The Lymphatic System

Lymphatic System consists of fluid called lymph flowing

inside the lymphatic vessels, some structure and tissues that
contain lymphatic tissue and bone marrow. Bone marrow
houses Stem cells that develop into lymphocytes and
provide immunity.
When interstitial fluid passes in to lymphatic vessels, it is
called Lymph i.e. Clear water. Interstitial fluid and lymph
are basically same except for location.
Filtration forces water and dissolved substances from the
capillaries into the interstitial fluid. Not all of this water is
returned to the blood by osmosis, and excess fluid is picked
up by lymph capillaries to become lymph.
Functions of the lymphatic system:
1) Draining Interstitial fluid: To maintain the pressure and
volume of the extracellular fluid by returning excess water
and dissolved substances from the interstitial fluid to the
circulation.
2) Protecting against invasion: Lymph nodes and other
lymphoid tissues are the site for production of immuno-
competent lymphocytes and macrophages in the specific
immune response. T lymphocytes rupture foreign cells or
produce toxins while B lymphocytes differentiate in to
plasma cells that secrete antibodies.
3) Transporting Dietary lipids: Lymphatic vessels carry
lipids and lipid soluble vitamins (ADEK) absorbed by
gastro- intestinal tract.
Lymph capillaries: Close ended vessels lies in the space
between cells. It carries many pores which allow interstitial
fluid including large lipids to get inside the lymphatic
circulation but do not allow coming out.
Lacteals: (Lacteal = Milky) Each Villi in the small
intestine has centrally placed lymphatic vessels called
Lacteal. It transport lipids absorbed in the intestine.
From lymph capillaries fluid flows into lymph veins
(lymphatic vessels) which virtually parallel the circulatory
veins and are structurally very similar to them, including
the presence of semilunar valves.
Lymphatic Vessels: Lymph capillaries unite to form
Lymphatic vessels. Resemble vein in structure except it is
thin and have more valves.
Lymph capillaries containing lymph are found through out
the body except in
1. Avascular tissue
2. Central Nervous System
3. Spleenic pulp
4. Bone marrow
Lymphatic Ducts: The lymphatic veins flow into one of
two lymph ducts.
1. The right lymph duct drains the right arm, shoulder area,
and the right side of the head and neck. It is half inch in
length.

2. The left lymph duct (thoracic duct), drains everything

else, including the legs, GI tract and other abdominal
organs, thoracic organs, and the left side of the head and
neck and left arm and shoulder. It is 15-18 inches in length
and is a major vessel of the system.
These ducts then drain into the subclavian veins on each
side where they join the internal jugular veins to form the
brachiocephalic veins.
Formation and flow of lymph:
The excess fluids in the interstitial space i.e. about 3 lit/ day
drains in to the lymphatic vessels and become lymph.
Arteries (blood plasma) Blood capillaries
Interstitial space Lymph capillaries (Lymph)
Lymphatic Vessels Lymphatic Ducts
Subclavian vein Heart
Lymph nodes lie along the lymph veins successively
filtering lymph. Afferent lymph veins enter each node,
efferent veins lead to the next node becoming afferent veins
upon reaching it.
Lymphokinetic motion (flow of the lymph) due to:
1) Lymph flows down the pressure gradient.
2) Muscular and respiratory pumps push lymph forward
due to function of the semilunar valves.

Other lymphoid tissue:

1. Lymph nodes: Lymph nodes are small
encapsulated organs located along the pathway of
lymphatic vessels. They vary from about 1 mm to 1 to 2 cm
in diameter and are widely distributed throughout the body,
with large concentrations occurring in the areas of
convergence of lymph vessels. They serve as filters through
which lymph percolates on its way to the blood. Antigen-
activated lymphocytes differentiate and proliferate by
cloning in the lymph nodes.
2. Diffuse Lymphatic Tissue and Lymphatic
nodules: The alimentary canal, respiratory passages, and
genitourinary tract are guarded by accumulations of
lymphatic tissue that are not enclosed by a capsule (i.e. they
are diffuse) and are found in connective tissue beneath the
epithelial mucosa. These cells intercept foreign antigens
and then travel to lymph nodes to undergo differentiation
and proliferation. Local concentrations of lymphocytes in
these systems and other areas are called lymphatic nodules.
In general these are single and random but are more
concentrated in the GI tract in the ileum, appendix, cecum,
and tonsils.
3. The Thymus gland: The thymus is bilobed organ
which is located in between the lungs, posterior to the
sternum. The thymus is where immature lymphocytes
differentiate into T-lymphocytes. The thymus is fully
formed and functional at birth. Characteristic features of
thymic structure persist until about puberty.
The transformation of primitive or immature
lymphocytes into T-lymphocytes and their proliferation in
the lymph nodes is promoted by a thymic hormone called
thymosin. Ocassionally the thymus persists and may
become cancerous after puberty and and the continued
secretion of thymosin and the production of abnormal T-
cells may contribute to some autoimmune disorders.
 5. The spleen: The spleen oval and largest lymphatic
mass which filters the blood and reacts
immunologically to blood-borne antigens. In addition
to large numbers of lymphocytes the spleen contains
specialized vascular spaces, a meshwork of reticular
cells and fibers, and a rich supply of macrophages
which monitor the blood.
The human spleen holds relatively little blood
compared to other mammals, but it has the capacity
for contraction to release this blood into the circulation
during anoxic stress. White pulp in the spleen contains
lymphocytes and is equivalent to other lymph tissue,
while red pulp contains large numbers of red blood
cells that it filters and degrades.
The spleen functions in both immune and
hematopoietic systems. Immune functions include:
proliferation of lymphocytes, production of antibodies,
removal of antigens from the blood. Hematopoietic
functions include: formation of blood cells during fetal
life, removal and destruction of aged, damaged and
abnormal red cells and platelets, retrieval of iron from
hemoglobin degradation, storage of red blood cells.
 Immune System

I. Non-specific responses -
General mechanisms for discouraging pathogens which do
not require the identity of the pathogen's antigenic nature.
These are the first line of defense against invasion by
pathogens.
A. Surface Membrane Barriers
1. Skin
a. acidic pH
 b. Keratinization protects unbroken skin against
acids and bases of bacterial enzymes and toxins.
2. Mucous membranes
a. HCl in the stomach kills many pathogens,
denatures proteins
b. Saliva contains lysozyme, a bactericide
c. Lacrimal fluid contains lysozyme
d. Mucus traps organisms
B. Cellular And Chemical Defenses
1. Phagocytes - engulf particulates, including
microorganisms, which pass through the external barriers.
Examples: histiocytes in the lungs, Langerhans cells in the
skin, Kupffer cells in the liver, microglia in the nervous
system, macrophages in other tissues.
2. Natural killer cells - these large lymphocytes lyse
and kill tumor and virus-infected cells before activation of
a specific immune response.
3. Inflammation
a. reduces spread of damaging agents to nearby tissues
b. increases disposal of cell debris and pathogens
c. facilitates repair processes
d. caused by histamine and prostaglandins released
by basophils and other cells.
4. Anti-microbial proteins
a. Non-Specific complement activation
b. Interferons - block tumor and viral reproduction
c. Interleukin I - stimulates the immune response
5. Fever
a. Due to pyrogens secreted by leucocytes
b. Disrupts metabolism of pathogens
II. Specific Responses –
These second line of defense responses are activated by,
and directed against, a specific antigen.
Antigen - a protein or other substance which elicits immune
system activation in a "foreign" host.
A. Humoral Immunity - the B-cell response
1. Antigen challenge - "non-self" antigen binds to
antigen-specific surface receptors on generic B-cell.
2. Clonal selection - multiplication of B-cells
produces cells which all contain the same antigen-specific
surface receptor.
a. Primary response - plasma cells secrete free
antibodies of the same structure as the antigen-specific
surface receptor. The primary response takes 7 to 10 days
to reach maximum antibody levels.
b. Secondary response - memory cells which
retain the ability to quickly clone to produce more plasma
cells should the antigen be encountered again. The
secondary response takes from 1 to 2 days to reach
maximum antibody levels.
3. Antibodies form antigen-antibody complexes which
have the following affects:
a. Opsonization - labeling of antigens or foreign
cells
b. Neutralization - inactivation of bacterial toxins
c. Agglutination - clumping of cell-bound antigens
d. Precipitation - removes soluble antigen from
solution
e. Complement fixation - which causes cell lysis.
Complement protein binds to a site on the constant (Fc)
portion of the antibody.
4. Classes of antibodies:
IgD - (monomer) antigen receptor on B-cell
IgM - (pentamer) first antibody released by plasma
cells during primary response
IgG - (monomer) comprises most circulating
antibodies, both 1o and 2o responses
IgA - (dimer) antibody found in secretions
IgE - (monomer) secreted in mucosae, mediates
inflammation in allergic reaction.
 B. Cell Mediated Immunity - the T-cell response -
requires an intermediary cell to be stimulated. These
intermediary cells can be infected body cells or
macrophages as below. Identification of these cells and
their antigens is by means of MHC proteins. MHC (Major
Histocompatibility Complex) antigens are recognition
proteins which identify a cell as being "self". They are
displayed together with part of the antigen from invading
viruses to be recognized by T-cell lymphocytes. There are
two classes of MHC antigens: Class I is present on all body
cells; Class II is present only on cells of the immune
system.
There are several types of T cells.
1. generic cytotoxic T-cells
a. respond to antigens complexed by MHC I
proteins from infected body cells.
b. attack and kill virus or bacteria-infected cells and
tumor cells
c. maintain immunologic surveillance
d. clone to produce mature cytotoxic cells and
cytotoxic memory cells
2. Helper T-cells
a. respond to antigens complexed with MHC II
proteins on antigen presenting cells
b. act as costimulator cells for B-cells and other T-
cells and . Activated Helper cells release interleukin II and
act as a costimulator for an effective B-cell response.
 c. release interleukin I which acts as a costimulator
for T-cell production.
3. Suppressor T-cells - regulatory cells which tend to
shut down B and T-cell responses.
4. Cytokines - chemical mediators involved in cellular
immunity.
a. interleukin I - costimulator for activated T-cells
b. interleukin II - stimulates both B and T-cell
proliferation
c. MAF - macrophage activating factor
d. MIF - macrophage migration inhibiting factor
e. perforin - causes cell lysis
f. lymphotoxin - kills cells by fragmenting their
DNA
g. tumor necrosis factor - specialized destruction
of tumors.
C. Immunocompetence: (often called immune
tolerance because it is the tolerance of your own cells) is
the ability of your immune system to recognize self vs.
non-self (anti-self, foreign) antigens. This ability is
conferred during childhood. For T cells the site for this is
the thymus gland which ceases this activity after puberty.
The site for the B cells is unknown. The name B cell comes
from the Bursa of Fabricus, a gut-associated site which is
the site of immunocompetence in chickens. Humans don't
have a Bursa, so a "Bursa Equivalent" confers
immunocompetence, possibly the marrow, but recent
evidence suggests an area analogous to the bursa in the
distal GI tract. During childhood, immature or pre-
lymphocytes originate in the marrow, travel to the thymus
(or other area) for immuno-competence, then travel to the
lymph nodes where they proliferate in response to antigenic
stimulation.
D. Hypersensitivity
1. Type I Hypersensitivity - this is the basis for
allergic reactions. Usually this occurs when you have been
exposed to non-pathogenic foreign antigen and built up
memory cells. Subsequent exposure causes these cells to
become plasma cells which release large amounts of IgE
antibodies. IgE antibodies bind to basophils and mast cells
causing them to release granules containing histamine and
other inflammatory chemicals. This is the basis for the
vascular changes seen in allergy and anaphylaxis.
2. Type II Hypersensitivity - this is a type of
autoimmunity. Autoimmune disorders can result when
host antigens are similar to invading antigens and cross
reactions occur, or from mutations of antigens, or by
antigens which are masked or not present during the period
of immunocompetence, or which are altered by
environmental or disease factors and cease to be recognized
as "self", or by lack of immune tolerance (another term for
immunocompetence). Among diseases which have been
classified as autoimmune are: multiple sclerosis,
myasthenia gravis, Graves disease, andsome forms of Type
1 diabetes mellitus.
 3. Type III Hypersensitivity occurs when the
antigen-antibody complexes produced by normal immune
system reactions are not removed and lodge in the
basement membrane of endothelial cells and in other
connective tissues. Their presence induces massive
inflammation by triggering the complement pathway with
resulting cell lysis, hemorrhage, and tissue destruction.
Examples include: systemic lupus erythematosus (SLE),
rheumatoid arthritis and acute glomerulonephritis.