1. Immunity
Chapter 38 Part 1

2. Impacts, Issues Frankie’s Last Wish
Infection with a common, sexually transmitted virus (HPV) causes most cervical cancers – including the one that killed Frankie McCullogh

3. 38.1 Integrated Responses to Threats
Immunity
The capacity to resist and combat infection by pathogens such as viruses, bacteria, and fungi
In vertebrates, innate and adaptive immune systems work together to combat infection and injury

4. Evolution of the Body’s Defenses
Proteins in eukaryotic cell membranes have unique patterns that the body recognizes as self
Cells of multicelled eukaryotes have receptors that recognize nonself cues (PAMPs) on or in pathogens, and trigger defense responses

5. Innate Immunity
Binding of a receptor with a PAMP triggers immediate, general defense responses that are part of inborn innate immunity
Complement
Proteins that destroy microorganisms or flag them for phagocytosis
An innate immune response

6. Adaptive Immunity
Adaptive immunity is a system of defenses that specifically targets billions of different antigens an individual may encounter during its lifetime
Antigen
PAMP or other molecule the body recognizes as nonself that triggers an active immune response

7. Three Lines of Defense 1. Physical, chemical, and mechanical barriers
Keep pathogens outside the body
2. Innate immunity
General responses destroy invaders inside the body before they become established
3. Adaptive immunity
Huge populations of white blood cells form to target and remember a specific antigen

8. Mucus and Cilia: Physical Barriers

9. Comparing Innate and Active Immunity

10. The Defenders
White blood cells (leukocytes) specialized for different tasks carry out all immune responses
Phagocytes (neutrophils, macrophages, dendritic cells)
Secretory cells (eosinophils, basophils, mast cells
Lymphocytes (B and T lymphocytes, natural killer cells)

11. The Defenders
All white blood cells secrete chemicals, including cell-to-cell signaling molecules (cytokines) that coordinate all aspects of immunity
Interleukins
Interferons
Tumor necrosis factors

12. White Blood Cells

13. Figure 38.3
White blood cells (leukocytes). Staining shows details such as cytoplasmic granules that contain enzymes, toxins, and signaling molecules.
Fig. 38-3a, p. 661

14. Figure 38.3
White blood cells (leukocytes). Staining shows details such as cytoplasmic granules that contain enzymes, toxins, and signaling molecules.
Fig. 38-3b, p. 661

15. Chemical Weapons of Immunity

16. 38.1 Key Concepts Overview of Body Defenses
The vertebrate body has three lines of immune defenses
Surface barriers prevent invasion by ever-present pathogens
General innate responses rid the body of most pathogens
Adaptive responses specifically target pathogens and cancer cells

17. 38.2 Surface Barriers Normal flora
Billions of microorganisms normally live on human surfaces, including interior tubes and cavities of digestive and respiratory tracts
A pathogen can cause infection only if it enters the internal environment by penetrating skin or other protective barriers at the body’s surfaces

18. Some Normal Flora

19. Vertebrate Surface Barriers
Physical, chemical, and mechanical barriers keep microorganisms outside body tissues
Skin
Mucus and cilia
Lysozyme
Gastric fluid and bile salts
Normal flora
Urination

20. Vertebrate Surface Barriers

21. Skin
Healthy, intact skin is an effective surface barrier

22. cells die and become filled with keratin as they are pushed toward
skin surface
epithelial
cells die and become filled
with keratin
as they are
pushed toward
skin surface
epidermis
dividing epithelial cells
Figure 38.5
One surface barrier to infection: epidermis of human skin.
0.1 mm
Fig. 38-5, p. 663

23. 38.3 Remember to Floss Dental plaque
A thick, sticky biofilm of glycoproteins, bacteria, and their products that contribute to tooth decay and gum disease (periodontitis)
Nine of every ten cardiovascular disease patients have serious periodontal disease
Oral bacteria associated with periodontitis are also found in atherosclerotic plaque

24. Plaque

25. 38.2-38.3 Key Concepts Surface Barriers
Skin, mucous membranes, and secretions at the body’s surfaces function as barriers that exclude most microbes

26. 38.4 Innate Immune Responses
Innate immune mechanisms nonspecifically eliminate pathogens that invade internal tissues before they become established
Phagocytes
Complement
Inflammation
Fever

27. Phagocytes Macrophages
Large phagocytes that patrol interstitial fluid and engulf and digest pathogens
Secrete cytokines when receptors bind to antigen
Cytokines attract more macrophages, neutrophils, and dendritic cells to infection site

28. Complement
Complement proteins become activated when they encounter antigen
Cascading enzyme reactions concentrate activated complement at infection site
Complement attracts phagocytes to infection site and tags pathogens for destruction
Forms attack complexes that puncture bacteria
Helps mediate active immunity

29. Complement Attack Complexes

30. activated complement antibody molecule
Figure 38.7
One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes.
A In some responses, complement proteins become activated when antibodies (the Y-shaped molecules) bind to antigen—in this case, antigen on the surface of a bacterium.
Fig. 38-7a, p. 664

31. B Complement also becomes activated when it binds directly to antigen.
activated complement
bacterial cell
Figure 38.7
One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes.
B Complement also becomes activated when it binds directly to antigen.
Fig. 38-7b, p. 664

32. activated complement
Figure 38.7
One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes.
C By cascading reactions, huge numbers of different complement molecules form and assemble into structures called attack complexes.
Fig. 38-7c, p. 664

33. attack complex that causes a pore to form through the lipid bilayer of the bacterium
Figure 38.7
One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes.
D The attack complexes become inserted into the target cell’s lipid envelope or plasma membrane. Each complex makes a large pore form across it.
E The pores bring about lysis of the cell, which dies because of the severe structural disruption.
Fig. 38-7de, p. 664

34. Inflammation Inflammation
A local response to tissue damage characterized by redness, warmth, swelling and pain, triggered by activated complement and cytokines
Mast cells release histamine, increasing capillary permeability
Phagocytes and plasma proteins leak out, attack invaders, form clots, and clean up debris

35. Inflammation Response to Bacterial Infection

36. A Bacteria invade a tissue and release toxins or metabolic products that damage tissue.
D Complement proteins attack bacteria. Clotting factors also wall off inflamed area.
E Neutrophils and macrophages engulf invaders and debris. Macrophage secretions kill bacteria, attract more lymphocytes, and initiate fever.
B Mast cells in tissue release histamine, which widens arterioles (causing redness and warmth) and increases capillary permeability.
C Fluid and plasma proteins leak out of capillaries; localized edema (tissue swelling) and pain result.
Figure 38.8
Inflammation in response to bacterial infection. Above, in this example, white blood cells and plasma proteins enter a damaged tissue. Right, the micrograph shows a phagocyte squeezing through a blood vessel wall.
Stepped Art
Fig. 38-8, p. 665

37. Fever
Fever
A temporary rise in body temperature – above the normal 37°C (98.6°F) – that often occurs in response to infection
Cytokines stimulate brain cells to release prostaglandins, which act on the hypothalamus
Fever enhances the immune response by speeding up metabolism and phagocyte activity
Fever over 40.6°C (105°F) can be dangerous

38. 38.4 Key Concepts Innate Immunity
Innate immune responses involve a set of general, immediate defenses against invading pathogens
Innate immunity includes phagocytic white blood cells, plasma proteins, inflammation, and fever

39. 38.5 Overview of Adaptive Immunity
Vertebrate adaptive immunity adapts to different antigens it encounters during its lifetime
Lymphocytes and phagocytes interact to effect four defining characteristics: Self/nonself recognition, specificity, diversity, and memory

40. Self/Nonself Recognition
Self versus nonself recognition
Each kind of cell or virus has a unique identity
MHC markers
Plasma membrane self-recognition proteins
T cell receptors (TCRs)
Antigen receptors that recognize MHC markers as self, antigens as nonself

41. Specificity and Diversity
Defenses are tailored to target specific antigens
Diversity
There are potentially billions of different antigen receptors on T and B cells

42. Memory
Memory
The capacity of the adaptive immune system to remember an antigen
If the same antigen appears again, B and T cells make a faster, stronger response

43. First Step – The Antigen Alert
Once a B or T cell recognizes and binds to a specific antigen, it begins to divide by mitosis
All descendent cells recognize the same antigen
T cells do not recognize an antigen unless it is presented by an antigen-presenting cell
Macrophages, B cells, and dendritic cells digest particles and display antigen-MHC complexes

44. Cell Types Effector cells Memory cells
Differentiated lymphocytes (B and T cells) that act at once to fight infection
Memory cells
Long-lived B and T cells reserved for future encounters with the same antigen

45. Antigen Processing

46. Figure 38.9
Antigen processing. (a) A macrophage ingests a foreign cell. (b) From encounter to display, what happens when a B cell, macrophage, or dendritic cell engulfs an antigenic particle—in this case, a bacterium. These cells engulf, process, and then display antigen bound to MHC markers. The displayed antigen is presented to T cells.
Fig. 38-9a, p. 666

47. cell engulfs an antigen-bearing particle
antigen–MHC complexes become displayed on cell surface
endocytic vesicle forms
MHC markers bind fragments
of particle
particle is digested into bits
lysosome fuses with endocytic vesicle
Figure 38.9
Antigen processing. (a) A macrophage ingests a foreign cell. (b) From encounter to display, what happens when a B cell, macrophage, or dendritic cell engulfs an antigenic particle—in this case, a bacterium. These cells engulf, process, and then display antigen bound to MHC markers. The displayed antigen is presented to T cells.
Stepped Art
Fig. 38-9b, p. 666

48. Two Arms of Adaptive Immunity
Antibody-mediated immune response
B cells produce antibodies that bind to specific antigen particles in blood or interstitial fluid
Cell-mediated immune response
Cytotoxic T cells and NK cells detect and destroy infected or altered body cells

49. Interactions Between Antibody-Mediated and Cell-Mediated Responses

50. Intercepting and Clearing Out Antigen
After engulfing antigen-bearing particles, dendritic cells or macrophages migrate to lymph nodes, where T cells bind and initiate responses
During an infection, lymph nodes swell due to accumulation of T cells
Antibody-antigen complexes bound by complement are cleared by the liver and spleen

51. The Lymphatic System

52. (thymus gland) lymph node, midsection
Figure 38.11
Battlegrounds of adaptive immunity. Lymph nodes along lymph vascular highways hold macrophages, dendritic cells, B cells, and T cells. The spleen filters antigenic particles from blood.
spleen
Fig , p. 667

53. 38.6 Antibodies and Other Antigen Receptors
Antigen receptors on B and T cells have the potential to recognize billions of different antigens
Antibody
Y-shaped antigen receptor (protein), made only by B cells, that binds only to the antigen that prompted its synthesis
Activates complement, facilitates phagocytosis, or neutralizes pathogens or toxins

54. Antibody Structure

55. binding site for antigen binding site for antigen
variable region (dark green) of heavy chain
variable region of light chain
constant region of light chain
constant region (bright green) of heavy chain, including a hinged region
Figure 38.12
Antibody structure. (a) An antibody molecule has four polypeptide chains joined in a Y-shaped configuration. In this ribbon model, the two heavy chains are shown in green, and the two light chains are teal. (b) Each chain has a variable and a constant region.
Fig b, p. 668

56. Five Classes of Antibodies
Constant regions determine 5 classes of antibodies (immunoglobins IgG, IgA, IgE, IgM, and IgD), each with different functions
B cell receptors are membrane-bound IgM or IgD antibodies

57. Five Classes of Antibodies

58. Making Antigen Receptors
Genes that encode antigen receptors occur in several segments on different chromosomes
Different versions are randomly spliced together during B or T cell differentiation, producing about 2.5 billion different combinations
T cells mature in the thymus, which stimulates production of MHC and T cell receptors

59. Antigen Receptor Diversity

60. 38.7 The Antibody-Mediated Immune Response
Antigen activates naïve B cells and dendritic cells
Naïve T cell binds to APC and differentiates into effector and memory helper T cells
Helper T cells bind antigen-MHC complexes on activated B cell and secrete cytokines
B cell differentiates into effector B cells, which produce antibodies targeting a specific antigen, and memory B cells

61. Antibody-Mediated Immune Response

62. antigen- presenting dendritic cellB
bacterium
antigen- presenting dendritic cell
B The dendritic cell engulfs the same kind of bacterium that the B cell encountered. A
naive B cell
B cell
complement
A The B cell receptors on a naïve B cell bind to a specific antigen on the surface of a bacterium
C The antigen-MHC complexes on the antigen-presenting cell are recognized by antigen receptors on a naïve T cell.
naive T cell
effector helper T cell
memory helper T cell C
D cytokines
D Antigen receptors of one of the effector helper T cells bind antigen-MHC complexes on the B cell. E
memory B cell
effector B cell
E The cytokines induce the B cell to divide, giving rise to many identical B cells. F
F The effector B cells begin making and secreting huge numbers of IgA, IgG, or IgE.
Figure 38.14
Example of an antibody-mediated immune response.
Stepped Art
Fig , p. 670

63. Clonal Selection and Memory Cells
Only B cells with receptors that bind antigen divide (clone) and differentiate into effector and memory B cells
First exposure (primary response) produces memory B and T cells; secondary response is stronger and faster

64. Clonal Selection and Memory Cells

65. to a matching B cell receptor.
antigen
Antigen binds only
to a matching B cell receptor.
mitosis
clonal population of effector
B cells
Figure 38.15
B cell maturation.
Many effector B cells secrete many antibodies.
Fig a, p. 671

66. B cell with bound antigen
mitosis
primary immune response
effector cells
memory cells
mitosis
Figure 38.15
B cell maturation.
secondary immune response
effector cells
memory cells
Fig b, p. 671

67. Primary and Secondary Immune Response

68. 38.8 The Cell-Mediated Response
Cell-mediated immune response
Dendritic cell ingests altered body cell, displays antigen-MHC complexes, migrates to lymph node
Naïve helper T and cytotoxic T cells bind to APC
Activated helper T divides and differentiates into memory and effector cells; cytokines signal division of activated cytotoxic T cells
Cytotoxic T cells circulate and touch-kill altered body cells

69. Primary Cell-Mediated Response

70. A A dendritic cell engulfs a virus-infected cell.
antigen- presenting dendritic
cell
A A dendritic cell engulfs a virus-infected cell. B
effector helper T cell
memory helper T cell
B Receptors on a naïve helper T cell bind to antigen-MHC complexes on the dendritic cell.
naive helper T cell
naive cytotoxic T cell C
activated cytotoxic
T cell
C Receptors on a naïve cytotoxic T cell bind to the antigen-MHC complexes on the surface of the dendritic cell. D
cytokines
memory cytotoxic T cell
effector cytotoxic T cell
D The activated cytotoxic T cell recognizes cytokines secreted by the effector helper T cells as signals to divide.
Figure 38.17
Example of a primary cell-mediated immune response.
Figure It Out: What do the large red spots represent?
Answer: Viruses E
E The new cytotoxic T cells circulate through the body.
Stepped Art
Fig , p. 672

71. Cytotoxic T Cells
Cytotoxic T cells touch-kill cells displaying antigen-MHC markers; perforin and proteases puncture cells and kill them by apoptosis

72. cytotoxic T cell cancer cell Figure 38.18
T cell receptor function. (a) A TCR (green) on a T cell binds to an MHC marker (tan) on an antigen-presenting cell. An antigen (red) is bound to the MHC marker. (b) A cytotoxic T cell caught in the act of touch-killing a cancer cell.
Fig b, p. 673

73. Natural Killer Cells
Cytokines secreted by helper T cells also stimulate natural killer (NK) cell division
Unlike cytotoxic T cells, NK cells can kill infected cells that are missing all or part of their MHC markers

74. 38.5-38.8 Key Concepts Adaptive Immunity
In an adaptive immune response, white blood cells destroy specific pathogens or altered cells
Some make antibodies in an antibody-mediated immune response; others destroy ailing body cells in a cell-mediated response

75. 38.9 Allergies
Allergy
An immune response to a typically harmless substance (allergen)
First exposure stimulates production of IgE, which becomes anchored to mast cells and basophils
Later exposure stimulates secretion of histamine and cytokines that initiate inflammation
Anaphylactic shock is a severe and potentially fatal allergic reaction

76. Allergies: Annoying or Life-Threatening

77. 38.10 Vaccines Immunization Vaccine (active immunization)
The administration of an antigen-bearing vaccine designed to elicit immunity to a specific disease
Vaccine (active immunization)
A preparation containing an antigen that elicits a primary immune response
Passive immunization
Administration of antibodies; no immune response

78. Smallpox Vaccine
Edward Jenner created the first vaccine against smallpox, which has now been eradicated

79. Recommended Immunizations

80. 38.11 Immunity Gone Wrong
Misdirected or compromised immunity is sometimes the result of mutation or environmental factors
The outcome is often severe or lethal

81. Autoimmune Disorders
Sometimes lymphocytes and antibodies fail to discriminate between self and nonself
Autoimmune response
An immune response that is misdirected against the person’s own tissues
Rheumatoid arthritis, Graves’ disease, multiple sclerosis

82. Immunodeficiency
In immunodeficiency, the immune response is insufficient to protect a person from disease
Primary immune deficiencies are present at birth
SCIDs, ADA
Secondary immune deficiency results from exposure to an outside agent, such as a virus
AIDS

83. Gene Therapy
Primary immunodeficiency is the result of mutation; Cindy Cutshwall was successfully treated for ADA, a type of severe combined immunodeficiency (SCID), using gene therapy

84. 38.12 AIDS Revisited—Immunity Lost
Acquired immune deficiency syndrome (AIDS)
A group of disorders resulting from a failure of the immune system due to HIV infection
Includes rare cancers and infections caused by normally harmless microorganisms
Human immunodeficiency virus (HIV)
A retrovirus that attacks specific cells of the immune system, including helper T cells

85. T Cells and AIDS

86. Global HIV and AIDS Cases

87. Transmission and Treatment
Common modes of HIV transmission
Unprotected sex, mother to child, shared syringes
HIV testing
Antibodies are found in blood, saliva or urine
Drugs
There is no cure; protease inhibitors and reverse transcriptase inhibitors can slow its progress

88. Prevention Vaccines Education
Experimental vaccines are mostly ineffective or risky; the virus’ high mutation rate is an obstacle
Education
The best option for preventing the spread of HIV is teaching people how to avoid being infected

89. The Global AIDS Program
The global battle continues; researchers are using several strategies to develop an HIV vaccine

90. 38.9-38.12 Key Concepts Immunity In Our Lives
Vaccines are an important part of any health program
Failed or faulty immune mechanisms can result in allergies, immune deficiencies, or autoimmune disorders
The immune system itself is a target of human immunodeficiency virus (HIV)

91. Animation: Inflammatory response

92. Animation: Complement proteins

93. Animation: Antibody-mediated response

94. Animation: Clonal selection of a B cell

95. Animation: Immune memory

96. Animation: Cell-mediated response

97. Animation: Antibody structure

98. Animation: Cell mediated response

99. Animation: Gene rearrangements

100. Animation: Human lymphatic system

101. Animation: Immune responses

102. Animation: Innate defenses

103. ABC video: Food Allergy Increase

104. Video: HPV vaccine

105. Video: Gene therapy