1. The Immune System: Innate and Adaptive Body Defenses21
P A R T A
The Immune System: Innate and Adaptive Body Defenses

2. Immunity: Two Intrinsic Defense Systems
Innate (nonspecific) system responds quickly and consists of:
First line of defense – skin and mucosae prevent entry of microorganisms
Second line of defense – antimicrobial proteins, phagocytes, and other cells
Inhibit spread of invaders throughout the body
Inflammation is its most important mechanism

3. Immunity: Two Intrinsic Defense Systems
Adaptive (specific) defense system
Third line of defense – mounts attack against particular foreign substances
Takes longer to react than the innate system
Works in conjunction with the innate system

4. Innate and Adaptive Defenses
Figure 21.1

5. First Line of Defense: Epithelial Mechanical Barriers (External)
Skin, mucous membranes, and their secretions make up the first line of defense
Keratin in the skin:
Presents a physical barrier to most microorganisms
Is resistant to weak acids and bases, bacterial enzymes, and toxins
Mucosae provide similar mechanical barriers

6. Respiratory Tract Mucosae
Mucus-coated hairs in the nose trap inhaled particles
Mucosa of the upper respiratory tract is ciliated
Cilia sweep dust- and bacteria-laden mucus away from lower respiratory passages

7. Epithelial Chemical Barriers (External)
Epithelial membranes produce protective chemicals that destroy microorganisms
Skin acidity (pH of 3 to 5) inhibits bacterial growth
Sebum contains chemicals toxic to bacteria
Stomach mucosae secrete concentrated HCl and protein-digesting enzymes
Saliva and lacrimal fluid (tears) contain lysozyme
Mucus traps microorganisms that enter the digestive, urinary, reproductive and respiratory systems
Acidic vagina inhibits growth of bacteria and fungus (yeast)

8. 2nd Line of Defense: Internal Defense
5 COMPONENTS
1. Phagocytes
2. Fever
3. Antimicrobial Proteins
4. Natural Killer (NK) Cells
5. Inflammatory Response

9. 1. Phagocytes – 3 Different Leukocytes
Neutrophils become phagocytic when encountering infectious material – attracted by chemicals (chemokines) released by injured tissues
First responders
Most numerous phagocyte
Shorter lifespan

10. Phagocytes, cont. - Monocytes
Reside in lymph nodes and spleen
Circulate in blood
Enter tissues (site of injury) and become large MACROPHAGES
More effective than neutrophils and longer lifespan

11. Mechanism of Phagocytosis
Microbes adhere to the phagocyte
Pseudopods engulf the microbes (antigen)
Antigen fuse with a lysosome
Antigen are digested inside lysosome by enzymes
Indigestible and residual material is removed by exocytosis

12. Microbe adheres to phagocyte.1
Microbe adheres to phagocyte. 2
Phagocyte forms pseudopods that
eventually engulf the particle.
Phagocytic vesicle
containing antigen
(phagosome).
Lysosome 3
Phagocytic vesicle is
fused with a lysosome.
Phagolysosome 4
Microbe in fused vesicle
is killed and digested by
lysosomal enzymes within
the phagolysosome, leaving
a residual body.
Acid
hydrolase
enzymes
Residual body 5
Indigestible and
residual material
is removed by
exocytosis.
(b)
Figure 21.2b

13. Microbe adheres to phagocyte.1
Microbe adheres to phagocyte.
(b)
Figure 21.2b

14. Microbe adheres to phagocyte.1
Microbe adheres to phagocyte. 2
Phagocyte forms pseudopods that
eventually engulf the particle.
(b)
Figure 21.2b

15. Microbe adheres to phagocyte.1
Microbe adheres to phagocyte. 2
Phagocyte forms pseudopods that
eventually engulf the particle.
Phagocytic vesicle
containing antigen
(phagosome).
Lysosome
(b)
Figure 21.2b

16. Microbe adheres to phagocyte.1
Microbe adheres to phagocyte. 2
Phagocyte forms pseudopods that
eventually engulf the particle.
Phagocytic vesicle
containing antigen
(phagosome).
Lysosome 3
Phagocytic vesicle is
fused with a lysosome.
Phagolysosome
Acid
hydrolase
enzymes
(b)
Figure 21.2b

17. Microbe adheres to phagocyte.1
Microbe adheres to phagocyte. 2
Phagocyte forms pseudopods that
eventually engulf the particle.
Phagocytic vesicle
containing antigen
(phagosome).
Lysosome 3
Phagocytic vesicle is
fused with a lysosome.
Phagolysosome 4
Microbe in fused vesicle
is killed and digested by
lysosomal enzymes within
the phagolysosome, leaving
a residual body.
Acid
hydrolase
enzymes
Residual body
(b)
Figure 21.2b

18. Microbe adheres to phagocyte.1
Microbe adheres to phagocyte. 2
Phagocyte forms pseudopods that
eventually engulf the particle.
Phagocytic vesicle
containing antigen
(phagosome).
Lysosome 3
Phagocytic vesicle is
fused with a lysosome.
Phagolysosome 4
Microbe in fused vesicle
is killed and digested by
lysosomal enzymes within
the phagolysosome, leaving
a residual body.
Acid
hydrolase
enzymes
Residual body 5
Indigestible and
residual material
is removed by
exocytosis.
(b)
Figure 21.2b

19. Phagocytes (cont.) – Eosinophils
Not as phagocytic as the other 2
Attach to wall of parasitic worms
Discharge destructive enzymes into the worms
Worms destroyed from the inside out
Figure 21.2a

20. 2. Fever
Abnormally high body temperature in response to invading microorganisms
The body’s thermostat is reset upwards by the hypothalamus in response to pyrogens, chemicals secreted by leukocytes and macrophages exposed to bacteria and other foreign substances
Low –grade fevers are beneficial (100.4 F, 38 C); indicates that the body is fighting!
Many pathogens die at increased temperatures

21. Fever (cont.)
Liver and spleen sequester Fe and Zn, essential minerals for pathogen’s survival
 in metabolism increases the speed of phagocytosis, blood clotting by platelets and tissue repair
High fevers are dangerous and can cause death because essential enzymes are denatured
varies by age, duration, response to treatment, location {oral, rectal, axillary}

22. 3. Antimicrobial Proteins
Enhance the innate defenses by:
Attacking microorganisms directly
Hindering microorganisms’ ability to reproduce
The most important antimicrobial proteins are:
Interferon
Complement proteins

23. Interferon (IFN)
Virus infected cells can do little to save themselves
They can help neighboring healthy cells by secreting small proteins called interferons.
Interferons attach to the cell membranes of healthy cells and block the virus from entering the cell
THUS, the name interferon ---interferes with the ability of the virus to infect healthy cells

24. Become activated when attached to foreign cells
Complement Proteins
Group of at least 20 proteins that circulate in the blood in an inactive state
Become activated when attached to foreign cells
Bacteria
Fungi
Mismatched Erythrocytes (RBC’s)

25. Complement Proteins (cont.)
Kills bacteria by producing pores in the membranes allowing water to rush in and the cells burst
Amplifies the inflammatory response by releasing chemicals that
Attract neutrophils to the injured site
Dilate blood vessels
Cause cell membranes of pathogens to become sticky – easier to phagocytize in a process called opsonization
Enhances the effectiveness of both nonspecific and specific defenses.

26. 4. Natural Killer (NK) Cells
Unique group of large granular lymphocytes that “police” the blood and lymph
Lyse cancer cells and virus infected cells BEFORE the adaptive immune system is enlisted
Lymphocytes of the adaptive immune system recognize and react ONLY against SPECIFIC cancer cells and virus infected cells
NK cells can I.D. ANY cell that is an intruder; i.e., by recognizing certain sugars on their cell membranes OR if the intruder lacks certain SELF cell membrane molecules

27. NK Cells cont.
Not phagocytes
Attack by releasing perforins – proteins that create pores in the membrane of the target cell allowing water to rush into the cell, causing it to burst
Secrete potent chemicals that enhance the inflammatory response

28. 5. Inflammation: Tissue Response to Injury
The inflammatory response is triggered whenever body tissues are injured
Prevents the spread of damaging agents to nearby tissues
Disposes of cell debris and pathogens
Sets the stage for repair processes
The four cardinal signs of acute inflammation are redness, heat, swelling (edema), and pain

29. Figure 21.3

30. Inflammatory Response
Begins with a flood of inflammatory chemicals released into the extracellular fluid
Released by injured tissue, phagocytes, lymphocytes, and mast cells (release histamine)
Cause local small blood vessels to dilate, resulting in hyperemia (increased blood flow) (HEAT) (REDNESS)
Activate pain receptors (PAIN)
Attract phagocytes to the injured tissue

31. Inflammatory Response: Vascular Permeability
MARGINATION –neutrophils accumulate and adhere to the capillary wall - increasing the permeability of local capillaries
EXUDATE—fluid containing proteins, clotting factors, and antibodies
Exudate seeps into tissue spaces causing local EDEMA (swelling), which contributes to the sensation of PAIN

32. Inflammatory Response: Phagocytic Mobilization NOTE: Study handout
Four main phases:
Leukocytosis – neutrophils are released from the bone marrow in response to leukocytosis-inducing factors released by injured cells
Margination – neutrophils cling to the walls of capillaries in the injured area
Diapedesis – neutrophils squeeze through capillary walls and begin phagocytosis
Chemotaxis – inflammatory chemicals attract neutrophils to the injury site – monocytes follow close behind → MACROPHAGES

33. Innate defenses
Internal defenses 4
Positive
chemotaxis
Inflammatory
chemicals diffusing
from the inflamed
site act as chemotactic
agents 1
Neutrophils enter blood
from bone marrow 3
Diapedesis 2
Margination
Endothelium
Basement membrane
Capillary wall
Figure 21.4

34. Innate defenses
Internal defenses
Inflammatory
chemicals diffusing
from the inflamed
site act as chemotactic
agents 1
Neutrophils enter blood
from bone marrow
Figure 21.4

35. Innate defenses
Internal defenses
Inflammatory
chemicals diffusing
from the inflamed
site act as chemotactic
agents 1
Neutrophils enter blood
from bone marrow 2
Margination
Endothelium
Basement membrane
Capillary wall
Figure 21.4

36. Innate defenses
Internal defenses
Inflammatory
chemicals diffusing
from the inflamed
site act as chemotactic
agents 1
Neutrophils enter blood
from bone marrow 3
Diapedesis 2
Margination
Endothelium
Basement membrane
Capillary wall
Figure 21.4

37. Innate defenses
Internal defenses 4
Positive
chemotaxis
Inflammatory
chemicals diffusing
from the inflamed
site act as chemotactic
agents 1
Neutrophils enter blood
from bone marrow 3
Diapedesis 2
Margination
Endothelium
Basement membrane
Capillary wall
Figure 21.4

38. Adaptive Defenses – 3rd Line of Defense
Works in conjunction with 2nd line of defense
Amplifies inflammatory response and activates complement proteins
Differs from Innate Defenses in 3 ways: It is
Specific – recognizes and acts against specific pathogens or foreign substances
Systemic – not restricted to the initial infection site
Has memory – recognizes and mounts even stronger attacks on previously encountered pathogens

39. Adaptive Immune Defenses (cont.)
Has two separate but overlapping arms:
Humoral, or antibody-mediated immunity
Antibodies produced by B lymphocytes circulate throughout the body in lymph and blood, attacking antigens
Cellular, or cell-mediated immunity
T Lymphocytes attack
Virus-infected cells, cancer cells, and foreign cells from transplanted organs/tissues

40. Antigens
Def. - Substances that can mobilize the immune system and provoke an immune response
Most are large, complex molecules not normally found in the body (nonself); foreign protein, nucleic acid, some lipids, and large polysaccharides
Proteins are the strongest antigens b/c they are most complex: have more antigenic determinants (antigen-binding sites) for different kinds of antibodies to recognize and attach

41. Antigenic Determinants
Figure 21.7

42. Incomplete Antigens - Haptens
Smaller molecules that are not true antigens but still elicit an immune response
Linkup with our own proteins; immune system recognizes the combination as foreign; results in an allergic response
Examples of allergens (haptens)
Rx such as penicillin, sulfa drugs, etc.
Chemicals found in pollen, animal dander, detergents, cosmetics, perfumes, poison ivy, etc.

43. Self-Antigens: MHC Proteins
Our cells are dotted with protein molecules (self-antigens) that are not antigenic to us but are strongly antigenic to others
Reason why transplanted organs are rejected unless the person takes drugs to weaken their immune response for the rest of their life
Coded for by genes of the major histocompatibility complex (MHC) and are unique to an individual
Mark a cell as self

44. Cells of the Adaptive Immune System
Two types of lymphocytes
B lymphocytes – oversee humoral immunity
T lymphocytes – non-antibody-producing cells that constitute the cell-mediated arm of immunity
Antigen-presenting cells (APCs): Macrophages
Present fragments of antigens they have “eaten” to T lymphocytes

45. Lymphocytes
Immature lymphocytes released from bone marrow are essentially identical
Whether a lymphocyte matures into a B cell or a T cell depends on where in the body it becomes immunocompetent (ability to recognize “self”)
B cells mature in the bone marrow
T cells mature in the thymus under the direction of thymus hormones

46. T Cell Selection in the Thymus
Figure 21.9

47. T Cells
T cells mature in the thymus under negative and positive selection pressures
Negative selection – eliminates T cells that are strongly anti-self
Positive selection – selects T cells with a weak response to self-antigens, which thus become both immunocompetent and self-tolerant

48. Immunocompetent B or T cells
Display a unique type of receptor that responds to a specific antigen
Become immunocompetent before they encounter antigens they may later attack
Are exported to secondary lymphoid tissue (lymph nodes, spleen, etc.) where encounters with antigens occur (antigen challenge)
Mature into fully functional antigen-activated cells upon binding with their recognized antigen
It is genes, not antigens, that determine which foreign substances our immune system will recognize and resist

49. Figure 21.8 Red bone marrow Key: = Site of lymphocyte origin
= Site of development of
immunocompetence as
B or T cells; primary
lymphoid organs
= Site of antigen challenge,
activation, and final
diff erentiation of B and
T cells
Immature
lymphocytes
Circulation
in blood 1 1 1
Lymphocytes destined
to become T cells
migrate to the thymus
and develop
immunocompetence
there. B cells develop
in red bone marrow.
Thymus
Bone marrow 2
Immunocompetent,
but still naive,
lymphocyte migrates
via blood 2
Lymph nodes,
spleen, and other
lymphoid tissues 2
After leaving the thymus
or bone marrow as naïve
immunocompetent cells,
lymphocytes “seed” the
lymph nodes, spleen, and
other lymphoid tissues
where the antigen
challenge occurs. 3 3 3
Antigen-activated
immunocompetent
lymphocytes circulate
continuously in the
bloodstream and lymph
and throughout the
lymphoid organs of
the body.
Activated
Immunocompetent
B and T cells
recirculate in
blood and lymph
Figure 21.8

50. Figure 21.8 Red bone marrow Key: = Site of lymphocyte origin
= Site of development of
immunocompetence as
B or T cells; primary
lymphoid organs
= Site of antigen challenge,
activation, and final
diff erentiation of B and
T cells
Immature
lymphocytes
Circulation
in blood 1 1
Lymphocytes destined
to become T cells
migrate to the thymus
and develop
immunocompetence
there.
Thymus
Figure 21.8

51. Figure 21.8 Red bone marrow Key: = Site of lymphocyte origin
= Site of development of
immunocompetence as
B or T cells; primary
lymphoid organs
= Site of antigen challenge,
activation, and final
diff erentiation of B and
T cells
Immature
lymphocytes
Circulation
in blood 1 1 1
Lymphocytes destined
to become T cells
migrate to the thymus
and develop
immunocompetence
there. B cells develop
in red bone marrow.
Thymus
Bone marrow
Figure 21.8

52. Figure 21.8 Red bone marrow Key: = Site of lymphocyte origin
= Site of development of
immunocompetence as
B or T cells; primary
lymphoid organs
= Site of antigen challenge,
activation, and final
diff erentiation of B and
T cells
Immature
lymphocytes
Circulation
in blood 1 1 1
Lymphocytes destined
to become T cells
migrate to the thymus
and develop
immunocompetence
there. B cells develop
in red bone marrow.
Thymus
Bone marrow 2
Immunocompetent,
but still naive,
lymphocyte migrates
via blood 2
Lymph nodes,
spleen, and other
lymphoid tissues 2
After leaving the thymus
or bone marrow as naïve
immunocompetent cells,
lymphocytes “seed” the
lymph nodes, spleen, and
other lymphoid tissues
where the antigen
challenge occurs.
Figure 21.8

53. Figure 21.8 Red bone marrow Key: = Site of lymphocyte origin
= Site of development of
immunocompetence as
B or T cells; primary
lymphoid organs
= Site of antigen challenge,
activation, and final
diff erentiation of B and
T cells
Immature
lymphocytes
Circulation
in blood 1 1 1
Lymphocytes destined
to become T cells
migrate to the thymus
and develop
immunocompetence
there. B cells develop
in red bone marrow.
Thymus
Bone marrow 2
Immunocompetent,
but still naive,
lymphocyte migrates
via blood 2
Lymph nodes,
spleen, and other
lymphoid tissues 2
After leaving the thymus
or bone marrow as naïve
immunocompetent cells,
lymphocytes “seed” the
lymph nodes, spleen, and
other lymphoid tissues
where the antigen
challenge occurs. 3 3 3
Antigen-activated
immunocompetent
lymphocytes circulate
continuously in the
bloodstream and lymph
and throughout the
lymphoid organs of
the body.
Activated
Immunocompetent
B and T cells
recirculate in
blood and lymph
Figure 21.8

54. Humoral Immunity Response
Antigen challenge – first encounter between an antigen and a naive immunocompetent cell
Takes place in the spleen or other lymphoid organ
If the lymphocyte is a B cell:
The challenging antigen provokes a humoral immune response
Antibodies are produced against the challenger
NOTE: Study handout

55. Clonal Selection
Stimulated B cell growth forms clones bearing the same antigen-specific receptors
A naive, immunocompetent B cell is activated when antigens bind to its surface receptors and cross-link adjacent receptors
Antigen binding is followed by receptor-mediated endocytosis of the cross-linked antigen-receptor complexes
These activating events, plus T cell interactions, trigger clonal selection

56. Proliferation to form a clone
Antigen
Primary Response
(initial encounter
with antigen)
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)
Proliferation to
form a clone
B lymphoblasts
Plasma
cells
Memory
B cell
Secreted
antibody
molecules
Secondary Response
(can be years later)
Clone of cells
identical to
ancestral cells
Subsequent
challenge by
same antigen
Plasma
cells
Secreted
antibody
molecules
Memory
B cells
Figure 21.10

57. Antigen Primary Response (initial encounter Antigen binding
with antigen)
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)
Figure 21.10

58. Proliferation to form a clone
Antigen
Primary Response
(initial encounter
with antigen)
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)
Proliferation to
form a clone
B lymphoblasts
Figure 21.10

59. Proliferation to form a clone
Antigen
Primary Response
(initial encounter
with antigen)
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)
Proliferation to
form a clone
B lymphoblasts
Plasma
cells
Memory
B cell
Secreted
antibody
molecules
Figure 21.10

60. Proliferation to form a clone
Antigen
Primary Response
(initial encounter
with antigen)
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)
Proliferation to
form a clone
B lymphoblasts
Plasma
cells
Memory
B cell
Secreted
antibody
molecules
Secondary Response
(can be years later)
Clone of cells
identical to
ancestral cells
Subsequent
challenge by
same antigen
Figure 21.10

61. Proliferation to form a clone
Antigen
Primary Response
(initial encounter
with antigen)
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)
Proliferation to
form a clone
B lymphoblasts
Plasma
cells
Memory
B cell
Secreted
antibody
molecules
Secondary Response
(can be years later)
Clone of cells
identical to
ancestral cells
Subsequent
challenge by
same antigen
Plasma
cells
Secreted
antibody
molecules
Memory
B cells
Figure 21.10

62. Fate of the Clones
Most clone cells become antibody-secreting plasma cells
Plasma cells secrete specific antibody at the rate of 2000 molecules per second

63. Fate of the Clones Secreted antibodies:
Bind to free antigens
Mark the antigens for destruction by specific or nonspecific mechanisms
Clones that do not become plasma cells become memory cells that can mount an immediate response to subsequent exposures of the same antigen

64. Importance of Humoral Response
Soluble antibodies
The simplest ammunition of the immune response
Interact in extracellular environments such as body secretions, tissue fluid, blood, and lymph
Fight against “free – floating” antigens that have not invaded a cell

65. Immunological Memory
Primary immune response – cellular differentiation and proliferation, which occurs on the first exposure to a specific antigen
Lag period: 3 to 6 days after antigen challenge
Peak levels of plasma antibody are achieved in 10 days
Antibody levels then decline
NOTE: Study graphing activity.

66. Secondary immune response – re-exposure to the same antigen
Immunological Memory
Secondary immune response – re-exposure to the same antigen
Sensitized memory cells respond within hours
Antibody levels peak in 2 to 3 days at much higher levels than in the primary response
Antibodies bind with greater affinity, and their levels in the blood can remain high for weeks to months

67. Primary and Secondary Humoral Responses
Figure 21.11

68. Active Humoral Immunity
B cells encounter antigens and produce antibodies against them. Memory is established for future exposures.
Naturally acquired – response to a bacterial or viral infection
Artificially acquired – response to a vaccine of dead or attenuated (live, but weakened) pathogens

69. Passive Humoral Immunity
Differs from active immunity:
B cells are not challenged by antigens
No memory for future exposures
Protection ends when antibodies naturally degrade in the body after a few weeks or months
Naturally acquired – mother’s antibodies given to her fetus via the placenta
Artificially acquired – from the injection of blood plasma containing antibodies – plasma was drawn from a person who had the illness and produced antibodies Ex. hepatitis

70. Types of Acquired Immunity
Figure 21.12