.08.

Chapter Summary: Lymphoid System

1 General

The body is under constant threat of invasion by disease-causing microorganisms. Thus, the
body employs several lines of defense.
The first of these defenses consist of the skin and mucous membranes (mucosae) that act
as physical barriers to the entry of harmful substances into the body.
When the first line of defense fails, the body releases cells that mounts to types of defense
systems: inflammatory response and immune response.

2 Infl ammatory Response

The inflammatory response is an immediate but mainly localized process that starts within
minutes of tissue damage or entry of a microorganism or a foreign antigen.
The effector cells of this process consists of phagocytes and macrophages. They are assisted
by other cells including eosinophils, basophils, mast cells, NK cells, and T-cells.
The inflammatory response is turned on by many ways: sometimes, invading microorganisms
produce chemotaxins (a chemical that attracts phagocytes) and sometimes the foreign
materials are detected by the complement system.
The complement system is a collection of more than 20 plasma proteins that are produced by
the liver. It is involved in both inflammatory and immune responses. In immune response, it is
activated by the antibodies (immunoglobulins).
The activation of the complement system during inflammation has the following effects:
production of chemotaxins, marking off of bacteria with proteins (opsonins) to facilitate
phagocytosis, and releasing cytokines, and triggering the release of other mediators of
inflammation such as histamine by mast cells and basophils.
Once the inflammatory process has been triggered, activated phagocytes congregate in the
injured area within minutes. Then they start to engulf and digest the invading microorganisms
or other foreign elements. In addition to digesting pathogens, macrophages and other antigen-
presenting cells (APC) process the antigens they have digested then they attach some parts
of the antigens on their surface for presentation to T-cells.
The cytokines and other mediators are responsible for the classical local signs and symptoms of
inflammation (swelling, redness, heat and pain).
Fever occurs when interleukin-1, a cytokine produced by activated macrophages enters the
bloodstream and reaches the hypothalamus where it responds by increasing body
temperature.

3 Immune Response

The immune response is a more powerful body defense system than the inflammatory response.
The immune response is not innate; it must be developed. It is antigen-specific which
means it must be developed for every antigen.
The principal effector cells of the immune response are the lymphocytes, classified into three
types based on the antigen receptors present on their surfaces: B-cells have B-cell receptors
(BCR), T-cells carry T-cell antigen receptors (TCR), and NK cells carry natural cytotoxicity
receptors (NCR).
All T-cells and NK cells express the CD3 molecular complexes.
All T-cells would either have a CD4 or a CD8 marker.
Those with CD4 markers can differentiate into helper T-cells.
Those with CD8 markers can differentiate into cytotoxic T-cells and suppressor T-cells.

4 Types of Immune Responses

There are two types of immune responses: humoral and cell-mediated. One predominated,
depending on the nature of the antigen.
Japhet MLS 2-2
4.1 Humoral Immunity (Antibody-mediated immunity)

Humoral immunity refers to immunity that is mediated by antibodies. Antibodies

(immunoglobulins) are substances that are synthesized by plasma cells. Thus, humoral
immunity is primarily the function of B-cells because plasma dells differentiate from B-cells.
Antibodies do not destroy antigens they simply bind to the antigens that have triggered their
production.
In certain instances, antibodies serve to pinpoint antigens to phagocytes then phagocytes
phagocytose them.
Humoral immunity is important in containing many viral and bacterial infections. It is also the
type of immunity that is conferred by vaccines against many childhood illnesses.

4.2 Cell-mediated immunity

Cell-mediated immunity is the primary function of T-cells.

The effector cells of cell-mediated immunity are mainly the cytotoxic T-cells.
The Tc cells eliminate antigens that are inside cells. Their target cells include virus-infected cells
and cells with intracellular bacteria.
Tc cells are able to destroy their target cells by a variety of means: one is by inducing
apoptosis when they release the proteins in their cytoplasmis granules into the area where
their target cells are.
Cellular immunity is also responsible for delayed hypersensitivity reaction and tissue and organ
transplant rejection.

5 Development of an Immune Response

The entry of a new antigen into the body elicits a primary immune response. Subsequent
entries of the same antigen elicits a secondary immune response.

5.1 Primary Immune Response

A primary immune response is designed to eliminate the new antigen and more importantly,
produce a population of lymphocytes (memory B-cells and memory T-cells) that retain the
image of the new antigen in their memory.
Invovled the following steps: 1. Antigen recognition 2. Lymphocytes activation 3. Effector phase

5.2 Antigen Recognition

A new antigen is almost immediately encountered by an antigen-presenting cell (APC)

APCs are cells that phagocytose, destroy, and process antigens, and then display fragments of
the antigen on their surface for presentation to nave CD4+ T-cells.
Nave CD4+ T-cells do not differentiate into Th cells unless they are presented by an antigen by
an APC.
Nave B-cells do not react to an antigen unless they are activated by cytokines produced by the
helper T-cells.
Nave CD8+ T-cells also do not differentiate into Tc cells unless they are activated by APCs or
helper T-cells.
Macrophages are the effector cells of the inflammatory response. They process the antigens and
attach fragments of the antigens on their surfaces for presentation to nave T-cells.
Dendritic cells are the most potent of the APCs and are classified into two borad categories:
myeloid-related dendritic cell and lymphoid-related dendritic cell.
The myeloid-related dendritic cell differentiates from the colony-forming unit-
monocyte/dendritic cell (CFU-M/DC), a progenitor cell that it shares with the monocyte.
B-cells often act as APCs too.

5.3 Lymphocyte Stimulation

When nave CD4++ T-cells are presented an antigen by APCs in the presense of co-stimulators,
they proliferate and differentiate into any or all the following: Th1 cells that synthesize the
cytokines needed for cell mediated immunity, Th2 cells that synthesize the cytokines neede
for humoral immunity and Th3 cells that elaborate the cytokines that mediate the
inflammatory process.
5.4 Eff ector Phase

In humoral immunity, when Th2 cells encounter nave cells, they differentiate into plasma cells
and memory B-cells.
Plasma cells produce antibodies while memory B-cells carry the image of the antigen and are
responsible for effecting the secondary immune response.
Th1 cells secrete a variety of cytokines that stimulate CD8+ T-cells to proliferate.
Once the offending antigen has been eradicated, all the remaining antigenic specific cells that
have been generated during the primary immune response, undergo apoptosis.

6 Secondary Immune Response

The secondary immune response is elicited by re-exposure to an antigen that has previously
triggered a primary immune response.
It has a short induction phase (1 to 2 days) and a more rapid build-up.
B-cells or memory T-cells are able to immediately recognize the thread and rapidly divide and
differentiate into effector cells.

6.1 Abnormal Immune Responses

An overwhelming reaction to an antigen causes an allergic reaction.

Anaphylactic shock.

7 Components of the Lymphoid System

Lymphoid tissue refers to tissue where the parenchyma consists mainly of lymphocytes. This is
formed mainly by reticular fibers and reticular cells.
Lymphoid tissues and organs are classified into central (primary) and peripheral (secondary)
lymphoid tissues.
The primary lymphoid organs are the bone marrow and the thymus.
The peripheral lymphoid tissues and organs consist of the lymph nodes, spleen, and the
mucosa-associated lymphoid tissue. The MALT includes the tonsils and the non-
encapsulated lymphoid tissues in the gastrointestinal, respiratory, and genitourinary tracts.

8 Lymphoid Tissue

Lymphoid tissue exists in the body in the form of either diffuse lymphoid tissue or nodular
lymphoid tissue.

8.1 Diff use Lymphoid Tissue

Diffuse lymphoid tissue refers to lymphoid tissue where the lymphocytes are evenly dispersed.
Lamina propria and submucosa of the gastrointestinal, respiratory, and genitourinary tracts.
Most of the cells in diffuse lymphoid tissue are T-cells.
Diffuse lymphoid tissue where the lymphocytes are relatively few and far apart is called loose
lymphoid tissue.
Diffuse lymphoid tissue where the lymphocytes are numerous and close to each other is called
dense lymphoid tissue.

8.2 Nodular Lymphoid Tissue

Nodular lymphoid tissue refers to ovoid masses or lumps called lymphoid nodules.
In lymphoid nodules, the lymphocytes are mainly B-cells.
Two types of lymphoid nodules are distinguishable: primary and secondary.
A primary nodule is where lymphocytes are idle or resting. It does not have a germinal center.
The lymphocytes that it contains are all small lymphocytes.

9 Thymus

The thymus is the central lymphoid tissue that is tasked to transform T-stem cells into mature
nave T-cells.
The lymphocytes that populate the thymus are T lymphocytes.
 While in the thymus, the cells of the T-cell lineage are called as thymocytes.

9.1 Histologic Organization of the Thymus

Each of the two lobes of the thymus is enclosed by a capsule.

The trabeculae from the capsule divide the lobes into lobules
A thymic lobule exhibits a peripheral, darker-staining region (cortex) that surrounds a central,
lighter staining region (medulla).
The stroma of the thymic lobules are mainly made of stellate cells called epitheoid cells.
During their stay in the cortex, the T-cells acquire their receptors.
Thymic interdigitating dendritic cells help in preventing autoimmunity by presenting self-
antigens to enable the T-cells to recognize self anigens.
Only about 10% to 30% leave the thymus as mature, immunocompetent, and self-tolerant nave
T-cells.

9.2 Blood Vessels of the Thymus

It is in the postcapillary venules of the medulla that the lymphocytes join circulating blood by
migrating through the blood vessel walls.
The blood-thymus barrier prevents antigen that are carried by the capillaries from getting
into contact with the developing T-cells.
The BTB consists of: endothelial cells, epitheloid cells, and perivascular space.

10 Lymphatic Vessels of the Thymus

Lymph that is formed within the organ is collected by efferent lymphatic capillaries that start as
blind tubes.

11 Lymph Node

A lymph node is an encapsulated collection of lymphoid tissue.

In these organs, activated B-cells and T-cells can proliferate and differentiate into various
functional types.
The lymph nodes are highly efficient filters for particulate matter and microorganisms that are
present in the lymph.
The filtering is performed primarily by macrophages.
Lymph nodes may become swollen and tender when an infection is present in the area of
jurisdiction.
A lymph ndoe presents a n indented area called the hilus.

11.1 Histologic organization of the Lymph Node

The lymph node is alsoenclosed by a capsule.

The capsule gives off the trabeculae whose stroma is formed by reticular tissue.
The DCs in B-cell rich areas are called follicular dendritic cells.
The have a large, pale nuclei, and indistinct borders.
The medulla is paler staining than the cortex.
It is made up of dense lymphoid tissue arranged to form strands called medullary cords in
between medullary sinuses.

11.2 Lymphatic Vessels of the Lymph Node

Afferent lymphatic vessels ramify and give rise to smaller branches as they approach the lymph.
These vessels are provided with one-way valves.
The sinuses are irregularly-shaped lymphatic vessels. Their walls which permit all the
constituents of lymph to pass freely consist simply of an endothelium.
The efferent lymphatic vessels are provided with one-way valves.
The lymph enters a lymph node via the afferent lymphatic vessels.
Lymphocytes enter the lymph node primarily from blood by passing though the endothelial
lining of the blood vessels in T-cell rich areas.
 The lymphocytes leave the lymph node to join the recirculating pool primarily via the efferent
lymphatic vessels.

12 Spleen

The spleen is the largest lymphoid organ in the body. Its medial surface presents a notch, the
hilus, where blood vessels enter and leave the organ.
In this organ, the lymphocytes, when activated by blood-borne antigens, proliferate and
differentiate into different functional types.
The spleen also filters blood. It has an enormous number of macrophages that destroy foreign
substances microorganisms, and abnormal cells present in the blood. It also removes and
destroys damaged and old red blood cells and platelets from circulating blood while recycling
the iron that is contained in the RBCs. It also acts as a storage area for blood.
The spleen is not a vital organ.

12.1 Histologic Organization of the Spleen

Like all lymphoid organs, the spleen is encased by a capsule made up of dense irregular
connective tissue.
Externally, the capsule is completely enveloped by peritoneum. This the spleen is lined on its
external surface by mesothelium.

12.2 White Pulp

The white pulp consists of lymphoid nodules that are embedded in dense lymphoid tissue.
The white pulp comprises the lymphocyte population of the spleen.
It also contains numerous macrophages and dendritic cells.

12.3 Red Pulp

The red pulp is made up of sinusoidal capillaries called splenic sinusoids that are separated by
strands of reticular tissue referred to as splenic cords of Billroth.

13 Mucosa-associated Lymphoid Tissue (MALT)

Mucosa-associated lymphoid tissue refers to the enormous amount of lymphoid tissue that
exists in the mucosa and submucosa of the gastrointestinal, respiratory, and genitourinary
tracts.
It consists of loose or dense diffuse lymphoid tissue.
MALTS are important sites for generating the lymphocytes that are needed in mounting an
immune response.

14 Tonsils

The tonsils form a ring (Waldeyers ring) underneath the epithelium around the entrances to
the respiratory and digestive passages.
They consist of paired palatine, lingual, and tubal tonsils, and an unpaired pharyngeal tonsil.
The palatine tonsils are located in the lateral aspect, one on each side, of the oropharynx.
The superficial surface of the palatine tonsils is covered by nonkeratinized stratified squamous
epithelium.
The lingual tonsils consist of several discrete masses in the dorsum of the posterior tongue.
The pharyngeal tonsil occupies the central area of the posterior and superior walls of the
nasopharynx.
The enlarged, the pharyngeal tonsil is referred to as adenoid.
The tubal tonsils are located in the nasopharynx.