39.1.
Lymphatic System
A. Lymphatic System Characteristics
1. Mammalian lymphatic system consists of lymphatic vessels and
lymphoid organs.
2. Closely associated with
cardiovascular system, it has three main functions.
a. Lymphatic
vessels take up excess tissue fluid and return it to bloodstream.
b. Lymphatic
capillaries absorb fats at intestinal villi; lymphatic vessels transport fats
to bloodstream.
c. Lymphatic
system helps defend the body against disease.
B. Lymphatic Vessels
1. Lymphatic vessels are extensive; most regions have lymphatic
capillaries.
2. Structure of larger lymphatic
vessels resembles veins, including valves.
3. Movement of fluid is dependent upon
skeletal muscle contraction; when muscles contract, fluid is
squeezed
past a valve that closes, preventing it from flowing backwards.
4. Lymphatic system is a one-way
system that begins with lymphatic capillaries.
a. They take
up fluid that has diffused from but has not been reabsorbed by blood
capillaries.
b. If excess
tissue fluid is not absorbed but instead accumulates, edema results.
c. Edema
is swelling caused by buildup of fluid from excessive production or inadequate
drainage.
5. Once tissue fluid enters
lymphatic capillaries, it is lymph.
6. Lymphatic capillaries join as lymphatic
vessels that merge before entering one of two ducts.
a. Thoracic
duct is larger than right lymphatic duct.
1) It serves lower extremities, abdomen, left arm, left side of head and neck,
and left thoracic region.
2) It delivers lymph to left subclavian vein of cardiovascular system.
b. Right
lymphatic duct is smaller.
1) It serves right arm, right side of head and neck, and right thoracic region.
2) It delivers lymph to the right subclavian vein of the cardiovascular
system..
C. Lymphoid Organs
1. Lymphoid organs are: lymph nodes, spleen, thymus gland,
bone marrow.
2. Lymph nodes are
small (about 1-25 mm) ovoid or round masses of lymphoid tissue located along
lymphatic vessels.
3. Lymph node has two regions: outer
cortex and inner medulla.
4. Lymph capillaries have
macrophages that phagocytize infectious organisms and any other debris.
5. Lymph nodes cluster in certain
regions of the body (e.g., in groin and armpits).
6. Tonsils are located in a ring
around the pharynx.
a. Adenoids
are on posterior wall above border of soft palate.
b. Larger
palatine tonsils on either side of posterior oral cavity are most apt affected.
7. Spleen is located
in upper left abdominal cavity just below diaphragm.
a.
Construction of spleen is similar to that of a lymph node but it is much
larger.
b. A capsule
divides spleen into lobules which contain sinuses filled blood instead of
lymph.
c. Spleen
nodule contains the following:
1) red pulp contains red blood cells, lymphocytes, and
macrophages; helps to purify blood that
passes through by removing microorganisms and worn-out or damaged red blood
cells.
2) white pulp contains mostly lymphocytes.
d. If spleen
ruptures due to injury, it can be removed; its functions are assumed by other
organs.
e. A person
without a spleen is more susceptible to infections; may require antibiotic
therapy.
8. Thymus gland is
located along trachea behind sternum in upper thoracic cavity.
a. Thymus
gland is larger in children than in adults and may disappear completely in old
age.
b. It is
divided into lobules by connective tissue; lobules are site of T lymphocyte
maturation.
c. Interior
(medulla) of each lobule consists mostly of epithelial cells which produce
thymic hormones
(e.g., thymosin), that promote maturation of T lymphocytes.
9. Red bone marrow
originates all blood cells including all leukocytes that function in immunity.
a. Stem
cells are continually-producing cells that differentiate into various
blood cells.
b. Most
bones of a child have red bone marrow; in adults it is only in skull, sternum,
ribs, clavicle, pelvic
bones and vertebral column.
c. Red bone
marrow consists of reticular fibers produced by reticular cells packed around
thin-walled sinuses.
d.
Differentiated blood cells enter the bloodstream from these bone sinuses.
39.2.
Nonspecific Defenses
A. Immunity is ability to defend against infectious agents, foreign
cells, and abnormal cancer cells.
1. Immunity includes nonspecific and specific defenses.
2. Four nonspecific defenses include
barrier to entry, inflammatory reaction, natural killer cells, and protective
proteins.
B. Barring Entry
1. Skin and mucous membranes lining respiratory, digestive, and urinary tracts
are mechanical barriers.
2. Oil gland secretions inhibit
growth of bacteria on skin.
3. Ciliated cells lining respiratory
tract sweep mucous and particles up into throat to be swallowed.
4. Stomach has a low pH (1.2-3.0)
that inhibits growth of many bacteria.
5. Normal bacteria that reside in
intestine or vagina prevent pathogens from colonizing.
6. Pathogens are disease causing
agents (viruses or bacteria).
C. Inflammatory Reaction
1.
If skin is broken, a series of events occurs:
the inflammatory reaction.
2. The inflamed area has four symptoms: redness, pain, swelling, and heat.
3. Mast cells occur in
tissues and resemble basophils.
4. When tissue damage occurs, a capillary
and several tissue cells rupture and release bradykinin.
a.
Bradykinin triggers nerve impulses in pain receptors and stimulates mast cells
to release histamine.
b.
Bradykinin and histamine cause vasodilation and increased permeability of
capillaries.
c. Enlarged
capillaries produce redness and local increase in temperature.
d. A rise in
local temperature reduces invading pathogens and increases phagocytosis by
WBCs.
5. Chemicals released by damaged
tissue cause neutrophils and monocytes to migrate by amoeboid movement
to site of
injury; they escape from blood by squeezing through capillary wall.
6. When monocytes enter tissue, they
differentiate into macrophages that ingest bacteria or viruses.
7. Connective and lymphoid tissues
have resident macrophages that devour old blood cells and debris.
8. Macrophages trigger an explosive
increase in leukocytes by releasing colony-stimulating hormones; this
diffuses
into blood and is transported to red bone marrow to stimulate production of
WBCs.
9. Pus is accumulation of dead
neutrophils along with tissue, cells, bacteria and, living WBCs.
10. Aspirin, ibuprofen, and
cortisone are anti-inflammatory agents that counter inflammatory chemistry.
D. Natural Killer Cells
1. Natural killer cells kill virus-infected cells and tumor
cells; they lack specificity and memory.
2. Complement system,
called complement, is plasma proteins designated by letter C and a subscript.
a. One
activated complement protein activates another protein in set series of domino
reactions.
b. A limited
amount of protein can activate many other proteins.
c.
Complement is activated when pathogens enter the body.
d. It
"complements" certain immune responses, which accounts for its name.
e. It
amplifies an inflammatory reaction by attracting phagocytic cells to site of
infection.
f.
Complement binds to antibodies already on the surface of pathogens, increasing
probability that pathogens
will be phagocytized by a neutrophil or macrophage.
g. Some
complement proteins form membrane attack complex that produces holes in
bacterial cell walls
and plasma membranes; fluids and salts enter to point where they burst.
3. Interferon is protein produced by virus-infected animal cells.
a. It binds
to receptors of non-infected cells, producing substances interfering with viral
replication.
b.
Interferon is specific to a species; only human interferon can be used in
humans.
39.3.
Specific Defenses
A. If nonspecific defenses fail, specific defenses are required
against a particular antigen.
1. Antigens are foreign substances, protein or polysaccharide,
that stimulate immune system to react.
2. Pathogens have antigens; antigens
can also be components of foreign or cancer cells.
3. We do not ordinarily become
immune to our own cells; immune system can tell self from nonself.
4. Immunity usually lasts for some
time; we do not ordinarily get the same illness a second time.
B. Specific immunity is primarily result of action of B lymphocytes and T
lymphocytes.
1. B lymphocytes mature in bone marrow; T lymphocytes mature in thymus.
2. B lymphocytes (B cells)
give rise to plasma cells that produce antibodies.
3. Antibodies are
large globular proteins that combine with and neutralize antigens.
4. Antibodies are secreted into
blood and lymph.
5. T lymphocytes
either directly attack cells that bear antigens or regulate immune response.
6. Lymphocytes are capable of
recognizing an antigen; they have receptor molecules on their surface.
a.
Receptor-antigen fit is compared to a lock and key.
b. During
our lifetime, we encounter a million different antigens; we need diversity of
lymphocytes.
c. During
maturation, diversification produces a different lymphocyte for each possible
antigen.
C. B Cells and Antibody-Mediated Immunity
1. Each type of B cell carries its specific antibody as a membrane-bound
receptor on its surface.
2. When a B cell (in lymph node or
spleen) encounters an appropriate antigen, it is activated to divide.
3. Resulting cells are plasma
cells, mature B cells that mass-produces antibodies in lymph nodes and
spleen.
4. Clonal selection theory:
antigen selects B cell to produce a clone of plasma cells.
5. B cell will not clone until its
antigen is present; it recognizes antigen directly.
6. However, B cells are stimulated
to clone by helper T cell secretions.
7. Some cloned B cells do not
participate in antibody production but remain in blood as memory B cells.
8. Once threat of infection has
passed, development of new plasma cells ceases; those present die.
9. Apoptosis is programmed cell death;
this is critical to maintaining tissue homeostasis.
10. B cells are responsible for antibody-mediated
immunity.
11. It is also called humoral
immunity because antibodies are present it blood; a humor is a body
fluid.
D. Structure of IgG
1. Most common antibody (IgG) is a Y-shaped
molecule with two arms.
2. Each arm has a "heavy"
and "light" polypeptide chain. (Fig. 42.6)
a. These
chains have constant regions and variable regions.
b. Constant
regions have amino acid sequences that do not change; not identical among all
antibodies.
c. Variable
regions have portions of polypeptide chains whose amino acid sequence changes
providing
antigen specificity; forms antigen binding sites of antibodies-their shape is
specific to antigen.
3. Antigen binds with a specific
antibody at antigen-binding site in a lock-and-key manner.
4. Antigen-antibody complex (or
immune complex) marks antigen for destruction by other mechanisms
(e.g.,
neutrophils or macrophages) or it may activate complement.
5. If complement attaches to
antigens on surface of pathogens, it renders them more easily phagocytized.
E. Other Types of Antibodies
1. There are five classes of circulating antibodies or immunoglobulins (Igs).
2. IgG Antibodies
a. These are
major type in blood; some in lymph and tissue fluid.
b. IgG
attacks pathogens and toxins.
3. IgM Antibodies
a. These
contain five Y-shaped structures.
b. They
appear in blood soon after an infection begins and disappear before it is over.
c. They are
good activators of the complement system.
4. IgA Antibodies
a. IgA
contains two Y-shaped structures.
b. They
attack pathogens before they reach the blood.
c. They are
main type of antibody in bodily secretions.
5. Role of IgD antibodies is to
serve as receptors for antigens on mature B cells.
6. IgE antibodies are involved in
immediate allergic reactions.
F. T Cells and Cell-Mediated Immunity
1. Cytotoxic and helper T cells are responsible for cell-mediated
immunity.
2. Cytotoxic T Cells
a. They
destroy antigen-bearing cells (e.g., virus-infected or cancer cells).
b. They have
storage vacuoles that contain perforin molecules.
c. Perforin
molecules perforate a plasma membrane; water and salts to enter causing
cell to burst.
3. Helper T Cells
regulate immunity by improving response of other immune cells.
a. When
exposed to an antigen, they enlarge and secrete cytokines.
b. Cytokines
stimulate helper T cells to clone and other immune cells to perform their
functions.
1) Cytokines stimulate macrophages to phagocytize.
2) They stimulate B cells to become antibody-producing plasma cells.
c. HIV
(cause of AIDS) infects primarily helper T cells and inactivates immune
response.
4. Memory T cells
remain and can jump-start an immune reaction when same antigen reenters body.
G. Activation of T Cells
1. Like B cells, T cells have receptors.
2. Receptors of cytotoxic and helper
T cells cannot recognize antigen simply present in lymph or blood.
3. Instead, antigen must be
presented to them by an antigen-presenting cell (APC).
a. When an antigen-presenting
cell, usually a macrophage, engulfs a microbe, it is enclosed within an
endocytic
vesicle and broken down to release fragments.
b. These
fragments are antigenic, each of which is linked to an MHC protein;
together they are presented to a
T cell.
4. Human MHC proteins are called HLA
(human leukocyte associated) proteins.
5. Importance of major
histocompatibility complex (MHC) proteins was recognized when it was
discovered
they
contribute to difficulty of transplanting tissues from one person to another.
6. When donor and recipient are
histocompatible, it is likely a transplant will be successful.
7. When a macrophage antigen to a T
cell, the T cell recognizes the antigen.
a. Once a helper
T cell recognizes antigen, it undergoes clonal expansion and produces cytokines
stimulating
immune cells to remain active.
b. Once a
cytotoxic T cell is activated, it undergoes clonal expansion and destroys any
cell that possesses
antigen if the cell bears the correct HLA.
c. As the
infection disappears, the immune reaction wanes and few cytokines are produced.
d. The few T
cells that do not undergo apoptosis survive as memory cells.
8. Apoptosis occurs in thymus if T
cell bears a receptor to recognize a self antigen; if apoptosis does not occur,
T-cell
cancers result (i.e. lymphomas and leukemias).
39.4.
Immunity in Other Animals
A. Nonspecific Immunity in Invertebrates
1. Russian Elie Metchnikoff (1882) observed phagocytes gathered around a thorn
in a starfish.
2. Swede Hans G. Boman discovered
antibacterial peptides in silkmoths.
3. Sea stars have cells similar to
macrophages that release interleukin-like chemicals.
B. Specific Immunity Only in Vertebrates.
1. Gary Litman studied sharks that rely on inherited immunity to familiar
pathogens.
2. Cell-mediated immunity based on T
cells probably predates antibody-mediated immunity of B cells.
39.5.
Induced Immunity
A. Two Types of Immunity
1. Immunity is acquired naturally through infection or artificially by medical
intervention.
a. Active
immunity is where persons make their own antibodies.
b. Passive
immunity is where an individual receives prepared antibodies.
B. Active Immunity
1. Active immunity sometimes develops naturally after a person is infected.
2. However, active immunity is often
induced when a person is well so future infection is prevented.
3. Immunization uses
vaccines to provide antigen to which immune system responds.
4. To prepare vaccines, pathogens
were treated so they were no longer virulent.
5. Genetically engineered bacteria
can produce proteins from pathogens; protein is used as a vaccine.
6. After vaccine is given, immune
response is measured by antibody level in serum-the antibody titer.
a. After
first exposure, a primary response occurs with no antibodies and then a slow
rise in titer.
b. A gradual
decline follows as antibodies bind to antigen or simply break down.
c. After
second exposure, a secondary response occurs and antibody titer rises rapidly
to a level much
greater than before; this is a "booster."
d. Higher
antibody titer is expected to prevent disease symptoms if individual is
infected.
e. Active
immunity depends on memory B and T cells responding to low doses of antigen.
C. Passive Immunity
1. Passive immunity occurs when an individual is given prepared
antibodies to combat a disease.
2. It is short-lived because
antibodies are not made by individual's B cells.
3. Newborn infants are immune to
disease because mother's antibodies have crossed placenta.
4. Breast-feeding promotes passive
immunity-antibodies are in mother's milk.
5. Passive immunity is needed when a
patient is in immediate danger from infectious disease or toxin.
6. A person may be given a gamma
globulin injection (serum that contains antibodies against the agent)
taken from
an individual or animal who has recovered from it.
7. If antibodies are made with
immunized horses, some individuals become sick with serum sickness.
E. Cytokines and Immunity
1. Cytokines are signaling molecules produced by either
lymphocytes, monocytes or other cells.
2. Cytokines stimulate white blood
cell formation; they may work as therapy for cancer and AIDS.
3. Interferon and interleukins are
used to improve ability of an individual's T cells to fight cancer.
4. Interferon produced by T cells is
a cytokine; it has only been partly effective as an anti-cancer drug.
5. Cancer cells with altered
proteins on their cell surface should be attacked by cytotoxic T cells.
6. Cytokines may awaken the immune
system and lead to the destruction of cancer.
a.
Researchers withdraw T cells from a patient and culture them in presence of
interleukin.
b. Cells are
re-injected into patient; doses of interleukin maintain killer activity of T
cells.
7. Interleukin antagonists may help
prevent skin or organ rejection, autoimmune diseases, and allergies.
F. Monoclonal Antibodies
1. Plasma cells derived from same B cell secrete antibodies against same
antigen; these are monoclonal antibodies.
2. Monoclonal antibodies can be
produced in vitro.
a. B
lymphocytes are removed from body (usually mice) and exposed to a particular
antigen.
b. Activated
B lymphocytes are fused with myeloma cells (malignant plasma cells that divide
indefinitely).
c. Fused
cells are hybridomas because they result from two different cells
and one is cancerous.
3. Monoclonal antibodies are used
for quick, reliable diagnosis of various conditions such as pregnancy.
4. They identify infections, sort
out different T cells, and distinguish between normal and cancer cells.
5. They can distinguish cancer and
normal cells and can carry isotopes or toxic drugs to kill tumors.
39.6.
Immunity Side Effects
A. Blood Types
1. As first blood transfusions were attempted, it was found only some types of
blood were compatible.
2. Red blood cell membranes carry
proteins or sugar residues that are antigens to some blood recipients.
3. The ABO system and the Rh system
are major blood types.
B. ABO System
1. Four blood types are designated by antigens present on red blood cells.
(Table 42.2)
2. Individuals have
naturally-occurring antigens to blood type proteins not present on their blood
cells.
3. RBCs with a particular antigen agglutinate
when exposed to corresponding antibodies.
4. Agglutination is
clumping of red blood cells due to a reaction between antigens on red blood
cells.
5. To receive blood, recipient's
plasma must not have an antibody that causes donor cells to agglutinate.
a.
Recipients with type AB blood can receive any type blood; universal recipient.
b.
Recipients with type O blood cannot receive A, B, or AB; universal donor.
c.
Recipients with type A blood cannot receive B or AB.
d.
Recipients with type B blood cannot receive A or AB.
C. Rh System
1. Rh (for rhesus monkey) factor is an important antigen in human blood types.
2. Rh positive (Rh+) has Rh factor on
red blood cells; Rh negative (Rh-) lacks Rh antigen on RBCs
3. Rh-negative individuals do not
have antibodies to Rh factor but make them if exposed to Rh+ blood.
4. Rh factor is particularly
important during pregnancy.
a. Hemolytic
disease of newborn is possible if mother is Rh negative and father is
Rh positive.
b. Rh
positive is genetically dominant; Rh negative mother and Rh positive father
pose a Rh conflict.
c. Child's
Rh positive RBCs can leak across placenta into mother's circulatory system when
placenta break down.
d. Presence
of the "foreign" Rh positive antigens causes mother to produce
anti-Rh antibodies.
e. Anti-Rh
antibodies pass across placenta and destroy RBCs of Rh positive child.
f. The Rh
problem has been solved by giving Rh- women an Rh immunoglobulin injection
either midway through
the first pregnancy or no later than 72 hours after giving birth to an Rh+
child.
1) Injection's anti-Rh antibodies attack child's RBCs before they trigger
mother's immune system.
2) Injection is not effective if a mother has already produced antibodies;
timing is important.
D. Tissue Rejection
1. Tissue rejection occurs because cytotoxic T cells cause disintegration of
foreign tissue.
2. Selection of compatible organs
and administration of immunosuppressive drugs prevent tissue rejection.
3. Transplanted organs should have
the same type of HLA antigens as the recipient.
4. Cyclosporine and tacrolimus
(FK-506) help in immunosuppression in liver transplants but may hurt kidneys.
E. Autoimmune Diseases
1. Autoimmune diseases result as an attack on tissues by body's own
antibodies and T cells.
2. Cause is not known but autoimmune
diseases often appear following recovery from an infection.
3. In myasthenia gravis,
neuromuscular junctions do not work properly and muscular weakness results.
4. In multiple sclerosis (MS),
myelin sheath of nerve fibers is attacked.
5. Persons with systemic lupus
erythematosus present many symptoms before dying from kidney damage.
6. Heart damage following rheumatic
fever and type I diabetes are also autoimmune diseases.
7. There are no cures for autoimmune
diseases but they are controlled by drugs.
F. Allergies
1. Allergy results from an immune system forming antibodies to
everyday substances.
2. A response to these antigens,
called allergens, usually involves tissue damage.
3. Immediate and delayed responses
are two of four possible responses.
4. Immediate Allergic Response
a. Immediate
responses occur within seconds of contact with an allergen.
b. Cold-like
symptoms are common.
c. A severe
systemic reaction is anaphylactic shock, a sudden drop in blood
pressure.
d. IgE
antibodies are attached to plasma membrane of mast cells in tissues and basophils
in blood.
e. When an allergen
attaches to IgE antibodies on these cells, they release large amounts of
histamine and other
substances, which cause symptoms or anaphylactic shock.
5. Allergy shots sometimes prevent the
onset of allergic symptoms.
a.
Injections of the allergen cause the body to build up high quantities of IgG
antibodies.
b. These
combine with allergens received from the environment before they have a chance
to reach IgE antibodies
located on the plasma membrane of mast cells.
6. Delayed Allergic Response
a. Delayed
responses are initiated by sensitized T cells at site of allergen.
b. It
responds to antigens that have been in the body before.
c.
Tuberculin skin test is example: positive test shows prior exposure to TB
bacilli but requires some time
to develop reddening of tissue.