Download detailed lecture outline

DETAILED LECTURE OUTLINE
Fundamentals of Anatomy and Physiology, 7th edition, ©2006 by Frederic H. Martini
Prepared by Professor Albia Dugger, Miami-Dade College, Miami, Florida
Please note:
 References to textbook headings, figures and tables appear in italics.
 “100 Keys” are designated by Key
 Important vocabulary terms are underlined.
Chapter 22: The Lymphatic System
I. An Overview of the Lymphatic System and Immunity, p. 764
Objective:
1. Explain the difference between nonspecific and specific defense, and the role of
lymphocytes in the immune response.

Microscopic organisms in the environment, called pathogens (including viruses,
bacteria, fungi and parasites) are responsible for many diseases of the human
body. Each pathogen attacks the body in a specific way.

The lymphatic system protects us against disease. Lymphatic system cells
(lymphocytes) respond to environmental pathogens, toxins, and abnormal body
cells (such as cancers).

Lymphocytes are part of the body’s specific defenses or immune response that
identifies and attacks a specific pathogen, and develops immunity (the ability to
resist infection and disease) to that specific pathogen.

The body also has several non-specific defenses that block or attack any potential
infectious organism, but cannot distinguish one type of attack from another.

All cells and tissues involved in the production of immunity, not just the
lymphatic system, are part of our immune system.
II. Organization of the Lymphatic System, p. 764
Objectives:
1. Identify the major components of the lymphatic system and explain their
functions.
2. Discuss the importance of lymphocytes and describe their distribution in the body.
3. Describe the structure of lymphoid tissues and organs and explain their functions.
Figure 22-1

The lymphatic system has 4 main parts:
1. lymph: a fluid similar to plasma, but without the plasma proteins.
2. lymphatic vessels (lymphatics): the network that carries lymph from
peripheral tissues to the venous system.
3. lymphoid tissues and lymphoid organs: found throughout the body.
4. lymphocytes, phagocytes and other immune system cells.
Functions of the Lymphatic System, p. 764

The main function of the lymphatic system is to produce, maintain and distribute
lymphocytes.

Lymphocytes are produced and stored in lymphoid tissues (such as the tonsils),
and lymphoid organs (such as the spleen and thymus), and are also produced in
red bone marrow. To function, the lymphocytes must detect problems and travel
to the site of injury or infection.

Lymphocytes circulate in the blood, enter the interstitial fluid through capillaries,
and return to the blood stream through lymphatic vessels. The circulation of fluids
from blood plasma to lymph and back to the venous system also transports other
immune system cells (such as macrophages and microphages) as well as
hormones, nutrients and waste products.
Lymphatic Vessels, p. 765

The vessels that carry lymph are lymphatic vessels. The lymphatic system begins
with the smallest vessels: the lymphatic capillaries (terminal lymphatics).

Lymphatic capillaries differ from blood capillaries in 4 ways:
1. They start as pockets rather than tubes.
2. They have larger diameters.
3. They have thinner walls.
4. In section, they are flat or irregular.
Figure 22-2
 The endothelial cells of lymphatic capillaries are not tightly bound together, but
they overlap. The overlap acts as a one-way valve that allows fluids, solutes and
larger materials such as viruses, bacteria and debris to enter the vessel, but
prevents them from returning to the intercellular space.

Special lymphatic capillaries (lacteals) in the small intestine transport lipids from
the digestive tract.
Figure 22-3
 From the lymphatic capillaries, lymph flows into a system of larger lymphatic
vessels similar to veins, containing many one-way valves that give lymph vessels
a lumpy, beaded appearance. Lymphatic vessels often travel toward the thoracic
cavity in association with veins, but are generally smaller.
Figure 22-4
 From the lymphatic capillaries, the lymphatic system is divided into the
superficial lymphatics and deep lymphatics. The superficial lymphatics are
located in the skin, mucus membranes, and serous membranes lining body
cavities. The deep lymphatics are larger vessels that accompany deep arteries and
veins.

The superficial lymphatics and deep lymphatics join to form the large lymphatic
trunks that empty into 2 major collecting vessels: the thoracic duct and the right
lymphatic duct.

The base of the thoracic duct expands into a chamber called the cisterna chyli,
which receives lymph from the right and left lumbar trunks and the intestinal
trunk. The inferior segment of the thoracic duct collects lymph from the left
bronchiomediastinal trunk, the left subclavian trunk, and the left jugular trunk,
then empties into the left subclavian vein.

The right jugular trunk, right subclavian trunk, and right bronchiomediastinal
trunk merge to form the right lymphatic duct, which empties into the right
subclavian vein.

Blockage of lymph drainage from a limb produces lymphedema, which causes
severe swelling and interferes with the proper functioning of the immune system.
Lymphocytes, p. 768

Lymphocytes make up 20-30% of circulating leukocytes; but most lymphocytes
are stored, not circulating.

There are 3 classes of circulating lymphocytes:
1. T cells (thymus-dependent)
2. B cells (bone-marrow derived)
3. NK cells (natural killer cells)

T cells make up 80% of circulating lymphocytes. There are 3 main types of T
cells:
1. Cytotoxic T cells:
- attack cells infected by viruses
- produce cell-mediated immunity
2. Helper T cells:
- stimulate the function of T cells and B cells
3. Suppressor T cells:
-
inhibit the function of T cells and B cells

Helper and suppressor T cells are regulatory T cells, because they control the
sensitivity of the immune response. Other types of T cells include inflammatory T
cells and suppressor/inducer T cells.

B cells make up 10-15% of circulating lymphocytes. B cells differentiate into
plasma cells, which produce and secrete antibodies (immunoglobin proteins).

Immunoglobin proteins bind to targets called antigens, which are the identifying
parts of any pathogen or foreign compound. The binding of a specific antibody to
its specific antigen starts a chain of events called antibody-mediated immunity
which destroys the target compound or organism.

NK cells or large granular lymphocytes make up 5-10% of circulating
lymphocytes. NK cells are responsible for immunological surveillance; attacking
foreign cells, virus-infected cells, and cancer cells.

Different tissues have different numbers and proportions of T cells and B cells.
All lymphocytes wander through tissues, entering blood vessels or lymphatic
vessels for transport.

Lymphocytes can survive for many years. Normal lymphocyte populations are
maintained by production in the bone marrow and lymphatic tissues.
Figure 22-5
 Lymphocyte production (lymphopoiesis) involves bone marrow, thymus, and
peripheral lymphoid tissues.

Hemocytoblasts in bone marrow divide to produce 2 types of lymphoid stem
cells.

One group of lymphoid stem cells remains in the bone marrow and produces B
cells and natural killer cells. B cells differentiate through contact with the
hormone interleukin-7 (a cytokine produced by stromal cells in the bone marrow).

The other group of lymphoid stem cells migrates to the thymus and produces T
cells in an environment isolated by the blood-thymus barrier. Exposure to several
thymic hormones differentiates the various types of T cells.

T cells and B cells migrate throughout the body to defend peripheral tissues. They
retain their ability to divide, which is essential to immune system function.
Lymphoid Tissues, p. 769
Figure 22-6

Lymphoid tissues are connective tissues dominated by lymphocytes. A lymphoid
nodule is areolar tissue with densely packed lymphocytes. Each nodule has
germinal center which contains dividing lymphocytes.

Lymphoid nodules are found in lymph nodes, the spleen, the respiratory tract
(tonsils), and along digestive and urinary tracts.

The lymphoid tissue associated with the digestive system is the mucosaassociated lymphoid tissue (MALT). Aggregated lymphoid nodules are clustered
deep to the epithelial lining of the intestine. The appendix also contains a mass of
fused lymphoid nodules.

The tonsils are located in the wall of the pharynx. The 5 tonsils are:
- the left and right palatine tonsils
- the pharyngeal tonsil (adenoid)
- a pair of lingual tonsils
Lymphoid Organs, p. 770

The lymphoid organs include the lymph nodes, the thymus and the spleen. A
fibrous connective-tissue capsule separates lymphoid organs from surrounding
tissues.
- Lymph Nodes
Figure 22-7
 Lymph nodes range from 1 mm to 25 mm in diameter. Bundles of collagen fibers
(trabeculae) extend from the capsule into the interior of the lymph node. Blood
vessels and nerves reach the lymph node at the hilus. Afferent lymphatic vessels
carry lymph from peripheral tissues to the lymph node. Efferent lymphatics leave
the lymph node at the hilus and carry lymph to the venous circulation.

Lymph from the afferent lymphatics flows through the lymph node in a network
of sinuses:
- the subcapsular sinus contains macrophages and dendritic cells (which
help initiate the immune response)
- the outer cortex contains B cells within germinal centers
- the deep cortex is dominated by T cells
- the core (medulla) contains B cells and plasma cells organized into
medullary cords
- lymph then flows into the hilus and efferent lymphatics

A lymph node is a filter that purifies the lymph before it is returned to the venous
circulation. Debris, pathogens, and 99% of the antigens are removed.

The extracted antigens are “presented” to lymphocytes, or attached to dendritic
cells to stimulate lymphocyte activity. Antigen presentation is the first step in the
immune response.

Lymphoid tissues and lymph nodes are distributed to monitor peripheral
infections and deal with them before they reach the vital organs of the trunk.
Large lymph nodes at the groin and base of the neck are often called lymph
glands. Lymph nodes associated with the gut, trachea, lungs and thoracic duct
protect against pathogens within the digestive and respiratory systems.

Lymph glands swell in response to inflammation. Chronic or excessive
enlargement (lymphadenopathy) may indicate infections, endocrine disorders or
cancer.
- The Thymus
Figure 22-8
 The thymus, located in the mediastinum, deteriorates after puberty, diminishing
the effectiveness of the early immune system. The thymus is divided into 2
thymic lobes. Septa divide the lobes into smaller lobules.

Each lobule is made up of a dense outer cortex, and a pale central medulla.
Lymphocytes in the cortex divide, and the T cells migrate into the medulla.
Mature T cells leave the thymus by the medullary blood vessels.

Lymphocytes in the cortex are surrounded by reticular epithelial cells which
maintain the blood-thymus barrier and secrete the thymic hormones that stimulate
stem cell divisions and T cell differentiation.

In the medulla, reticular epithelial cells form concentric layers known as
Hassall’s corpuscles (function unknown). The medulla has no blood-thymus
barrier; T cells can enter or leave the bloodstream.

The thymus produces several hormones (thymosins) that promote the
development of lymphocytes.
- The Spleen
Figure 22-9
 The spleen contains a large collection of lymphoid tissues. The main functions of
the spleen are:
1. the removal of abnormal blood cells and other blood components by
phagocytosis
2. the storage of iron recycled from red blood cells
3. the initiation of immune responses by B cells and T cells in response to
antigens in circulating blood

The spleen is attached to the border of the stomach by the gastrosplenic ligament.
It is also in contact with the diaphragm and the left kidney. The splenic veins and
arteries, and lymphatic vessels, communicate with the spleen at the hilus.

Inside its fibrous capsule, the spleen is made up of red pulp, which contains large
numbers of red blood cells, and white pulp, which resembles lymphoid nodules.

A network of trabecular arteries within the spleen branch and radiate toward the
capsule. The finer branches are surrounded by white pulp. The capillaries
discharge red blood cells into the red pulp.

Red pulp contains the elements of circulating blood, plus fixed and free
macrophages. Blood passes through a network of reticular fibers then enters large
sinusoids (also lined by macrophages), which finally empty into the trabecular
veins.

During this circulation, phagocytes and other lymphocytes identify and attack
damaged or infected cells in the blood.

The spleen is a very fragile organ. The surgery to remove a ruptured spleen is a
called a splenectomy.
The Lymphatic System and Body Defenses, p. 775

The body’s defense mechanisms provide resistance to fight infection, illness and
disease. There are 2 general categories of defenses:
1. Nonspecific defenses work the same against any type of invading agent. The 7
types of nonspecific resistance are:
- physical barriers
- phagocytic cells
- immunological surveillance
- interferons
- complement
- inflammation
- fever
2. Specific defenses protect against specific pathogens. Specific resistance or
immunity is developed after exposure to environmental hazards. Specific defenses
depend on the activities of lymphocytes.

Nonspecific and specific defenses operate together to provide resistance to
infection and disease.
III. Nonspecific Defenses, p. 775
Objectives:
1. List the body’s nonspecific defenses and explain the function of each.
2. Describe the components and mechanisms of each nonspecific defense.
Figure 22-10
 The 7 categories of nonspecific defenses block pathogens or limit their spread.
Physical Barriers, p. 775

Physical barriers keep hazardous materials outside the body.

Physical barriers include:
- the outer layer of skin
- hair
- epithelial layers of internal passageways
- secretions that flush away materials (sweat glands, mucus, urine)
- secretions that kill or inhibit microorganisms (enzymes, antibodies and
stomach acid)
Phagocytes, p. 777

Phagocytes attack and remove dangerous microorganisms. There are 2 classes of
phagocytes:
- microphages (neutrophils and eosinophils)
- macrophages (large phagocytic cells derived from monocytes)

Microphages leave the bloodstream and enter peripheral tissues to fight
infections.

Macrophages are distributed throughout the body, making up the monocytemacrophage system or reticuloendothelial system. Activated macrophages
respond to pathogens in several ways:
1. Engulf the pathogen and destroy it with lysosomal enzymes.
2. Bind to the pathogen so that other cells can destroy it.
3. Destroy the pathogen by releasing toxic chemicals into the interstitial
fluid.

Macrophages are divided into 2 types: fixed macrophages and free macrophages.

Fixed macrophages (histiocytes) stay in specific tissues or organs, such as the
dermis and bone marrow. Special histiocytes include:
- microglia are found in the central nervous system
- Kupffer cells are found in the liver sinusoids

Free macrophages travel through the body in the blood stream. Special free
macrophages include:

alveolar macrophages or phagocytic dust cells
Free macrophages and microphages share several functional characteristics:
1. They move through capillary walls (emigration).
2. They are attracted or repelled by chemicals in surrounding fluids
(chemotaxis).
3. Phagocytosis begins when the phagocyte attaches to the target (adhesion),
and surrounds it with a vesicle.
Immunological Surveillance, p. 778
Figure 22-11
 The constant monitoring of normal tissues by natural killer cells (NK cells) is
called immunological surveillance.

NK cells identify cells that have components not found on normal cells (antigens)
sticking out of their cell membranes, and attach to the abnormal cell. NK cells are
not selective about their targets; they will attack any abnormal cells, anywhere in
the body.

The Golgi apparatus in the attached NK cell forms vesicles full of perforin, which
migrate to the abnormal cell and perforate (lyse) it.

NK cells attack cancer cells and cells infected with viruses.

Cancer cells that have tumor specific antigens are identified as abnormal by NK
cells. Some cancer cells avoid detection or resist NK cells (immunological
escape).

Cells that are infected with viruses present abnormal proteins on their outer
membranes, which allow NK cells to identify and destroy them.
Interferons, p. 779

Interferons are proteins released by activated lymphocytes and macrophages
which trigger the production of antiviral proteins in normal cells. Antiviral
proteins do not kill viruses, but block their replication in the cell.

There are 3 types of interferons:
1. alpha interferons, produced by leukocytes, stimulate NK cells
2. beta interferons, secreted by fibroblasts, slow inflammation
3. gamma interferons, secreted by T cells and NK cells, stimulate
macrophage activity

Interferons are cytokines: chemical messengers released by tissue cells to
coordinate local activities, or that act as hormones to affect tissues throughout the
body.
Complement, p. 779
Figure 22-12
 Plasma contains 11 special complement (C) proteins that form the complement
system (a system that complements the action of antibodies).

Complements work together in cascades similar to those in the clotting system.
There are 2 pathways that can activate the complement system:
1. the classical pathway:
- the fast method
- C1 binds to an antibody molecule already attached to an antigen
(bacterium)
- bound protein acts as an enzyme that catalyzes a chain reaction
2. the alternative pathway
- the slow method
3. exposed to an antigen, factor P (properdin), factor B and factor D interact
in plasma

Both pathways end with the conversion of an inactive complement protein (C3) to
the active form (C3b).

Complement activation has several effects:
1. Stimulation of inflammation
2. Attraction of phagocytes
3. Enhancement of phagocytosis:
- Opsonization: complements working with antibodies called
opsonins
4. Destruction of target cell membranes:
- 5 complement proteins join to form a membrane attack complex
(MAC)
Inflammation, p. 781

Inflammation (the inflammatory response) is a localized response that causes
certain cardinal signs and symptoms:
- swelling (tumor)
- redness (rubor)
- heat (calor)
- and pain (dolor)

Any stimulus that kills cells or injures tissue can trigger inflammation.

The effects of inflammation include:
1. Temporary repair and barrier against pathogens.
2. Retards spread of pathogens into surrounding areas.
3. Mobilization of local and systemic defenses
4. Facilitation of repairs (regeneration)
Figure 22-13
 Inflammation and tissue repair occur in several steps:
- When tissue is damaged, injured cells release prostaglandins, proteins and
potassium ions that change the interstitial environment and stimulate mast
cells.
- Mast cells release histamine, which increases capillary permeability, and
heparin, which inhibits clotting.
- Increased blood flow raises the local temperature, causing the area to
swell, redden and become painful.
- A blood clot forms around the damaged area, isolating it.
- Complements break down bacteria and attract phagocytes.
- Activated neutrophils attack debris and bacteria.
- Phagocytes and foreign proteins activate the body’s specific defense
system.
- Macrophages clean up pathogens and cell debris.
- Fibroblasts form scar tissue.

Local tissue destruction in the area of the injury is called necrosis. The mixture of
debris and necrotic tissue is called pus. Pus accumulated in an enclosed space is
an abscess.
Fever, p. 782

Fever is a maintained body temperature above 37.2 degrees C (99 degrees F).

The hypothalamus, which maintains normal body temperature, is affected by
circulating pyrogens (pathogens, toxins, antibody complexes). The pyrogen
released by active macrophages is a cytokine called endogenous pyrogen or
interleukin-1 (IL-1).

High body temperature increases body metabolism (accelerating defenses) and
inhibits some viruses and bacteria.
IV. Specific Defenses: An Overview of the Immune Response, p. 782
Objectives:
1. Define specific resistance and identify the forms and properties of immunity.
2. Distinguish between cell-mediated (cellular) immunity and antibody-mediated
(humoral) immunity.

Specific resistance (immunity) responds to specific antigens with the coordinated
action of T cells and B cells. T cells are responsible for cell-mediated immunity,
which defends against abnormal cells and pathogens inside cells. B cells provide
antibody-mediated immunity, which defends against antigens and pathogens in
body fluids.
Forms of Immunity, p. 782
Figure 22-14

Immunity can be either innate (present at birth) or acquired (after birth).

Acquired immunity can be either active (antibodies develop through the immune
response after exposure to an antigen) or passive (antibodies are transferred from
another source).

Active immunity can be either naturally acquired (through environmental
exposure to pathogens) or induced (through vaccines containing pathogens).

Passive immunity can also be either naturally acquired (antibodies acquired from
the mother) or induced (by an injection of antibodies).
Properties of Immunity, p. 783

All types of immunity have 4 general properties:
1. specificity
2. versatility
3. memory
4. tolerance

Specificity means that each T cell or B cell responds only to an antigen with a
specific molecular structure, ignoring all others.

Versatility means the body produces a small number of many types of
lymphocytes with different capabilities, so the immune system has the tools to
fight many types of antigens. When an antigen activates a particular lymphocyte,
that lymphocyte clones itself to produce a population of cells that can fight that
specific antigen.

Memory means that some activated lymphocytes (memory cells) stay in the
circulation and provide immunity. If exposed to the same antigen at a later date,
the immune system recognizes it and responds immediately.

Tolerance means the immune system will ignore antigens it recognizes as
“normal.”
An Introduction to the Immune Response, p. 784
Figure 22-15 is an overview of the immune response.

We will examine cell mediated immunity (T cells) and antibody mediated
immunity (B cells) in detail.
V. T Cells and Cell-Mediated Immunity, p. 784
Objectives:
1. Discuss the types of T cells and the role played by each in the immune response.
2. Describe the mechanisms of T cell activation and the differentiation of the major
classes of T cells.

To review the 3 types of T cells:
1. Cytotoxic T cells (Tc cells):
- attack cells infected by viruses
- are responsible for cell-mediated immunity
2. Helper T cells (Th cells):
- stimulate the function of T cells and B cells
3. Suppressor T cells (Ts cells):
- inhibit the function of T cells and B cells

T cells are activated by exposure to an antigen, but not by direct exposure. T cells
only recognize antigens bound to glycoproteins in cell membranes, a process
called antigen presentation.
Antigen Presentation, p. 784
Figure 22-16
 The membrane glycoproteins that bind to antigens (MHC proteins) are genetically
coded in a part of chromosome 6 called the major histocompatibility complex
(MHC), and differ among individuals.

There are 2 major classes of MHC proteins:
-
Class I MHC proteins are found in the membranes of all nucleated cells.
During formation, they pick up small peptides in the cell and carry them to
the surface. As long as the peptides are normal, T cells will ignore the cell.
If abnormal peptides or viral proteins appear, T cells are activated to
destroy the cell.
-
Class II MHC proteins are found only in the membranes of antigenpresenting cells (APCs) and lymphocytes. Antigenic processing of
pathogens creates antigenic fragments which are bound to Class II proteins
and inserted in the cell membrane to stimulate T cells.

APCs are responsible for activating T cell defenses against foreign cells and
proteins.

Phagocytic antigen-presenting cells include:
1. free and fixed macrophages in connective tissues
2. Kupffer cells of the liver
3. microglia in the CNS

Langerhans cells (in the skin) and dendritic cells (in the lymph nodes and spleen
are non-phagocytic antigen-presenting cells. (They remove antigens by
pinocytosis.)
Navigator: An Overview of the Immune Response, p. 785
Antigen Recognition, p. 786

Inactive T cells have receptors that recognize either Class I or Class II MHC
proteins, and receptors that recognize a specific antigen. Binding occurs only if
the MHC protein has the correct antigen (antigen recognition).

Recognition depends on the structure of the T cell membrane, which contains
cluster of differentiation or CD markers. There are more than 70 types of CD
markers (designated by number) found in lymphocytes, macrophages and other
related cells.

All T cells have a CD3 receptor complex. Two other CD markers are found in
specific groups of T cells:
1. CD8 markers are found on cytotoxic T cells and suppressor T cells, which
respond to antigens on Class I MHC proteins.
2. CD4 markers are found on helper T cells, which respond to antigens on
Class II MHC proteins.

CD8 or CD4 markers bind to the CD3 receptor complex, preparing the cell for
activation. For the T cell to be activated, it must be costimulated by binding to the
stimulating cell at a second site, which confirms the first signal.
Activation of CD8 T Cells, p. 787
Figure 22-17
 There are 2 different classes of CD8 T cells activated by exposure to antigens on
MHC proteins. One responds quickly, producing cytotoxic T cells and memory T
cells. The other responds slowly, producing suppressor T cells.

Cytotoxic T cells or killer T cells seek out and immediately destroy target cells
by:
1. releasing perforin to destroy the antigenic cell membrane
2. secreting poisonous lymphotoxin to destroy the target cell
3. activating genes in the target cell nucleus that cause the cell to die

It can take 2 days or more, from the time of first exposure to an antigen, for
cytotoxic T cells to reach effective levels.

Memory Tc cells are produced by the same cell divisions that produce cytotoxic T
cells. Memory cells stay in circulation, and if the same antigen appears again, the
memory T cells immediately differentiate into cytotoxic T cells, producing an
immediate, effective response.

Suppressor T cells secrete suppression factors that inhibit the responses of T cells
and B cells, after the initial immune response, limiting the immune reaction to a
single stimulus.
Activation of CD4 T Cells, p. 788
Figure 22-18
 Activated CD4 T cells divide into active helper T cells and memory T cells. The
memory T cells remain in reserve. The helper T cells secrete cytokines that:
1. stimulate T cell divisions that produce memory T cells and accelerate
maturation of cytotoxic T cells
2. attract macrophages and stimulate their activity
3. attract and stimulate NK cells
4. promote activation of B cells
Figure 22-19 reviews antigen presentation and T cell stimulation.

Key



T cell activation is the main cause of graft rejection in organ transplants. Donated
tissues contain foreign cells and present foreign antigens.
Cell-mediated immunity involves close physical contact between activated Tc
cells and foreign, abnormal or infected cells.
T cell activation usually involves (1) antigen presentation by a phagocytic cell and
(2) costimulation by cytokines released by active phagocytes.
Tc cells may destroy target cells through the local release of cytokines,
lymphotoxins, or perforin.
VI. B Cells and Antibody-Mediated Immunity, p. 789
Objectives:
1. Describe the mechanisms of B Cell activation and the differentiation of plasma
cells and memory B cells.
2. Describe the structure of an antibody and discuss the types of antibodies in body
fluids and secretions.
3. Explain the functions of antibodies and how they perform those functions.
4. Discuss the primary and secondary responses to antigen exposure.

B cells attack antigens by producing specific antibodies.

B Cell Sensitization and Activation, p. 789

The body has millions of B cell populations, each carrying its own particular
antibody molecules in its cell membrane. Corresponding antigens in interstitial
fluids bind to the B cell receptors, and the B cell prepares for activation. The
preparation process before activation is called sensitization.
Figure 22-20
 During sensitization, antigens are taken into the B cell, processed, and reappear
on the surface bound to a Class II MHC protein. The sensitized B cell is now
prepared, but needs the help of a helper T cell for activation.

A sensitized B cell must encounter a T cell that has been activated by the same
antigen. The helper T cell binds to the MHC complex and secretes cytokines that
promote B cell activation and division.

The activated B cell divides to produce plasma cells and memory B cells.

Plasma cells synthesize and secrete large quantities of antibodies into the
interstitial fluid.

Memory B cells, like memory T cells, remain in reserve to respond to the next
infection.
Antibody Structure, p. 790
Figure 22-21
 An antibody consists of 2 parallel pairs of polypeptide chains: one pair of heavy
chains and one pair of light chains. Each chain contains constant segments and
variable segments.

B cells produce 5 types of heavy-chain constant segments, which determine the 5
types of antibodies: IgG, IgE, IgD, IgM, and IgA.

The specificity of an antibody molecule is determined by the structure of the
variable segments of the light and heavy chains. The free tips of the 2 variable
segments form the antigen binding sites of the antibody molecule, which bind to
the antigenic determinant sites of the antigen molecule.

An antibody bound to an antigen forms an antigen-antibody complex.

A complete antigen (with 2 antigenic determinant sites) binds to both of the
antigen binding sites of the variable segments of the antibody. Exposure to a
complete antigen leads to B cell sensitization and immune response.

A hapten or partial antigen must attach to a carrier molecule to act as a complete
antigen, and the antibodies produced will attack both the hapten and the carrier
molecule. If the carrier molecule is normally present, the antibody will attack
normal cells. This is the basis of drug reactions such as penicillin allergy.
Table 22-1
 The 5 classes of antibodies or immunoglobins (Igs) in body fluids (determined by
constant segments) have no effect on antibody specificity.

Key



The formation of antigen-antibody complexes can eliminate antigens in 7 ways:
1. neutralization of antigen binding sites
2. precipitation and agglutination (formation of immune complex)
3. activation of complement
4. attraction of phagocytes
5. opsonization (increasing phagocyte efficiency)
6. stimulation of inflammation
7. prevention of bacterial and viral adhesion
Antibody-mediated immunity involves the production of specific antibodies by
plasma cells derived from activated B cells.
B cell activation usually involves (1) antigen recognition, through binding to
surface antibodies, and (2) costimulation by a TH cell.
The antibodies produced by active plasma cells bind to the target antigen and
either inhibit its activity, destroy it, remove it from solution, or promote its
phagocytosis by other defense cells.
Primary and Secondary Responses to Antigen Exposure, p. 793
Figure 22-22
 The first exposure to an antigen produces an initial response. The next time the
same antigen appears, it triggers a more extensive and prolonged secondary
response, because memory cells are already primed for the arrival of the antigen.

Primary and secondary responses occur in both cell-mediated and antibodymediated immunity.

The primary response takes time to develop. Antigens must activate the
appropriate B cells before plasma cells can differentiate and the concentration of
circulating antibodies (the antibody titer) rises. IgM is produced more quickly
than IgG (but is less effective). Peak response can take 2 weeks to develop, and
declines rapidly.

Key


In a secondary response, memory B cells are activated at lower antigen
concentrations than the original B cells, and activated memory B cells secrete
antibodies in massive qualities. IgG rises very high, very quickly -- and can
remain elevated for extended periods of time. IgM production is also quicker, and
is slightly extended.
Immunization produces a primary response to a specific antigen under controlled
conditions.
If the same antigen is encountered at a later date, it triggers a powerful secondary
response that is usually sufficient to prevent infection and disease.
Summary of the Immune Response, p. 795
Figure 22-23 summarizes specific and nonspecific defenses in the immune response.
Figure 22-24 shows the course of the body’s response to bacterial infection.
Figure 22-25 shows the combined immune system response to bacteria and viruses:

In a bacterial infection:
- neutrophils and NK cells begin killing bacteria
- cytokines draw phagocytes to the area
- antigen presentation activates helper T cells and cytotoxic T cells
- B cells are activated and differentiate
- plasma cells increase antibody levels

Viral infections are similar, but cytotoxic T cells and NK cells are activated by
contact with virus-infected cells.
Key



Viruses replicate inside cells, whereas bacteria may live independently.
Antibodies (and administered antibiotics) work outside cells, so they are primarily
effective against bacteria rather than viruses. (That’s why antibiotics can’t fight
the common cold or flu.)
T cells, NK cells, and interferons are the primary defense against viral infection.
VII. Normal and Abnormal Resistance, p. 796
Objectives:
1. Describe the origin, development, activation, and regulation of normal resistance
to disease.
2. Explain the origin of autoimmune disorders, immunodeficiency diseases, and
allergies and list important examples of each type of disorder.
3. Discuss the effects of stress on the immune function.

The ability to produce an immune response after exposure to an antigen
(immunological competence) develops in the fetus at about 3 months.
The Development of Immunological Competence, p. 796

Cells from the fetal thymus migrate to various tissues that will form the T cells of
immune or lymphoid tissues. B cells are produced in the liver and bone marrow.
A fetus may begin producing IgM antibodies as early as 4 month of age, if
exposed to certain pathogens.

Normally, maternal IgG antibodies, passed through the placenta, provide passive
immunity to protect the fetus. After birth, mother’s milk provides IgA antibodies
while passive immunity is lost.

The infant begins producing its own IgG antibodies through exposure to
environmental antigens. Antibody levels, B-cell and T-cell levels continue to rise
toward adult levels through about age 12.
Focus: Hormones of the Immune System, p. 798
Table 22-3 Hormones and the Immune Response

6 groups of hormonal cytokines:
1. interleukins
2. interferons
3. tumor necrosis factors
4. chemicals that regulate phagocytic activities
5. colony stimulating factors
6. miscellaneous cytokines (including leukotrienes, perforins, defensins and
suppression factors)
Immune Disorders, p. 800

Disorders of the immune system include autoimmune disorders,
immunodeficiency disease, and allergies.

Autoimmune disorders result when the system that recognizes and ignores
normal or self-antigens malfunctions, and activated B cells make antibodies
against body cells and tissues (autoantibodies). Some common examples are:
thyroiditis, rheumatoid arthritis, and insulin-dependent diabetes mellitus.

Many autoimmune disorders are caused by a similarity between proteins in
invading viruses and amino acid sequences in normal tissues. The antibody
produced against the virus also attacks the similar body tissue.

Immunodeficiency diseases can result from:
1. problems with embryological development of lymphoid tissues:
- can result in severe combined immunodeficiency disease (SCID)
2. viral infections such as HIV:
- (can result in AIDS)
3. immunosuppressive drugs or radiation treatments:
- can lead to complete immunological failure

Allergies are inappropriate or excessive immune responses to antigens. Antigens
that trigger allergic reactions are called allergens.

There are 4 categories of allergic reactions:
Type I: immediate hypersensitivity
Type II: cytotoxic reactions
Type III: immune complex disorders
Type IV: delayed hypersensitivity

The most commonly recognized type of allergy is Type I, immediate
hypersensitivity, which includes allergic rhinitis (environmental allergies).
Immediate hypersensitivity is a rapid and severe response to the presence of an
antigen. Sensitization leads to the production of large quantities of IgE antibodies
that are distributed throughout the body. A second exposure leads to a massive
inflammation of all affected tissues.

The severity of the reaction depends on individual sensitivity and the locations
involved. Allergen exposure at the body surface may restrict the allergic response.
Reaction to allergens in the blood stream may result in fatal anaphylaxis.

Anaphylaxis affects cells throughout the body. Changes in capillary permeability
produce swelling (hives) on the skin, smooth muscles of the respiratory system
contract, making breathing difficult, and peripheral vasodilatation can lead to
circulatory collapse (anaphylactic shock).

Mild symptoms of immediate hypersensitivity can be reduced by antihistamine
drugs that block the action of histamine.
Stress and the Immune Response, p. 801

Glucocorticoids produced during the immune response help control the extent of
the immune response. But long-term secretion of glucocorticoids due to chronic
stress can inhibit the immune response and lower resistance to disease by:
1. Depression of the inflammatory response
2. Reduction in the abundance and activity of phagocytes in peripheral
tissues
3. Inhibition of interleukin secretion
VIII. Aging and the Immune Response, p. 802
Objective:
1. Describe the effects of aging on the lymphatic system and the immune response.

The immune system becomes less effective with age, increasing vulnerability to
infections and cancer:
1. Thymic hormone production is greatly reduced
2. T cells become less responsive to antigens
3. Fewer T cells reduce the responsiveness of B cells
4. Immune surveillance against tumor cells declines
IX. Integration with Other Systems, p. 802
Figure 22-27 summarizes interactions between the lymphatic system and other systems.

Thymic hormones are especially interactive with the nervous and endocrine
systems. In turn, the nervous system adjusts the sensitivity of the immune
response.

Disorders of the lymphatic system that affect the immune response fall into 3
categories:
1. Disorders resulting from an insufficient immune response.
2. Disorders resulting from an inappropriate immune response.
3. Disorders resulting from an excessive immune response.
SUMMARY
In chapter 22 we learned about:
- The divisions of the lymphatic system:
- lymphatic vessels (lymphatics)
- lymph
- lymphoid tissues and organs
- The types of lymphocytes:
- T cells
- B cells
- NK cells
- Lymphoid tissues and organs:
- nodules
- nodes
- MALT
- thymus
- spleen ( red and white pulp)
- 7 nonspecific defenses of the immune system:
- physical barriers
- phagocytes
- immunological surveillance
- interferons
- complement
- inflammation
- fever
- Specific defenses of the immune system:
- cell-mediated immunity
- antibody mediated immunity
- Forms of immunity:
- innate or acquired
- active or passive
- Properties of immunity:
- specificity, versatility, memory, tolerance
- T cells and cell-mediated immunity:
- antigen presentation
- MHCs and APCs
- antigen recognition
- CD8 T cell activation
- CD4 T cell activation
- B cells and antibody-mediated immunity:
- sensitization
- plasma cells and memory B cells
- antibody structure
- antigen-antibody complex
- 5 classes of antibodies (immunoglobins, Ig)
- Primary and secondary responses to antigen exposure
- Hormones and the immune system:
- interleukins, interferons, TNFs and CSFs
- Immune disorders
- The effects of aging on the immune response