2 J3 J4 J5 Intron C 1 DNA deleted between randomly selected V and J segments DNA of differentiated B cell V37 V38 V39 J5 Intron C Functional gene 2 Transcription pre-mRNA V39 J5 Intron C 3 RNA processing Figure Immunoglobulin (antibody) gene rearrangement B cell receptor mRNA Cap V39 J5 C Poly-A tail V V 4 Translation V V C C Light-chain polypeptide V C C C Variable region Constant region B cell

47 Origin of Self-Tolerance
Antigen receptors are generated by random rearrangement of DNA As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity Lymphocytes with receptors specific for the body’s own molecules are destroyed by apoptosis, or rendered nonfunctional

48 Amplifying Lymphocytes by Clonal Selection
In the body there are few lymphocytes with antigen receptors for any particular epitope The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly This proliferation of lymphocytes is called clonal selection Two types of clones are produced: short-lived activated effector cells and long-lived memory cells

49 Antigen molecules B cells that differ in antigen specificity Antigen
Fig Antigen molecules B cells that differ in antigen specificity Antigen receptor Figure Clonal selection of B cells Antibody molecules Clone of memory cells Clone of plasma cells

50 Animation: Role of B Cells
The first exposure to a specific antigen represents the primary immune response During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms In the secondary immune response, memory cells facilitate a faster, more efficient response Animation: Role of B Cells

51 Antibody concentration
Fig Primary immune response to antigen A produces antibodies to A. Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. 104 103 Antibody concentration (arbitrary units) Antibodies to A 102 Antibodies to B 101 Figure The specificity of immunological memory 100 7 14 21 28 35 42 49 56 Exposure to antigen A Exposure to antigens A and B Time (days)

52 Concept 43.3: Acquired immunity defends against infection of body cells and fluids
Acquired immunity has two branches: the humoral immune response and the cell-mediated immune response Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells Helper T cells aid both responses

53 Figure 43.16 An overview of the acquired immune response
Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) + Stimulates Gives rise to Engulfed by Antigen- presenting cell + + + B cell Helper T cell Cytotoxic T cell + + Memory Helper T cells + + + Figure An overview of the acquired immune response Antigen (2nd exposure) + Memory Cytotoxic T cells Active Cytotoxic T cells Plasma cells Memory B cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells.

54 Humoral (antibody-mediated) immune response
Fig a Humoral (antibody-mediated) immune response Key Antigen (1st exposure) + Stimulates Gives rise to Engulfed by Antigen- presenting cell + + B cell Helper T cell + Memory Helper T cells + + Figure An overview of the acquired immune response Antigen (2nd exposure) Memory B cells Plasma cells + Secreted antibodies Defend against extracellular pathogens

55 Cell-mediated immune response
Fig b Cell-mediated immune response Antigen (1st exposure) Key + Stimulates Gives rise to Engulfed by Antigen- presenting cell + + Helper T cell Cytotoxic T cell + Memory Helper T cells Figure An overview of the acquired immune response + + Antigen (2nd exposure) Active Cytotoxic T cells + Memory Cytotoxic T cells Defend against intracellular pathogens

56 Helper T Cells: A Response to Nearly All Antigens
A surface protein called CD4 binds the class II MHC molecule This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs Activated helper T cells secrete cytokines that stimulate other lymphocytes Animation: Helper T Cells

57 Antigen- presenting cell Peptide antigen Bacterium
Fig Antigen- presenting cell Peptide antigen Bacterium Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Cytokines + Humoral immunity (secretion of antibodies by plasma cells) + Cell-mediated immunity (attack on infected cells) Figure The central role of helper T cells in humoral and cell-mediated immune responses + + B cell Cytotoxic T cell

58 Cytotoxic T Cells: A Response to Infected Cells
Cytotoxic T cells are the effector cells in cell-mediated immune response Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer The activated cytotoxic T cell secretes proteins that destroy the infected target cell Animation: Cytotoxic T Cells

59 Released cytotoxic T cell
Fig Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 TCR Dying target cell Class I MHC molecule Pore Target cell Figure The killing action of cytotoxic T cells For the Discovery Video Fighting Cancer, go to Animation and Video Files. Peptide antigen

60 B Cells: A Response to Extracellular Pathogens
The humoral response is characterized by secretion of antibodies by B cells Activation of B cells is aided by cytokines and antigen binding to helper T cells Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity

61 Antigen-presenting cell Bacterium
Fig Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule + Clone of plasma cells Secreted antibody molecules TCR CD4 Cytokines Endoplasmic reticulum of plasma cell Activated helper T cell Helper T cell Clone of memory B cells Figure B cell activation in the humoral immune response 2 µm

62 Antigen-presenting cell Bacterium
Fig Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule + Clone of plasma cells Secreted antibody molecules TCR CD4 Cytokines Figure B cell activation in the humoral immune response Activated helper T cell Helper T cell Clone of memory B cells

63 Antibody Classes The five major classes of antibodies, or immunoglobulins, differ in distribution and function Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen Monoclonal antibodies are prepared from a single clone of B cells grown in culture

64 Figure 43.20 The five antibody, or immunoglobulin (Ig), classes
Class of Immuno- globulin (Antibody) Distribution Function IgM (pentamer) First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutraliza- tion and cross- linking of antigens; very effective in complement system activation J chain IgG (monomer) Most abundant Ig class in blood; also present in tissue fluids Promotes opsoniza- tion, neutralization, and cross-linking of antigens; less effec- tive in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus IgA (dimer) Present in secretions such as tears, saliva, mucus, and breast milk Provides localized defense of mucous membranes by cross-linking and neutralization of antigens J chain Presence in breast milk confers passive immunity on nursing infant Secretory component Figure The five antibody, or immunoglobulin (Ig), classes IgE (monomer) Present in blood at low concen- trations Triggers release from mast cells and basophils of hista- mine and other chemicals that cause allergic reactions IgD (monomer) Present primarily on surface of B cells that have not been exposed to antigens Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) Trans- membrane region

65 Class of Immuno- globulin (Antibody) IgM (pentamer)
Fig a Class of Immuno- globulin (Antibody) Distribution Function IgM (pentamer) First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutraliza- tion and cross- linking of antigens; very effective in complement system activation J chain Figure The five antibody, or immunoglobulin (Ig), classes

66 Class of Immuno- globulin (Antibody) IgG (monomer)
Fig b Class of Immuno- globulin (Antibody) Distribution Function IgG (monomer) Most abundant Ig class in blood; also present in tissue fluids Promotes opsoniza- tion, neutralization, and cross-linking of antigens; less effec- tive in activation of complement system than IgM Figure The five antibody, or immunoglobulin (Ig), classes Only Ig class that crosses placenta, thus conferring passive immunity on fetus

67 Class of Immuno- globulin (Antibody) IgA (dimer)
Fig c Class of Immuno- globulin (Antibody) Distribution Function IgA (dimer) Present in secretions such as tears, saliva, mucus, and breast milk Provides localized defense of mucous membranes by cross-linking and neutralization of antigens J chain Figure The five antibody, or immunoglobulin (Ig), classes Presence in breast milk confers passive immunity on nursing infant Secretory component

68 Class of Immuno- globulin (Antibody) IgE (monomer)
Fig d Class of Immuno- globulin (Antibody) Distribution Function IgE (monomer) Present in blood at low concen- trations Triggers release from mast cells and basophils of hista- mine and other chemicals that cause allergic reactions Figure The five antibody, or immunoglobulin (Ig), classes

69 Class of Immuno- globulin (Antibody) IgD (monomer)
Fig e Class of Immuno- globulin (Antibody) Distribution Function IgD (monomer) Present primarily on surface of B cells that have not been exposed to antigens Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) Trans- membrane region Figure The five antibody, or immunoglobulin (Ig), classes

70 The Role of Antibodies in Immunity
Neutralization occurs when a pathogen can no longer infect a host because it is bound to an antibody Opsonization occurs when antibodies bound to antigens increase phagocytosis Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis Animation: Antibodies

71 Figure 43.21 Antibody-mediated mechanisms of antigen disposal
Viral neutralization Opsonization Activation of complement system and pore formation Bacterium Complement proteins Virus Formation of membrane attack complex Flow of water and ions Macrophage Pore Figure Antibody-mediated mechanisms of antigen disposal Foreign cell

72 Viral neutralization Virus Fig. 43-21a
Figure Antibody-mediated mechanisms of antigen disposal

73 Opsonization Bacterium Macrophage Fig. 43-21b
Figure Antibody-mediated mechanisms of antigen disposal

74 Activation of complement system and pore formation
Fig c Activation of complement system and pore formation Complement proteins Formation of membrane attack complex Flow of water and ions Figure Antibody-mediated mechanisms of antigen disposal Pore Foreign cell

75 Active and Passive Immunization
Active immunity develops naturally in response to an infection It can also develop following immunization, also called vaccination In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory

76 Passive immunity provides immediate, short-term protection
It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk It can be conferred artificially by injecting antibodies into a nonimmune person

77 Immune Rejection Cells transferred from one person to another can be attacked by immune defenses This complicates blood transfusions or the transplant of tissues or organs

78 Blood Groups Antigens on red blood cells determine whether a person has blood type A (A antigen), B (B antigen), AB (both A and B antigens), or O (neither antigen) Antibodies to nonself blood types exist in the body Transfusion with incompatible blood leads to destruction of the transfused cells Recipient-donor combinations can be fatal or safe

79 Tissue and Organ Transplants
MHC molecules are different among genetically nonidentical individuals Differences in MHC molecules stimulate rejection of tissue grafts and organ transplants

80 Chances of successful transplantation increase if donor and recipient MHC tissue types are well matched Immunosuppressive drugs facilitate transplantation Lymphocytes in bone marrow transplants may cause the donor tissue to reject the recipient

81 Concept 43.4: Disruption in immune system function can elicit or exacerbate disease
Some pathogens have evolved to diminish the effectiveness of host immune responses

82 Exaggerated, Self-Directed, and Diminished Immune Responses
If the delicate balance of the immune system is disrupted, effects range from minor to often fatal

83 Allergies Allergies are exaggerated (hypersensitive) responses to antigens called allergens In localized allergies such as hay fever, IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells

84 IgE Histamine Allergen Granule Mast cell Fig. 43-23
Figure Mast cells, IgE, and the allergic response Mast cell

85 The next time the allergen enters the body, it binds to mast cell–associated IgE molecules
Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms An acute allergic response can lead to anaphylactic shock, a life-threatening reaction that can occur within seconds of allergen exposure

86 Autoimmune Diseases In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis

87 Exertion, Stress, and the Immune System
Moderate exercise improves immune system function Psychological stress has been shown to disrupt hormonal, nervous, and immune systems

88 Immunodeficiency Diseases
Inborn immunodeficiency results from hereditary or developmental defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses Acquired immunodeficiency results from exposure to chemical and biological agents Acquired immunodeficiency syndrome (AIDS) is caused by a virus

89 Acquired Immune System Evasion by Pathogens
Pathogens have evolved mechanisms to attack immune responses

90 Antigenic Variation Through antigenic variation, some pathogens are able to change epitope expression and prevent recognition The human influenza virus mutates rapidly, and new flu vaccines must be made each year Human viruses occasionally exchange genes with the viruses of domesticated animals This poses a danger as human immune systems are unable to recognize the new viral strain

91 1.5 Antibodies to variant 1 appear Antibodies to variant 2 appear
Fig 1.5 Antibodies to variant 1 appear Antibodies to variant 2 appear Antibodies to variant 3 appear 1.0 Variant 1 Variant 2 Variant 3 Millions of parasites per mL of blood 0.5 Figure Antigenic variation in the parasite that causes sleeping sickness 25 26 27 28 Weeks after infection

92 Latency Some viruses may remain in a host in an inactive state called latency Herpes simplex viruses can be present in a human host without causing symptoms

93 Attack on the Immune System: HIV
Human immunodeficiency virus (HIV) infects helper T cells The loss of helper T cells impairs both the humoral and cell-mediated immune responses and leads to AIDS HIV eludes the immune system because of antigenic variation and an ability to remain latent while integrated into host DNA Animation: HIV Reproductive Cycle

94 Helper T cell concentration
Fig Latency AIDS Relative antibody concentration 800 Relative HIV concentration 600 Helper T cell concentration in blood (cells/mm3) Helper T cell concentration 400 Figure The progress of an untreated HIV infection 200 1 2 3 4 5 6 7 8 9 10 Years after untreated infection

95 People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse The spread of HIV is a worldwide problem The best approach for slowing this spread is education about practices that transmit the virus

96 Two suggested explanations are
Cancer and Immunity The frequency of certain cancers increases when the immune response is impaired Two suggested explanations are Immune system normally suppresses cancerous cells Increased inflammation increases the risk of cancer

97 You should now be able to:
Distinguish between innate and acquired immunity Name and describe four types of phagocytic cells Describe the inflammation response

98 Distinguish between the following pairs of terms: antigens and antibodies; antigen and epitope; B lymphocytes and T lymphocytes; antibodies and B cell receptors; primary and secondary immune responses; humoral and cell-mediated response; active and passive immunity Explain how B lymphocytes and T lymphocytes recognize specific antigens Explain why the antigen receptors of lymphocytes are tested for self-reactivity

99 Describe clonal selection and distinguish between effector cells and memory cells
Describe the cellular basis for immunological memory Explain how a single antigen can provoke a robust humoral response Compare the processes of neutralization and opsonization

100 Describe the role of MHC in the rejection of tissue transplants
Describe an allergic reaction, including the roles of IgE, mast cells, and histamine Describe some of the mechanisms that pathogens have evolved to thwart the immune response of their hosts List strategies that can reduce the risk of HIV transmission


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