1. Adaptive Immunity: Specific Defenses of the Host17
Adaptive Immunity: Specific Defenses of the Host

3. The Adaptive Immune System
Learning Objective 17-1 Compare and contrast adaptive and innate immunity.

4. The Adaptive Immune System
Adaptive immunity: defenses that target a specific pathogen
Acquired through infection or vaccination
Primary response: first time the immune system combats a particular foreign substance
Secondary response: later interactions with the same foreign substance; faster and more effective due to "memory"

5. Host Defenses: The Big Picture
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Animation: Host Defenses: The Big Picture

6. Check Your Understanding
Is vaccination an example of innate or adaptive immunity? 17-1

7. Dual Nature of the Adaptive Immune System
Learning Objective 17-2 Differentiate humoral from cellular immunity.

8. Dual Nature of the Adaptive Immune System
Humoral immunity
Produces antibodies that combat foreign molecules known as antigens
B cells are lymphocytes that are created and mature in red bone marrow
Recognize antigens and make antibodies
Named for bursa of Fabricius in birds

9. Humoral Immunity: Overview
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Animation: Humoral Immunity: Overview

10. Dual Nature of the Adaptive Immune System
Cellular immunity (cell-mediated immunity)
Produces T lymphocytes
Recognize antigenic peptides processed by phagocytic cells
Mature in the thymus
T cell receptors (TCRs) on the T cell surface contact antigens, causing the T cells to secrete cytokines instead of antibodies

11. Figure 17.1 Differentiation of T cells and B cells.
Stem cells develop
in bone marrow or
in fetal liver
Stem cell
(diverges into
two cell lines)
Red bone
marrow
of adults
Thymus
Differentiate to
B cells in adult
red bone marrow
Differentiate to
T cells in thymus
B cell
T cell
Migrate to lymphoid
tissue such as spleen,
but especially lymph
nodes

12. Dual Nature of the Adaptive Immune System
Cellular immunity attacks antigens found inside cells
Viruses; some fungi and parasites
Humoral immunity fights invaders outside cells
Bacteria and toxins

13. Check Your Understanding
What type of cell is most associated with humoral immunity, and what type of cell is the basis of cellular immunity? 17-2

14. Cytokines: Chemical Messengers of Immune Cells
Learning Objective 17-3 Identify at least one function of each of the following: cytokines, interleukins, chemokines, interferons, TNF, and hematopoietic cytokines.

15. Cytokines: Chemical Messengers of Immune Cells
Cytokines are chemical messengers produced in response to a stimulus
Interleukins: cytokines between leukocytes
Chemokines: induce migration of leukocytes
Interferons (IFNs): interfere with viral infections of host cells
Tumor necrosis factor (TNF): involved in the inflammation of autoimmune diseases
Hematopoietic cytokines: control stem cells that develop into red and white blood cells
Overproduction of cytokines leads to a cytokine storm

16. Check Your Understanding
What is the function of cytokines? 17-3

17. Antigens and Antibodies
Learning Objectives 17-4 Define antigen, epitope, and hapten Explain antibody function, and describe the structural and chemical characteristics of antibodies Name one function for each of the five classes of antibodies.

18. Antigens Antigens: substances that cause the production of antibodies
Usually components of invading microbes or foreign substances
Antibodies interact with epitopes, or antigenic determinants, on the antigen
Haptens: antigens too small to provoke immune responses; attach to carrier molecules

19. Epitopes (antigenic determinants) on antigen
Figure Epitopes (antigenic determinants).
Antibody A
Epitopes (antigenic determinants)
on antigen
Antigens:
components
of cell wall
Binding sites
Bacterial cell
Antibody B

20. Figure Haptens.

21. Antibodies Globular proteins called immunoglobulins (Ig)
Valence is the number of antigen-binding sites on an antibody
Bivalent antibodies have two binding sites

22. Antibodies Four protein chains form a Y-shape
Two identical light chains and two identical heavy chains joined by disulfide links
Variable (v) regions are at the ends of the arms; bind epitopes
Constant (Fc) region is the stem, which is identical for a particular Ig class
Five classes of Ig (IgG, IgM, IgA, IgD, IgE)

23. Figure 17.4 The structure of a typical antibody molecule.
Antigen-
binding
site V
Heavy chain V V V
Antigen
Light chain C C
Epitope
(antigenic
determinant)
Antibodies
Fc (stem) region C C
Hinge region
Antigen-binding
site
Antibody molecule
Enlarged antigen-binding site bound to an epitope
Antibody molecules
shown by atomic force microscopy

24. IgG Monomer 80% of serum antibodies In the blood, lymph, and intestine
Cross the placenta; trigger complement; enhance phagocytosis; neutralize toxins and viruses; protect fetus

25. IgM Pentamer made of five monomers held with a J chain
6% of serum antibodies
Remain in blood vessels
Cause clumping of cells and viruses
First response to an infection; short-lived

26. IgA Monomer in serum; dimer in secretions 13% of serum antibodies
Common in mucous membranes, saliva, tears, and breast milk
Prevent microbial attachment to mucous membranes

27. IgD Monomer 0.02% of serum antibodies Structure similar to IgG
In blood, in lymph, and on B cells
No well-defined function; assists in the immune response on B cells

28. IgE Monomer 0.002% of serum antibodies
On mast cells, on basophils, and in blood
Cause the release of histamines when bound to antigen; lysis of parasitic worms

29. Table 17.1 A Summary of Immunoglobulin Classes

30. Check Your Understanding
Does an antibody react with a bacterium as an antigen or as an epitope? 17-4
The original theoretical concepts of an antibody called for a rod with antigenic determinants at each end. What is the primary advantage of the Y-shaped structure that eventually emerged? 17-5
Which class of antibody is most likely to protect you from a common cold? 17-6

31. Humoral Immunity Response Process
Learning Objectives 17-7 Compare and contrast T-dependent and T-independent antigens Differentiate plasma cell from memory cell Describe clonal selection Describe how a human can produce different antibodies.

32. Clonal Selection of Antibody-Producing Cells
Major histocompatibility complex (MHC) genes encode molecules on the cell surface
Class I MHC are on the membrane of nucleated animal cells
Identify "self"
Class II MHC are on the surface of antigen-presenting cells (APCs), including B cells

33. Clonal Selection of Antibody-Producing Cells
Inactive B cells contain surface Ig that bind to antigen
B cell internalizes and processes antigen
Antigen fragments are displayed on MHC class II molecules
T helper cell (TH) contacts the displayed antigen fragment and releases cytokines that activate B cells
B cell undergoes proliferation (clonal expansion)

34. Figure 17.5 Activation of B cells to produce antibodies.
Extracellular
antigens
MHC class II with
antigen displayed
on surface
B cell
receptors
Antigen
fragments
Cytokines
Plasma cell
Antibodies
TH cell
B cell
B cell
B cell receptors
recognize and
attach to antigen.
Antigen is
internalized into
the B cell.
Fragments of the
antigen are presented
on MHC proteins on
the surface of the cell.
A T helper cell that recognizes
this antigen fragment is
activated and releases
cytokines, activating the B cell.
The activated B cell begins
clonal expansion, producing an
army of antibody-producing
plasma cells and memory cells.

35. Clonal Selection of Antibody-Producing Cells
Clonal selection differentiates activated B cells into:
Antibody-producing plasma cells
Memory cells
Clonal deletion eliminates harmful B cells

36. Figure 17.6 Clonal selection and differentiation of B cells.
Stem cell
Stem cells differentiate into mature B cells,
each bearing surface immunoglobulins
against a specific antigen.
B cell
Immunoglobin I II
Antigens
B cell II encounters its specific antigen
and proliferates.
Some B cells proliferate into long-lived
memory cells, which at a later date can be
stimulated to become antibody-
producing plasma cells.
Other B cells proliferate
into antibody-producing
plasma cells.
Memory
cell
Plasma
cell
Plasma cells secrete antibodies
into circulation.
Blood vessel of cardiovascular system

37. Clonal Selection of Antibody-Producing Cells
T-dependent antigen
Antigen that requires a TH cell to produce antibodies
T-independent antigens
Stimulate the B cell without the help of T cells
Provoke a weak immune response, usually producing IgM
No memory cells generated

38. (T-independent antigen)
Figure T-independent antigens.
Polysaccharide
(T-independent antigen)
Epitopes
B cell receptors

39. Antigen Processing and Presentation: Overview
PLAY
Animation: Antigen Processing and Presentation: Overview

40. Humoral Immunity: Clonal Selection and Expansion
PLAY
Animation: Humoral Immunity: Clonal Selection and Expansion

41. Check Your Understanding
Would pneumococcal pneumonia (see Figure 24.12, page 689) require a TH cell to stimulate a B cell to form antibodies? 17-7
Plasma cells produce antibodies; do they also produce memory cells? 17-8
In what way does a B cell that encounters an antigen function as an antigen-presenting cell? 17-9

42. Check Your Understanding
On what part of the antibody molecule do we find the amino acid sequence that makes the huge genetic diversity of antibody production possible? 17-10

43. Antigen–Antibody Binding and Its Results
Learning Objective Describe four outcomes of an antigen–antibody reaction.

44. Antigen–Antibody Binding and Its Results
An antigen–antibody complex forms when antibodies bind to antigens
Strength of the bond is the affinity
Protects the host by tagging foreign molecules or cells for destruction
Agglutination
Opsonization
Antibody-dependent cell-mediated cytotoxicity
Neutralization
Activation of the complement system

45. Figure 17.8 The results of antigen–antibody binding.
PROTECTIVE MECHANISM
OF BINDING ANTIBODIES
TO ANTIGENS
Agglutination
Activation of complement
Reduces number of infectious
units to be dealt with
Causes inflammation and cell lysis
Complement
Antibody
Bacteria
Bacterium
Lysis
Opsonization
Antibody-dependent cell-mediated cytotoxicity
Coating antigen with antibody
enhances phagocytosis
Antibodies attached to target cell
cause destruction by macrophages,
eosinophils, and NK cells
Phagocyte
Eosinophil
Epitopes
Perforin
and lytic
enzymes
Large target cell (parasite)
Neutralization
Blocks adhesion of bacteria
and viruses to mucosa
Blocks attachment
of toxin
Virus
Toxin
Bacterium

46. Humoral Immunity: Antibody Function
PLAY
Animation: Humoral Immunity: Antibody Function

47. Check Your Understanding
Which antibodies may activate the complement system, and which antibodies are usually associated with agglutination? 17-11

48. Cellular Immunity Response Process
Learning Objectives Describe at least one function of each of the following: M cells, TH cells, TC cells, CTLs, Treg cells, NK cells Differentiate T helper, T cytotoxic, and T regulatory cells Differentiate TH1, TH2, and TH17 cells Define apoptosis Define antigen-presenting cell.

49. Cellular Immunity Response Process
T cells combat intracellular pathogens
Mature in the thymus
Thymic selection eliminates immature T cells
Migrate from the thymus to lymphoid tissues
Attach to antigens via T-cell receptors (TCRs)

50. Cellular Immunity Response Process
Pathogens entering the gastrointestinal tract pass through microfold cells (M cells) located over Peyer's patches
Transfer antigens to lymphocytes and antigen-presenting cells (APCs)

51. Figure M cells.
M cell on Peyer's patch. Note the tips of the closely
packed microvilli on the surrounding epithelial cells.
Microvilli on
epithelial cell
Antigen
M cell
TH cell
Pocket
B cells
Macrophage
Epithelial cell
M cells facilitate contact between antigens passing through the intestinal
tract and cells of the body's immune system.

52. Antigen-Presenting Cells (APCs)
Dendritic cells (DCs)
Engulf and degrade microbes and display them to T cells
Found in the skin, genital tract, lymph nodes, spleen, thymus, and blood
Macrophages
Activated by cytokines or the ingestion of antigenic material
Migrate to the lymph tissue, presenting antigen to T cells

53. Figure 17.10 A dendritic cell.

54. Activated macrophages Resting (inactive) macrophage
Figure Activated macrophages.
Activated
macrophages
Resting (inactive)
macrophage

55. Antigen Processing and Presentation: MHC
PLAY
Animation: Antigen Processing and Presentation: MHC

56. Classes of T Cells Clusters of differentiation (CD) CD4+ CD8+
T helper cells (TH)
Cytokine signaling with B cells; interact directly with antigens
Bind MHC class II molecules on B cells and APCs
CD8+
Cytoxic T lymphocytes (CTL)
Bind MHC class I molecules

57. T Helper Cells (CD4+ T Cells)
TCR on the TH cell recognize and bind to the antigen fragment and MHC class II on APC
APC or TH secrete a costimulatory molecule, activating the TH cell
TH cells produce cytokines and differentiate into:
TH1cells
TH2 cells
TH17 cells
Memory cells

58. Figure 17.12 Activation of CD4+ T helper cells.
Microorganism
carrying
antigens
TH cell
receptor
(TCR)
Cytokines
Activated
T cell
Activated T cells proliferate
T helper
cell
Costimulatory molecule,
(required to activate T
cells that have not previously
encountered antigen)
Complex of MHC
class II molecule and
antigen fragment
MHC class II
molecules
Antigen
fragments
(short peptides)
APC (dendritic cell)
An APC encounters and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC.
A receptor (TCR) on the surface of the CD4+ T helper cell (TH cell) binds to the MHC–antigen complex. This includes a Toll-like receptor. The TH cell or APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines.
The cytokines cause the TH cell (which recognizes a dendritic cell
that is producing costimulatory molecules) to become activated.

59. T Helper Cells (CD4+ T Cells)
TH17 cells produce IL-17 and contribute to inflammation
TH1 cells produce IFN-g, which activates macrophages, enhances complement, and stimulates antibody production that promotes phagocytosis
TH2 cells activate B cells to produce IgE; activate eosinophils

60. Figure 17.13 Lineage of effector T helper cell classes and pathogens targeted.
Antigen-presenting
cell
TH cells of various
classes
TH17 cells secrete cytokines that
promote inflammatory responses;
recruit neutrophils for protection
against extracellular bacteria
and fungi.
TH1 cells are an important element of cellular immunity. Their cytokines (such as IFN-γ and IL-2) activate CD8+ T cells and NK cells, which control intracellular pathogens by killing infected host cells. They also enhance phagocytosis by antigen-presenting cells such as macrophages.
IL-17
IFN-γ
IL-4
TH2 cells
Fungi
Extracellular bacteria
Neutrophil
Intracellular
bacteria and
protozoa
Macrophage
Important in allergic responses, especially by production of IgE. Activate eosinophils to control extracellular parasites such as helminths (see ADCC discussion).
Mast cell
Basophil
Eosinophil
Helminth

61. Antigen Processing and Presentation: Steps
PLAY
Animation: Antigen Processing and Presentation: Steps

62. T Regulatory Cells T regulatory cells (Treg)
Subset of CD4+ cells; carry an additional CD25 molecule
Suppress T cells against self; protect intestinal bacteria required for digestion; protect fetus

63. T Cytotoxic Cells (CD8+ T Cells)
Activated into cytotoxic T lymphocyte (CTL) with the help of TH cell and costimulatory signals
CTLs recognize and kill self-cells altered by infection
Self-cells carry endogenous antigens on a surface presented with MHC class I molecules
CTL releases perforin and granzymes that induce apoptosis in the infected cell

64. Figure 17.14 Killing of virus-infected target cell by cytotoxic T lymphocyte.
Processed
antigen
Processed antigen
presented with
MHC class I
MHC
class I
T cell
receptors
Virus-infected cell (example
of endogenous antigen)
Virus-infected cell
TH1 cell
Cytokines
CTLp
CTL
Infected target
cell is lysed
A normal cell will not trigger a response
by a cytotoxic T lymphocyte (CTL), but a
virus-infected cell (shown here) or a cancer cell produces abnormal endogenous antigens.
The abnormal antigen is presented on the cell surface in association with MHC class I molecules. Binding of a TH1 cell promotes secretion of cytokines.
The cytokines activate a precursor CTL, which produces a clone of CTLs.
The CTL induces destruction of the virus-infected cell by apoptosis.

65. T Cytotoxic Cells (CD8+ T Cells)
Apoptosis
Programmed cell death
Prevents the spread of infectious viruses into other cells
Cells cut their genome into fragments, causing the membranes to bulge outward via blebbing

66. Figure Apoptosis.

67. Cell-Mediated Immunity: Cytotoxic T Cells
PLAY
Animation: Cell-Mediated Immunity: Cytotoxic T Cells

68. Check Your Understanding
Which antibody is the primary one produced when an antigen is taken up by an M cell? 17-12
Which T cell type is generally involved when a B cell reacts with an antigen and produces antibodies against the antigen? 17-13
Which T cell type is generally involved in allergic reactions? 17-14

69. Check Your Understanding
What is another name for apoptosis, one that describes its function? 17-15
Are dendritic cells considered primarily part of the humoral or the cellular immune system? 17-16 

70. Extracellular Killing by the Immune System
Learning Objective Describe the function of natural killer cells.

71. Extracellular Killing by the Immune System
Natural killer (NK) cells
Granular leukocytes destroy cells that don't express MHC class I self-antigens
Kill virus-infected and tumor cells and attack parasites
Not always stimulated by an antigen
Form pores in the target cell, leading to lysis or apoptosis

72. Table 17.2 Principal Cells That Function in Cell-Mediated Immunity

73. Check Your Understanding
How does the natural killer cell respond if the target cell does not have MHC class I molecules on its surface? 17-17

74. Antibody-Dependent Cell-Mediated Cytotoxicity
Learning Objective Describe the role of antibodies and natural killer cells in antibody-dependent cell- mediated cytotoxicity.

75. Antibody-Dependent Cell-Mediated Cytotoxicity
Protozoans and helminths are too large to be phagocytized
Protozoan or helminth target cell is coated with antibodies
Immune system cells attach to the Fc regions of antibodies
Target cell is lysed by chemicals secreted by the immune system cell

76. Figure 17.16 Antibody-dependent cell-mediated cytotoxicity (ADCC ).
KEY
Macrophage
Cytotoxic cytokines
Lytic enzymes
Perforin enzymes
Eosinophil
Extracellular
damage
Fc region
Large
parasite
Epitope
Antibody
Organisms, such as many parasites, that are too large for ingestion
by phagocytic cells must be attacked externally.
Eosinophils
Fluke
Eosinophils adhering to the larval stage of a
parasitic fluke

77. Check Your Understanding
What makes a natural killer cell, which is not immunologically specific, attack a particular target cell? 17-18

78. Immunological Memory
Learning Objective Distinguish a primary from a secondary immune response.

79. Immunological Memory
Secondary (memory or anamnestic) response occurs after the second exposure to an antigen
More rapid, lasts many days, greater in magnitude
Memory cells produced in response to the initial exposure are activated by the secondary exposure
Antibody titer is the relative amount of antibody in the serum
Reflects intensity of the humoral response
IgM is produced first, followed later by IgG

80. Second exposure to antigen Initial exposure to antigen
Figure The primary and secondary immune responses to an antigen.
IgG
Second
exposure
to antigen
IgM
Initial
exposure
to antigen

81. Humoral Immunity: Primary Immune Response
PLAY
Animation: Humoral Immunity: Primary Immune Response

82. Humoral Immunity: Secondary Immune Response
PLAY
Animation: Humoral Immunity: Secondary Immune Response

83. Check Your Understanding
Is the anamnestic response primary or secondary? 17-19

84. Types of Adaptive Immunity
Learning Objective Contrast the four types of adaptive immunity.

85. Types of Adaptive Immunity
Naturally acquired active immunity
Resulting from infection
Naturally acquired passive immunity
Transplacental or via colostrum
Artificially acquired active immunity
Injection of vaccination (immunization)
Artificially acquired passive immunity
Injection of antibodies

86. Figure 17.18 Types of adaptive immunity.

87. Types of Adaptive Immunity
Antiserum: blood-derived fluids containing antibodies
Serology: the study of reactions between antibodies and antigens
Globulins: serum proteins
Gamma () globulin: serum fraction containing antibodies

88. Protein migration Cathode Anode γ β α Trough Globulins Albumin
Figure The separation of serum proteins by gel electrophoresis.
Protein migration
Cathode
Anode γ β α
Trough
Globulins
Albumin
Globulins

89. Check Your Understanding
What type of adaptive immunity is involved when gamma globulin is injected into a person? 17-20

90. Figure 17.20 The Dual Nature of the Adaptive Immune System.