1. Immunity

2. A Neutrophil (Blue) Phagocytizing Aspergillus Spores (Red)

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

7. 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

8. 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

9. 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

10. Figure 16.1 A Section Through Human Skin

11. 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

12. 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

13. Figure 16.3 The Ciliary Escalator

14. 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

15. 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

16. 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

17. Figure 16.4 Hematopoiesis

18. 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

19. Table 16.1 Leukocytes (White Blood Cells) (1 of 2)
Granulocytes
Blank
Neutrophils (PMNs)(60–70% of leukocytes)
Function: Phagocytosis
In the L M view, a light purple oval structure of diameters 12 micrometers contains dark purple oval structures of diameters 2 to 5 micrometers.
Basophils (0.5–1%)
Function: Production of histamine
In L M view, a light purple oval structure of diameter 10 to 15 micrometers contains dark purple oval structures of diameter 1 micrometer.
Eosinophils (2–4%)
Functions: Production of toxic proteins against certain parasites; some phagocytosis
In L M view, an oval structure of diameter 12 to 15 micrometers contains light grey-purple oval structures of diameter up to 1 micrometer, as well as two dark purple oval structures of diameter 5 to 10 micrometers.

20. 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

21. Table 16.1 Leukocytes (White Blood Cells) (2 of 2)
Agranulocytes
Blank
Monocytes (3–8% total)
Function: Phagocytosis (when they mature into macrophages)
In the L M view, the monocyte is an oval structure of diameter 14 micrometers. The monocyte becomes a macrophage, which appears as an irregularly shaped structure of diameter 15 to 22 micrometers.
Dendritic cells
Functions: Phagocytosis and initiation of adaptive immune responses
In the L M view, a dendritic cell has a central body of diameter 10 to 12 micrometers, with tapering extensions of length 2 to 5 micrometers projecting from the central body.
Lymphocytes (20–25%)
• Natural killer (NK) cells
Function: Destroy target cells by cytolysis and apoptosis
• T cells
Function: Cell-mediated immunity
• B cells
Function: Produce antibodies
In L M view, a lymphocyte is an irregularly shaped structure of diameter 18 to 27 micrometers. An irregular dark purple body fills roughly half of the lymphocyte’s interior. A T cell is an oval structure of diameter 23 to 30 micrometers. A dark purple oval body occupies roughly 80% of the T cell’s interior. A B cell is an oval structure of diameter 18 to 23 micrometers. A circular dark purple body occupies approximately two-thirds of the B cell’s interior.

22. 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

23. Figure 16.7 A Macrophage Engulfing Rod-Shaped Bacteria

24. 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

25. Figure 16.8 The Phases of Phagocytosis

26. 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

27. 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

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

29. Figure 16.9a-b The Process of Inflammation

30. 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

31. Figure 16.9b The Process of Inflammation

32. 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

33. Figure 16.9c The Process of Inflammation

34. 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

35. 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

36. 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

37. Figure 16.10a Pathways of Complement Activation

38. 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

39. Figure 16.10b Pathways of Complement Activation

40. 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

41. Figure 16.10c Pathways of Complement Activation

42. Outcomes of Complement Activation (1 of 2)
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

43. Figure 16.11 The MAC Results in Cytolysis

44. Figure 16.12 Outcomes of Complement Activation

45. Figure 16.13 Inflammation Stimulated by Complement

46. 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

47. 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-γ: causes neutrophils and macrophages to kill bacteria

48. Figure 16.14 Antiviral Action of Alpha and Beta Interferons (IFNs)

49. 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

50. 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

51. 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"

52. 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

53. 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

54. Figure 17.1 Differentiation of T Cells and B Cells

55. 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

56. 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

57. 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

58. Figure 17.2 Epitopes (Antigenic Determinants)

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

60. 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)

61. Figure 17.4 The Structure of a Typical Antibody Molecule

62. 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

63. 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

64. 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

65. 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

66. 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

67. Table 17.1 A Summary of Immunoglobulin Classes (1 of 2)
Characteristics
IgG
IgM
IgA
IgD
IgE
Blank
A Y-shaped structure with the branching segments having cleft ends.
A central pentagonal body has Y-shaped structures extending from the vertices, so that the branches of each Y open outward. A curved J chain connects the interior ends of two adjacent Y structures.
Two Y structures are positioned along a common axis, so that their branches open in opposite directions. A J chain connects the adjacent ends of the Y structures, and a curved secretory component extends from the junction of one Y structure to the junction of the other Y structure.
Structure
Monomer
Pentamer
Dimer (with secretory
component)
Percentage of Total Serum Antibody
80% 6%
13%*
0.02%
0.002%
Location
Blood, lymph, intestine
Blood, lymph, B cell surface (as monomer)
Secretions (tears, saliva,
mucus, intestine, milk),
blood, lymph
B cell surface, blood, lymph
Bound to mast
and basophil cells
throughout body, blood
Molecular Weight
150,000
970,000
405,000
175,000
190,000

68. Table 17.1 A Summary of Immunoglobulin Classes (2 of 2)
Characteristics
IgG
IgM
IgA
IgD
IgE
Half-Life in Serum
23 days
5 days
6 days
3 days
2 days
Complement Fixation
Yes
No† No
Placental Transfer
Known Functions
Enhances phagocytosis;
neutralizes toxins and viruses; protects fetus and newborn
Especially effective
against microorganisms
and agglutinating
antigens; first
antibodies produced
in response to initial
infection
Localized protection on mucosal surfaces
Serum function not
known; presence on
B cells functions in
initiation of immune
response
Allergic reactions;
possibly lysis of
parasitic worms
*Percentage in serum only; if mucous membranes and body secretions are included, percentage is much higher. †May be yes via alternative pathway.

69. 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

70. 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)

71. Figure 17.5 Activation of B Cells to Produce Antibodies

72. 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

73. Figure 17.6 Clonal Selection and Differentiation of B Cells

74. 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

75. 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

76. Figure 17.8 The Results of Antigen–Antibody Binding

77. 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)

78. 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)

79. Figure 17.9 M Cells

80. 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

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

82. T Helper Cells ​ T Cells) (1 of 2)
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

83. Figure Activation of
T Helper Cells

84. T Helper Cells
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

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

86. T Cytotoxic Cells​ 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

87. Figure 17.14 Killing of Virus-Infected Target Cell by Cytotoxic T Lymphocyte

88. T Cytotoxic Cells 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

89. Figure Apoptosis

90. 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

91. Table 17.2 Principal Cells That Function in Cell-Mediated Immunity
T Helper (TH1) Cell
Activates cells related to cell-mediated immunity: macrophages, Tc cells, and natural killer cells
T Helper (TH2) Cell
Stimulates production of eosinophils, IgM, and IgE
T Helper (TH17) Cell
Recruits neutrophils; stimulates production of antimicrobial proteins
Cytotoxic T Lymphocyte
(CTL)
Destroys target cells on contact; generated from T cytotoxic (Tc) cell
T Regulatory (Treg) Cell
Regulates immune response and helps maintain self-tolerance
Activated Macrophage
Enhanced phagocytic activity; attacks cancer cells
Natural Killer (NK) Cell
Attacks and destroys target cells; participates in antibody-dependent cellmediated cytotoxicity

92. 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

93. Figure 17.17 The Primary and Secondary Immune Responses to an Antigen

94. Types of Adaptive Immunity (2 of 3)
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

95. Figure 17.18 Types of Adaptive Immunity