Lymphoid System

Lymphoid System
• a system of cells that has the ability to distinguish
"self" (the organism's own molecules) from "non-
self" (foreign substances).

• this system has the ability to neutralize or

inactivate foreign molecules and to destroy
microorganisms or other cells (such as virus-
infected cells, cells of transplanted organs, and
cancer cells)
• On occasion, the immune system of an individual reacts against its own
normal body tissues or molecules, causing autoimmune diseases.
 Lymphoid System
• cells distributed throughout the body in the blood,
lymph, and epithelial and connective tissues

• lymphoid nodules found in the mucosa of the

digestive system (including the tonsils, Peyer's
patches, and appendix), the respiratory system,
the reproductive system, and the urinary system
are collectively known as mucosa-associated
lymphoid tissue (MALT)

• lymphoid organs—the bone marrow, the thymus,

the lymph nodes, the spleen

The wide distribution of immune system cells and

the constant traffic of lymphocytes through the
blood, lymph, connective tissues, and lymphoid
organs provide the body with an efficient system of
defense
 First line of defence
saliva tears
antibacterial antibacterial
enzymes enzymes

mucus linings traps

skin prevents dirt and microbes
entry

stomach acid “good” gut

low pH kills bacteria out
harmful microbes compete bad
 Second line of defence
• Non-specific
response
– invading
pathogens are
targeted by
leukocytes

• Specific response
– lymphocytes
produce
antibodies and kill
infected cells
 Macrophages
• Larger than neutrophils.
• Found in the tissues, not the blood.
• Made in bone marrow as monocytes, called
macrophages once they reach organs.
• Long lived
• Can be antigen presenting cells
• Initiate immune responses as they display
antigens from the pathogens to the
lymphocytes.
 Antigen Presentation
• All pathogens that made their way to our
body should be presented to T
lymphocytes since they can not directly
recognize them

• Macrophages, Dendritic Cells and B

lymphocytes are types of Antigen
Presenting Cells

• They engulf the evaded pathogen, break

it down and present part of it in complex
with MHC II molecule on the surface

• Now T lymphocytes can bind to these

complexes and begin the immune
response
 Major Histocompatibility Complex
(MHC)
• A complex of chromosomal loci encoding several proteins known as class I and
class II MHC molecules
• There is great variation of these molecules among the general population
• One individual, however, expresses only one set of class I proteins and one set of
class II proteins; these proteins are unique to that person
• MHC molecules are integral membrane proteins present on the cell surface. They
are synthesized by the RER like regular membrane proteins. However, on their way
to the cell surface, they couple with small peptides of 10–30 amino acids whose
origin differs depending on whether class I or class II molecules are involved
• MHC class I proteins - all nucleated cells
• MHC class II proteins - exist on only a small
group of cells called antigen-presenting cells
(APCs)
 Lymphocytes
• B and T lymphocytes have receptors on their surface. These
receptors are fundamental for recognition of antigens and,
thus, for triggering an immune response.

• Each B lymphocyte that leaves the bone marrow or each

T lymphocyte that leaves the thymus has just one type of
surface receptor that recognizes one specific antigen.
T and B lymphocytes
 B-lymphocytes
• The surface receptors able to recognize antigens are
molecules of IgM
• Each B cell is covered by about 150,000 molecules of IgM
• The encounter of a B lymphocyte with the epitope it
recognizes leads to several cycles of cell proliferation
forming plenty of plasma cells
• This population of plasma cells secretes antibodies against
the same epitope as that recognized by the B cell from
which it arose.
• Not all activated B cells, however, become plasma cells;
some remain as long-lived B memory cells, which are able
to react very rapidly to a second exposure to the same
epitope.
 Antibodies
• Also known as immunoglobulins
• The heavy and light chains are
polypeptides
• The chains are held together by
disulphide bridges
• 2 identical antigen binding sites –
variable regions and one cell binding –
constant region
• The order of amino acids in the variable
region determines the shape of the
binding site
Type Number of Site of action Functions
ag binding
sites
IgG 2 •Blood •Increase
•Tissue fluid macrophage activity
•CAN CROSS •Antitoxins
PLACENTA •Agglutination

IgM 10 •Blood Agglutination

•Tissue fluid

IgA 2 or 4 •Secretions (saliva, •Stop bacteria

tears, small intestine, adhering to host
vaginal, prostate, cells
nasal, breast milk) •Prevents bacteria
forming colonies on
mucous membranes
IgE 2 Tissues •Activate mast cells
 HISTAMINE
 Role of antibodies
• Antibodies released into the
blood stream will bind to the
antigens that they are specific for
- opsonization

• Antibodies may disable some

microbes, or cause them to stick
together - agglutination. They
“tag” microbes so that the
microbes are quickly recognized
by various white blood cells.
 T lymphocytes
• Constitute 65–75% of blood lymphocytes

• T cells have a molecule called a T cell receptor (TCR) on their surfaces which
recognize only epitopes (mostly small peptides) that form complexes with
special proteins on the cell surface of other cells (proteins of the major histocompatibility
complex)

• Three important subpopulations of T cells are the following:

- Helper cells, which produce cytokines that promote differentiation of B cells into plasma cells, activate
macrophages to become phagocytic, activate cytotoxic T lymphocytes, and induce many parts of an inflammatory reaction.
Helper cells have a marker called CD4 on their surfaces and are, hence, called CD4+ T cells.
- Cytotoxic T cells are CD8+ and act directly against foreign cells or virus-infected cells by two main
mechanisms. First, they attach to the cells to be killed and release proteins called perforins that create holes in the cell
membrane of the target cell, with consequent cell lysis. Second, they attach to a cell and kill it by triggering mechanisms that
induce programmed cell death, or apoptosis.
- Regulatory T cells are CD4+CD25+ and play crucial roles in allowing immune tolerance, maintaining
unresponsiveness to self-antigens and suppressing excessive immune responses.

• The first encounter of a CD4 or CD8 T cell with its specific epitope is followed by amplification of that clone; some of
the cells of this increased population become effector cells, doing the job for which they are specialized, and some
remain memory helper or memory cytotoxic T cells, reacting rapidly to the next presentation of the same epitope

 One of the primary causes of the immunodeficiency syndrome known as AIDS involves the killing of helper T cells by the
infecting retrovirus. This cripples the patients' immune system rendering them susceptible to opportunistic infections by
microorganisms that usually do not cause disease in immunocompetent individuals.
 NK cells
• The natural killer lymphocytes lack the markers characteristic of B and T cells.

• They comprise about 10–15% of the lymphocytes of circulating blood.

• Their name derives from the fact that they attack virus-infected cells,
transplanted cells, and cancer cells without previous stimulation; for this reason
they are involved in what is called an innate immune response.

• Do not require activation to kill cells that are missing "self" markers of MHC
class I, allowing for a much faster immune reaction.
Types of lymphocyte
 Lymphoid organs
• Primary organs - • Secondary organs -
where lymphocytes are where lymphocytes
formed and mature: are activated:

- Bone Marrow • Lymph nodes

(see “Blood and Hematopoiesis”)

• Spleen
- Thymus
• Mucosal associated
lymphoid tissues (tonsils,
Payers patches and etc.)
 The Thymus
• The thymus is a primary lymphoid organ
located in the superior mediastinum

• The thymus is the site of T lymphocyte

differentiation and removal of T lymphocytes
reactive against self-antigens

• Connective tissue surrounds the thymus and

subdivides it into thymic lobules

• Each lobule has a peripheral darkly stained

zone known as the cortex and a central light
zone called the medulla.

• The cortex is richer in small lymphocytes

than the medulla and therefore it stains C
more darkly

• The thymus reaches its maximum

development in relation to body weight M
immediately after birth; it undergoes
M
involution after attaining its greatest size in
puberty, but continues to produce
lymphocytes until old age
 The Thymic Cortex
• The thymic cortex is composed of an
extensive population of T lymphoblasts (also
called thymocytes) and macrophages in a
stroma of epithelial reticular cells.

• The epithelial reticular cells usually have

large nuclei and are diverse morphologically,
but generally either squamous or stellate
with long processes.

• They are typically joined to similar adjacent

cells by desmosomes forming an
unusual cytoreticulum.

• Arterioles and capillaries in the thymic cortex

are sheathed by flattened epithelial reticular
cells with tight junctions. The capillary
endothelium is continuous and has a thick
basal lamina. These features create a blood-
thymus barrier and prevent most circulating
antigens from entering the thymus cortex
 The Thymic Medulla
• Contains epithelial reticular cells, many less densely packed differentiated T lymphocytes,
and structures called thymic (Hassall's) corpuscles, which are characteristic of this region
• Thymic corpuscles consist of epithelial reticular cells arranged concentrically, filled with
keratin filaments, and sometimes calcified.
• No blood-thymus barrier is present in the medulla and mature T lymphocytes exit the
thymus via venules in this zone.
 Role of the Thymus in T Cell Maturation
• T lymphoblasts populate the cortex where they proliferate extensively, but do not yet
exhibit the T cell receptor or the CD4 and CD8 markers.
• As thymocytes mature and express T cell markers, they undergo thymic selection
• Thymocytes whose TCRs cannot bind MHC molecules on epithelial cells at all are
nonfunctional and have no future as T cells; these cells (as many as 80% of the total) are
induced to undergo apoptosis (positive selection).
• Thymocytes that strongly bind MHCs containing self-peptides are also deleted since such T
cells could cause a damaging autoimmune response (negative selection).
• Only 2–3% of the thymocytes pass both these positive and negative selection tests and
survive to migrate into the thymic medulla.
• Besides their structural roles, the epithelial reticular cells produce a number of paracrine
factors required for differentiation, selection and migration of mature T lymphocytes,
notably thymopoietin and thymosins
 Lymph nodes
• Lymph nodes are bean-shaped, encapsulated
structures, generally 2–10 mm in diameter, distributed
throughout the body along the course of the lymphatic
vessels

• The nodes are found in the axillae (armpits) and groin,

along the great vessels of the neck, and in large
numbers in the thorax and abdomen, especially in
mesenteries

• Lymph nodes constitute a series of in-line filters that

are important in the body's defense against
microorganisms and the spread of tumor cells.

• A convex surface that is the entrance site of lymphatic

vessels and a concave depression, the hilum, through
which arteries and nerves enter and veins and
lymphatics leave the organ

• A connective tissue capsule surrounds the lymph node,

sending trabeculae into its interior
 Lymph nodes

• The most common cells of

lymph nodes are lymphocytes,
macrophages, plasma cells,
and reticular cells

• The different arrangement of

the cells and of the reticular
fiber stroma supporting the
cells creates a cortex,
a medulla, and an
intervening paracortex
 Low mag of a lymph node

Cx = cortex w/ lymphatic nodules (F); M = medulla; C = CT capsule

 The cortex of the Lymph node
Situated under the capsule, consists of the following components:

• Many reticular cells, macrophages, APCs, and lymphocytes

• Lymphoid nodules, with or without germinal centers, formed mainly of B lymphocytes, embedded within
the diffuse population of other cells
• Subcapsular sinuses, where the lymphoid tissue has wide reticular fiber meshes. Lymph containing
antigens, lymphocytes, and APCs drains here after being delivered by the afferent lymphatic vessels
• Cortical sinuses, running between the lymphoid nodules, which arise from the subcapsular sinuses

 The paracortex does not have precise boundaries with

the cortex and medulla. It can be distinguished from the outer
cortex by its lack of B cell lymphoid nodules
and its accumulation of T cells, which can be
determined only by immunohistochemistry.
Vessels have an unusual endothelial lining of tall
cuboidal cells - high endothelial venules
(HEVs), whose apical surface glycoproteins and
integrins facilitate rapid diapedesis of lymphocytes out
of the blood into the paracortex of the lymph node. That’s
where 90% of lymphocytes return to
a lymph node.
A lymphatic nodule with germinal center (GC)
 The medulla of the lymph node
The medulla has two major
components:

• Medullary cords are branched

cordlike extensions of lymphoid
tissue arising from the paracortex.
They contain primarily B
lymphocytes and often plasma cells
and macrophages.

• Medullary cords are separated by

dilated spaces called medullary
sinuses. They contain lymph,
lymphocytes, often many
macrophages. These sinuses are
continuous with the cortical sinuses
and join at the hilum to deliver
lymph to the efferent lymph vessel
of the lymph node
 Role of Lymph Nodes in the Immune Response
• Lymph nodes are distributed throughout the body and
lymph formed in tissues must pass through at least one
node before entering the bloodstream.

• The lymph that arrives at a lymph node contains

antigens as soluble molecules, portions of destroyed
microorganisms, or antigens already internalized and
being transported by macrophages and other APCs. It
may also contain microorganisms and cytokines,
particularly if it is coming from a region with an
infection or inflammation.

• All antigens are presented to B lymphocytes, to T

helper cells, and to T cytotoxic lymphocytes to initiate
an immune response.

• The lymph node is an important site of lymphocyte

proliferation (especially of B cells in the germinal
centers) as well as of transformation of B lymphocytes
into plasma cells. Because of this, the lymph that
leaves a lymph node may be enriched in antibodies.
When the lymph is returned to the blood circulation,
these antibodies will be delivered to the entire body.

 Malignant tumor cells often reach lymph nodes and are distributed to
other parts of the body via the efferent lymph vessels and blood
vessels, a process known as metastasis.
 Infection and antigenic stimulation often cause lymph nodes to
enlarge. These swollen nodules, which may be palpated under the skin
as indicators of inflammation, have multiple germinal centers with
active cell proliferation.
 The Spleen
• Involved in filtration of blood,
making it an important organ
in defense against blood
circulating antigens.
• The main site of destruction
of aged erythrocytes.
• Is a production site of
antibodies and activated
lymphocytes, which are
delivered to the blood.

• Surrounded by a capsule of
dense connective tissue from
which emerge trabeculae,
which partially subdivide the
parenchyma or splenic pulp.
 The White Pulp of the Spleen
• Consists of lymphoid
nodules and the periarteriolar
lymphoid sheathes (PALS)

• Lymphoid nodules – B
lymphocytes, germinal centers

• PALS – T lymphocytes

• Marginal zone - surrounds the

lymphoid nodules, consists of
many blood sinuses,
lymphocytes, many
macrophages, and an abundance
of blood antigens, plays an
important role in the
immunological activities of the
spleen.
 The Red Pulp of the Spleen
• Red pulp contains blood-filled sinusoids and splenic cords
• The splenic cords contain a network of reticular cells or reticular fibers
that support T and B lymphocytes, macrophages, plasma cells, and many
blood cells (erythrocytes, platelets, and granulocytes)
• Cords are separated by wide, irregularly shaped sinusoids
Immune system functions of the spleen include:

 antigen presentation by APCs (mostly dendritic

cells and macrophages) and initiation of immune
response;

 activation and proliferation of B and T

lymphocytes;

 production of antibodies against antigen present

in circulating blood; and removal of
macromolecular antigens from the blood.
 Hemopoietic functions of the spleen include:

removal and destruction of senescent,

damaged, and abnormal erythrocytes and
platelets;

retrieval of iron from erythrocyte hemoglobin;

formation of erythrocytes during early fetal

life and storage of blood
 Mucosa-Associated Lymphoid Tissue
(MALT)
• Organs of the digestive, respiratory, genital and urinary systems are common sites of invasion by
pathogens because their lumens are open to the external environment.
• Collectively MALT is one of the largest lymphoid organs, containing up to 70% of all the body's
immune cells.
• To protect the organism, the mucosal connective tissue of these tracts contains large and diffuse
collections of dendritic cells, lymphocytes, IgA-secreting plasma cells, APCs, and lymphoid nodules.
• In some places, these aggregates form structures such as the tonsils and the Peyer patches in the
ileum, aggregates with lymphoid follicles are found in the appendix.
 The Pathway of Specific Immune Response

Step 1
Pathogens eaten by Macrophage

Step 2
Displays portion of Pathogen on
surface

Step 3

Pathogens

Helper-T cell recognizes

Pathogen
 Immune Response Summary
Antigen
Displays copy of antigen on
surface of cell
Macrophage

Helper T - Cell
Cellular Immunity Humoral Immunity

Active Cytotoxic
Active B - Cell
T-Cell

Kills Infected
Memory T- Cell Plasma Cell Memory B-Cell
Cells

Antibodies

Deactivates
Antigens
Thank You for Attention