Exam 4 Lymphatic System and Immunity

Lymphatic System
I. Introduction
A. The lymphatic system consists of organs, ducts, and nodes. It transports a watery clear fluid called
lymph. 
B. Main functions of lymphatic system:  
1. To collect and return interstitial fluid, including plasma protein to the blood, and thus help
maintain fluid balance
2. To defend the body against disease by maturing lymphocytes
3. To absorb lipids from the intestine and transport them to the blood
Lacteals are specialized lymphatic capillaries that carry dietary lipids into lymphatic vessels
and ultimately the blood. The presence of fats in the lymph gives it a milky appearance;
such lymph is called chyle.
II. Lymph formation and lymph circulation
A. Lymph formation: "Lymph” is basically the fluid and protein that has been squeezed out of the
blood (i.e. blood plasma). The flow if lymph through lymph vessels is:
Lymph capillaries àLymphatic Vessels à Lymph Trunks à Thoracic Duct & Right Lymphatic Duct

Major Lymphatic Trunks of the Body

1. Lumbar - drain lymph from the lower limbs, the viscera of the pelvis, the kidneys, adrenal glands
and the abdominal wall
2. Intestinal – drains lymph from the stomach, pancreas, intestines, the spleen and part of the liver.
3. Bronchomediastinal – drains lymph from the thoracic wall, lungs and heart
4. Subclavian – drains lymph from the upper limbs
5. Jugular – drains lymph from the head and neck
Lymph will eventually be dumped back into the Blood system
1. Thoracic Duct (Left lymphatic duct) - This structure begins as dilation called the cisterna chyli.
The thoracic duct is the main duct that returns lymph back to the blood stream at the point of the left
subclavian vein.
2. Right Lymphatic Duct – theoretically receives lymph from the upper right side of the body.
Lymph moves through the lymphatic system as the result of:
1. The milking action of skeletal muscle contractions (Skeletal Muscle Pump)
2. Respiratory movements called the (Respiratory Pump).
3. Lymphatic vessels have valves which prevent backflow of lymph
III. Lymphatic Organs and Tissues
A. Lymphatic organs and tissues are classified into twp groups based on their functions.
1. Primary lymphatic organs and tissues are the sites where stem cells divide and
become immunocompetent. These organs/tissues are:
a. Red bone marrow – in flat bones and the epiphyses of long bones in adults.
b. Thymus is a bilobed organ located in the mediastinum between the sternum and the aorta.
The thymus is most active during childhood and atrophies greatly as a person matures.
2. Secondary lymphatic organs and tissues are the sites where most immune responses occur.
These organs/tissues are:
a. Lymph nodes are encapsulated oval structures located along lymphatic vessels
they are scattered throughout the body, usually in groups.
1. Lymph enters nodes through afferent lymphatic vessels, is filtered to remove
damaged cells and microorganisms, and exits through efferent lymphatic vessels.
a. Foreign substances filtered by the lymph nodes are trapped by nodal reticular
fibers.
b. Macrophages then destroy some foreign substances by phagocytosis and
lymphocytes bring about the destruction of others by immune responses.
2. Lymph nodes are the site of proliferation of B cells and T cells.
b. Spleen is the largest mass of lymphatic tissue in the body and is found in the
left hypochondriac region between the fundus of the stomach and the diaphragm.
1. It is a site of B cell proliferation into plasma cells, phagocytosis of bacteria and
worn-out or damaged red blood cells and platelets, and storage of blood.
c. Lymphatic nodules (follicles) are egg-shaped masses of lymphatic tissue that
are not surrounded by a capsule.
1. MALT (mucosa-associated lymphatic tissue) lymphatic nodules
 located throughout the connective tissue of the mucous membranes lining
the gastrointestinal, urinary and reproductive tracts and the respiratory airways.
2. Tonsils are multiple aggregations of large lymphatic nodules embedded in
a mucous membrane at the junction of the oral cavity and the pharynx..
a. They include the pharyngeal (adenoid), palatine, and lingual tonsils.
b. They are situated strategically to protect against invasion of
foreign substances and participate in immune responses by producing
lymphocytes and antibodies.
The Immune System: Non-Specific Immunity
I. Introduction: The body possesses two mechanisms which protect it from potentially dangerous
viruses, bacteria, other pathogens and abnormal cells which could develop into cancer.
1. One of these mechanisms is nonspecific, that is, it does not distinguish between infective agents.
2. The second mechanism is specific in that it responds in a very specific manner to the particular
type of infective agent.
A. Nonspecific resistance refers to a wide variety of body responses against a wide range of pathogens
and their toxins.
1. Nonspecific resistance or immunity consists of both mechanical and chemical factors
are involved.
a. Mechanical defenses include the intact epidermis layer of the skin, mucous membranes, the
lachrymal apparatus, saliva, mucus, cilia, the epiglottis, and the flow of urine. Defecation and
vomiting also may be considered mechanical processes that expel microbes.
b. Chemical factors are localized on the skin, in loose connective tissue, stomach and vagina.
1. Oil and sweat acidify the surface of the skin (pH 3-5). The normal bacterial flora that is on
our skin also contributes to the skins acidic pH by releasing metabolic wastes. Acidity inhibits
microbial growth.
2. Saliva, tears and mucous secretions wash away potential invading microbes in addition to
containing antimicrobial substances. An enzyme (lysozyme) in perspiration, tears, and saliva
attacks the cell walls of many bacteria and destroys other microbes entering the respiratory
system and eyes.
3. In the digestive tract, stomach acid kills many bacteria that enter with foods or those
trapped in swallowed mucus from the upper respiratory system.
4. Areolar (loose) connective tissue contains hyaluronic acid, which helps to contain
infections to a localized area.
2. Antimicrobial substances, such as transferrins, interferon, complement, and properdin, work
against colonization by viruses and bacteria and provide a second line of defense should microbes
penetrate the skin and mucous membranes.
a. Interferons (IFNs) are released by cells infected by viruses. Once produced interferon diffuses
to uninfected neighboring cells and binds to surface receptors, inducing uninfected cells to
synthesize antiviral proteins that interfere with or inhibit viral replication. INFs also enhance the
activity of phagocytes and natural killer (NK) cells, inhibit cell growth, and suppress tumor
formation. They are most effective against short-term infections (colds and influenza).
b. Complement proteins are a group of about 20 proteins present in blood plasma and on cell
membranes. When activated, these proteins “complement” or enhance certain immune, allergic,
and inflammatory reactions.
Complement proteins also have the ability to kill pathogens in three ways
1. Membrane attack complex - The complex lyses the pathogen.
2. Opsonization is a cooperative mechanism in which complement proteins attach to
a foreign cell and stimulate phagocytes to engulf the cell.
3. Immune adherence - complement proteins and antibodies coat a microbe
which causes it to adhere to blood vessel walls and other surfaces; this makes the
cell easy prey for circulating phagocytes.
3. Phagocytic White Blood Cells and Natural Killer Cells
a. Neutrophils comprise 60% -70% of total white cells. They are attracted by
chemical signals to infected areas. Once they arrive to an infected area they have
two methods of killing.
1. Phagocytosis
2. Respiratory burst *
b. Monocytes comprise only about 5% of the total white blood cells. When monocytes
enter the tissues they enlarge and become macrophages. Most wander through
 interstitial fluid phagocytizing bacteria, viruses and cell debris. Some are fixed in
place in certain locations of the body where they will come into contact with infectious agents.
Macrophages kill using two methods.
1. Phagocytosis *
2. Respiratory burst
Types of Macrophages
1. Alveolar macrophages/dust cells in the lungs
2. Histiocytes in the connective tissue
3. Kupffer cells in the liver
4. Microglial cells in the neural tissue
Related Cells
1. Dendritic cells found in the epidermis, oral mucosa, esophagus, vagina
and lymphatic organs
c. Eosinophils represent about 1.5% of the total white cell count but have limited
phagocytic activity.
1. Contain destructive enzymes in cytoplasm granules which are discharged against
the outer covering of the invading pathogen.
2. Main contribution is defense against larger invaders such as parasitic worms.
d. Natural killer cells
1. Kill aberrant cells that could form tumors.
2. Destroy the body’s own infected cells, especially those harboring viruses. Are not
phagocytic, but attack the membrane, causing cell lysis. When a NK cell recognizes that
a cell is abnormal, it secretes proteins called perforins, which bind to the enemy cell and
make holes in the membranes.
3. Theory of Immunological Surveillance
4. The Inflammatory Response - occurs when there is damage to a tissue due to physical
injury or infection.
a. The purpose of the inflammatory response is to restore tissue homeostasis by:
1. Protecting and defending the body by eliminating microbes, toxins, or foreign material
from the site of injury
2. Preventing the spread of microbes, toxins, or foreign material to other organs
3. Preparing the site for tissue repair.
b. The stages of the inflammatory response are:
1. Vasodilation
2. Increased permeability of the blood vessels
3. Phagocyte migration
4. Repair
c. Inflammation is usually characterized by four symptoms:
1. Redness
2. Pain,
3. Heat,
4. Swelling.
5. Loss of function- depending on the site and extent of the injury.
d. Chemical signals are important in initiating an inflammatory response.
1. Histamine is released from injured circulating basophils and mast cells in the connective
tissue. Released histamine causes localized vasodilation and the capillaries in the area to
become more permeable =leakier.
2. Prostaglandins are released from white blood cells and damaged tissues. Prostaglandins
promote increased blood flow to the injured area.
e. Migration of phagocytic cells into the injured area is also a result of increased blood flow and
increased leakage from the capillaries.
1. Phagocytes are attracted to the damaged tissues by several chemical mediators.
CHEMOTAXIS
 2. Neutrophils arrive first, followed closely by monocytes which develop into macrophages.
3. The neutrophils eliminate microorganisms and then die.
4. Macrophages destroy pathogens and clean up the remains of damaged tissue cells and
dead neutrophils.
5. Dead cells and fluid leaked from the capillaries may accumulate as pus in the area before it
is absorbed by the body.
5. Fever (Pyrexia)- A fever may develop in response to toxins produced by pathogens or due to pyrogens
released by leukocytes. While a high fever is dangerous (104 0F), moderate fevers inhibit the growth of
some microorganisms. The high body temperature inhibits some microbial growth and speeds up body
reactions that aid repair
Specific Immunity
I. General Aspects of Specific Immunity
A. The immune system is not an organ system but a group of widely distributed cells that recognize
foreign substances and act to neutralize or destroy them.
Two characteristics distinguish immunity from non-specific resistance.
1. Specificity – Immunity is directed against a particular pathogen. Immunity to
one pathogen usually does not confer immunity to others.
2. Memory in general function in secondary immune responses.

The primary immune response is the proliferation of lymphocytes to form clones of effector
cells specific to an antigen during the body’s first exposure to the antigen. There is a 5 to 10
day lag period between exposure and maximum production of effector cells.

A secondary immune response occurs when the body is exposed to a previously

encountered antigen. The response is faster (3 to 5 days) and more prolonged than a primary
response. This ability to recognize a previously encountered antigen is known as
immunological memory and specifically when discussing T cells is called T cell recall
response. When discussing B cell pathways it is referred to as the anamnestic
response.

B. Forms of Specific Immunity – there are two pathways of immunity that interact extensively with
each other.

1. Cell Mediated Immunity (CMI) depends on the action of T lymphocytes (T cells).

2. Antibody Mediated Immunity (AMI) depends on the action of B lymphocytes
(B cells).

Immunity can also be classified as Active vs. Passive. Under this scheme we can recognize 4
classes of immunity:
Active Immunity
1. Natural Active Immunity. This refers to the production of one’s own specific immunity cells as a
result of infection or other natural exposure to something that is foreign to the body (antigenic).
2. Artificial Active Immunity. This refers to the production of one’s own specific immunity cells as a
result of vaccination against disease. A vaccine consists of either dead or attenuated (weakened)
pathogens which can stimulate the body’s immune response but normally cause little or no discomfort
or disease. Active Immunity is long lasting because memory cells are produced
Passive Immunity
3. Natural Passive Immunity. This is temporary immunity that results from acquiring antibodies
produced from another individual. The only natural way for this to happen is for a fetus to acquire it
through the placenta before birth or for the baby to acquire it through the colostrums or breast milk
after birth.
4. Artificial Passive Immunity. This is a temporary immunity that results from the injection of an
immune serum obtained from another individual or from an animal that produced antibodies against a
certain pathogen. Passive Immunity is short term typically lasts for about 2-3 weeks
 C. Cells of the Immune System
1. Lymphocytes
a. B cells (B lymphocytes) are responsible for the humoral immune response or Antibody
Mediated Immunity. B cells defend against pathogens in body fluids by generating specific
antibodies. B cells are made in the red bone marrow and remain there to complete their
maturation.
b. T cells (T lymphocytes) are responsible for the cell-mediated immune response. They also
form in the red bone marrow, and then migrate to the thymus gland to mature. T cells respond
only to antigenic epitopes displayed on the surfaces of the body’s own cells. T cells cannot
detect free antigens in the body fluids.
2. Mature B cells and T cells are concentrated in the lymph nodes, spleen, and other
lymphatic organs.
a. These positions place lymphocytes where they are most likely to contact antigens.
b. Antigen receptors are present on the membranes of both B cells and T cells.
c. The antigen receptors on a B cell are membrane-bound antibody molecules which
will recognize specific antigens.
d. The T cell antigen receptors are proteins (not antibodies) embedded in the
membrane which recognize specific antigens.
3. Effector cells are the cells which actually defend the body during an immune response.
E. Antigen-Presenting Cells (APCs)
1. In addition to their other roles, B cells, and macrophages function as antigen presenting cells.
This means that after these cells phagocytize a pathogen they will display or present the pathogen’s
epitope on their plasma membranes. This ability hinges on a family of genes called the major
histocompatibility complex (MHC). The function of these MCH markers is to act as markers that
label your cells as belonging to you. You can think of them as “Me Markers” or “Identification Tags”.
The antigenic marker will always be displayed in conjunction with the MHC marker.
2. There are two main classes of MHC molecules in the body:
a. Class I MHC molecules are located on all nucleated cells of the body.
b. Class II MHC molecules are found only on macrophages, B cells, and T cells.
F. Chemical Messengers: Cytokines
1. Cytokines - Chemicals secreted by one cell as a regulator of neighboring cells. Cytokines help
regulate both B and T cells and thus are involved in both the humoral and cell-mediated responses.
a. Interferon – secreted by virally infected cells
b. Interleukin – secreted by leukocytes
II. Cell Mediated Immunity = The Players
A. Cells and Chemicals involved:
1. Cytotoxic T (Tc) cells are the “effector cells” (warriors) of cellular immunity which carry out the
attack on foreign cells.
a. Attack by docking to an enemy cell and delivering a lethal hit of cytotoxic chemicals.
1. Perforin – creates holes in plasma membranes
2. Lymphotoxin – destroys the targets cell’s DNA
3. Tumor necrosis factor (TNF) – kills cancer cells by unknown mechanisms
2. Helper T (Th) cells promote the action of Tc cells as well as playing key roles in AMI and
nonspecific defense. All other T cells are involved in CMI only.
3. Suppressor T (Ts) cells limit CMI attack and keep the immune system from running out of
control. Th and Ts cells are regulatory lymphocytes. T helper = on switch Suppressor T = off switch
4. Memory T cells are descended from helper T and cytotoxic T cells and are responsible for
memory in CMI.
5. Antigen Presenting Cells (APC’s) = macrophages and infected body cells
a. APCs and the Activation of T Cells
1. The receptor of a helper T cell (Th) called a protein recognizes the molecular
combination of an antigen fragment with a class II MHC (Macrophage). The presence
of a T cell surface molecule called CD4 enhances the interaction between Th cells and
antigen-presenting cells (APC).
 2. The receptor of a cytotoxic T cell (Tc) recognizes the combination of an antigen
fragment with a class I MHC molecule (Infected Body cell). Tc cells carry a surface
molecule called CD8 which has an affinity for class I MHC molecules.
6. Cytokines: Interferon and Interleukin 1 and 2
E. Pathway Steps CMI
1. A macrophage calls the Th cells to him by releasing interleukin I.
2. A Th cell with the correct surface receptor will hook up with the macrophage. When a Th cell binds
to antigen-presenting macrophage recognition occurs which causes the Th cells to begin to multiple.
Clonal Selection
3. When the Th helpers multiply we also at this time set some of these aside to become T helper
memory cells.
4. Activated T helpers secrete interleukin II
5. Interleukin II does two important things:
1) calls cytotoxic T cells to the infected area so that they can become activated
2) Activates B cells that also have the ability to recognize this particular antigen.
6. Activated cytotoxic T cells go out and destroy infected host cells.
7. Once the pathogen has been defeated suppressor T cells down regulate the
immune response.
III. Antibody Mediated Immunity= AMI
A. Cells and Chemicals involved:
1. B cells defend against pathogens in body fluids by generating specific antibodies. The surface
receptor of a B cell is called an antibody.
2. Plasma cells are the effector cells of this pathway. Their function is to produce and
secrete antibodies into the blood and lymph. Antibodies, in general, function to tag antigens
for destruction by other means. The rate of production is remarkable – 2000
antibodies per second.
3. Th cells - on-switch of both CMI and AMI.
4. Suppressor T (Ts) cells limit CMI attack and keep the immune system from running out of
control. Th and Ts cells are regulatory lymphocytes. T helper = on switch Suppressor T = off switch
5. Memory B cells - Memory B cells are found mainly in the germinal centers of lymph nodes. The
secondary immune response is also sometimes referred to as the anamnestic response.
6. Antigen Presenting Cells (APC’s) = macrophages
7. Cytokines: Interferon and Interleukin 1 and 2
B. Pathways - There are 2 sub-pathways to AMI (T-Dependent and T – Independent)
1. T-independent Pathway – In this pathway antigens, Usually long chains of repeating units
such as polysaccharides or protein subunits often found in bacterial capsules and flagella,
trigger humoral immune responses without macrophage or T cell involvement.
a. Pathway Steps:
1. B cells are stimulated directly by the antigen.
2. The B cell phagocytizes the antigen and begins to present the antigen on its surface
in conjunction with the MHC marker (in this case a MHC class II marker)
3. This pathway usually stops right here.
4. The antibody production from this pathway is usually much weaker than that of T dependent
antigens.
5. No memory cells are generated in T-independent responses.
2. T-Dependent - In this pathway involves the cooperative response of macrophages,
helper T cells, and B cells. (Most antigens illicit the T-dependent pathway)
a. Pathway Steps:
1. A macrophage calls B cells and Th cells to him by releasing interleukin I.
2. The B cell along with the Th cell with the correct surface receptor will hook up with
the macrophage. When a Th cell binds to antigen-presenting macrophage recognition
occurs and the Th cells will secrete interleukin II. Interleukin II causes B cells and Th
cells to begin to multiple.
5. Interleukin II activates B cells that also have the ability to recognize this particular
 antigen.
6. Some of the activated B cells turn into Plasma cells. Plasma cells secrete
antibodies into the surrounding blood and lymph. Memory cells are also made at this
time.
7. Once the pathogen has been defeated suppressor T cells down regulate the
immune response.
C. How antibodies work
1. Antibodies comprise a specific class of proteins called immunoglobulins (Ig).
a. The structure of the immunoglobulin is associated with its function.
b. Antibodies are Y-shaped molecules comprised of four polypeptide chains: two identical
light chains and two identical heavy chains. All four chains have constant (C) regions that
vary little in amino acid sequence among antibodies that perform a particular type of
defense.
c. At the tips of the Y are found variable (V) regions in all four chains; the amino acid
sequences in the variable region show extensive variation from antibody to antibody.
The variable regions function as antigen-binding sites and their amino acid sequences
result in specific shapes that fit and bind to specific antigen epitopes.
d. The antigen-binding site is responsible for the antibody’s ability to identify its specific
antigen epitope and the stem (constant) regions are responsible for the mechanism by
which the antibody inactivates or destroys the antigenic invader .
2. Types of antibodies
a. There are five types of constant regions, each of which characterizes one of the
five major classes of mammalian immunoglobins.
1. IgM. Consists of five Y-shaped monomers arranged in a pentamer structure. Circulating
antibodies which appear in response to an initial exposure to an antigen.
2. IgG. A Y-shaped monomer. Most abundant circulating antibody; readily crosses blood
vessels and enters tissue fluids; protects against bacteria, viruses, and toxins circulating
in blood and lymph; triggers complement system action.
3. IgA. A dimer consisting of two Y-shaped monomers. Produced primarily by cells abundant
in mucous membranes; prevents attachment of bacteria and viruses to epithelial surfaces;
also found in saliva, tears, perspiration, and colostrum.
4. IgD. A Y-shaped monomer. Found primarily on external membranes of B cells; probably
functions as an antigen-receptor which initiates differentiation of B cells.
5. IgE. A Y-shaped monomer. Stem regions attach to receptors on mast cells and basophils;
stimulates these cells to release histamine and other chemicals that cause allergic
reactions when triggered by an antigen.
3. How Antibodies Work
a. Antibodies do not directly destroy an antigenic pathogen. The antibody binds to the antigen
to form an antigen-antibody complex which tags the invader for destruction by one of several
effector mechanisms.
1. Neutralization is the simplest mechanism. The antibody blocks viral attachment
sites or coats a bacterial toxin, making them ineffective. Phagocytic cells
eventually destroy the complex.
2. Agglutination is another mechanism. Each antibody has two or more antigen-binding
sites and can cross-link adjacent antigens. The cross-linking can result in clumps of a
bacteria being held together by the antibodies, making it easier for phagocytes to engulf the
mass.
3. Precipitation is similar to agglutination but involves the cross-linking of
soluble antigen molecules instead of cells. These immobile precipitates are
easily engulfed by phagocytes.
4. Complement Fixation Activation of the complement system is another mechanism.
Antibodies combine with complement proteins; this combination activates the complement
proteins which produce lesions in the foreign cell’s membrane that result in cell lysis.