Human Anatomy and Physiology

Eleventh Edition, Global Edition

Chapter 21
The Immune System: Innate
and Adaptive Body Defenses

PowerPoint® Lectures Slides prepared by Karen Dunbar Kareiva, Ivy Tech Community College

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The Immune System
• Immune system provides resistance to disease

• Made up of two intrinsic systems

– Innate (nonspecific) defense system
 Constitutes first and second lines of defense
– First line of defense: external body membranes (skin and mucosae)
– Second line of defense: antimicrobial proteins, phagocytes, and other
cells (inhibit spread of invaders; inflammation most important mechanism)
– Adaptive (specific) defense system
 Third line of defense attacks particular foreign substances (takes longer to
react than innate)

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 Surface barriers
• Skin
• Mucous membranes

Innate
defenses Internal defenses
• Phagocytes
• Natural killer cells
• Inflammation
Simplified • Antimicrobial proteins
• Fever
Overview of
Innate and
Adaptive Humoral immunity
• B cells
Defenses
Adaptive
defenses

Cellular immunity
• T cells

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Part 1 – Innate Defenses
• Innate system uses the first and/or second lines of defense to stop attacks by
pathogens (disease-causing microorganisms)

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21.1 First Line of Defense: Surface Barriers

• Surface barriers are skin and mucous membranes, along with their secretions
– Physical barrier to most microorganisms
– Keratin is resistant to weak acids and bases, bacterial enzymes, and toxins
– Mucosae provide similar mechanical barriers

• Skin and mucous membranes produce protective chemicals that inhibit or destroy
microorganisms
– Acid: acidity of skin and some mucous secretions inhibits growth; called acid
mantle
– Enzymes: lysozyme of saliva, respiratory mucus, and lacrimal fluid kills many
microorganisms; enzymes in stomach kill many microorganisms

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21.1 First Line of Defense: Surface Barriers

– Mucin: sticky mucus that lines digestive and respiratory tract traps microorganisms
– Defensins: antimicrobial peptides that inhibit microbial growth
– Other chemicals: lipids in sebum and dermicidin in sweat are toxic to some
bacteria

• Respiratory system also has modifications to stop pathogens

– Mucus-coated hairs in nose trap inhaled particles
– Cilia of upper respiratory tract sweep dust- and bacteria-laden mucus toward
mouth

• Surface barriers breached by nicks or cuts trigger the internal second line of defense
that protects deeper tissues

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Table 21.1 The First Line of Defense:
Surface Membrane Barriers

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21.2 Second Line of Defense: Cells and
Chemicals
• Innate system necessary if microorganisms invade deeper tissues; includes:
– Phagocytes
– Natural killer (NK) cells
– Inflammatory response (macrophages, mast cells, WBCs, and inflammatory
chemicals)
– Antimicrobial proteins (interferons and complement proteins)
– Fever

• Many second-line cells have pattern recognition receptors that recognize and bind
tightly to structures on microbes, disarming them before they do harm
• One class, Toll-like receptors (TLRs), play central role in triggering immune
responses.
 Humans have 11 different TLRs, each recognizes a particular class of attaching
microbe

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Phagocytes
• Phagocytes: white blood cells that ingest and digest (eat) foreign invaders

• Neutrophils: most abundant phagocytes, but die fighting; become phagocytic on

exposure to infectious material

• Macrophages: develop from monocytes and are chief phagocytic cells; most robust
phagocytic cell
– Free macrophages: wander through tissue spaces; example: alveolar
macrophages
– Fixed macrophages: permanent residents of some organs; examples: stellate
macrophages (liver) and microglia (brain)

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Phagocytosis
Innate defenses Internal defenses

(a) A macrophage (purple) about to engulf rod-shaped

bacteria (green). Scanning electron micrograph (2000×).
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Phagocytes
• Phagocytosis
1. Process starts when phagocyte recognizes and adheres to pathogen’s
carbohydrate “signature”
 Some microorganisms have external capsules that hide their surface
carbohydrates, helping them evade phagocytosis
– Opsonization: immune system uses antibodies or complement proteins
as opsonins that coat pathogens
• Act as “handles” for phagocytes to grab on to, enhancing
phagocytosis

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Phagocytosis
1 Phagocyte adheres
to pathogens or debris
(using receptors).

Phagosome
(phagocytic
vesicle)
Lysosome

Acid
hydrolase
enzymes

(b) Events of phagocytosis.

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Phagocytes
• Phagocytosis
2. Cytoplasmic extensions (pseudopods) bind to and engulf particle in vesicle
called phagosome
3. Phagosome fuses with lysosome, forming phagolysosome
4. Phagolysosome is acidified, and lysosomal enzymes digest particles
5. Indigestible and residual waste is exocytosed from phagocyte

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Phagocytosis
1 Phagocyte adheres
to pathogens or debris
(using receptors).
2 Phagocyte forms
pseudopods that
Phagosome
eventually engulf the
(phagocytic
vesicle) particles, forming a
phagosome.
Lysosome

Acid
hydrolase
enzymes

(b) Events of phagocytosis.

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Phagocytosis
1 Phagocyte adheres
to pathogens or debris
(using receptors).
2 Phagocyte forms
pseudopods that
Phagosome
eventually engulf the
(phagocytic
vesicle) particles, forming a
phagosome.
Lysosome
3 Lysosome fuses with
the phagocytic vesicle,
forming a phagolysosome.

Acid
hydrolase
enzymes

(b) Events of phagocytosis.

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Phagocytosis
1 Phagocyte adheres
to pathogens or debris
(using receptors).
2 Phagocyte forms
pseudopods that
Phagosome
eventually engulf the
(phagocytic
vesicle) particles, forming a
phagosome.
Lysosome
3 Lysosome fuses with
the phagocytic vesicle,
forming a phagolysosome.

Acid
hydrolase
enzymes 4 Toxic compounds
and lysosomal enzymes
destroy pathogens.

(b) Events of phagocytosis.

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Phagocytosis
1 Phagocyte adheres
to pathogens or debris
(using receptors).
2 Phagocyte forms
pseudopods that
Phagosome
eventually engulf the
(phagocytic
vesicle) particles, forming a
phagosome.
Lysosome
3 Lysosome fuses with
the phagocytic vesicle,
forming a phagolysosome.

Acid
hydrolase
enzymes 4 Toxic compounds
and lysosomal enzymes
destroy pathogens.

5 Sometimes exocytosis
of the vesicle removes
indigestible and residual
material.

(b) Events of phagocytosis.

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Phagocytes
• Phagocytosis
– Some pathogens are not killed with acidified lysosomal enzymes (e.g., tuberculosis
bacteria)
 Helper T cells trigger macrophage to produce respiratory burst, which kills
pathogens resistant to lysosomal enzymes by:
– Releasing cell-killing free radicals
– Producing oxidizing chemicals (e.g., H2O2)
– Increasing pH and osmolarity of phagolysosome
– Defensins (in neutrophils) also help by piercing membrane of pathogen

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Natural Killer (NK) Cells
• Nonphagocytic, large granular lymphocytes that police blood and lymph
– Can kill cancer and virus-infected cells before adaptive immune system is activated

• Attack cells that lack “self” cell-surface receptors

• Kill by inducing apoptosis in cancer cells and virus-infected cells

• Secrete potent chemicals that enhance inflammatory response

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Inflammation: Tissue Response to Injury

• Inflammation is triggered whenever body tissues are injured

– Injuries can be due to trauma, heat, irritating chemicals, or infections by
microorganisms

• Benefits of inflammation:
– Prevents spread of damaging agents
– Disposes of cell debris and pathogens
– Alerts adaptive immune system
– Sets the stage for repair

• Four cardinal signs of acute inflammation:

1. Redness
2. Heat
3. Swelling
4. Pain
– Sometimes a fifth sign, impairment of function, is seen if movement or use of area
is hampered
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Inflammation: Tissue Response to Injury

• Stages of inflammation
– Inflammatory chemical release
– Vasodilation and increased vascular permeability
– Phagocyte mobilization

• Inflammatory chemical release

– Chemicals are released into ECF by injured tissues or immune cells
 Example: histamine released by mast cells is key inflammatory chemical

• Other inflammatory mediators besides histamine

– Kinins, prostaglandins (PGs), cytokines and if pathogens are involved,
complement
 All cause vasodilation of local arterioles
 All make capillaries leaky
 Many attract phagocytes to area

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Table 21.2 Inflammatory Chemicals

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Inflammation: Tissue Response to Injury
• Vasodilation and increased vascular permeability
– Vasodilation causes hyperemia—congestion with blood—which leads to redness
and heat
– Increased capillary permeability causes
exudate—fluid containing clotting factors and antibodies—to leak into tissue
 Results in local swelling (edema)
 Swelling also pushes on nerve endings, resulting in pain

• Vasodilation and increased vascular permeability

– Pain can also result from release of toxins from bacteria or released prostaglandins
and kinins
– Benefits of edema
 Surge of fluid in tissue sweeps foreign material into lymphatic vessels for
processing in lymph nodes
 Delivers clotting proteins and complement to area
– Clotting factors form fibrin mesh that acts as scaffold for repair
• Mesh also isolates injured area so invaders cannot spread

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Inflammation: Tissue Response to Injury
• Phagocyte mobilization
– Neutrophils flood area first; macrophages follow
– If inflammation is due to pathogens, complement is activated; adaptive immunity
elements arrive

• Steps for phagocyte mobilization

1. Leukocytosis: release of neutrophils from bone
marrow in response to leukocytosis-inducing factors from injured cells
– 2. Margination: endothelial cells of capillaries in inflamed area project cell
adhesion molecules (CAMs) into vessel lumen that grab onto passing neutrophils,
causing them to slow and roll along, clinging to vessel wall
– 3. Diapedesis: neutrophils flatten and squeeze between endothelial cells, moving
into interstitial spaces

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Inflammation: Tissue Response to Injury
• Steps for phagocyte mobilization
4. Chemotaxis: inflammatory chemicals act as
chemotactic agents that promote positive
chemotaxis of neutrophils toward injured area
– As attack continues, monocytes arrive later
 12 hours after leaving bloodstream, they are transformed into macrophages
 These “late-arrivers” replace dying neutrophils and remain for cleanup prior to
repair

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 Innate defenses Internal defenses

Phagocyte
mobilization
Inflammatory
chemicals
diffusing from
the inflamed
site act as
chemotactic
agents.
Capillary wall
Basement
membrane
Endothelium

1 Leukocytosis.
Neutrophils enter
blood from bone
marrow.
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 Innate defenses Internal defenses

Phagocyte
mobilization
Inflammatory
chemicals
diffusing from
the inflamed
site act as
chemotactic
agents.
Capillary wall
Basement
membrane
Endothelium

1 Leukocytosis. 2 Margination.
Neutrophils enter Neutrophils cling
blood from bone to capillary wall.
marrow.
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 Innate defenses Internal defenses

Phagocyte
mobilization
Inflammatory
chemicals
diffusing from
the inflamed
site act as
chemotactic
agents.
Capillary wall
Basement
membrane
Endothelium

1 Leukocytosis. 2 Margination. 3 Diapedesis.

Neutrophils enter Neutrophils cling Neutrophils flatten
blood from bone to capillary wall. and squeeze out of
marrow. capillaries.
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 Innate defenses Internal defenses

Phagocyte
mobilization
Inflammatory
chemicals
diffusing from 4 Chemotaxis.
the inflamed Neutrophils
site act as follow chemical
chemotactic trail.
agents.
Capillary wall
Basement
membrane
Endothelium

1 Leukocytosis. 2 Margination. 3 Diapedesis.

Neutrophils enter Neutrophils cling Neutrophils flatten
blood from bone to capillary wall. and squeeze out of
marrow. capillaries.
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Innate defenses Internal defenses
Events of Acute
Inflammation Initial stimulus
Physiological response
Signs of inflammation
Tissue injury Result

Release of inflammatory chemicals Release of leukocytosis-

(histamine, complement, inducing factors
kinins, prostaglandins, etc.)

Leukocytosis
(increased numbers of white
blood cells in bloodstream)
Arterioles Increased capillary Attract neutrophils,
dilate permeability monocytes, and
Leukocytes migrate to
lymphocytes to
injured area
area (chemotaxis)
Local hyperemia Capillaries Margination
(increased blood leak fluid (leukocytes cling to
flow to area) (exudate formation) capillary walls)

Diapedesis
Leaked protein-rich Leaked clotting proteins (leukocytes pass through
fluid in tissue spaces form interstitial clots capillary walls)
that wall off area to
prevent injury to
surrounding tissue Phagocytosis of pathogens
Heat Redness Pain Swelling and dead tissue cells

Locally increased Possible temporary Temporary fibrin

Pus may form
temperature increases impairment of patch forms
metabolic rate of cells function Scaffolding for repair Area cleared of debris

Healing
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Antimicrobial Proteins
• Antimicrobial proteins enhance innate defense by:
– Attacking microorganisms directly, or
– Hindering microorganisms’ ability to reproduce

• Most important antimicrobial proteins

– Interferons
– Complement proteins

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Antimicrobial Proteins
• Interferons
– Interferons (IFN): family of immune modulating proteins
– Cells infected with viruses can secrete IFNs that “warn” healthy neighboring cells
 IFNs enter neighboring cells, stimulating production of proteins that block viral
reproduction and degrade viral RNA
 IFN type α (alpha) and β (beta) work this way
 IFN-α and IFN-β also activate NK cells
– IFN-γ (gamma, also called immune interferon):
 Is secreted by lymphocytes
 Has widespread immune mobilizing effects
 Activates macrophages
– IFNs activate NK cells and macrophages, so they indirectly fight cancer
– Artificial IFNs are used to treat disorders such as hepatitis C, genital warts, and
multiple sclerosis

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Antimicrobial Proteins
• Complement
– Complement system consists of ~20 blood proteins that circulate in blood in
inactive form
– Includes proteins C1–C9, factors B, D, and P, and regulatory proteins
– Provides major mechanism for destroying foreign substances
– Activation enhances inflammation and also directly destroys bacteria
 Enhances both innate and adaptive defenses
– Complement system can be activated by three different pathways:
1. Classical pathway
– Antibodies first bind to invading organisms and then bind to complement
components, activating them
• Double binding called complement fixation
– Once initial complement proteins are activated,
an activation cascade is triggered

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Antimicrobial Proteins
• Complement
2. Lectin pathway
– Lectins are produced by innate system to recognize foreign invaders
– When lectin is bound to specific sugars on foreign invaders, it can also
bind and activate complement
3. Alternative pathway
– Complement cascade is activated spontaneously when certain
complement factors bind directly to foreign invader
• Lack of inhibitors on microorganism’s surface allows process to
proceed

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Antimicrobial Proteins
• Fever
– Abnormally high body temperature that is systemic response to invading
microorganisms
– Leukocytes and macrophages exposed to foreign substances secrete pyrogens
– Pyrogens act on body’s thermostat in hypothalamus, raising body temperature
– Benefits of moderate fever
 Causes liver and spleen to sequester iron and zinc (needed by
microorganisms)
 Increases metabolic rate, which increases rate
of repair

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Table 21.3 The Second Line of Defense:
Innate Cellular and Chemical Defenses

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Part 2 – Adaptive Defenses
• Adaptive immune system is a specific defensive system that eliminates almost any
pathogen or abnormal cell in body

• Activities
– Amplifies inflammatory response
– Activates complement

• Shortcoming: must be primed by initial exposure to specific foreign substance

– Priming takes time

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Adaptive Defenses
• Characteristics of adaptive immunity
– It is specific: recognizes and targets specific antigens
– It is systemic: not restricted to initial site
– It has memory: mounts an even stronger attack to “known” antigens (second and
subsequent exposures)

• Two main branches of adaptive system

1. Humoral (antibody-mediated) immunity
2. Cellular (cell-mediated) immunity

1. Humoral immunity
– Antibodies, produced by lymphocytes, circulate freely in body fluids
– Bind temporarily to target cell
 Temporarily inactivate
 Mark for destruction by phagocytes or complement
– Humoral immunity has extracellular targets

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Adaptive Defenses
2. Cellular Immunity
– Lymphocytes act against target cell
 Directly—by killing infected cells
 Indirectly—by releasing chemicals that enhance inflammatory response; or
activating other lymphocytes or macrophages
– Cellular immunity has cellular targets

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21.3 Antigens
• Antigens: substances that can mobilize adaptive defenses and provoke an immune
response

• Targets of all adaptive immune responses

• Most are large, complex molecules not normally found in body (non-self)

• Characteristics of antigens
– Can be a complete antigen or hapten (incomplete)
– Contain antigenic determinants
– Can be a self-antigen

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Complete Antigens and Haptens
• Antigens can be complete or incomplete

• Complete antigens have two important functional properties:

– Immunogenicity: ability to stimulate proliferation of specific lymphocytes
– Reactivity: ability to react with activated lymphocytes and antibodies released by
immunogenic reactions
– Examples: foreign proteins, polysaccharides, lipids, and nucleic acids; seen on
many foreign invaders such as pollen and microorganisms

• Incomplete antigens, also called haptens, involve molecules too small to be seen so
are not immunogenic by themselves
– Examples: small peptides, nucleotides, some hormones

• May become immunogenic if hapten attaches to body’s own proteins

– Combination of protein and hapten is then seen as foreign

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Complete Antigens and Haptens
• Causes immune system to mount attack that is harmful to person because it attacks
self-proteins as well as hapten

• Examples: poison ivy, animal dander, detergents, and cosmetics

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Antigenic Determinants
• Antigenic determinants: parts of antigen that antibodies or lymphocyte receptors bind
to

• Most naturally occurring antigens have numerous antigenic determinants that:

– Mobilize several different lymphocyte populations
– Form different kinds of antibodies against them

• Large, chemically simple molecules (such as plastics) have little or no immunogenicity

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Most Antigens Have Several Different
Antigenic Determinants

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Self-Antigens: MHC Proteins
• Self-antigens: all cells are covered with variety of proteins located on surface that are
not antigenic to self, but may be antigenic to others in transfusions or grafts
• One set of important self-proteins are group of glycoproteins called MHC proteins
– Coded by genes of major histocompatibility complex (MHC) and unique to each
individual
– Contain groove that can hold piece of self-antigen or foreign antigen
 T lymphocytes can recognize only antigens that are presented on MHC
proteins

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21.4 Lymphocytes and Antigen-Presenting
Cells
• Adaptive immune system involves three crucial types of cells
– Two types of lymphocytes
 B lymphocytes (B cells)—humoral immunity
 T lymphocytes (T cells)—cellular immunity
– Antigen-presenting cells (APCs)
 Do not respond to specific antigens
 Play essential auxiliary roles in immunity

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Lymphocytes
• Lymphocyte development, maturation, and activation
– T and B lymphocytes share common development and steps in their life cycles
– Five general steps:
1. Origin: both lymphocytes originate in red bone marrow
2. Maturation
– Lymphocytes are “educated” in a 2-3 day process and mature in primary
lymphoid organs (B cells in bone marrow and thymus)
– Lymphocytes are educated for 2 reasons:
• 1. Immunocompetence: lymphocytes must be able to recognize
only 1 specific antigen
• B or T cells display only one unique type of antigen receptor on
surface when mature so bind only one specific antigen
• 2. Self-tolerance: lymphocytes must be unresponsive to own
antigens

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Lymphocytes
3. Seeding secondary lymphoid organs and circulation
– Immunocompetent B and T cells not yet exposed to antigen are called
naive
– Exported from primary lymphoid organs (bone marrow and thymus) to
“seed” (colonize) secondary lymphoid organs (lymph nodes, spleen,
etc.)
• Increases chance of encounter with antigen
4. Antigen encounter and activation
– Naive lymphocyte’s first encounter with antigen triggers lymphocyte to
develop further
– Lymphocyte is selected to differentiate into active cell by binding to its
specific antigen
• Referred to as clonal selection
– If correct signals are present, lymphocyte will complete its differentiation
into active cell

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Lymphocytes
5. Proliferation and differentiation
– Once selected and activated, lymphocyte proliferates
• Forms army of exact copies of itself
• Referred to as clones
– Most clones become effector cells that fight infections
– A few remain as memory cells
• Able to respond to same antigen more quickly second time it is
encountered
– B and T memory cells and effector T cells circulate continuously

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Lymphocyte Development, Maturation,
and Activation

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Lymphocytes
• Antigen receptor diversity
– Genes, not antigens, determine which foreign substances the immune system will
recognize
 Variety of immune cell receptors are result of acquired genetic knowledge of
microbes
– ∼25,000 different genes codes for up to a billion different types of lymphocyte
antigen receptors
 Huge variety of receptors: gene segments are shuffled around, resulting in
many combinations

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Lymphocytes
• Lymphocyte Education during Maturation
– T cells mature in thymus under negative and positive selection pressures
(“tests”)
• Positive selection process
• Selects T cells capable of recognizing self-MHC proteins (MHC
restriction); those that can’t are destroyed by apoptosis
• Negative selection
• Prompts apoptosis of T cells that bind to self-antigens
displayed by self-MHC
• Process, called clonal deletion, ensures self-tolerance

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T Cell Education in the Thymus

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Antigen-Presenting Cells (APCs)
• Engulf antigens and present fragments of antigens to T cells for recognition

• Major types
– Dendritic cells
– Macrophages
– B cells

• Dendritic cells
– Found in connective tissues and epidermis
 Act as mobile sentinels of boundary tissues
– Phagocytize pathogens that enter tissues, then enter lymphatics to present
antigens to T cells in lymph node
 Most effective antigen presenter known
 Key link between innate and adaptive immunity

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Dendritic Cell

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Antigen-Presenting Cells (APCs)
• Macrophages
– Widely distributed in connective tissues and lymphoid organs
– Present antigens to T cells, which not only activates T cell, but also further
activates macrophage
 Activated macrophage becomes voracious phagocytic killer
 Also trigger powerful inflammatory responses and recruit additional defenses

• B lymphocytes
– Do not activate naive T cells
– Present antigens to helper T cell to assist their own activation

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Table 21.4 Overview of B and T
Lymphocytes

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21.5 Humoral Immune Response
• When B cell encounters target antigen, it provokes humoral immune response
– Antibodies specific for that particular antigen are then produced

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Activation and Differentiation of B Cells
• B cells are activated when antigens bind to surface receptors, cross-linking them

• Triggers receptor-mediated endocytosis of cross-linked antigen-receptor complexes

(clonal selection), leading to proliferation and differentiation of B cell into effector cells

• Most clone cells become plasma cells, antibody-secreting effector cells

– Secrete specific antibodies at rate of 2000 molecules per second for 4 to 5 days,
then die
– Antibodies circulate in blood or lymph, binding to free antigens, marking them for
destruction by innate or other adaptive mechanisms

• Clone cells that do not become plasma cells become memory cells
– Provide immunological memory
– Mount an immediate response to future exposures to same antigen

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Clonal selection of a B cell

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Primary and Secondary Humoral Responses

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Active and Passive Humoral Immunity
• Active humoral immunity occurs when B cells encounter antigens and produce specific
antibodies against them
– Two types of active humoral immunity
1. Naturally acquired: formed in response to
actual bacterial or viral infection
2. Artificially acquired: formed in response to
vaccine of dead or attenuated pathogens
– Provide antigenic determinants that are immunogenic and reactive
– Spare us symptoms of primary response

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Active and Passive Humoral Immunity
• Passive humoral immunity occurs when ready-made antibodies are introduced into
body
– B cells are not challenged by antigens; Immunological memory does not occur
– Protection ends when antibodies degrade
– Two types of passive humoral immunity
1. Naturally acquired: antibodies delivered to fetus via placenta or to infant
through milk
2. Artificially acquired: injection of serum, such as gamma globulin
– Protection immediate but ends when antibodies naturally degrade in body

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Active and passive humoral immunity

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Antibodies
• Antibodies—also called Immunoglobulins (Igs)—are proteins secreted by plasma cells
– Make up gamma globulin portion of blood

• Capable of binding specifically with antigen detected by B cells

• Grouped into one of five Ig classes

• Basic antibody structure

– Overall T- or Y-shaped antibody monomer consists of four looping polypeptide
chains linked by disulfide bonds
– Four chains consist of:
 Two identical heavy (H) chains with hinge region at “middles”
 Two identical light (L) chains
– Variable (V) regions at one end of each arm combine to form two identical antigen-
binding sites

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Antibody Structure

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21.6 Cellular Immune Response
• T cells provide defense against intracellular antigens
– Example: cells infected with viruses or bacteria, cancerous or abnormal cells, foreign
(transplanted) cells

• Some T cells directly kill cells; others release chemicals that regulate immune response

• T cells are more complex than B cells both in classification and function

• Two populations of T cells are based on which cell differentiation glycoprotein receptors
are displayed on their surface
– CD4 cells usually become helper T cells (TH) that can activate B cells, other T cells,
and macrophages; direct adaptive immune response
• Some become regulatory T cells, which moderate immune response
– Can also become memory T cells

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21.6 Cellular Immune Response
– CD8 cells become cytotoxic T cells (TC) that are capable of destroying cells
harboring foreign antigens
 Also become memory T cells

• Helper, cytotoxic, and regulatory T cells are activated T cells

• Naive T cells are simply termed CD4 or CD8 cells

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Major Types of T Cells

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MHC Proteins and Antigen Presentation
• T cells respond only to processed fragments of antigens displayed on surfaces of cells by
major histocompatibility complex (MHC) proteins

• Antigen presentation is vital for activation of naive T cells and normal functioning of
effector T cells

• Two classes of MHC proteins:

– Class I MHC proteins: displayed by all cells except RBCs
– Class II MHC proteins: displayed by APCs (dendritic cells, macrophages, and B
cells)

• Both types are synthesized in ER and bind to peptide fragments

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Activation and Differentiation of T Cells
• T cells can be activated only when antigen is presented to them

• Activation is a two-step process

1. Antigen binding
2. Co-stimulation

• Both occur on surface of same APC

• Both are required for clonal selection of T cell

- Step 1. Antigen binding:
– T cell antigen receptors (TCRs) bind to antigen-MHC complex on APC surface
– TCR must perform double recognition by recognizing both MHC and foreign antigen
it displays
– Binding of TCR to complex triggers multiple intracellular signaling pathways that start
T cell activation
– Other T cell surface proteins are involved in T cell activation (e.g., CD4 and CD8 help
maintain coupling during antigen recognition)

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Activation and Differentiation of T Cells
• - Step 2. Co-stimulation:
– Complete T cell activation requires T cell to also bind to one or more co-stimulatory
signals on surface of APC
– Without co-stimulation, anergy occurs, in which T cells:
 Become tolerant to that antigen
 Are unable to divide
 Do not secrete cytokines
– Two-step process is a safeguard against unwanted T cell activation

• Proliferation and differentiation

– T cells that are activated enlarge and proliferate in response to cytokines
 Differentiate and perform functions according to their T cell class
– Primary T cell response peaks within a week

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Activation and Differentiation of T Cells
• Proliferation and differentiation
– T cell apoptosis occurs between days 7 and 30
 Activated T cells are a hazard because they produce large amounts of
inflammatory cytokines
 Could result in hyperplasia or cancer if not cleared from system
– Memory T cells remain and mediate secondary responses

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Clonal selection of T cells involves simultaneous
recognition of self and nonself

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Activation and Differentiation of T Cells
• Cytokines
– Chemical messengers of immune system
– Mediate cell development, differentiation, and responses in immune system
– Include interferons and interleukins
 Interleukin 1 (IL-1) is released by macrophages and stimulates T cells to:
– Release interleukin 2 (IL-2)
– Synthesize more IL-2 receptors
– IL-2 is a key growth factor, acting on same cells that release it and other T cells
 Encourages activated T cells to divide rapidly
– Other cytokines amplify and regulate innate and adaptive responses
 Example: gamma interferon—enhances killing power of macrophages

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Roles of Specific Effector T Cells
• Helper T (TH) cells
– Play central role in adaptive immune response
– Activate both humoral and cellular arms
– Once primed by APC presentation of antigen, helper T cells:
 Help activate B cells and other T cells
 Induce T and B cell proliferation
 Secrete cytokines that recruit other immune cells

• Without TH, there is no immune response

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Roles of Specific Effector T Cells
– Activation of B cells
 Helper T cells interact directly with B cells displaying antigen fragments bound
to MHC II receptors
 Stimulate B cells to divide more rapidly and begin antibody formation
 B cells may be activated without TH cells by binding to T cell–independent
antigens
– Response is weak and short-lived
 Most antigens are T cell–dependent antigens that require TH co-stimulation
to activate B cells

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Roles of Specific Effector T Cells

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Roles of Specific Effector T Cells
– Activation of CD8 cells
 CD8 cells require TH cell to become activated into destructive cytotoxic T cells
 Cause dendritic cells to express co-stimulatory molecules required for CD8 cell
activation
– Amplification of innate defenses
 Amplify responses of innate immune system
 Activate macrophages, leading to more potent killers
 Mobilize lymphocytes and macrophages and attract other types of WBCs
– Subsets of TH cells
 TH1—mediates most aspects of cellular immunity
 TH2—defends against parasitic worms, mobilizes eosinophils; activates
responses dependent on humoral immunity; promotes allergies
 TH17—links adaptive and innate immunity by releasing IL-17
– May play role in autoimmune disease

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Roles of Specific Effector T Cells
• Cytotoxic T (TC) cells
– Directly attack and kill other cells
– Activated TC cells circulate in blood and lymph and lymphoid organs in search of
body cells displaying antigen they recognize
– Activated TC cells target:
 Virus-infected cells
 Cells with intracellular bacteria or parasites
 Cancer cells
 Foreign cells (transfusions or transplants)
– Cytotoxic T cells deliver lethal hit using two mechanisms
1. TC cell releases perforins and granzymes by exocytosis
– Perforins create pores through which granzymes enter target cell
– Granzymes stimulate apoptosis
2. TC cell binds specific membrane receptor on target cell and stimulates
apoptosis

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Cytotoxic T cells attack infected and
cancerous cells

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Cytotoxic T cells attack infected and
cancerous cells

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Roles of Specific Effector T Cells
• Cytotoxic T (TC) cells
– Natural killer cells recognize other signs of abnormality that cytotoxic T cells do not
look for, such as:
 Cells that lack class I MHC proteins
 Antibodies coating target cell
 Different surface markers seen on stressed cells
– NK cells use same key mechanisms as TC cells for killing their target cells
– Immune surveillance: NK and TC cells prowl body looking for markers they each
recognize

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Table 21.8 Cells and Molecules of the
Adaptive Immune Response

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 Homework

 Organ Transplants and Prevention of Rejection (Slide 86)

 Immunodeficiencies (Slides 87 - 89)

 Autoimmune Diseases (Slides 90 - 92)

 Hypersensitivities (Slides 93 - 97)

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Organ Transplants and Prevention of
Rejection
• Most common type of organ transplant is an allograft: transplant from same species

• Success depends on similarity of tissues

– ABO, other blood antigens, and MHC antigens are matched as closely as possible

• After surgery
– Patient treated with immunosuppressive therapy
– Many of these therapies have severe side effects

• When patient’s immune system is suppressed, it:

– Cannot protect body from foreign agents such as bacterial and viral infections
 Leading cause of death among transplant recipients
– Best circumstances: rejection after 10 years in 50% of patients

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Immunodeficiencies
• Immunodeficiency: congenital or acquired conditions that impair function or production
of immune cells or molecules

• Severe combined immunodeficiency (SCID) syndrome: genetic defect with marked

deficit in B and T cells
– Defective adenosine deaminase (ADA) enzyme allows accumulation of metabolites
lethal to T cells; fatal if untreated
– Treatment: bone marrow transplants

• Hodgkin’s disease is an acquired immunodeficiency that causes cancer of B cells, which

depresses lymph node cells and thus leads to immunodeficiency

• Acquired immune deficiency syndrome (AIDS)

– Human immunodeficiency virus (HIV) cripples immune system by interfering with
activity of helper T cells
– Characterized by severe weight loss, night sweats, and swollen lymph nodes
– Opportunistic infections occur, including Pneumocystis pneumonia and Kaposi’s
sarcoma

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Immunodeficiencies
• HIV is transmitted via body fluids: blood, semen, and vaginal secretions

• HIV can enter the body via:

– Blood transfusions; blood-contaminated needles; sexual intercourse and oral sex;
mother to fetus

• HIV destroys TH cells, thereby depressing cellular immunity

• HIV multiplies in lymph nodes throughout asymptomatic period, ∼10 years if untreated

• Symptoms begin when immune system collapses

• Virus also can invade brain, leading to dementia

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Immunodeficiencies
• HIV-coated glycoprotein complex attaches to CD4 receptors

• HIV enters cell and uses reverse transcriptase to produce DNA from its viral RNA
– HIV reverse transcriptase is prone to frequent errors, leading to high mutation rate
and resistance to drugs

• The DNA copy (a provirus) directs host cell to make viral RNA and proteins, enabling
virus to reproduce

• No cure for AIDS found; four major classes of antivirals in combination help but can fail as
virus becomes resistant

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Autoimmune Diseases
• Autoimmune disease results when immune system loses ability to distinguish self from
foreign

• Autoimmunity: production of autoantibodies and sensitized TC cells that destroys body

tissues

• Examples
– Rheumatoid arthritis: destroys joints
– Myasthenia gravis: impairs nerve-muscle connections
– Multiple sclerosis: destroys white matter myelin
– Graves’ disease: causes hyperthyroidism
– Type 1 diabetes mellitus: destroys pancreatic cells
– Systemic lupus erythematosus (SLE): affects multiple organs
– Glomerulonephritis: damages kidney

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Autoimmune Diseases
• Treatment of autoimmune diseases
– Suppress entire immune system
• Anti-inflammatory drugs, such as corticosteroids
• Blocking cytokine action
• Blocking co-stimulatory molecules
– Research
• Activating regulatory T cells; inducing self-tolerance using vaccines; directing
antibodies against self-reactive immune cells

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Autoimmune Diseases
• Failure of self-tolerance
– Autoimmunity may be caused by weakly self-reactive lymphocytes that are activated
by:
 Foreign antigens that resemble self-antigens
– Antibodies against foreign antigen may cross-react with self-antigen
 Appearance of new self-antigens, generated by:
– Gene mutations
– Changes in self-antigens by hapten attachment or infectious damage
– Release of novel self-antigens by trauma to barrier

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Hypersensitivities
• Hypersensitivities: immune responses to perceived (otherwise harmless) threat that
cause tissue damage

• Different types are distinguished by:

1. Their time course
2. Whether antibodies or T cells are involved

• Antibodies cause immediate and subacute hypersensitivities

• T cells cause delayed hypersensitivity

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Hypersensitivities
• Immediate hypersensitivity
– Also called acute (type I) hypersensitivities (allergies); begin in seconds after
contact with allergen, antigen that causes allergic reaction
– Initial contact with allergen is asymptomatic but sensitizes person
– Activated IgE against antigen binds to mast cells and basophils
– Later encounter with same allergen causes flood of histamine release from IgEs,
resulting in induced inflammatory response

• Immediate hypersensitivity
– Histamines causes vasodilation and leakiness of the vessels, leading to symptoms of
runny nose, itchy hives, or watery eyes
 Asthma can occur if allergen is inhaled
 Antihistamines are needed to control
– Allergic reactions can be local or systemic
 Local reaction involves mast cells of skin or respiratory or gastrointestinal
mucosa

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Hypersensitivities
• Immediate hypersensitivity
– Systemic response is anaphylactic shock
 Usually seen with injected allergens (example: bee sting)
 Bronchioles constrict, making breathing difficult
 Vasodilation results in low blood volume, which could cause circulatory
collapse
 Treatment: epinephrine

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Hypersensitivities
• Subacute hypersensitivities
– Immune complex (type III) hypersensitivity
 Antigens widely distributed in body or blood
 Insoluble antigen-antibody complexes form
 Complexes cannot be cleared from particular area of body
 Intense inflammation, local cell lysis, and cell killing by neutrophils
 Example: systemic lupus erythematosus (SLE)

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Hypersensitivities
• Delayed hypersensitivities (type IV)
– Slow onset (1–3 days)
– Mechanism depends on helper T cells
– Cytokine-activated macrophages and cytotoxic T cells cause damage
– Example: allergic contact dermatitis (e.g., poison ivy)
– Agents act as haptens
– TB skin test depends on this reaction

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