Anatomy &
Physiology
AN INTEGRATIVE APPROACH
Third Edition
Michael P. McKinley
Valerie Dean O’Loughlin
Theresa Stouter Bidle
See separate PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes.
© 2019 McGraw-Hill Education. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw-Hill Education.
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Chapter 22
Lecture Outline
© 2019 McGraw-Hill Education
22.1 Overview of Diseases Caused by
Infectious Agents
Learning Objectives:
1. Compare and contrast the five major classes
of infectious agents.
2. Describe prions, and name a disease they
cause.
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22.1 Overview of Diseases Caused by
Infectious Agents
1
Infectious agents can damage or kill a host
• Pathogenic agents are ones that cause harm
• Five major categories: bacteria, viruses, fungi,
protozoans, and multicellular parasites
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22.1 Overview of Diseases Caused by
Infectious Agents
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Bacteria: single-celled prokaryotes
• Small (1 to 2 µm) cell with both a
membrane and a cell wall Varied
types: spherical (cocci), rodlike
(bacilli), or coiled (spirilla)
• Most bacteria harmless; some
virulent (cause serious illness)
• Virulent bacteria may have pili, capsule,
or release toxins or damaging enzymes
• Examples of virulent bacteria: Clostridium
tetani (tetanus), streptococcal bacteria
(strep throat)
From Figure 22.1
© 2019 McGraw-Hill Education
(bacteria) Dr. William A. Clark/CDC;
22.1 Overview of Diseases Caused by
Infectious Agents
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Viruses: pieces of DNA or RNA in a
protein shell
• Viruses are not cells—they are
much smaller
• Only about one-hundredth of a
micrometer
• Obligate intracellular parasites
• Virus must enter a cell to reproduce
• Direct infected cell to make copies
of nucleic acid and capsid (shell)
• The virus or immune response may
kill the host cell
• E.g., common cold, ebola,
chickenpox
From Figure 22.1
© 2019 McGraw-Hill Education
(viruses) Centers for Disease Control;
22.1 Overview of Diseases Caused by
Infectious Agents
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Fungi: eukaryotic cells with
membrane and cell wall
• Include molds, yeasts, multicellular
fungi that produce spores
• Release proteolytic enzymes
inducing inflammation
• Cause superficial diseases in the
integument (e.g., ringworm)
• Can infect mucosal linings (e.g.,
vaginal yeast infections) or cause
internal infections (e.g.,
histoplasmosis)
From Figure 22.1
© 2019 McGraw-Hill Education
(fungi) Centers for Disease Control;
22.1 Overview of Diseases Caused by
Infectious Agents
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Protozoans: eukaryotic cells without
a cell wall
• Intracellular and extracellular parasites
• Disease examples: malaria and
trichomoniasis
Multicellular parasites are
nonmicroscopic
• Take nourishment from host they live in
• E.g., tapeworm
From Figure 22.1
© 2019 McGraw-Hill Education
(protozoans) Janice Haney Carr/CDC; (multicellular parasites) CDC
22.1 Overview of Diseases Caused by
Infectious Agents
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Prions: fragments of infectious proteins
• Neither cells nor viruses
• Cause disease in nervous tissue
• E.g., Variant Creutzfeldt-Jakob disease (“mad cow
disease”)
• Can be spread from cows to humans by consuming
infected meat
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Section 22.1 What did you learn?
1. Which pathogen must enter a cell to
replicate? Which type of pathogen is
composed of prokaryotic cells?
© 2019 McGraw-Hill Education
22.2 Overview of the Immune System
Learning Objectives:
3. List the types of leukocytes of the immune
system, and describe where they may be
found.
4. Define cytokines, and describe their
similarities to hormones.
5. List the general categories of cytokines
6. Compare and contrast the primary features of
innate and adaptive immunity.
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22.2a Immune Cells and Their Locations
Leukocytes (white blood cells)
• Formed in red bone marrow
• Include:
• Granulocytes: neutrophils, eosinophils, basophils
• Monocytes
• Become macrophages when they leave blood and enter tissues
• Lymphocytes
• B-lymphocytes, T-lymphocytes, NK (natural killer) cells
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22.2a Immune Cells and Their Locations
Structures that house immune system cells
Most leukocytes are in body tissues (instead of blood)
Secondary lymphatic structures
• T- and B-lymphocytes, macrophages, dendritic cells, and NK
cells housed in lymph nodes, spleen, tonsils, MALT, lymphatic
nodules
Select organs house macrophages
• May be permanent residents of the organ, or migrating
macrophages
• Some permanent ones named for location (e.g., alveolar
macrophages)
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22.2a Immune Cells and Their Locations
Structures that house immune system cells (continued)
Epithelial layers of skin and mucosal membranes house
dendritic cells
• These dendritic cells are usually derived from monocytes
• Engulf pathogens and migrate into lymph
Connective tissue houses mast cells
• Mast cells typically in close proximity to small blood
vessels
• Abundant in dermis and mucosa of respiratory, GI, and urogenital
tracts
• Also found in connective tissue of organs (e.g., endomysium of
muscle)
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Primary Location of Immune Cells
Figure 22.1
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22.2b Cytokines
Cytokines: small proteins that regulate immune activity
• Produced by cells of both innate and adaptive immune system
• Chemical messengers released from one cell that bind to
receptors of target cells
• Can act on cell that released it (autocrine); on local cells (paracrine); or
on distant cells after circulating through blood (endocrine)
• Have short half-life
• Effects
• Signaling cells (including non-immune cells, e.g., neurons)
• Controlling development and behavior of immune cells
• Regulating inflammatory response
• Destroying cells
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22.2c Comparison of Innate Immunity and
Adaptive Immunity 1
Two types of immunity differ based on
• Cells involved
• Specificity of cell response
• Mechanisms of eliminating harmful substances
• Amount of time for response
Although innate and adaptive immunities are
distinct, they work together in body defense
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22.2c Comparison of Innate Immunity and
Adaptive Immunity 2
Innate immunity: present at birth
• Protects against variety of different substances (nonspecific)
• No prior exposure to substance necessary
• Includes barriers of skin and mucosal membranes, nonspecific
cellular and molecular internal defenses
• Respond immediately to potentially harmful agents
Adaptive immunity: acquired/specific immunity
• Response to antigen involves specific T- and B-lymphocytes
• A particular cell responds to one specific foreign substance but not another
• Takes several days to be effective
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Overview of the Immune System
Figure 22.2
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Section 22.2 What did you learn?
2. Identify the specific type of immune cell(s)
within each of these structures: (a)
connective tissue, (b) skin, (c) organs, and (d)
secondary lymphatic organs.
3. What is the definition of a cytokine? How are
cytokines similar to hormones?
4. What are the cells that provide adaptive
immunity?
© 2019 McGraw-Hill Education
22.3 Innate Immunity
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Learning Objectives: 1
7.
Describe the physical, chemical, and biological
barriers to entry of harmful agents into the body.
8.
Describe the cells that function as part of the
nonspecific internal defenses in providing innate
immunity.
9.
Explain the general function of interferons.
10. Define the complement system, and describe how it
is activated.
11. Describe the four major means by which complement
participates in providing innate immunity.
© 2019 McGraw-Hill Education
22.3 Innate Immunity
Learning Objectives: 2
12. Define inflammation, and discuss the basic
steps involved, including the formation of
exudate and its role in removing harmful
substances.
13. Describe the benefits of inflammation.
14. List the cardinal signs of inflammation, and
explain why each occurs.
15. Define fever, and describe how it occurs.
16. List the benefits and risks of a fever.
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22.3 Innate Immunity
Characteristics of innate immunity
• Prevents entry of potentially harmful substances
• Responds nonspecifically to a range of harmful substances
• First line of defense is skin and mucosal membrane
• Second line of defense involves internal processes
• Activities of neutrophils, macrophages, dendritic cells,
eosinophils, basophils, and NK cells
• Chemicals such as interferon and complement
• Physiological processes such as inflammation and fever
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22.3a Preventing Entry
Few microbes can penetrate intact skin
• Physical barrier of epidermis and dermis
• Skin releases antimicrobial substances
• Dermicidin, lysozyme, sebum, defensins
• Has normal nonpathogenic flora (microorganisms)
• Help prevent growth of pathogenic microorganisms
Mucous membranes line body openings
• Produce mucus and release antimicrobial substances
• Defensins, lysozyme, IgA
• Lined by harmless bacteria that suppress growth of more
virulent types
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22.3b Nonspecific Internal Defenses: Cells
Phagocytic cells
Neutrophils, macrophages, and dendritic cells
• Engulf unwanted substances by phagocytosis
• Neutrophils and macrophages destroy engulfed particles
• Intake vesicle fuses with lysosome forming phagolysosome
• Digestive enzymes break down the unwanted substances
• Respiratory burst produces reactive oxygen-containing molecules
that help destroy the microbes
• Degraded residue is released by exocytosis
• Dendritic cells destroy particles and then present fragments
• Antigens are presented on dendritic cell surface to T-lymphocytes
• Necessary for initiating adaptive immunity
• Macrophages can also perform antigen presentation
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Phagocytic Cells: Neutrophil, Macrophage, and
Dendritic Cell
Figure 22.3a
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22.3b Nonspecific Internal Defenses: Cells
Proinflammatory chemical-secreting cells
Basophils and mast cells promote inflammation
• Basophils circulate in the blood
• Mast cells reside in connective tissue, mucosa, internal organs
• They release granules containing chemicals
• The chemicals increase movement of fluid from blood to injured tissue
• They serve as chemotaxis chemicals – they attract immune cells
• Histamine increases vasodilation and capillary permeability
• Heparin acts as an anticoagulant
• Eicosanoids released from their plasma membrane also
increase inflammation
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Proinflammatory Chemical-Secreting
Cells: Basophil and Mast Cell
Figure 22.3b
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22.3b Nonspecific Internal Defenses: Cells
Apoptosis-initiating cells
NK (natural killer) cells destroy unhealthy/unwanted cells
• Form in bone marrow, circulate in blood, and accumulate in
secondary lymphatic structures
• Perform immune surveillance—patrol the body, detect unhealthy cells
• They destroy virus-infected cells, bacteria-infected cells, tumor
cells, cells of transplanted tissue
• They kill by releasing cytotoxic chemicals
• Perforin creates a transmembrane pore in unwanted cell
• Granzymes enter pore and cause apoptosis of cell
• Apoptosis is cell death that causes shriveling rather than lysis
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Apoptosis-Initiating Cells: NK Cell
Figure 22.3c
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22.3b Nonspecific Internal Defenses: Cells
Eosinophils
Eosinophils attack multicellular parasites
• Degranulate, release enzymes and other toxic substances
• Can release proteins that form transmembrane pores in parasite’s cells
• Participate in immune responses of allergy and asthma
• Engage in phagocytosis of antigen-antibody complexes
Cells of innate immune system recognize microbes as
foreign because of receptors
• Pattern recognition receptors (toll-like receptors) on cell
surface bind to patterns on microbe surface
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Parasite-Destroying Cells: Eosinophils
Figure 22.3d
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22.3c Nonspecific Internal Defenses:
Antimicrobial Proteins
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1
Antimicrobial proteins are molecules that function
against microbes
Interferons: a class of cytokines that nonspecifically
impedes viral spread
• IFN-α and IFN-β produced by leukocytes and virus-infected cells
• Bind to neighboring cells and prevent their infection
• Trigger synthesis of enzymes that destroy viral nucleic acids, inhibit synthesis
of viral proteins
• Stimulate NK cells to destroy virus-infected cells
• IFN-g produced by T-lymphocytes and NK cells
• Stimulates macrophages to destroy virus-infected cells
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Effects of Interferon
Figure 22.4
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22.3c Nonspecific Internal Defenses:
Antimicrobial Proteins
2
Complement system: group of over 30 plasma proteins
• Work along with (“complement”) antibodies
• Identified with letter “C” and number (e.g., C2)
• Synthesized by liver, continuously released in inactive form
• Activation occurs by enzyme cascade
• Complement activation follows pathogen entry
• Classical pathway
•
Antibody attaches to foreign substance, then complement binds to antibody
• Alternative pathway
•
Complement binds to polysaccharides of bacterial or fungal cell wall
• Especially potent against bacterial infections
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22.3c Nonspecific Internal Defenses:
Antimicrobial Proteins
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Effects of activated complement:
• Opsonization: complement protein (opsonin) binds to pathogen
• Enhances likelihood of phagocytosis of pathogenic cell
• Inflammation is enhanced by complement
• Activates mast cells and basophils; attracts neutrophils and macrophages
• Cytolysis: complement triggers splitting of target cell
• Complement proteins form membrane attack complex (MAC) that
creates channel in target cell’s membrane
• Fluid enters, causing cell lysis
• Elimination of immune complexes
• Complement links antigen-antibody complexes to erythrocytes
• Cells move to liver and spleen where complexes are stripped off
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Complement System
Figure 22.5
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22.3d Nonspecific Internal Defenses:
Inflammation
1
Inflammation: an immediate response to ward off
unwanted substances
• Local, nonspecific response of vascularized tissue to
injury
• Part of innate immunity
Events of inflammation
• Injured tissue, basophils, mast cells, and infectious
organisms release chemicals that initiate response
• The chemicals include histamine, leukotrienes, prostaglandins,
chemotactic factors
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22.3d Nonspecific Internal Defenses:
Inflammation
2
Events of inflammation (continued)
• Released chemicals cause vascular changes
• Vasodilation
• Increased capillary permeability
• Increased endothelial expression of molecules for leukocyte adhesion
• Cell-adhesion molecules, CAMs
• Recruitment of leukocytes
• Margination: adherence of leukocytes to endothelial CAMs
• Diapedesis: cells escape blood vessel walls
• Chemotaxis: leukocytes migrate toward chemicals released from
damaged, dead, or pathogenic cells
• Leukocytes release cytokines stimulating leukopoiesis in marrow
• Macrophages may release pyrogens (fever-inducing molecules)
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22.3d Nonspecific Internal Defenses:
Inflammation
3
Events of inflammation (continued)
• Delivery of plasma proteins to site
• Immunoglobulins, complement, clotting proteins, and
kinins
• Clotting proteins form clots that wall off microbes
• Kinins stimulate pain receptors, increase capillary
permeability, increase production of CAMs by capillary cells
• Kinins are produced from inactive kininogens (from liver and other
cells)
• Include bradykinin
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22.3d Nonspecific Internal Defenses:
Inflammation
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Effects of inflammation
• Fluid (exudate) moves from blood to injured or infected area
• Fluid, protein, immune cells to eliminate pathogens, promote healing
• Vasodilation brings more blood to the area
• Contraction of vessel endothelial cells opens gaps between them,
increasing capillary permeability
• Loss of plasma proteins decreases capillary osmotic pressure, thus
decreasing fluid reabsorption into blood
• Extra fluid is taken up by lymphatic capillaries in the area (“washing”)
• Carries away debris and allows lymph node monitoring of its contents
• Within 72 hours, inflammatory response slows
• Macrophages eat bacteria, damaged host cells, dying neutrophils
• Tissue repair begins as fibroblasts form new connective tissue
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Inflammation
Figure 22.6
© 2019 McGraw-Hill Education
22.3d Nonspecific Internal Defenses:
Inflammation
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Cardinal signs of inflammation
• Redness from increased blood flow
• Heat from increased blood flow and increased
metabolic activity within the area
• Swelling from increase in fluid loss from capillaries
• Pain from stimulation of pain receptors
• Due to compression (extra fluid) and chemical irritants (kinins,
prostaglandins, microbial secretions)
• Loss of function from pain and swelling in severe cases
Duration of acute inflammation: about 8 to 10 days
• Chronic inflammation has detrimental effects
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22.3e Nonspecific Internal Defenses: Fever
1
Fever (pyrexia): abnormal body temperature
elevation
• 1°C or more from normal (37°C)
• Results from the release of pyrogens (e.g., IL-1) from
immune cells or infectious agents
Events of fever
• Pyrogens circulate through blood and target hypothalamus
• In response, hypothalamus releases prostaglandin E2
• Hypothalamus raises temperature set point leading to
fever
• Fever stages: onset, stadium, and defervescence
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22.3e Nonspecific Internal Defenses: Fever
Events of fever (continued)
• Onset: temperature begins to rise
• Hypothalamus stimulates constriction of dermal BV (less heat loss)
• Shivering of muscle generates more heat (may be in response to chills)
• Stadium: elevated temperature is maintained
• Metabolic rate increases to promote elimination of harmful substance
• Liver and spleen bind zinc and iron thereby slowing microbial
reproduction
• Defervescence: time when temperature returns to normal
• Hypothalamus no longer stimulated by pyrogens
• Prostaglandin release decreases
• Hypothalamus stimulates mechanisms to release heat
• E.g., vasodilation of skin blood vessels, sweating
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22.3e Nonspecific Internal Defenses: Fever
Benefits of fever
• Inhibits reproduction of bacteria and viruses
• Promotes interferon activity
• Increases activity of adaptive immunity
• Accelerates tissue repair
• Increases CAMs on endothelium of capillaries in lymph
nodes
• Additional immune cells migrating out of blood
• Recommended to leave a low fever untreated
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22.3e Nonspecific Internal Defenses: Fever
Risks of a high fever
• High fevers potentially dangerous
• 103 degree Fahrenheit in children, slightly lower in adult
• Changes in metabolic pathways and denaturation of
proteins pose risks
• Possible seizures
• Irreversible brain damage at greater than 106F
• Death likely if temperature greater than 109F
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Clinical View: Pus and Abscesses
Pus, exudate
• Contains destroyed pathogens, dead leukocytes,
macrophages, cellular debris
• Removed by lymphatic system or through skin
• If not completely cleared, may form abscess
• Pus walled off with collagen fibers
• Usually requires surgical intervention to remove
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Clinical View: Applying Ice
for Acute Inflammation
Ice recommended for acute inflammation
Causes vasoconstriction of blood vessels
• Decreases inflammatory response
Numbs area and makes less painful
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Clinical View: Chronic Inflammation
Inflammation continuing for longer than two weeks
Characterized by macrophages and lymphocytes (not
neutrophils)
Can occur from overuse injuries
• E.g., tennis elbow or shin splints
May occur if acute inflammation unable to eliminate
pathogen
May be due to autoimmune disorder
Can lead to tissue destruction and scar tissue formation
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Section 22.3 What did you learn?
5.
What is the role of the skin and mucous membranes in the
body’s defenses?
6.
What distinguishes neutrophils from dendritic cells? How
do basophils differ from mast cells?
7.
How do NK cells accomplish the task of eliminating
unwanted cells?
8.
How is the complement system defined? What are the four
major means by which complement participates in
providing innate immunity?
9.
What is inflammation, and what are the basic steps
involved in the inflammatory response?
10. In what ways does exudate assist in the body’s defense?
© 2019 McGraw-Hill Education
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22.4 Adaptive Immunity: An Introduction
Learning Objectives: 1
17. Describe the features of an antigen, and explain
what is meant by antigenic determinant.
18. Explain immunogenicity, and list attributes that
affect it.
19. Discuss how haptens stimulate immune
responses.
20. Describe receptors of both T-lymphocytes and
B-lymphocytes.
21. Define antigen presentation.
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22.4 Adaptive Immunity: An Introduction
Learning Objectives: 2
22. Describe antigen-presenting cells, and list cells that
serve this function.
23. Explain the process of formation of MHC class I
molecules in nucleated cells and MHC class II
molecules in professional antigen-presenting cells.
24. Diagram the interaction of TCR and CD receptors of
a T-lymphocyte with antigen associated with the
MHC molecules of other cells.
25. Identify the three significant events that occur in
the lifetime of a lymphocyte.
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22.4 Adaptive Immunity: An Introduction
Adaptive immunity involves specific lymphocyte
responses to an antigen
• Contact with antigen causes lymphocyte proliferation
• Immune response consists of lymphocytes and their products
• Longer response time than innate immunity
• Since it takes days to develop, adaptive immunity is considered the
third line of body’s defense
Two branches of adaptive immunity
• Cell-mediated immunity involving T-lymphocytes
• Humoral immunity involving B-lymphocytes, plasma cells,
and antibodies
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Two Branches of Adaptive Immunity
Figure 22.8
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22.4a Antigens
1
Pathogens are detected by lymphocytes because they
contain antigens
Antigen: substance that binds a T-lymphocyte or antibody
• Antigen is usually a protein or large polysaccharide
• Examples of antigens
• Protein capsid of viruses
• Cell wall of bacteria or fungi
• Bacterial toxins
• Abnormal proteins or tumor antigens
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22.4a Antigens
2
Foreign antigens versus self-antigens
• Foreign antigens differ from human body’s
molecules
• Bind body’s immune components
• Self-antigens are body’s own molecules
• Typically do not bind immune components
• Immune system generally able to distinguish
• However in autoimmune disorders the system reacts to
self-antigens as if foreign
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22.4a Antigens
Antigenic determinant
• Also known as epitope
• Specific site on antigen
recognized by immune
system
• Each has a different shape
• Pathogenic organisms can
have multiple determinants
Figure 22.9
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22.4a Antigens
4
Immunogen: antigen that induces an immune response
• Immunogenicity: ability to trigger response
• Increases with antigen’s degree of foreignness, size,
complexity, or quantity
Haptens are too small to function an antigen alone;
become immunogenic when attached to carrier molecule
• E.g., toxin in poison ivy
• Account for hypersensitivity reactions
• E.g., pollen, drugs such as penicillin
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Clinical View: Autoimmune Disorders
Immune system lacking tolerance for specific
self-antigen
• Initiates immune response as if cells were foreign
• Due to cross-reactivity, altered self-antigens, or
entering areas of immune privilege
• E.g., rheumatic heart disease, type 1 diabetes,
multiple sclerosis
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22.4b General Structure of Lymphocytes
T- and B-lymphocytes have unique receptor
complexes
• About 100,000 per cell
• Each complex binds one specific antigen
• TCR (T-cell receptor) is antigen receptor of Tlymphocyte
• BCR (B-cell receptor) is antigen receptor of Blymphocyte
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22.4b General Structure of Lymphocytes
Lymphocyte contact with antigen
• B-lymphocytes make direct contact with antigen
• T-lymphocytes have antigen presented by another cell
• Antigen is processed and presented by another cell type
• T-lymphocyte coreceptors (e.g., CD proteins) facilitate the interaction
T-lymphocyte subtypes
• Helper T-lymphocytes are CD4+ cells
• Assist in cell-mediated, humoral, and innate immunity
• E.g., activate NK cells and macrophages
• Cytotoxic T-lymphocytes are CD8+ cells
• Release chemicals that destroy other cells
• Other types include memory T-cells and regulatory T-cells
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T-Lymphocytes and B-Lymphocytes
Figure 22.10
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22.4c Antigen-Presenting Cells and MHC
Molecules
1
Antigen presentation: cells display antigen on plasma
membrane so T-cells can recognize it
• Two categories of cells present antigens
• All nucleated cells of the body
• Antigen-presenting cells (APCs)
• Immune cells that present to both helper T-cells and cytotoxic T-cells
• Include: dendritic cells, macrophages, B-lymphocytes
• Requires attachment of antigen to major histocompatibility
complex (MHC)
• MHC is group of transmembrane proteins
• MHC I is found on all nucleated cells
• MHC II is found on APCs (in addition to MHC I)
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22.4c Antigen-Presenting Cells and MHC
Molecules
2
Synthesis and display of MHC class I molecules on
nucleated cells
• MHC class I molecules are glycoproteins
• Have genetically determined structure that is unique to
individual
• Continuously synthesized and modified by rough
endoplasmic reticulum (RER); then inserted into cell
membrane
• Display fragments of proteins that were bound in RER
• If fragments are from endogenous proteins, immune system
recognizes them as “self ” and ignores them
• If fragments are from an infectious agent, immune system considers
the antigen “nonself ”
• Communicates to cytotoxic T-cells that they should destroy cell
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Formation and “Docking” of MHC Class I
Molecules in a Healthy Cell
Figure 22.11a
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Formation and “Docking” of MHC Class I
Molecules in an Unhealthy Cell
Figure 22.11b
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22.4c Antigen-Presenting Cells and MHC
Molecules
3
Display of MHC class II molecules on professional
antigen-presenting cells
• MHC class II molecules are also glycoproteins
• Synthesized and modified by RER, sent to membrane
• Exogenous antigens brought into cell through endocytosis
• Phagosome merges with lysosome, forming phagolysosome
• Substance digested into peptide fragments
• Fragments “loaded” onto MHC class II molecules within vesicle
• Vesicle merges with plasma membrane with antigen bound to MHC
molecule
• Provides means of communicating with helper T-lymphocytes
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Formation and “Docking” of MHC Class II
Molecules in Antigen-Presenting Cells
Figure 22.12
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Interaction of Receptors of T-Lymphocytes
with MHC Molecules of Other Cells
Figure 22.13
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Clinical View: Organ Transplants and MHC
Molecules
Transfer of organ from one individual to another
• E.g., kidney, liver, heart
Individuals tested prior to donation for MHC antigens
and ABO group
• No two individuals with exactly same MHC molecules
Components of innate and adaptive immune system
• Attempt to destroy transplanted tissue
• Recipient’s immune system suppressed with drugs
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22.4d Overview of Life Events of
Lymphocytes
Three main events in life of lymphocyte
• Formation of lymphocytes
• Occurs in primary lymphatic structures (red marrow and thymus)
• Become able to recognize one specific foreign antigen
• Activation of lymphocytes
• In secondary lymphatic structures they are exposed to antigen and
become activated
• Replicate to form identical lymphocytes
• Effector response: action of lymphocytes to eliminate antigen
• T-lymphocytes migrate to site of infection
• B-lymphocytes stay in secondary lymphatic structure (as plasma cells)
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Synthesize and release large quantities of antibodies
•
Antibodies are transported to infection site through blood and lymph
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Formation of Lymphocytes
Figure 22.14a
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Activation of Lymphocytes and
Effector Response
Figure 22.14b,c
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Section 22.4 What did you learn?
13. How is an antigenic determinant related to an antigen?
14. What distinguishes a hapten from an antigen?
15. What features distinguish the receptors of helper Tlymphocytes, cytotoxic T-lymphocytes, and B-lymphocytes?
16. Which type of MHC-class molecule is found on all nucleated
cells and is used to communicate with cytotoxic Tlymphocytes? Which classes are displayed on APCs, and
which class is used specifically to communicate with (a)
helper T-lymphocytes and (b) cytotoxic T-lymphocytes?
17. Where does a lymphocyte typically encounter an antigen
for the first time: primary lymphatic structure, secondary
lymphatic structure, or site of infection?
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22.5 Formation and Selection of TLymphocytes in Primary Lymphatic Structures
Learning Objectives:
26. Explain how T-lymphocytes mature.
27. Compare and contrast positive and negative
selection of T-lymphocytes and what is
meant by central tolerance.
28. Explain why T-lymphocytes leaving the
thymus are called both immunocompetent
and naive.
29. Describe the formation and function of Tlymphocytes (Tregs) in peripheral tolerance.
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22.5a Formation of T-lymphocytes
T-lymphocytes originate in red bone marrow
• Migrate to thymus as pre-T-lymphocytes to
complete maturation
• Initially have both CD4 and CD8 proteins
• Possess unique TCR receptor produced randomly
• Each cell has its TCR “tested” through a process of
selection
• Whether it can bind MHC with antigen
• Whether it binds only foreign (“nonself ”) antigen
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22.5b Selection and Differentiation
of T-lymphocytes
Thymic selection eliminates 98% of T-cells produced
• Positive selection
• Selects for the ability of T-cells to bind thymic epithelial cells with MHC
molecules (those that can bind survive)
• Negative selection
• Tests ability of T-lymphocyte to NOT bind self-antigens (self-tolerance)
• Occurs in primary lymphatic structures, specifically called central tolerance
• Thymic dendritic cells present self-antigens and T-cells that bind to
them are destroyed
T-lymphocytes differentiate
• Helper T-lymphocytes lose CD8 protein, keep CD4 protein
• Cytotoxic T-lymphocytes lose CD4 protein, keep CD8 protein
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Positive Selection
Figure 22.15, step 1
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Negative Selection
Figure 22.15, step 2
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Selective Loss of Either CD4 or CD8
Proteins
Figure 22.15, step 3
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22.5c Migration of T-Lymphocytes
T-lymphocytes migrate from thymus to secondary
lymphatic structures
• They are immunocompetent
• Able to bind antigen and respond to it
• Naive T-lymphocyte: not yet exposed to antigens they
recognize
Regulatory T-lymphocytes (Tregs)
• CD4+ cells formed from T-cells that bind self-antigens
• Inhibit immune response
• Function in tolerance outside of primary lymphatic structures; this is
called peripheral tolerance (a form of self-tolerance)
• Some tumors foster Treg proliferation; some cancer treatments try to
inhibit tumor Tregs
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Section 22.5 What did you learn?
18. Where does the maturation of T-lymphocytes
take place?
19. What would happen if a thymocyte that failed
the negative selection test was not destroyed
and instead entered the blood to circulate as
20. In general, how does central tolerance differ
from peripheral tolerance? T-lymphocyte?
© 2019 McGraw-Hill Education
22.6 Activation and Clonal Selection of
Lymphocytes
Learning Objectives:
30. Describe how both helper T-lymphocytes
and cytotoxic T-lymphocytes are activated,
including the specific role of IL-2 in both
activations.
31. Compare the activation of B-lymphocytes
with that of T-lymphocytes.
32. Describe lymphocyte recirculation, and
explain its general function.
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22.6 Activation and Clonal Selection of
Lymphocytes
Clonal selection: forming clones in response to an
antigen
• All formed cells have same TCR or BCR that matches
specific antigen
Antigen challenge: first encounter between antigen
and lymphocyte
• Usually occurs in secondary lymphatic structures
• Antigen in blood taken to spleen
• Antigen penetrating skin transported to lymph node
• Antigen from respiratory, GI, urogenital tracts, in tonsils or MALT
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22.6a Activation of T-Lymphocytes
1
Activation of helper T-lymphocytes
First signal: direct contact with MHC molecule of APC
• APC presents exogenous antigen with MHC class II molecules
• Occurs in secondary lymphatic structure
• Specific TCR site of T-cell binds to antigen peptide fragment
• Interaction stabilized by CD4 molecule of helper T-lymphocyte
• If it doesn’t recognize antigen, T-cell disengages quickly
• If it does recognize antigen, contact lasts several hours
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22.6a Activation of T-Lymphocytes
2
Activation of helper T-lymphocytes (continued)
Second signal
• Other receptors of APC and T-cell interact
• Helper T-cell secretes interleukin-2, stimulating itself
• Helper T-cells proliferate forming clones of helpers T-cells
(with same TCR)
• Some cells become activated helper T-lymphocytes that produce IL-2
• Some cells become memory helper T-lymphocytes, available for
future encounters
Lack of a second signal results in helper T-cells
becoming Tregs
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Activation of Helper T-Lymphocytes
Figure 22.16b
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22.6a Activation of T-Lymphocytes
3
Activation of cytotoxic T-lymphocytes
• First signal
• Direct contact between TCR of cytotoxic T-cell and peptide fragment
with MCH I molecule (on APC or infected cell)
• Interaction stabilized by CD8 of cytotoxic T-lymphocyte
• Second signal
• IL-2 released from helper T-cells binds to and stimulates cytotoxic Tlymphocytes
• Activated cytotoxic T-cells proliferate and differentiate
• Some become activated cytotoxic T-lymphocytes
• Others become memory cytotoxic T-lymphocytes
• Activated upon reexposure to same antigen
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Activation of Cytotoxic T-Lymphocytes
Figure 22.16a
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22.6b Activation of B-Lymphocytes
1
B-lymphocytes need to be activated, but can
respond to antigens outside of cells
• First signal
• Intact antigen binds to BCR, cross-linking 2 BCRs
• Stimulated B-cell engulfs, processes, and presents antigen
to helper T-cell for recognition
• Second signal
• Activated helper T-cell releases IL-4, stimulating Blymphocyte
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Activation of B-Lymphocytes
Figure 22.16c
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22.6b Activation of B-Lymphocytes
2
B-lymphocyte activation
• Causes B-lymphocytes to proliferate and differentiate
• Most differentiate into plasma cells that produce
antibodies
• Remainder become memory B-lymphocytes
• Retain BCRs and activate with reexposure to same antigen
• Have much longer life span than plasma cells
• In some cases activation occurs without T-cells
• But production of memory B-cells and various antibodies
requires helper T-cell involvement in activation
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22.6c Lymphocyte Recirculation
Lymphocyte recirculation
• After a period of time, a lymphocyte exits secondary
lymphatic structure
• Circulates through blood and lymph for several days
• Different lymphocytes delivered to secondary lymphatic
structures
• Makes it more likely lymphocyte will encounter specific
antigen
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Section 22.6 What did you learn?
21. What type of cell is required to activate both helper Tlymphocytes and naive cytotoxic T-lymphocytes?
22. How do cytokines released by helper T-lymphocytes
participate in activation of both helper and cytotoxic Tlymphocytes?
23. Is a separate APC required for B-lymphocyte activation,
or is a B-lymphocyte able to serve the role of an APC?
24. Explain the role of cytokines that are released from
helper T-lymphocytes in the activation of B-lymphocytes.
25. What advantage is provided by lymphocyte
recirculation?
© 2019 McGraw-Hill Education
22.7 Effector Response at Infection Site
Learning Objectives:
33. Explain the effector response of helper
T-lymphocytes.
34. Explain how an unhealthy cell is destroyed by
cytotoxic T-lymphocytes.
35. Explain why the processes of T-lymphocytes are
collectively called the cell-mediated branch of
adaptive immunity.
36. Describe the function of plasma cells in the effector
response of B-lymphocytes.
37. Define antibody titer.
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22.7 Effector Response at Infection Site
Effector response: Mechanisms used by lymphocytes
to help eliminate antigen
Each lymphocyte type has its own
• Helper T-lymphocytes
• Release IL-2 and other cytokines
• Regulate cells of adaptive and innate immunity
• Cytotoxic T-lymphocytes
• Destroy unhealthy cells by apoptosis
• Plasma cells
• Produce antibodies
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22.7a Effector Response of T-Lymphocytes
Effector response of helper T-lymphocytes
• After exposure to antigen (in secondary lymphatic
structures), activated and memory helper T-cells
migrate to infection site
• Continually release cytokines to regulate other immune
cells
• Help activate B-lymphocytes
• Activate cytotoxic T-lymphocytes with cytokines
• Stimulate activity of innate immune system cells
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Effector Response of Helper
T-Lymphocytes
Figure 22.17a
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22.7a Effector Response of T-Lymphocytes
Effector response of cytotoxic T-lymphocytes
• After exposure to antigen, activated and memory
cytotoxic T-cells migrate to infection site
• They destroy infected cells that display the antigen
• Make physical contact with unhealthy or foreign cell
• After recognizing antigen, cytotoxic T-cell releases granules
containing perforin and granzymes (cytotoxic chemicals)
• Perforin forms channel in target cell membrane
• Granzymes enter channel and induce death by apoptosis
• Because this works against antigens associated with
cells, the system is called cell-mediated immunity
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Effector Response of Cytotoxic TLymphocytes
Figure 22.17b
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22.7b Effector Response of B-Lymphocytes
Most activated B-lymphocytes become plasma cells
Plasma cells synthesize and release antibodies
• The cells remain in the lymph nodes
• They produce millions of antibodies during 5-day life
span
• Antibodies circulate through lymph and blood until
encountering antigen
• Antibody titer: circulating blood concentration of antibody
against a specific antigen
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Section 22.7 What did you learn?
26. Are cells of both the innate and adaptive
immune systems regulated by cytokines
released by helper T-lymphocytes?
27. Cell-mediated immunity is specifically
effective against what type of target?
Provide examples.
28. What is the specific role of plasma cells?
© 2019 McGraw-Hill Education
22.8 Immunoglobulins
Learning Objectives:
38. Describe the general structure of an
immunoglobulin molecule, including its two
functional regions.
39. List the functions of the antigen-binding site
and Fc region of antibodies, and briefly
describe how each occurs.
40. Describe the structure, location, and specific
function of the five major classes of
immunoglobulins.
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22.8a Structure of Immunoglobulins
1
Antibodies: immunoglobulin (Ig) proteins produced
against a particular antigen
• Antibodies “tag” pathogens for destruction by immune cells
• Good defense against viruses, bacteria, toxins, yeast spores
• Soluble antigens are combatted by “humoral immunity”
Structure: Y-shaped, soluble proteins
• Composed of four polypeptide chains
• Two identical heavy chains and two identical light chains
• Flexibility at hinge region of two heavy chains
• Held together by disulfide bonds to form antibody monomer
• Two important functional areas, variable and constant regions
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22.8a Structure of Immunoglobulins
2
Variable regions
• Located at the ends of the antibody “arms”
• Contain antigen-binding site (most antibodies have two sites)
• Bind antigens through weak intermolecular forces
• Hydrogen bonds, ionic bonds, and hydrophobic interactions
Constant region
• Contains the Fc region, which determines biological function
• Same in structure for antibodies of a given class
• Five major classes of immunoglobulins: IgG, IgM, IgA, IgD, IgE
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Antibody Structure
Figure 22.18
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22.8b Actions of Antibodies
1
Neutralization
• Antibody physically covers antigenic determinant of pathogen
• Makes it ineffective in establishing infection
• E.g., covers region of virus used to bind cell receptor
Agglutination (clumping)
• Antibody cross-links antigens of foreign cells causing clumping
• Especially effective against bacterial cells
Precipitation
• Antibody cross-links circulating antigens (e.g., viral particles)
• Forms antigen-antibody complex that becomes insoluble and
precipitates out of body fluids
• Precipitated complexes engulfed and eliminated by phagocytes
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Antibody Functions
Table 22.5, top
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22.8b Actions of Antibodies
2
Fc region (of constant region) actions
• Complement fixation
• Fc region of IgG and IgM can bind complement for activation (classical
complement activation)
• Opsonization
• Fc region of certain antibody classes makes it more likely target cell will
be “seen” by phagocytic cells
• Some phagocytes have receptors for these Fc regions
• Bind to Fc region and engulf antigen and antibody
• Activation of NK cells
• Fc region of some antibodies (IgG) trigger NK cells to release cytotoxins
• This destroys abnormal cells through antibody-dependent cellmediated cytotoxicity (ADCC)
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Antibody Functions
Table 22.5, bottom
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22.8c Classes of Immunoglobulins
1
Five classes of immunoglobulins: IgG, IgM, IgA, IgD, and
IgE
IgG make up 75–85% of antibodies in blood
• Also predominant antibody in other fluids (e.g., lymph, CSF)
• Can participate in all types of antibody actions
• Can cross placenta and cause hemolytic disease of newborn
IgM is found mostly in blood
• Normally has pentamer structure
• Most effective at agglutination and binding complement
• Responsible for rejection of mismatched transfusions
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22.8c Classes of Immunoglobulins
2
IgA is found in areas exposed to environment
• Produced in mucus, saliva, tears, breastmilk
• Protects respiratory and GI tract
• Dimer composed of two antibody molecules
• Helps prevent pathogens adhering to and penetrating
epithelium
• Especially good at agglutination
IgD
• Functions as antigen-specific B-lymphocyte receptor
• Identifies when immature B-lymphocytes ready for activation
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22.8c Classes of Immunoglobulins
3
IgE usually formed in response to parasites and in
allergic reactions
• Otherwise low rate of synthesis
• Causes release of products from basophils and mast cells
• Attracts eosinophils
Class switching: when a plasma cell changes the type
of antibody it produces
• Requires contact between helper T-cell and plasma cell
• T-cell must release particular cytokines to specify antibody class that
will be formed
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Section 22.8 What did you learn?
29. What is the significance of the variable
regions of an immunoglobulin molecule?
30. What are the six major functions of
antibodies? Which occur due to antigenbinding, and which depend on the Fc
region?
31. Which subclass of antibodies is most
prevalent? Which specific functions of
antibodies can it engage in?
© 2019 McGraw-Hill Education
22.9 Immunologic Memory and Immunity
Learning Objectives:
41. Define immunologic memory, and explain
how it occurs.
42. Discuss the difference between the primary
response and the secondary response to
antigen exposure.
43. Define active immunity and passive
immunity.
44. Describe how both active and passive
immunity can be acquired naturally and
artificially.
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22.9a Immunologic Memory
1
Memory results from formation of a long-lived
army of lymphocytes upon immune activation
• Adaptive immunity activation requires contact
between lymphocyte and antigen
• There is lag time between first exposure and direct
contact
• Activation leads to formation of many memory cells
against specific antigen
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22.9a Immunologic Memory
2
With subsequent antigen exposure
• Many memory cells make contact with antigen more
rapidly
• Produce powerful secondary response
• Pathogen typically eliminated before disease symptoms develop
• E.g., person who develops measles will not have it again, even if
exposed
• Virus eliminated by memory T- and B-lymphocytes, antibodies before causing
harm
• Vaccines are typically effective in developing memory
© 2019 McGraw-Hill Education
Primary and Secondary (Anamnestic)
Response in Humoral Immunity
Figure 22.21
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22.9b Measure of Immunologic Memory
Antibody titer: concentration of antibody
Initial exposure and the primary response:
• Initial exposure can be active infection or vaccine
• Primary response: antibody production to first exposure
• Lag or latent phase: initial period of no detectable antibody
• Lasts 3 to 6 days
• Includes antigen detection, activation, proliferation, differentiation
• Production of antibody: plasma cells produce IgM and then IgG
• Occurs within 1 to 2 weeks
• Antibody levels peak, then decline over time
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22.9b Measure of Immunologic Memory
Subsequent exposures and the secondary response:
• Next exposure occurs after variable length of time
• Measurable response to subsequent exposure is the
secondary response
• Lag or latent phase
• Much shorter than primary response due to memory lymphocytes
• Production of antibody
• Antibody levels rise rapidly
• Large proportion of IgG antibodies
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22.9c Active and Passive Immunity
Active immunity
• Results from direct encounter with pathogen
• Can occur naturally by direct exposure to antigen
• Can occur artificially through exposure through vaccine
• Memory cells against specific antigen are formed
Passive immunity: obtained from another individual
• Obtained from another individual
• Can occur naturally via transfer of antibodies from mother to fetus
(through placenta or milk)
• Can occur artificially when serum transferred from one person to
another (e.g., antibodies to snake venom)
• Neither form of passive immunity produces memory cells
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Active and Passive Immunity
Figure 22.22
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Clinical View: Vaccinations
Weakened or dead microorganism or component
Stimulate immune system to develop memory Blymphocytes
Provide relatively safe means for initial exposure to
microorganism
If later exposed, secondary response triggered
Immune system response predominantly from the
humoral branch
May provide lifelong immunity or require booster shot
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Clinical View: Hypersensitivities
1
Abnormal and exaggerated response of immune
system to antigen
Acute hypersensitivities occurring with seconds
Subacute hypersensitivities occurring within 1 to 3
hours
• Both involve humoral immunity
Delayed hypersensitivities occur within 1 to 3 days
• Involve cell-mediated immunity
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Clinical View: Hypersensitivities
Acute hypersensitivity (allergy)
• Exaggerated response of immune system to a
noninfectious substance, or allergen
• E.g., pollen, latex, peanuts
• Sensitization, activation, and effector phases
• May cause multiple symptoms
• Runny nose and watery eyes
• Labored breathing and coughing (allergic asthma)
• Red welts and itchy skin (hives)
• Vomiting and diarrhea
• Systemic vasodilation and inflammation
• May result in anaphylactic shock
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Clinical View: HIV and AIDS
AIDS (acquired immunodeficiency syndrome)
Result of human immunodeficiency virus (HIV)
• Infects and destroys helper T-lymphocytes
• Resides in body fluids of infected individuals
• Can be transmitted by intercourse, needle sharing,
breastfeeding
Diagnosis is AIDS when helper T-lymphocyte count
drops below 200 cells per cubic milliliter
Death is usually from opportunistic infections or cancer
Prevention through safe sex
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Section 22.9 What did you learn?
32. Briefly describe immunologic memory, and
explain its significance.
33. How does the secondary response differ
from the primary response? What is the
advantage of the secondary response?
34. Which type of immunity—active or
passive—results in the production of
memory cells and generally provides lifelong
protection from that antigen?
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