1. Innate Immunity: Nonspecific Defenses of the Host16
Innate Immunity: Nonspecific Defenses of the Host

3. Big Picture: Immunity

4. Big Picture: Immunity

5. Big Picture: Immunity
White blood cell (WBC) counts measure leukocytes in the blood
High WBC counts may indicate bacterial infections, autoimmune diseases, or side effects of medications
Low WBC counts may indicate viral infections, pneumonia, autoimmune diseases, or cancers

6. Big Picture: Immunity NORMAL RANGES AND PERCENTAGES
for men and nonpregnant women
White blood cell count:
5,000–10,000 WBCs per cubic millimeter
(mm3) or 5.0–10.0 x 109 WBCs per liter.
Plasma
Neutrophils: 60% to 70%
Lymphocytes: 20% to 25%
White
blood cells
Monocytes: 3% to 8%
Eosinophils: 2% to 4%
Basophils: 0.5% to 1%
Red blood
cells

7. The Concept of Immunity
Learning Objectives 16-1 Differentiate innate and adaptive immunity Define Toll-like receptors.

8. The Concept of Immunity
Immunity: ability to ward off disease
Susceptibility: lack of resistance to a disease
Innate immunity: defenses against any pathogen; rapid, present at birth
Adaptive immunity: immunity or resistance to a specific pathogen; slower to respond, has memory component

9. The Concept of Immunity
Toll-like receptors (TLRs) on host cells attach to pathogen-associated molecular patterns (PAMPs)
TLRs bound to PAMPs induce the release of cytokines from the host cell that regulate the intensity and duration of immune responses

10. Host Defenses: The Big Picture
PLAY
Animation: Host Defenses: The Big Picture

11. Check Your Understanding
Which defense system, innate or adaptive immunity, prevents entry of microbes into the body? 16-1
What relationship do TLRs have to pathogen-associated molecular patterns? 16-2

12. First Line of Defense: Skin and Mucous Membranes
Learning Objectives 16-3 Describe the role of the skin and mucous membranes in innate immunity Differentiate physical from chemical factors, and list five examples of each Describe the role of normal microbiota in innate immunity.

13. Physical Factors
Skin
Dermis: inner portion made of connective tissue
Epidermis: outer portion made of tightly packed epithelial cells containing keratin, a protective protein
Shedding and dryness of skin inhibits microbial growth

14. Figure 16.1 A section through human skin.
Top layers
of epidermis
with keratin
Epidermis
Dermis

15. Physical Factors Mucous membranes
Epithelial layer that lines the gastrointestinal, respiratory, and genitourinary tracts
Mucus: viscous glycoproteins that trap microbes and prevent tracts from drying out
Lacrimal apparatus: drains tears; washes eye

16. Lacrimal glands Upper eyelid Lacrimal canal Nasolacrimal duct
Figure The lacrimal apparatus.
Lacrimal glands
Upper eyelid
Lacrimal canal
Nasolacrimal
duct

17. Physical Factors
Ciliary escalator transports microbes trapped in mucus away from the lungs
Earwax prevents microbes from entering the ear
Urine cleans the urethra via flow
Vaginal secretions move microorganisms out of the vaginal tract
Peristalsis, defecation, vomiting, diarrhea

18. Trapped particles in mucus Cilia Goblet cells Ciliated cells
Figure The ciliary escalator.
Trapped
particles
in mucus
Cilia
Goblet cells
Ciliated cells
Computer-enhanced

19. Chemical Factors
Sebum forms a protective film and lowers the pH (3–5) of skin
Lysozyme in perspiration, tears, saliva, and urine destroys bacterial cell walls
Low pH (1.2–3.0) of gastric juice destroys most bacteria and toxins
Low pH (3–5) of vaginal secretions inhibit microbes

20. Normal Microbiota and Innate Immunity
Normal microbiota compete with pathogens via microbial antagonism
Produce substances harmful to pathogens
Alter conditions that affect pathogen survival
Commensalism: one organism benefits while the other (host) is unharmed
Probiotics: live microbial cultures administered to exert a beneficial effect

21. Check Your Understanding
Identify one physical factor and one chemical factor that prevent microbes from entering the body through skin and mucous membranes. 16-3
Identify one physical factor and one chemical factor that prevent microbes from entering or colonizing the body through the eyes, digestive tract, and respiratory tract. 16-4
Distinguish microbial antagonism from commensalism. 16-5

22. Second Line of Defense
Learning Objectives 16-6 Classify leukocytes, and describe the roles of granulocytes and monocytes Describe the eight different types of WBCs, and name a function for each type Differentiate the lymphatic and blood circulatory systems.

23. Formed Elements in Blood
Cells and cell fragments suspended in plasma
Erythrocytes (red blood cells)
Leukocytes (white blood cells)
Platelets
Created in red bone marrow stem cells via hematopoiesis

24. Figure Hematopoiesis.

25. Formed Elements in Blood
Granulocytes are leukocytes with granules in their cytoplasm that are visible with a light microscope
Neutrophils: phagocytic; work in early stages of infection
Basophils: release histamine; work in allergic responses
Eosinophils: phagocytic; toxic against parasites and helminths

26. Table 16.1 Leukocytes (White Blood Cells)

27. Formed Elements in Blood
Agranulocytes are leukocytes with granules in their cytoplasm that are not visible with a light microscope
Monocytes: mature into macrophages in tissues where they are phagocytic
Dendritic cells: found in the skin, mucous membranes, and thymus; phagocytic
Lymphocytes: T cells, B cells, and NK cells; play a role in adaptive immunity

28. Table 16.1 Leukocytes (White Blood Cells)

29. The Lymphatic System
Learning Objective 16-8 Differentiate the lymphatic and blood circulatory systems.

30. The Lymphatic System
Lymph, lymphatic vessels, lymphoid tissue, and red bone marrow
Contains lymphocytes and phagocytic cells
Lymph carries microbes to lymph nodes where lymphocytes and macrophages destroy the pathogen

31. Right lymphatic duct Thoracic (left lymphatic) duct Tonsil Right
Figure The lymphatic system.
Right
lymphatic duct
Thoracic (left
lymphatic) duct
Tonsil
Right
subclavian
vein
Left
subclavian
vein
Thymus
Lymph node
Thoracic duct
Spleen
Large intestine
Small intestine
Peyer’s patch
Lymphatic vessel
Red bone marrow

32. Flow of fluid between arteriole, blood capillaries,
Figure Lymphatic capillaries.
Interstitial fluid
(between cells)
Venule
Tissue cell
Lymph in lymphatic
capillary
Arteriole
Lymphatic capillary
Blood capillary
Flow of fluid between arteriole, blood capillaries,
lymphatic capillaries, and venule
Lymph in lymphatic
capillary
One-way
opening
Lymphatic capillary
Interstitial fluid flow
Tissue cells
Lymphatic vessel
Toward lymph node
Lymphatic capillaries and lymphatic vein

33. Host Defenses: Overview
PLAY
Animation: Host Defenses: Overview

34. Check Your Understanding
Compare the structures and functions of monocytes and neutrophils. 16-6
Define differential white blood cell count. 16-7
What is the function of lymph nodes? 16-8

35. Phagocytes
Learning Objectives 16-9 Define phagocyte and phagocytosis Describe the process of phagocytosis, and include the stages of adherence and ingestion Identify six mechanisms of avoiding destruction by phagocytosis.

36. Phagocytes Phago: from the Greek, meaning eat
Cyte: from the Greek, meaning cell
Fixed macrophages are residents in tissues and organs
Free (wandering) macrophages roam tissues and gather at sites of infection

37. Figure 16.7 A macrophage engulfing rod-shaped bacteria.
Bacterium

38. The Mechanism of Phagocytosis
Chemotaxis
Chemical signals attract phagocytes to microorganisms
Adherence
Attachment of a phagocyte to the surface of the microorganism
Ingestion
Opsonization: microorganism is coated with serum proteins, making ingestion easier
Digestion
Microorganism is digested inside a phagolysosome

39. Figure 16.8 The Phases of Phagocytosis.

40. Phagocytosis: Overview
PLAY
Animation: Phagocytosis: Overview

41. Phagocytosis: Mechanism
PLAY
Animation: Phagocytosis: Mechanism

42. Microbial Evasion of Phagocytosis
Inhibit adherence: M protein, capsules
Streptococcus pyogenes, S. pneumoniae
Kill phagocytes:
leukocidins
Staphylococcus aureus
Lyse phagocytes: membrane attack complex
Listeria monocytogenes
Escape phagosome
Shigella, Rickettsia
Prevent phagosome–lysosome fusion
HIV, Mycobacterium tuberculosis
Survive in phagolysosome
Coxiella burnetii

43. Virulence Factors: Hiding from Host Defenses
PLAY
Animation: Virulence Factors: Hiding
from Host Defenses

44. Virulence Factors: Inactivating Host Defenses
PLAY
Animation: Virulence Factors: Inactivating
Host Defenses

45. Phagocytosis: Microbes That Evade It
PLAY
Animation: Phagocytosis: Microbes
That Evade It

46. Check Your Understanding
What do fixed and wandering macrophages do? 16-9
What is the role of TLRs in phagocytosis? 16-10
How does each of these bacteria avoid destruction by phagocytes? Streptococcus pneumoniae, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium tuberculosis, Rickettsia 16-11

47. Inflammation
Learning Objectives List the stages of inflammation Describe the roles of vasodilation, kinins, prostaglandins, and leukotrienes in inflammation Describe phagocyte migration.

48. Inflammation
Four signs and symptoms: redness, swelling (edema), pain, heat
Destroys injurious agent or limits its effects on the body
Repairs and replaces tissue damaged by the injurious agent

49. Inflammation
Inflammation activates acute-phase proteins by the liver that cause vasodilation and increased permeability of blood vessels
Histamine
Kinins
Prostaglandins
Leukotrienes
Cytokines

50. Figure 16.9a-b The process of inflammation.
Tissue damage
Bacteria
Epidermis
Blood
vessel
Dermis
Nerve
Subcu-
taneous
tissue
Vascular reactions and phagocytosis
Chemicals such as histamine,
kinins, prostaglandins,
leukotrienes, and cytokines
(represented as blue dots) are
released by damaged cells.
Blood clot forms.
Abscess starts to form
(orange area).

51. Inflammation: Overview
PLAY
Animation: Inflammation: Overview

52. Inflammation: Steps
PLAY
Animation: Inflammation: Steps

53. Phagocyte Migration and Phagocytosis
Margination is the sticking of phagocytes to blood vessels in response to cytokines at the site of inflammation
Phagocytes squeeze between endothelial cells of blood vessels via diapedesis

54. Margination—phagocytes stick to endothelium.
Figure 16.9b The process of inflammation.
Blood vessel
endothelium
Monocyte
Margination—phagocytes
stick to endothelium.
RBC
Bacterium
Diapedesis—phagocytes
squeeze between endothelial
cells.
Phagocytosis of
invading bacteria occurs.
Macrophage
Neutrophil

55. Tissue Repair
Cannot be completed until all harmful substances are removed or neutralized
Stroma is the supporting connective tissue that is repaired
Parenchyma is the functioning part of the tissue that is repaired

56. Regenerated epidermis (parenchyma) Blood clot
Figure 16.9c The process of inflammation.
(c) Tissue repair
Scab
Regenerated epidermis
(parenchyma)
Blood clot
Regenerated dermis
(stroma)

57. Check Your Understanding
What purposes does inflammation serve? 16-12
What causes the redness, swelling, and pain associated with inflammation? 16-13
What is margination? 16-14

58. Fever
Learning Objective Describe the cause and effects of fever.

59. Fever Abnormally high body temperature
Hypothalamus is normally set at 37°C
Cytokines cause the hypothalamus to release prostaglandins that reset the hypothalamus to a higher temperature
Body constricts the blood vessels, and shivering occurs (which raises temperature)
As body temperature falls (crisis), vasodilation and sweating occurs

60. Check Your Understanding
Why does a chill indicate that a fever is about to occur? 16-15

61. Antimicrobial Substances
Learning Objectives List the major components of the complement system Describe three pathways of activating complement Describe three consequences of complement activation.

62. Antimicrobial Substances
Learning Objectives Define interferons Compare and contrast the actions of IFN-α and IFN-β with IFN- Describe the role of iron-binding proteins in innate immunity Describe the role of antimicrobial peptides in innate immunity.

63. The Complement System
Serum proteins produced by the liver that assist the immune system in destroying microbes
Act in a cascade in a process called complement activation
Proteins are designated with uppercase C and numbered in order of discovery
Activated fragments are indicated with lowercase a and b

64. Complement: Overview
PLAY
Animation: Complement: Overview

65. Complement: Activation
PLAY
Animation: Complement: Activation

66. The Classical Pathway Antibodies bind to antigens, activating C1
C1 splits and activates C2 and C4
C2a and C4b combine and activate C3
C3a functions in inflammation
C3b functions in cytolysis and opsonization

67. pathway of complement activation
Figure 16.10a Pathways of complement activation.
pathway of complement activation
classical
Microbe
Antigen
Antibody C1 C2 C4
C2b
C2a
C4b
C4a C3
C3a
C3b
inflammation
cytolysis
opsonization

68. The Alternative Pathway
C3 present in the blood combines with factors B, D, and P on microbe surface
C3 splits into C3a and C3b, functioning the same as in the classical pathway

69. alternative Figure 16.10b Pathways of complement activation. Microbe
Lipid–
carbohydrate
complex
Microbe B D P
Factors C3
C3a
C3b
inflammation
cytolysis
opsonization

70. The Lectin Pathway
Macrophages ingest pathogens, releasing cytokines that stimulate lectin production in the liver
Mannose-binding lectin (MBL) binds to mannose, activating C2 and C4
C2a and C4b activate C3, which functions the same as in the classical and alternative pathways

71. lectin Figure 16.10c Pathways of complement activation. Microbe
Carbohydrate
containing
mannose
Mannose-binding
lectin (MBL) C2 C4
C2b
C2a
C4b
C4a C3
C3a
C3b
inflammation
cytolysis
opsonization

72. Outcomes of Complement Activation
Cytolysis
Activated complement proteins create a membrane attack complex (MAC)
Opsonization
Promotes attachment of a phagocyte to a microbe
Inflammation
Activated complement proteins bind to mast cells, releasing histamine

73. Figure 16.11 The MAC results in cytolysis.

74. outcomes of complement activation
Figure Outcomes of Complement Activation
outcomes of complement activation C3
Splits into activated C3a and C3b
cytolysis
opsonization
inflammation
C3a
C3b
C3a
C3b
C3a
C3b C5 C5
C5a
C5b
C5a
C5b C6
Histamine C7 C8
C3a
C5a
Microbe
C3a
receptor
C5a
receptor C9
Mast cell
Channel
C3b protein
Microbes
Phagocytesa C6 C7
C5b C8 C9
Phagocyte
Microbes burst as extracellular
fluid flows in through transmembrane channel
formed by membrane attack complex.
Coating microbes with C3b
enhances phagocytosis.
Blood vessels become more
permeable, and chemotactic agents
attract phagocytes to area.
KEY CONCEPTS
The complement system is another way the body fights infection and destroys pathogens. This component of innate immunity
“complements” other immune reactions.
Complement is a group of over 30 proteins circulating in serum that are activated in a cascade: one complement protein triggers
the next.
The cascade can be activated by a pathogen directly or by an antibody–antigen reaction.
Together these proteins destroy microbes by (1) cytolysis, (2) enhanced phagocytosis, and (3) inflammation.

75. Mast cell Phagocytes C5a receptor C5a Histamine Neutrophil Histamine-
Figure Inflammation stimulated by complement.
Mast cell
Phagocytes
C5a receptor
C5a
Histamine
Neutrophil
Histamine-
containing
granule
C5a
Macrophage
Histamine-
releasing
mast cell
C3a
C3a receptor

76. Complement: Results
PLAY
Animation: Complement: Results

77. Outcomes of Complement Activation
Regulation of complement
Regulatory proteins readily break down complement proteins, minimizing host cell destruction
Complement and disease
Lack of complement proteins causes susceptibility to infections
Evading the complement system
Capsules prevent complement activation

78. Check Your Understanding
What is complement? 16-16
List the steps of complement activation via the classical, alternative, and lectin pathways
Summarize outcomes of complement activation

79. Interferons Cytokines produced by cells; have antiviral activity
IFN-α and IFN-β: produced by cells in response to viral infections; cause neighboring cells to produce antiviral proteins (AVPs) that inhibit viral replication
IFN-: causes neutrophils and macrophages to kill bacteria

80. Figure 16.14 Antiviral action of alpha and beta interferons (IFNs).
New viruses replicated
in host cell infect
neighboring cells.
Transcription
Translation
Transcription
Translation
Viral
RNA
Viral
RNA
Viral
RNA
Virus
replicates
Alpha
and beta
interferons
Infecting
virus
Antiviral
proteins
(AVPs)
Viral
replication
inhibited
Nucleus
IFN-mRNA
Virus-infected host cell
Neighboring cell
Viral RNA from
an infecting virus
enters the cell.
The virus induces the host cell to
produce interferon mRNA
(IFN-mRNA), which is translated
into alpha and beta interferons.
Interferons make contact with uninfected
neighboring host cells, where they bind either
to the plasma membrane or to nuclear
receptors. Interferons induce the cells to
synthesize antiviral proteins (AVPs).
AVPs degrade viral mRNA and
inhibit protein synthesis—and
thus interfere with viral
replication.

81. Iron-Binding Proteins
Transferrin: found in blood and tissue fluids
Lactoferrin: found in milk, saliva, and mucus
Ferritin: found in the liver, spleen, and red bone marrow
Hemoglobin: located in red blood cells
Bacteria produce siderophores to compete with iron-binding proteins

82. Antimicrobial Peptides
Short peptides produced in response to protein and sugar molecules on microbes
Inhibit cell wall synthesis
Form pores in the plasma membrane
Broad spectrum of activity

83. Check Your Understanding
What is interferon? 16-19
Why do IFN-α and IFN-β share the same receptor on target cells, yet IFN- has a different receptor? 16-20
What is the role of siderophores in infection? 16-21
Why are scientists interested in AMPs? 16-22