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Anatomy and Physiology Lecture
Biology 2402
CHAPTER 22
LYMPHATIC SYSTEM AND IMMUNITY
LYMPHATIC SYSTEM AND IMMUNITY
Pathogens are disease-producing organisms.
Survival and good health depends on fending off attacks of pathogen.
Resistance is the ability to ward off diseases through our defenses.
Susceptibility is vulnerability or lack of resistance.
Resistance grouped in two broad areas:
(1)
Nonspecific resistance - Includes defense mechanism that
provide general protection against invasion by a wide range
pathogens, such as the many different kinds of bacteria and
viruses.
These include:
(a) Mechanical barriers provided by the skin and mucus
membranes;
(b) Antimicrobial chemicals;
(c) Phagocytosis;
(d) Inflammation; and
(e) Fever
(Example: The acidity of the stomach contents kills many
bacteria ingested in food).
(2)
Immunity - Involves activation of specific lymphocytes that
combat a particular pathogen or other foreign substance.
Specific resistance.
The body system that carries out immune response is the
lymphatic system.
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Lymphatic System - Consist of:
1) Liquid called lymph
2) Lymphatic vessels (lymphatics) - that transport lymph
3) Structures and organs that contain lymphatic (lymphoid) tissue
4) Bone marrow which houses stem cells that develop into
lymphocytes.
Interstitial (tissue) fluid and Lymph are basically the same.
The major difference between the two is location.
Fliud from interstitial tissue becomes lymph after it passes from
interstitial space to lymphatic vessels.
Lymphatic tissue is a specialized form of reticular connective tissue
(blood) that contains large number of lymphocytes.
FUNCTIONS OF THE LYMPHATIC SYSTEM
1.
Fluid Balance - Lymphatic vessels drain tissue spaces of excess
interstitial fluid.
2.
Fat absorption - Lymphatic system absorbs fats and other
substances from the digestive tract. Fats enter the lacteals (special
lymphatic vessels located in the small intestine) and pass through the
lymphatic vessels to the venous circulation.
3.
Defense – Microorganisms and other foreign substances are filtered
from lymph by lymph nodes and from blood by the spleen.
Lymphocytes (A type of white blood cell found in lymph nodes), aided
by macrophages (phagocytic cell derived from a monocyte), recognize
foreign cells and substances, microbes, and cancer cells.
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Respond to foreign cells in two basic ways:
1.
Some lymphocytes (T cells) destroy the intruders directly
(by causing them to rupture) or indirectly by releasing
cytotoxic (cell-killing) substances.
2.
Other lymphocytes (B cells) differentiate into plasma cells
that secrete antibodies.
These are proteins that combine with and cause destruction
of specific foreign substances.
LYMPHATIC VESSELS AND LYMPH CIRCULATION
Lymphatic Vessels begin as closed-ended vessel called lymphatic
capillaries in spaces between cells.
Lymphatic Capillaries unit to form large tubes called lymphatic vessels; just
as blood capillaries unit to form venules and veins.
Lymphatic vessels resemble veins in structure but have thinner walls and
more valves.
At intervals, have structures called lymph nodes.
In the skin, lymphatic vessels lie in subcutaneous tissue and generally
follow veins.
Lymphatic vessels of the Viscera (the organs inside the ventral (anterior)
body cavity) generally follow arteries, forming plexuses around them.
Lymph capillaries
Are microscopic vessels in spaces between cells from which lymphatic
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vessels originate.
Capillaries containing lymph are found throughout the body, except in:
(1)
(2)
(3)
(4)
Avascular tissue (bloodless)
Central Nervous system
Splenic pulp and
Bone marrow
Lymphatic capillaries have a slightly larger diameter than blood capillaries.
Permits interstitial fluid to flow into them but not out.
Anchoring filaments attach lymphatic endothelial cells to surrounding
tissues.
Fingerlike projection (villi) of the small intestine contains blood capillaries
and a specialized lymphatic capillary called lacteal.
Formation and Flow of Lymph
Most components of blood plasma freely move through the capillary
walls to form interstitial fluid.
More fluid seeps out of blood capillaries by filtration than returns to
them by absorption.
The excess fluid, about 3 liters per day, drains into lymphatic vessels
and becomes lymph.
Lymph drains into venous blood through the right and left lymphatic
ducts at the junction of the internal jugular and subclavian veins.
Sequence of Fluid Flow
Arteries (blood plasma)
blood capillaries (blood plasma)
interstitial spaces (interstitial fluid)
lymphatic capillaries (lymph)
lymphatic vessels (lymph)
lymphatic ducts (lymph) subclavian
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veins (blood plasma)
Since most plasma proteins are too large to leave blood vessels,
interstitial fluid contains only small amounts of protein.
Any protein that do escape, however, cannot return to the blood by
diffusion.
(The concentration gradient (high level of proteins inside blood
capillaries, low level outside) prevent diffusion back to the blood).
Important function of lymphatic vesel is to return leaked plasma
proteins to the blood.
Factor that maintain lymph flow:
(1)
Contracting of the skeletal muscle (milking action)
(2)
One-way valve (similar to those found in veins) within the
lymphatic vessels prevent backflow of lymph.
(3)
Breathing movement;
(With each inhalation, lymph flows from the abdominal region,
where the pressure is higher, toward the thoracic region, where it
is lower).
Lymph Trunks and Ducts
Lymph passes from lymphatic capillaries into lymphatic vessels and
through lymph nodes.
Lymphatic vessels exiting lymph nodes pass lymph toward another
node of the same group or on to another group of nodes.
From the most proximal group of each chain of nodes, the exiting
vessels unite to form lymph trunks.
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Principal Lymph Trunks:
(1) Lumba trunk
(2) Intestinal trunk
(3) Bronchomediastinal trunk
(4) Subclavian trunk
(5) Jugular trunk
Pricipal trunks pass their lymphs into two main channels:
(1) Thoracic (Left Lymphatic) Duct
(2) Right Lymphatic Duct
Ducts pass lymphs into venous blood.
Thoracic (Left Lymphatic) Duct
Is about 38-45 cm (15-18 in.) in length.
Begins as a dilation called cisterna chyli (sis-TER-na Kile).
Thoracic duct is the main collecting duct of the lymphatic system
Receives lymph from the left side of the head, neck and chest, the left
upper limb, and the entire body inferior to the ribs
Right Lymphatic Duct
Is about 1.25 cm (1/2 in.) in length.
Drains lymph from the upper right side of the body
LYMPHATIC TISSUES
Primary Lymphatic (Lymphoid) Organs of the body are:
(1)
Bone Marrow (in flat bones and the epiphyses of long bones),
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(2)
Thymus gland
Are both called primary lymphatic organs because they produce B and
T cells, the lymphocytes that carry out immune responses.
Hemopoietic stem cells in red bone marrow give rise to B cells and
pre-T cells.
The pre-T cells then migrate to the thymus gland.
Secondary Lymphatic Organs of the body are:
(1)
(2)
(3)
Lymph nodes
Spleen
Lymphatic nodules (not discrete organs because they are not
surrounded by a capsule).
THYMUS GLAND
A bilobed (2 lobes) lymphatic organ.
Located in the superior mediastinum, posterior to the sternum and
between the lungs.
An enveloping layer of connective tissue holds the two thymic lobes
closely together.
Capsule, a connective tiisue, encloses each lobe.
Trabeculae, extension given off by the capsule, divides the lobes into
lobules.
Each lobule consists of:
(a) A deeply staining outer cortex, and
(b) A lighter-staining central medulla.
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Pre-T cells migrate (via the blood) from red bone marrow to the
thymus, where they proliferate and develop into mature T cells.
Thymus gland is large in the infant, reaches its maximum size of about
40 g (about 1.4 oz) at 10-12 years of age.
After puberty, much of the thymic tissue is replaced by fat and areolar
connective tissue.
By maturity, the gland has atrophied considerably (involution with age).
Although most T cells arise before puberty, some continue to mature
through out life.
LYMPH NODES
Are oval or bean-shaped structures located along the length of
lymphatic vessels.
They range from 1 to 25 mm (0.04 to 1 in.) in length.
Are scattered throughout the body, usually in groups:
Heavily concentrated in areas such the mammary glands, axillae,
and groin.
Each node is covered by capsule, and capsular extension is called
trabeculae.
The parenchyma of a lymph node is specialized into two regions:
(a) Cortex, and
(b) Medulla
Cortex contains many follicles. The outer rim of each follicle contains
T cells (T lymphocytes) plus macrophages and follicular dendritic
cells). Follicles have germinal centers, where B cells (B
lymphocytes) proliferate into antibody-secreting plasma cells.
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Medulla is the inner region of a lymph node. Contain macrophages
and plasma cells.
Lymph flows through a node in one direction.
Enter through afferent lymphatic vessels, which penetrate the
convex surface of the node at several points.
Contain valves that open toward the node so that the lymph is directed
inward.
Lymph flows through sinuses in the cortex (cortical sinuses) and then
in the medulla (medullary sinuses).
Exit through efferent lymphatic vessels through a depression called
hilus. Blood vessels also enter and leave the node at the hilus.
Among lymphatic tissues, only lymph nodes filter lymph by
having it enter at one end and exit at other.
Lymph is filtered of foreign substances, which are trapped by the
reticular fibers within the node.
Macrophages then destroy some foreign substance by phagocytosis
and lymphocytes bring about destruction of others by immune
responses.
Cancerus lymph nodes feel enlarged, firm, and nontender.
Most lymph nodes that enlarge during an infection, by contrast, are not
firm and very tender.
Structure:
1.
2.
3.
Hilus or Hilium - a slight depression on one side of lymph node,
where blood vessels and efferent lymphatic vessels leave the
node
Capsule - covers each node
Cortex - contains densely packed lymphocytes arranged in
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4.
5.
6.
7.
masses called lymphatic nodules
Germinal Center - lighter-staining central areas, where the
lymphocytes are produced
Medulla - the inner region of a lymph node
Afferent lymphatic vessels - contain valves that open toward the
node so that lymph is directed inward
Efferent lymphatic vessels - contain valves that open away from
the node to convey lymph out of the node
Medical Application: Metastasis through the lymphatic system.
SPLEEN:
Is the largest single mass of lymphatic tissues in the body.
Measures about 12 cm (5 inches) in length
Situated in the left hypochondriac region between the fundus of the
stomach and diaphragm lateral to the liver.
Like lymph nodes, has a hilus, where the splenic artery and vein and
the efferent lymphatic vessels pass through.
(Note: There is no afferent lymphatic vessels or lymph sinuses,
therefore does not filter lymph).
A parenchyma of the spleen consists of two different kinds of tissue:
(1)
White pulp: Lymphatic tissue, mostly lymphocytes (B cells),
arranged around central arteries.
Functions in immunity as a site of B cell proliferation into
antibody-producing plasma cells.
(2)
Red pulp: Consists of venous sinuses filled with blood and thin
plates of tissue called splenic (Billroth's) cords between the
sinuses.
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Splenic cords consist of red blood cells, macrophages,
lymphocytes, plasma cells, and granulocytes.
Veins are closely associated with red pulps.
Function - Carries out the main function of the spleen:
Phagocytosis of bacteria and worn-out and damaged red blood
cells and platelets.
Other functions of the Spleen:
Stores and releases the blood in case of demand, such as during
hemorrhage.
Participates in blood cell formation during early fetal
development.
Lymphatic Nodules
Are oval-shape concentration of lymphatic tissue.
Most are solitary, small, and discret.
Are scattered throughout the lamina propria (connective tissue) of
mucus membranes lining the gastrointestinal tract, respiratory
airways, urinary tract, and reproductive tract.
This lymphatic tissue is referred to as mucosa-associated lymphoid
tissue (MALT).
Some lymphatic nodules occur in multiple, large aggregations in
specific parts of the body:
(a)
(b)
(c)
Tonsils in the pharyngeal region
Aggregated lymphatic follicles (Peyer's patches) in the
ileum of the small intestine.
Aggregation of lymphatic nodules also occur in the
appendix.
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There are five tonsils, which form a ring at the junction of the oral cavity
and oropharynx and at the junction of the nasal cavity and
nasopharynx.
Are strategically positioned to participate in immune response against
foreign substances that are inhaled or ingested.
Their T cells destroy foreign intruders directly;
Their B cells develop into antibody-secreting plasma cells and
the antibodies dispose of foreign substances.
Pharyngeal tonsil or adenoid (single) is embedded in the posterior
wall of the nasopharynx.
Palatine tonsil (double) lie at the posterior region of the pral cavity,
one on each side.
Commonly removed by a tonsillectomy.
Lingual tonsil (paired) are located at the base of the tongue, may also
be removed by tonsillectomy.
IMMUNITY
Immunity – Is the ability to resist damage from foreign substances such as
microorganisms and harmful chemicals.
Two Categories of Immunity:
1.
Innate Immunity (Nonspecific Resistance) – The body
recognizes and destroys certain foreign substances, but the
response to them is the same each time the body is exposed to
them.
2.
Adaptive Immunity (Specific Resistance) – The body recognizes
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and destroys foreign substances, but the response to them
improves each time the foreign substance is encountered.
Are characterized by: (a) Specificity, and (b) Memory.
Specificity – Is the ability of adaptive immunity to recognize a
particular substance.
Memory – Is the ability of adaptive immunity to remember previous
encounters with a particular substance and, as a result, to respond
to it more rapidly.
Innate Immunity
There are three main components of Innate Immunity.
1.
Mechanical Mechanisms – Prevent the entry of microbes into the
body or that prevent the entry of microbes into the body or that
physically remove them from body surfaces.
2.
Chemical Mediators – Act directly against microorganisms or
activate others mechanisms, leading to the destruction of
microorganisms. (Table 22.1, Page 781)
3.
Cells – Involve in phagocytosis and the production of chemicals
that participate in the response of the immune system.
(Table 22.2, Page 783)
Inflammatory Response
Inflammatory Response – Is a complex sequence of events involving many
of the chemical mediators and cell of innate immunity.
Types of Inflammatory Responses:
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1.
Local Inflammation – Is an inflammatory response confined to a
specific area of the body.
2.
Systemic inflammation – Is an inflammatory response that occurs
in many parts of the body.
Adaptive Immunity
Adaptive Immunity involves the ability to recognize, respond to, and
remember a particular substance.
Antigens – Are substances that stimulate adaptive immunity.
Two Groups of antigens:
1.
Foreign antigens – Are not produced by the body but are
introduced from outside it.
2.
Self-antigens – Are molecules produced by the body that stimulate
an adaptive immune system response.
Two Types of Adaptive Immunity
Immunity results from the activity of lymphocytes called B and T cells.
1.
Humoral (Antibody-mediated immunity) – B cells give rise to
cells that produce proteins called antibodies, which are found in the
plasma.
2.
Cell-mediated Immunity – T cells are responsible for
cell-mediated immunity.
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ORIGIN AND EVELOPMENT OF LYMPHOCYTES
All blood cells, including lymphocytes, are derived from stem cells in the red
bone marrow.
- Some stem cells give rise to pre-T cells that migrate through the blood
to the thymus, where they divide and are processed into T cells.
- Other stem cells produce pre-B cells, which are processed in the red
bone marrow into B cells.
Positive selection process – Results in the survival of pre-B and pre-T
cells that are capable of an immune response.
Clones - Are the B and T cells that can respond to antigens and are
composed of small groups of identical lymphocytes.
Negative selection process – Eliminates or suppresses clones acting
against self-antigens, thereby preventing the destruction of self-cells.
- B cells are released from red bone marrow, T cells are released from
the thymus, and both types of cells move through the blood to
lymphatic tissue.
- There are approximately five T cells for every B cell in the blood.
Primary Lymphatic Organs – Are the sites where lymphocytes mature into
functional cells.
- Red bone marrow
- Thymus
Secondary Lymphatic Organs and Tissues – Are the sites where
lymphocytes interact with each other, antigen-presenting cells, and antigens
to produce an immune response.
- Diffuse lymphatic tissue
- Lymphatic nodules
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- Tonsils
- Lymph nodes
- Spleen
Activation of Lymphocytes
Two general principles of Lymphocyte activation;
1.
Lymphocytes must be able to recognize the antigen.
2.
After recognition, the lymphocytes must increase in number to
effectively destroy the antigen.
Antigenic Determinants and Antigen Receptors
Antigenic Determinants (Epitopes) – Are specific regions of a given
antigen recognized by a lymphocyte, and each antigen has many different
antigen determinants.
Antigen Receptors – It is a surface identical protein found on all the
lymphocytes of a given clone.
T-Cell Receptor – Consists of two polypeptide chains, which are subdivided
into a variable and a constant region.
B-Cell Receptor – Consists of four polypeptide chains with two identical
variables regions.
Major Histocompatibility Complex Molecules
SUMMARY OF CELLS THAT ARE IMPORTANT IN IMMUNE
RESPONSES
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1. Macrophage: Phagocytosis; processing and presentation of foreign
antigens to T cells; secretion of interleukin-1 that
stimulated secretion of interleukin -2 by helper T cells
(stimulates proliferation of cytotoxic T cells) and induces
proliferation of B cells; secretion of interferons that
stimulate T cell growth.
2. Cytotoxic
(Killer) T Cell:
Lysis of foreign cells by lymphotoxin and release of various
other lymphokines that recruit and intensify cytotoxic T cell
action (transfer factor), increase phagocytic activity of
macrophages (macrophage activating factor), prevent
macrophage migration from site of action *macrophage
migration inhibitation factor), and proliferation of
uncommitted or nonsensitized lymphocytes (mitogenic
factor). Cytotoxic T cells also secrete interferons.
3. Helper T Cell: Cooperates with B cells to amplify antibody production by
plasma cells and secretes interleukin-2, which stimulates
proliferation of cytotoxic T cells.
4. Suppressor
T Cell:
Inhibits secretion of injurious substances by cytotoxin T
cells and inhibits antibody production by plasma cells.
5. Delayed HyperSensitivity T Cell: Secretes macrophage activation factor and macrophage
migration inhibition factor, by substances related to
hypersensitivity (allergy).
6. Amplifier T Cell:
Stimulates helper T cells, suppressor T cells, and B
cells to exaggerated levels of activity.
7. Memory T Cell:
Remains in lymphoid tissue and recognizes original
invading antigens, even years after infection.
8. Natural Killer
(NK) Cell:
Lymphocyte that destroys foreign cells by lysis and
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produces interferon.
Interferon - A substance formed within a virus-infected cell
which prevents the entrance of or replication of virus
particles.
9. B Cell:
Differentiates into antibody-producing plasma cell.
10. Plasma Cell: Descendant of B cell that produces antibodies.
11. Memory B
Cell:
Ready to respond more rapidly and forcefully than initially
should the same antigen challenge the body in the future.
SUMMARY OF LYMPHOKINE (CYTOKINES) CYTOTOXIC (KILLER) T
CELLS SECRETE
1. Lymphotoxin (LT):
Destroys antigens directly by lysis.
2. Perforin:
Perforates cell membranes of target cells.
3. Transfer factor (TF):
Recruits additional lymphocytes and converts
them into sensitized cytotoxic cells.
4. Macrophage
Chemotactic Factor:
5. Macrophage
Activating Factor (MAF):
6. Macrophage Migration
Inhibiting Factor:
Attracts macrophages to site of invasion to
destroy antigens by phagocytosis.
Increases activity of macrophages.
Prevents macrophages from migrating away
from site of infection.
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7. Mitogenic Factor:
Induces uncommitted or nonsensitized
lymphocytes to divide more rapidly.
8. Interleukin-1 (IL-1)
(Lymphocyte-activating Factor):
9. Interleukin-2 (IL-2)
(T cell growth Factor):
10. Interleukin-3 (IL-3)
(Multipotential CSF):
11. Interleukin-4 (IL-4)
(B Cell Stimulating Factor 1):
12. Colony Stimulating
Factors (CSFs):
13. Interferons (IFNS):
Produced by antigen-stimulated
macrophages and stimulates T cell and B
cell growth; stimulates secretion of
interleukin-2 by helper cell.
Produced by helper T cells to stimulate the
proliferation of cytotoxic (killer) T cells and
natural killer cells.
Produced by activated T cells; supports to
growth of bone marrow stem cells and is a
growth factor for mast cells.
Produced by activated T cells; growth
factor for activated B cells and resting T
cells.
Produced by white blood cells and function in
their proliferation.
Produced by virus-infected cells to inhibit viral
replication in uninfected cells; produced by
antigen-stimulated macrophage to stimulate T
cell growth.
Produced by cytotoxic T cells to augment
killing action of cytotoxic T cells; Produced by
natural killer cells to inhibit viral replication.
14. Tumor Necrosis
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Factor (TNF) (Cachectic):
Produced by macrophages in the presence of
bacterial endotoxins; kills some tumor cells,
stimulate synthesis of lymphokines, activates
macrophages, and mediates inflammation.
Immunology and Cancer
Cancer cells contain tumor-specific antigens and are frequently destroyed by
the body's immune system (Immunological surveillance).
Some cancer cells escape detection and destruction, a phenomenon called
immunologic Escape.
*Immunotherapy - induction of the immune system against cancer.
Aging and The Immune System
1. With advancing age, individuals become more susceptible to infections
and malignancies, response to vaccines is decreased, and more antibodies
are produced.
2. Cellular and humoral responses also diminish.
Developmental Anatomy of The Lymphatic System
1. Lymphatic vessels develop from lymph sacs, which develop from veins.
Thus, they are derived from mesoderm.
2. Lymph nodes develop from lymph sacs that become invaded by
mesenchymal cells.
CLINICAL FOCUS – Acquired Immunodeficiency Syndrome
1. Acquired Immune Deficiency Syndrome (AIDS) lowers the body's
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immunity by decreasing the number of helper T cells and reversing the ratio
of Helper T cells to Suppressor T cells.
- Aids victims frequently develop Kaposi's Sacroma (KS) and Pneumocystis
carinii pneumonia (PCP).
-HumanImmunodeficiencyy Virus (HIV) - the can satire agent of AIDS.
2. Autoimmune diseases result when the body does not recognize "self"
antigens and produces antibodies against them.
-Several human autoimmune diseases are rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE), rheumatic fever, homolyctic and
pernicious anemias, myatheria gravis, and multiple sclerosis (MS).
3. Severe Combined Immunodeficiency (SCID) is an immunodeficiency
disease in which both B and T cells are missing or inactive in providing
immunity.
4. Hypersensitivity (Allergy) - is overactivity to an antigen.
- Localized anaphylactive reactions include hay fever, asthma, eczema, and
hives; acute anaphylaxis is a severe reaction with systemic effects.
5. Tissue Rejection of a transplant tissue or organ involves antibody
production against the proteins (antigens) in the transplant.
-It may be overcome with immunosuppressive drugs.
6. Hodgkin's disease (HD) is a malignant disorder, usually arising in lymph
nodes.