1. The IMMUNE SYSTEM AP Bio Chapter 43
Antibody Immune System Response - Medical Animation

3. Organs of the Immune System

4. Lymphatic system Interstitial fluid Adenoid Tonsil Blood capillary
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 system
Lymphatic
vessels
Lymph
node
Masses of
defensive cells

5. The Lymphatic System
The lymphatic system aids the immune system in removing and destroying waste, debris, dead blood cells, pathogens, toxins, and cancer cells.
The lymphatic system absorbs fats and fat-soluble vitamins from the digestive system and delivers these nutrients to the cells of the body where they are used by the cells.
The lymphatic system also removes excess fluid, and waste products from the interstitial spaces between the cells.

6. What about the spleen?
It acts as a filter for blood as part of the immune system. Old red blood cells are recycled in the spleen, and platelets and white blood cells are stored there.

7. The immune system recognizes foreign bodies and responds with the production of immune cells and proteins

8. Two major kinds of defense have evolved:
innate immunity and
acquired immunity

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

10. 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

11. 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

12. Innate immunity of vertebrates
Physical
Skin – low pH of skin secretions
Mucous membranes lining digestive, respiratory, genitourinary tracts trap and remove microbes (with cilia in resp)

13. Chemical
Lysozyme – enzymes that attack microbial walls, found in tears, saliva, and mucus
Gastric juice – low pH
Interferons – proteins produced by viral-infected cells to alert other cells to defend against viral reproduction also stimulates macrophages
Complement – proteins in plasma that when activated by microbial contact may lyse cells, trigger inflammation, or assist acquired defensive immunity

14. Complement aiding the acquired immunity system

15. Cellular
Macrophages – attack microbes in the spleen and interstitial fluid (known as monocytes in the blood)
Neutrophils – most numerous phagocytizing cells, phagocytize bacteria
Eosinophils – attack multicellular parasites
Dendritic cells – in contact with environment, stimulate acquired immunity system
Natural killer cells (NK cells) – recognize absence of self-markers on infected cells

16. macrophage

18. Neutrophils – first on the job

19. Eosinophils – attack multicellular parasites

20. A dendritic cell

21. Dendritic cell
alerting the
acquired
immune
system

22. NK cell doing its job!

23. What are toll-like receptors?
TLR’s are proteins that span membranes in leukocytes and other cells that recognize nonspecific microbes that breach physical barriers such as the skin or intestinal tract.
They in turn activate the immune system.
Originally identified in insects.

25. TLR’s spanning the membrane.
Response

26. Alert! Microbes entering!
Toll-like receptors
Alert! Microbes entering!

27. Inflammatory response
Redness, swelling, heat
Damaged mast cells in connective tissue release histamine which triggers dilation and leakiness of blood vessels, activates macrophages, promotes blood flow to the area
Fever – triggered by toxins or pyrogens released by macrophages, stimulates production of wbc’s, speeds tissue healing
Septic shock – overwhelming systemic inflammatory response

28. 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

29. ACQUIRED IMMUNITY (adaptive immunity)
Job of lymphocytes that circulate in the blood and lymph, conc in spleen and lymph nodes
Develop from pluripotent stem cells in the bone marrow and liver of fetuses
Become T cells after cells have migrated to the Thymus or
B cells that develop in the Bone marrow

30. How do they work with the innate immune system?
Signaling molecules (cytokines) from macrophages and dendritic cells activate them.

31. What are antigens?
Antigens – proteins or polysaccharides protruding from microbes or toxins floating around
Epitope (antigenic determinants) – portion of the antigen recognized by immune cells

32. 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

33. There are millions of lymphocytes with their own types of antigen receptors. How is the great diversity of B and T cells produced?
They are determined during early embryonic development by genetic recombination
Receptors have constant regions and variable regions that are specific for antigens.

34. 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

35. Antigen- binding site Variable regions V V Constant regions C C
Fig. 43-9b
Antigen-
binding
site
Variable
regions V V
Constant
regions C C
Transmembrane
region
Plasma
membrane
Figure 43.9 Antigen receptors on lymphocytes
 chain
 chain
Disulfide bridge
Cytoplasm of T cell
T cell
(b) T cell receptor

36. What prevents B and T cells from reacting against the body’s own molecules?
Lymphocytes with receptors specific for body’s own molecules are either inactivated or destroyed by apoptosis. This is called self-tolerance.

37. How to distinguish self from nonself
MHC molecules are so named because they are encoded by a family of genes called the Major Histocompatibility Complex
They identify cells as belonging to you!
(histo = tissue)

39. Class I MHC molecules are found on almost all nucleated cells of the body
Class II MHC molecules are found on immune cells such as dendritic cells, macrophages, and B cells.
They digest antigens and display pieces of the antigen with their MHC complex and are called antigen-presenting cells (APC’s).

40. Class I – body cells
Class II- immune cells
Once the cells engulf the antigens, they display them on their MHC complexes:
“SELF-NONSELF”.

41. Cytotoxic-T cells will bind to the MHC I complexes (recognize infected cells)
Helper T- cells will bind to the MHC II complexes. MHC II cells are called APC’s (Antigen Presenting 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. Immunological Memory
When antigens react with the immune cells, the cells that are specific for that antigen are activated to divide repeatedly and differentiate into clones:
Effector cells – combative cells
Memory cells – which carry receptors for that particular antigen
This is called CLONAL SELECTION.

44. This one! Clonal selection Antigen molecules B cells that differ in
Fig
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
This one!
Clonal
selection
Figure Clonal selection of B cells
Antibody
molecules
Clone of memory cells
Clone of plasma cells

45. Monoclonal Antibody Production

46. 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

47. 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)

48. Remembering the antigen!

49. Vaccines stimulate a mild primary response so body can wage a secondary response to recognize another attack.

50. Acquired Immunity: 2 types: Humoral and Cell-mediated
Humoral Immune Response (antibody-mediated response)
involves B cells and
production of antiBodies in response to free-floating antigens or those on surface of foreign cells

51. B cells mature into plasma cells that produce antibodies.

52. Cell-mediated Response
involves cytotoxic T cells that destroy target infected cells

53. The central role of Helper-T’s
Immune cells (class II MHC) engulf antigens and display them on their MHC.
Specific helper-T’s recognize the MHC-antigen complex.
Binding to the helper-T
Displaying the antigen

54. A T-cell surface protein called CD4 binds the helper-T to the MHC-II.
Activated helper-T’s release cytokines (interleukins)
- result in more specific help-T’s and memory cells being produced.
- stimulate both cell-mediated and humoral responses

55. The central role of Helper-T’s
Fig
The central role of Helper-T’s
Antigen-
presenting
cell
Peptide antigen
Binds
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
Animation: The Immune Response

56. Cell-mediated Response, how?
When a nucleated regular cell becomes infected, pieces of antigens are combined with the MHC I and they bond to cytotoxic T cells with the help of CD8 surface proteins.
The cytotoxic cell becomes a killer cell which releases perforin that punches holes in the infected cell.

57. CD 8’s and CD 4’s are like bungy cords.
They hold
the MHC
to the T or
B cells

58. Cell Mediated Immunity Response of Cytotoxic T cells
Cytotoxic T-cell Activity Against Target 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. Humoral Response, how?
The B cell takes in a few foreign molecules and presents antigen fragments in its class II MHC to activated helper-T cells.
The activated B cell then proliferates into a clone of plasma cells that will produce antibodies and a clone of memory B cells. (Some do not require T-cell binding or cytokines.)

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. Humoral Immunity T-Cell Dependent Antigens
Interaction of Antigen Presenting Cells and T-helper Cells

63. The cartoon illustrates how an antibacterial antigen-specific immune response is generated.
Microbes invade the body and are captured by dendritic cells (DCs, the ‘policemen’). The DC presents the antigen to the B and Th cells.
The B cells respond by
“bombing” the microbes with antibodies.

64. Putting it all together…

65. 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.

66. Types of Antibodies
Antibodies are proteins that are made of light and heavy chains.
There are 5 different antibodies: IgM, IgG, IgA, IgD, and IgE. IgG is the most abundant.
IgE – antibodies involved in allergies
Respond to
Different
antigens

67. IgE Mediated Hypersensitivity

68. Antibodies label antigens for disposal by
1) Neutralization – blocking the ability of a virus or bacterium to infect a host cell by binding to its surface

69. 2) Opsonization – antibodies (opsonins) coat microbes for phagocytosis by macrophages

70. opsonization

71. 3) Antigen-antibody complexes on microbes can activate the complement system and trigger a membrane attack complex (MAC).

72. Y’s and C’s
having a party!

73. 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

74. Active and Passive immunity:
Active – production of antibodies from exposure or from immunization
Passive – temporary immunity by antibodies supplied from the placenta, mother’s milk, or antibody injection

75. Immune Rejection
Blood Matching: Antibodies to blood group antigens can stimulate an immune response.
A person will make antibodies to other blood antigens than its own.

76. You make antibodies against any
blood antigens you do not have.

77. Transplanted tissue and organs are rejected due to foreign MHC molecules. The use of closely related donors and immune suppression drugs help to minimize rejection.

78. In bone marrow transplants, the recipient’s bone marrow cells are destroyed by radiation, eliminating the recipient’s immune system.
The lymphocytes in the bone marrow transplant may produce a graft versus host reaction to the host cells if the MHC
molecules are not
closely matched.

79. Immune System Disorders
Allergies are hypersensitivities to certain environmental antigens, or allergens.
- IgE antibodies produced in an initial exposure may bind to mast cells and cause a histamine response.

80. Anaphylactic shock is a severe allergic response in which vasodilation leads to a life-threatening drop in blood pressure

81. Autoimmune disease – immune system turns against itself
Ex - lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis.
rheumatoid arthritis

82. Lupus
Systemic lupus erythematosus (SLE) is a long-term autoimmune disorder that may affect the skin, joints, kidneys, brain, and other organs.

83. Multiple Sclerosis
Multiple sclerosis (or MS) is a chronic, often disabling disease that attacks the central nervous system (CNS).
Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.

84. The body’s own defense system attacks myelin, the fatty substance that surrounds and protects the nerve fibers in the central nervous system. The nerve fibers themselves can also be damaged.

85. Immunodeficiency – may be developmental (genetic) or in response to a chemical, drugs, cancer, viruses (HIV).
Severe combined immunodeficiency (SCID), is a genetic disorder in which both B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes.

86. Exercising to exhaustion and stress can impair the immune system.

88. How tricky are pathogens
Antigenic variation – changing their surface epitopes to be unrecognizable
Some viruses go into a latency period and “hide” from the immune cells
AIDS does both of these.