1. Chapter 43
The Immune System

2. Overview: Reconnaissance, Recognition, and Response
An animal must defend itself from the many dangerous pathogens it may encounter
Two major kinds of defense have evolved: innate immunity and acquired immunity

3. 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
Key internal defenses are macrophages and other phagocytic cells

4. LE 43-1
3 µm

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
Recognition is by white blood cells called lymphocytes
Some lymphocytes produce antibodies; others destroy infected cells, cancer cells, or foreign tissue

6. broad range of microbes
LE 43-2
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses
Internal defenses
Skin
Phagocytic cells
Humoral response
(antibodies)
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Invading
microbes
(pathogens)
Cell-mediated response
(cytotoxic
lymphocytes)
Natural killer cells

7. Concept 43.1: Innate immunity provides broad defenses against infection
A pathogen that breaks through external defenses encounters innate cellular and chemical mechanisms that impede its attack

8. External Defenses
Skin and mucous membranes are physical barriers to entry of microorganisms and viruses
Mucous membrane cells produce mucus, a viscous fluid that traps microbes and other particles
In the trachea, ciliated epithelial cells sweep mucus and any entrapped microbes upward, preventing microbes from entering the lungs

9. LE 43-3
10 µm

10. Secretions of the skin and mucous membranes provide an environment hostile to microbes
Secretions give the skin a pH between 3 and 5, acidic enough to prevent colonization of many microbes
Skin secretions include proteins such as lysozyme, which digests bacterial cell walls

11. Internal Cellular and Chemical Defenses
Internal cellular defenses depend mainly on phagocytosis
White blood cells called phagocytes ingest microorganisms and initiate inflammation

12. Phagocytic Cells
Phagocytes attach to prey via surface receptors and engulf them, forming a vacuole that fuses with a lysosome

13. LE 43-4 Microbes Pseudopodia MACROPHAGE Vacuole Lysosome containing
enzymes

14. Macrophages, a type of phagocyte, migrate through the body and are found in organs of the lymphatic system
The lymphatic system defends against pathogens

15. LE 43-5
Interstitial
fluid
Lymphatic
capillary
Adenoid
Tonsil
Blood
capillary
Lymph
nodes
Spleen
Lymphatic
vessel
Tissue
cells
Peyer’s patches
(small intestine)
Appendix
Lymphatic
vessels
Lymph
node
Masses of
lymphocytes and
macrophages

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

17. Inflammatory Response
In local inflammation, histamine and other chemicals released from injured cells promote changes in blood vessels
These changes allow more fluid, phagocytes, and antimicrobial proteins to enter tissues

18. LE 43-6 Pathogen Pin Blood clot Macrophage Blood clotting elements
Chemical signals
Phagocytic cells
Capillary
Phagocytosis
Red blood cell

19. Natural Killer Cells
Natural killer (NK) cells attack virus-infected body cells and cancer cells
They trigger apoptosis in the cells they attack

20. Invertebrate Immune Mechanisms
Many invertebrates defend against infection by many of the same mechanisms in the vertebrate innate response

21. Concept 43.2: In acquired immunity, lymphocytes provide specific defenses against infection
Acquired immunity is the body’s second major kind of defense
An antigen is a foreign molecule that is recognized by lymphocytes and elicits a response from them
A lymphocyte recognizes and binds to a small portion of the antigen called an epitope

22. Antigen- binding Epitopes sites (antigenic determinants) Antibody A
LE 43-7
Antigen-
binding
sites
Epitopes
(antigenic
determinants)
Antibody A
Antigen
Antibody B
Antibody C

23. Antigen Recognition by Lymphocytes
Two main types of lymphocytes circulate in the blood of vertebrates: B lymphocytes (B cells) and T lymphocytes (T cells)
A single B cell or T cell has about 100,000 identical antigen receptors
All antigen receptors on a single cell recognize the same epitope

24. B Cell Receptors for Antigens
B cell receptors bind to specific, intact antigens
Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane
Video: T Cell Receptors

25. LE 43-8 Antigen- binding site Antigen- binding site Antigen- binding
Disulfide
bridge V V
Light
chain V V
Variable regions C V V C C C
Constant regions C C
Transmembrane
region
Plasma
membrane
 chain
b chain
Heavy chains
Disulfide bridge
B cell
Cytoplasm of B cell
Cytoplasm of T cell
T cell
A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges.
A T cell receptor consists of one a chain and one b chain linked by a disulfide bridge.

26. T Cell Receptors for Antigens and the Role of the MHC
Each T cell receptor consists of two different polypeptide chains V V C C

27. T cells bind to antigen fragments that 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

28. Infected cells produce MHC molecules, which bind to antigen fragments and are transported 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

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

30. Infected cell Microbe Antigen- presenting cell Antigen fragment
LE 43-9
Infected cell
Microbe
Antigen-
presenting
cell
Antigen
fragment
Antigen
fragment
Class I MHC
molecule
Class II MHC
molecule
T cell
receptor
T cell
receptor
Cytotoxic T cell
Helper T cell

31. Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells
They display antigens to helper T cells

32. Lymphocyte Development
Lymphocytes arise from stem cells in bone marrow
Newly formed lymphocytes are alike but later develop into B cells or T cells, depending on where they mature

33. Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others)
Bone marrow
Thymus
Lymphoid
stem cell
B cell
T cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)

34. Generation of Lymphocyte Diversity by Gene Rearrangement
Random, permanent gene rearrangement forms functional genes encoding the B or T cell antigen receptor chains

35. LE 43-11 V4–V39 DNA of undifferentiated B cell V1 V2 V3 V40 J1 J2 J3
Intron C
Deletion of DNA between a V segment
and J segment and joining of the segments
DNA of differentiated
B cell V1 V2 V3 J5
Intron C
Functional gene
Transcription of resulting permanently
rearranged, functional gene
pre-mRNA V3 J5
Intron C
RNA processing (removal of intron;
addition of cap and poly (A) tail)
mRNA
Cap V3 J5 C
Poly (A)
Translation
Light-chain polypeptide V C
B cell receptor
Variable
region
Constant
region
B cell

36. Testing and Removal of Self-Reactive Lymphocytes
As B and T cells mature in the bone and thymus, their antigen receptors are tested for self-reactivity
Lymphocytes with receptors for antigens that are already in the body are destroyed by apoptosis or rendered nonfunctional

37. Clonal Selection of Lymphocytes
In a primary immune response, binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation
This process is called clonal selection
Clonal selection of B cells generates a clone of short-lived activated effector cells and a clone of long-lived memory cells
Animation: Role of B Cells

38. LE 43-12 Antigen molecules B cells that differ in antigen specificity
receptor
Antibody
molecules
Clone of memory cells
Clone of plasma cells

39. In the secondary immune response, memory cells facilitate a faster, more efficient response

40. Antibody concentration
LE 43-13
104
103
Antibodies
to A
Antibody concentration
(arbitrary units)
102
Antibodies
to B
101
100 7 14 21 28 35 42 49 56
Time (days)

41. Concept 43.3: Humoral and cell-mediated immunity defend against different types of threats
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

42. LE 43-14_3 Humoral immune response Cell-mediated immune response
First exposure to antigen
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Intact antigens
Activate
Activate
Activate
Secreted
cytokines
activate
B cells
Helper
T cell
Cytotoxic
T cell
Gives rise to
Gives rise to
Gives rise to
Active and
memory
helper
T cells
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Plasma
cells
Memory
B cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Defend against infected cells, cancer
cells, and transplanted tissues

43. 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

44. LE 43-15 Peptide antigen Dendritic cell Cytotoxic T cell Class II MHC
molecule
Helper T cell
Cell-mediated
immunity
(attack on
infected cells)
Bacterium
TCR
Humoral
immunity
(secretion of
antibodies by
plasma cells)
CD4
Dendritic
cell
Cytokines
B cell

45. Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells
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

46. LE 43-16 Released cytotoxic T cell Cytotoxic T cell Perforin Cancer
Granzymes
TCR
CD8
Apoptotic
target cell
Class I MHC
molecule
Pore
Target
cell
Peptide
antigen
Cytotoxic
T cell

47. Animation: Cytotoxic T Cells

48. Antibody Classes
The five major classes of antibodies, or immunoglobulins, differ in distribution and function

49. B Cells: A Response to Extracellular Pathogens
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

50. LE 43-17 Macrophage Bacterium Peptide antigen B cell Class II MHC
molecule
Secreted antibody
molecules
Clone of plasma cells
TCR
CD4 +
Endoplasmic
reticulum of
plasma cell
Cytokines
Helper T cell
Activated
helper T cell
Clone of memory
B cells

51. LE 43-18a
IgM
(pentamer)
First lg class produced after initial exposure to antigen; then its concentration in the blood declines
Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19)
J chain

52. LE 43-18b
IgG
(monomer)
Most abundant lg class in blood; also present in tissue fluids
Only lg class that crosses placenta, thus conferring passive immunity on fetus
Promotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation than lgM (see Figure 43.19)

53. LE 43-18c
IgA
(dimer)
Present in secretions such as tears, saliva, mucus, and breast milk
Provides localized defense of mucous membranes by agglutination and neutralization of antigens (see Figure 43.19)
J chain
Presence in breast milk confers passive immunity on nursing infant
Secretory
component

54. LE 43-18d
IgE
(monomer)
Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20)

55. LE 43-18e
IgD
(monomer)
Present primarily on surface of naive B cells that have not been exposed to antigens
Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)
Transmembrane
region

56. Antibody-Mediated Disposal of Antigens
The binding of antibodies to antigens is also the basis of antigen-disposal mechanisms
Microbes are eliminated by phagocytosis and complement-mediated lysis
Animation: Antibodies

57. LE 43-19 Binding of antibodies to antigens inactivates antigens by
Viral neutralization
(blocks binding to host
and opsonization increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Activation of complement system
and pore formation
Complement
proteins
Virus
Bacteria
MAC
Pore
Bacterium
Soluble
antigens
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage

58. 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

59. 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

60. The immune system can wage war against cells from other individuals
Concept 43.4: The immune system’s ability to distinguish self from nonself limits tissue transplantation
The immune system can wage war against cells from other individuals
Transplanted tissues are usually destroyed by the recipient’s immune system

61. Blood Groups and Transfusions
Antigens on red blood cells determine whether a person has type A, B, AB, or O blood
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

63. A red blood cell antigen called the Rh factor creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses

64. Tissue and Organ Transplants
MHC molecules stimulate rejection of tissue grafts and organ transplants

65. 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 a graft versus host reaction in recipients

66. Concept 43.5: Exaggerated, self-directed, or diminished immune responses can cause disease
If the delicate balance of the immune system is disrupted, effects range from minor to often fatal

67. 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

68. 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

69. LE 43-20
IgE
Histamine
Allergen
Granule
Mast cell

70. Autoimmune Diseases
In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body
Rheumatoid arthritis is an autoimmune disease leading to damage and inflammation of joints

72. Other examples of autoimmune diseases:
Systemic lupus erythematosus
Multiple sclerosis
Insulin-dependent diabetes

73. Immunodeficiency Diseases
Inborn or primary immunodeficiency results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses
Acquired or secondary immunodeficiency results from exposure to chemical and biological agents

74. Inborn (Primary) Immunodeficiencies
In severe combined immunodeficiency (SCID), both the humoral and cell-mediated branches of acquired immunity fail to function

75. Acquired (Secondary) Immunodeficiencies
Acquired immunodeficiencies range from temporary states to chronic diseases

76. Stress and the Immune System
Growing evidence shows that physical and emotional stress can harm immunity

77. Acquired Immunodeficiency Syndrome (AIDS)
People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse
Because AIDS arises from loss of helper T cells, it impairs both the humoral and cell-mediated immune responses
The loss of helper T cells results from infection by the human immunodeficiency virus (HIV)
Animation: HIV Reproductive Cycle

78. LE 43-22
1 µm

79. The spread of HIV is a worldwide problem
The best approach for slowing this spread is education about practices that transmit the virus