1. 15
Innate
Immunity

2. Innate Resistance Resistance to most plant and animal pathogens
Resistance due to physiological processes of humans that are incompatible with those of the pathogen
Correct chemical receptors not present on human cells
Temperature and pH may be incompatible with those necessary for the pathogens survival
Number of pathogens for which humans don’t have innate resistance to that can cause disease

3. First Line of Defense
Structures, chemicals, processes that work to prevent pathogens entering the body
Nonspecific defenses
Includes the skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems
Animation:
Host Defenses
PLAY

4. Skin – Physical Components of Defense
Two major layers
Epidermis
Outer layer composed of multiple layers of tightly packed cells
Few pathogens can penetrate these layers
Shedding of dead skin cells removes attached microorganisms
Epidermal dendritic cells
Also termed Langerhans cells
Phagocytize pathogens

5. Skin – Physical Components of Defense
Dermis
Contains protein fibers called collagen
Give skin strength and pliability to resist abrasions that could introduce microorganisms

6. Skin – Chemical Components of Defense
Perspiration secreted by sweat glands
Salt – inhibits growth of pathogen by drawing water from their cells
Antimicrobial peptides – sweat glands secret dermicidins
Lysozyme – destroys cell wall of bacteria
Sebum secreted by sebaceous (oil) glands
Helps keep skin pliable and less likely to break or tear
Lowers the pH of the skin to a level inhibitory to many bacteria

7. Mucous Membranes
Line all body cavities open to the outside environment
Two distinct layers
Epithelium
Deeper connective layer that supports the epithelium

8. Epithelium Thin, outer covering of the mucous membranes
Unlike surface epidermal cells, epithelial cells are living
Tightly packed to prevent entry of pathogens
Continual shedding of cells carries attached microorganisms away

9. Respiratory System
Figure 15.2

10. Microbial Antagonism
Normal microbiota help protect the body by competing with potential pathogens
Various activities of the normal microbiota make it hard for pathogens to compete
Consumption of nutrients makes them unavailable to pathogens
Create an environment unfavorable to other microorganisms by changing pH

11. Microbial Antagonism Helps stimulate the body’s second line of defense
Promote overall health by providing vitamins to host

12. Other First-Line Defenses
Many body organs secrete chemicals with antimicrobial properties
Lacrimal glands that bathe the eye

13. Lacrimal Apparatus
Figure 15.3

14. Second Line of Defense
Operates when pathogens succeed in penetrating the skin or mucous membranes
Nonspecific defense
Composed of cells, antimicrobial chemicals, and processes but no physical barriers
Many of these components are contained or originate in the blood

15. Blood
Composed of cells and portions of cells within a fluid called plasma
Plasma is mostly water containing electrolytes, dissolved gases, nutrients, and proteins
When the clotting factors, a group of plasma proteins, are removed from plasma, the remaining fluid is called serum
Include iron-binding compounds
Other plasma proteins include complement proteins and antibodies
The cells and cell fragments in plasma are called formed elements

16. Formed Elements Three types of formed elements
Erythrocytes – carry oxygen and carbon dioxide in the blood
Platelets – involved in blood clotting
Leukocytes – involved in defending the body against invaders
Two groups
Granulocytes
Agranulocytes

17. Blood Cell Formation: WBC

18. Granulocytes
Contain large granules that stain different colors based on the dye used
Three types
Basophils – stain blue with the basic dye methylene blue
Eosinophils – stain red/orange with the acidic dye eosin
Neutrophils – stain lilac with a mixture of acidic and basic dyes
Neutrophils and eosinophils can phagocytize pathogens
Neutrophils and eosinophils are capable of diapedesis

19. Agranulocytes Cytoplasm appears uniform under a light microscope
Two types
lymphocytes – most involved in adaptive immunity
monocytes – leave the blood and mature into macrophages

20. Macrophages Phagocytic cells of the second line of defense
Wandering macrophages leave the blood via diapedesis and phagocytize throughout the body
Fixed macrophages do not move throughout the body and often phagocytize within a specific organ
Include alveolar macrophages (lungs), microglia (central nervous system), Küpffer cells (liver)
All macrophages, plus monocytes attached to endothelial cells, constitute the mononuclear phagocytic system

21. Phagocytic System

22. Lab Analysis of Leukocytes
The differential white blood cell count test can signal signs of disease
Increased eosinophils can indicate allergies or parasitic worm infection
Bacterial diseases often show increase in leukocytes and in neutrophils
Viral infections show increase in lymphocytes

23. Components of the Second Line of Defense
Phagocytosis
Extracellular killing by leukocytes
Nonspecific chemical defenses
Inflammation
Fever

24. Phagocytosis Cells capable of phagocytosis are called phagocytes
Phagocytosis is not completely understood
Can be divided into five stages
Animation:
Phagocytosis
PLAY

25. Phagocytosis
Figure 15.8

26. Host Cell Protection
The host’s cells are protected from destruction by the phagocytes
Some phagocytes have receptors for bacterial surface components, such as flagellar proteins or cell wall components, that are lacking on the body’s cells
Opsonins such as complement and antibody provide a signal to the phagocyte

27. Extracellular Killing by Leukocytes
Three Cell types that kill extracellularly
Eosinophils
Mainly attack parasitic helminths (worms) by attaching to their surface
Secrete toxins that weaken or kill the helminth
Eosinophilia, or elevated eosinophil levels, is often indicative of a helminth infestation

28. Extracellular Killing by Leukocytes
Natural killer lymphocytes (NK cells)
Secrete toxins onto the surface of virally infected cells and tumors
Differentiate normal body cells because they have membrane proteins similar to the NK cells
Neutiophils
Produce chemicals that kill nearby invaders
Generate extracellular fibers that bind to and kill bacteria

29. Nonspecific Chemical Defenses
Augment phagocytosis
Some attack pathogens directly
Some enhance other features of innate immunity
Includes various chemicals
Lysozyme
Complement
Interferon
Defensins

30. Complement System
Set of serum proteins designated numerically according to the order of their discovery
Complement activation results in lysis of the foreign cell
Complement can be activated in several ways
Classical pathway
Alternate pathway

31. Complement – Two Pathways
Figure 15.10

32. The Classical Pathway
Complement named for the events of this originally discovered pathway
Various complement proteins act nonspecifically to “complement” the action of antibodies

33. Classical Complement Cascade
Figure 15.11

34. The Alternate Pathway Activation occurs independent of antibodies
Useful in early stages of infection before antibodies have been made
Initiated by the cleavage of C3 into C3a and C3b which occurs naturally at a slow rate in the plasma

35. The Alternate Pathway
Stabilized C3b combines with the properdin factors to form an enzyme that cleaves C3 to produce more C3b
C3b combines with properdin B to form a different enzyme which cleaves C5 molecules
The complement cascade then continues

36. Inactivation of Complement
Body’s own cells withstand complement cascade
Membrane-bound proteins on many cells bind with and break down activated complement proteins
Animation:
The Complement System
PLAY

37. Interferons
Protein molecules released by host cells to nonspecifically inhibit the spread of viral infections
Cause many symptoms typically associated with viral infections
Three Classes
Alpha
Beta
Gamma

38. Interferons
Interferon alpha and beta are present early in the infection
Interferon gamma appears later in the course of infection

39. The Characteristics of Human Interferons
Table 15.3

40. Interferon Therapy
It was thought that this might be a good antiviral treatment
Recombinant DNA technology used to produce various interferons
Interferons produced in this way are pure and can be made in large quantities

41. Inflammation
Nonspecific response to tissue damage resulting from various causes
Characterized by redness, heat, swelling, and pain
Two types
Acute
Chronic
Animation:
Inflammation
PLAY

42. Acute vs. Chronic Inflammation
Acute inflammation
Develops quickly and is short lived
Is usually beneficial
Important in the second line of defense
Dilation and increased permeability of the blood vessels
Migration of phagocytes
Tissue repair
Chronic inflammation
Develops slowly and lasts a long time
Can cause damage to tissues

43. Events in Inflammation
Figure

44. Events in Inflammation
Figure

45. Chemical Mediators of Inflammation
Table 15.4

46. Fever A body temperature over 37C
Results when chemicals called pyrogens trigger the hypothalamus to increase the body’s core temperature
Various types of pyrogens
Bacterial toxins
Cytoplasmic contents of bacteria released by lysis
Antibody-antigen complexes
These signal for the production of interleukin-I (IL-1)

47. Fever Production
IL-1 production causes the hypothalamus to secrete prostaglandin which resets the hypothalamic “thermostat”
Communication with the brain initiates muscle contractions, increased metabolic activity, and constriction of blood vessels which raises the body’s temperature
Chills associated with fever are due to the reduced blood flow of constricted vessels
Decrease in IL-1 production results in the body’s temperature returning to normal

48. Benefits of Fever Enhances the effects of interferons
Inhibits growth of some microorganisms
May enhance the performance of phagocytes, cells of specific immunity, and the process of tissue repair

49. A Summary of Some Nonspecific Components of the First and Second Lines of Defense
Table 15.5

50. Specific Defense: Adaptive Immunity16
Specific Defense: Adaptive Immunity

51. Third Line of Defense Is called adaptive immunity
The body’s ability to recognize and defend itself against distinct invaders and their products
Is a “smart” system whose “memory” allows it to respond rapidly to a second encounter with a pathogen

52. Elements of Adaptive Immunity
Is acquired over time
Immunologists are scientists who study the cells and chemicals involved in specific immunity
Antigens trigger specific immune responses
Various cells, tissues, and organs are part of specific immunity
Includes B and T lymphocytes

53. Antigens Molecules that trigger a specific immune response
Include components of bacterial cell walls, capsules, pili, and flagella, as well as proteins of viruses, fungi, and protozoa
Food and dust can also contain antigenic particles
Enter the body by various methods
Through breaks in the skin and mucous membranes
Direct injection, as with a bite or needle
Through organ transplants and skin grafts
Animation:
Antigen Processing and Presentation
PLAY

54. Antigens
Figure 16.1

55. Lymphatic System Screens the tissues of the body for foreign antigens
Composed of lymphatic vessels and lymphatic cells

56. Lymphatic Vessels
Form a one-way system that conducts lymph from local tissues and returns it to the circulatory system
Lymph is a liquid with similar composition to blood plasma that arises from fluid leaked from blood vessels into surrounding tissues

57. The Lymphatic System
Figure 16.2

58. Lymphoid Cells Develop from stem cells in the red bone marrow
Includes lymphocytes, the smallest of the leukocytes

59. Lymphocytes
Figure 16.3

60. Lymph Node
Figure 16.4

61. Lymph Nodes
Houses leukocytes that recognize and attack foreign antigens present in the lymph
Concentrated in the cervical (neck), inguinal (groin), axillary (armpit), and abdominal regions
Receives lymph from afferent lymphatic vessels and drains lymph into efferent lymphatic vessels

62. Other Lymphoid Tissues and Organs
Spleen
Similar in structure and function to the lymph nodes
Filters bacteria, viruses, toxins, and other foreign matter from the blood
Tonsils and mucosa-associated lymphoid tissue (MALT)
Physically trap foreign particles and microbes
MALT includes the appendix, lymphoid tissue of the respiratory tract, vagina, urinary bladder, mammary glands, and Peyer’s patches in the wall of the small intestine

63. B Lymphocytes Arise and mature in the red bone marrow
Found primarily in the spleen, lymph nodes, and MALT
Small percentage of B cells circulate in the blood
Major function is the secretion of antibodies

64. Antibodies Also called immunoglobulins (Ig)
Soluble proteins that bind antigen
Secreted by plasma cells, which are B cells actively fighting exogenous antigen
Considered part of the humoral immune response since bodily fluids such as lymph and blood were once called humors

65. Antibody Structure
Figure 16.5

66. Antibody Function
Antigen-binding sites are complementary to antigenic determinants (epitopes)
Due to the close match can form strong, noncovalent interactions
Hydrogen bonds and other attractions may also be involved

67. Antibody Function Function in several ways Activation of complement
Stimulation of inflammation
Neutralization
Opsonization
Agglutination

68. Functions of Antibodies
Figure 16.6

69. Classes of Antibodies
A single type of antibody is not sufficient for the multiple types of invaders to the body
The class involved in the immune response depends on the type of foreign antigen, the portal of entry, and the antibody function needed
Five different classes of antibodies

70. Classes of Antibodies
Figure 16.7

71. Characteristics of the Five Classes of Immunoglobulins
Table 16.1

72. B Cell Receptor (BCR)
Is an antibody that remains associated with the cytoplasmic membrane
Each B lymphocyte has multiple copies of a single type of BCR
Antigen binding site is identical to that of the secreted antibody for that particular cell
The randomly generated antibody variable region determines the BCR (it is not formed in response to antigens)

73. B Cell Receptor (BCR)
Each BCR is complementary to only one antigenic determinant
The BCRs on all of an individual’s B cells are capable of recognizing millions of different antigenic determinants

74. T Lymphocytes
Produced in the red bone marrow and mature under the influence of the thymus
Circulate in the lymph and blood and migrate to the lymph nodes, spleen, and Peyer’s patches
Part of the cell-mediated immune response because they act directly against various antigens
Endogenous invaders
Many of the body’s cells that harbor intracellular pathogens
Abnormal body cells such as cancer cells that produce abnormal cell surface proteins

75. T Lymphocytes Three types Cytotoxic T cells
Two types of helper T cells

76. T Cell Receptor
Figure 16.9

77. Cytotoxic T cells (TC Cells)
Distinguished by the CD8 cell-surface glycoprotein
Directly kill certain cells
Cells infected with viruses and other intracellular pathogens
Abnormal cells, such as cancer cells

78. Helper T Cells (TH Cells)
Distinguished by the CD4 cell-surface glycoprotein
Function to “help” regulate the activities of B cells and cytotoxic T cells during an immune response
Secrete various soluble protein messengers, called cytokines, that determine which immune response will be activated

79. Helper T Cells (TH Cells)
Two types
Type 1 helper T cell (TH1)
Assist cytotoxic T cells
Express a cytokine receptor named CCR5
Type 2 helper T cell (TH2)
Assist B cells
Have cytokine receptors CCR3 and CCR4

80. Cytokines
Soluble regulatory proteins that act as intercellular signals when released from certain body cells
Immune system cytokines signal among various leukocytes
The complex web of signals among all the cell types of the immune system is referred to as the cytokine network

81. Cytokines of the Immune System
Interleukins (ILs) – signal among leukocytes
Interferons (IFNs) – antiviral proteins that may act as cytokines
Growth factors – proteins that stimulate stem cells to divide, maintaining a adequate supply of leukocytes
Tumor necrosis factor (TNF) – Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammation
Chemokines – signal leukocytes to go to a site of inflammation or infection and stimulate other leukocytes

82. Lymphocyte Editing by Clonal Deletion
Vital that immune responses not be directed against autoantigens
Body “edits” lymphocytes to eliminate any self-reactive cells

83. Lymphocyte Editing by Clonal Deletion
Figure 16.10

84. Major Histocompatibility Complex (MHC)
Group of antigens first identified in graft patients
Important in determining the compatibility of tissues in successful grafting
Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals
Function to hold and position antigenic determinants for presentation to T cells

85. Major Histocompatibility Complex (MHC)
Antigens bind in the antigen-binding groove of MHC molecules
Two classes of MHC proteins
MHC class I
MHC class II

86. MHC: Two Classes
Figure 16.11

87. Antigen Processing T-independent antigen
Large antigen molecules with readily accessible, repeating antigenic determinants
B cells can bind these directly without being processed
Stimulates B cells to differentiate into a plasma cell and produce antibodies

88. Antigen Processing T-dependent antigens
Smaller antigens with less accessible antigenic determinants
B cells require involvement from helper T cells to target these antigens
Helper T cells are assisted by leukocytes that process the antigen to make the antigenic determinants more accessible
Processing is different based on whether the antigen is exogenous or endogenous

89. Processing of Exogenous Antigens
APC internalizes the invading pathogen and enzymatically digests it into smaller antigenic fragments which are contained within a phagolysosome
Phagolysosome fuses with a vesicle containing MHC II molecules
Each fragment binds to the antigen-binding groove of a complementary MHC II molecule
The fused vesicle then inserts the MHC II-antigen complex into the cytoplasmic membrane so the antigen is presented on the outside of the cell

90. Processing of Endogenous Antigens
The intracellular pathogens are also digested into smaller antigenic determinants
Each fragment binds to a MHC I molecule located in the endoplasmic reticulum membrane
The membrane is packaged into a vesicle by a Golgi body which is inserted into the cytoplasmic membrane so the antigen is displayed on the cell’s surface

91. Humoral Immune Response
Body mounts humoral immune responses against exogenous pathogens
Components of a humoral immune response
B cell activation and clonal selection
Memory B cells and the establishment of immunological memory
Animation:
Humoral Immunity
PLAY

92. Humoral Immune Response
Figure 16.14

93. Plasma Cells
Make up the majority of cells produced during B cell proliferation
Each plasma cell secretes only antibody molecules complementary to the specific antigenic determinant
Are short-lived cells that die within a few days of activation, though their antibodies and progeny can persist

94. Memory B Cells
Cells produced by B cell proliferation that do not secrete antibodies
Cells that have BCRs complementary to the specific antigenic determinant that triggered their production
Long-lived cells that divide only a few times and then persist in the lymphoid tissue
Are available to initiate antibody production if the same antigen is encountered again

95. Primary and Secondary Responses
Figure 16.15

96. Cell-Mediated Immune Response
Responds to intracellular pathogens and abnormal body cells
The most common intracellular pathogens are viruses but the response is also effective against intracellular bacteria
Triggered when antigenic determinants of the pathogen are displayed on the host cell’s surface

97. Activation of TC Cells
Figure 16.16

98. A Cell-Mediated Immune Response
Animation:
Cell-Mediated Immunity
PLAY
Figure 16.17

99. T Cell Regulation
Careful regulation of cell-mediated immune response to prevent T cells from responding to autoantigens
T cells require additional signals from an antigen presenting cell
Interaction of the T cell and antigen presenting cell at an immunological synapse stimulates the T cell to respond to the antigen

100. Acquired Immunity
Specific immunity acquired during an individuals life
Two types
Naturally acquired- immune response against antigens encountered in daily life
Artificially acquired- response to antigens introduced via a vaccine
Further distinguished as either active or passive
Active- active response to antigens via humoral or cell-mediated responses
Passive- passively receive antibodies from another individual

101. A Comparison of the Types of Acquired Immunity
Table 16.3