Primary Lymphoid organs
Objective.
1. To give an overview on the importance of the primary lymphoid organs on generation
of the Immune response.
2. To learn about the classification of lymphoid organs including both primary and
secondary lymphoid organs.
3. To understand the components of primary lymphoid organ, which include the bone
marrow and Thymus gland.
4. Immunological function of both bone marrow and Thymus gland will be review.
Introduction.
The immune system consists of a series of organs and vessels that connect them. Organs
of the immune system have been divided into primary and secondary lymphoid tissue.
The primary lymphoid organs in most mammals are consisting of thymus gland and bone
marrow.
The term of primary is used because these are organs in which naïve lymphocytes are
developed; B cells developed in the bone marrow and T cells in thymus gland. Once
lymphocytes are formed they migrate to the secondary lymphoid organs and tissue.
Peripheral or secondary lymphoid tissue includes (lymph nodes, spleen, gastrointestinal
and mucosa-associated lymphoid tissue)
Lymphocytes.
Lymphocytes are wholly responsible for the specific immune recognition of pathogens
and foreign material, so they initiate adaptive immune response. They represent about
20% of the total white blood cells (leukocyte) present in the adult circulation.
Two main types of lymphocytes:
A. B-cells. Developed and mature in Bone marrow, they produce antibodies
B. T cells. Originate in bone marrow and migrate to thymus to complete their
development and maturation their.
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T-lymphocytes have a number of functions including 1) helping B cells to make
antibody , 2) recognizing and destroying cells infected with virus, 3) activating
phagocytes to destroy the pathogens they have taken up and 4) controlling the level and
quality of the immune response.
After Maturation both T and B-lymphocytes migrate from primary lymphoid organ
(Thymus & bone marrow) to secondary lymphoid organs though blood circulation.
Cells of Immune system
Primary lymphoid organs.
The primary lymphoid organ is sites where lymphocytes differentiate from hematopoietic
stem cells (HSC) are proliferating and mature into effectors cells. From birth to old age,
these functions are carried out only in the bone marrow and thymus.
A. Bone
marrow (BM).
All lymphocytes arise from HSC in BM, the B cells continue their development,
maturation and their function in the bone marrow, where T-cell migrate to Thymus gland
to continue their maturation and their function.
In birds, B cells differentiate into the bursa of Fabricious, hence the term of B cells.
The early development of HSC is located in yolk sac (in embryo), then shift to liver.
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liver remain the major site of fetal hemopoiesis until shortly before birth when HSC
travel by blood to the spleen and then to bone marrow (BM). The bone marrow remains
the primary site of hematopoisis in adult until death.
Location of bone marrow.
At birth, the site of all bone marrow is found mainly in the flat bones, such as the hip
bone, skull, ribs, sternum and shoulder blades, and in ends of the long bones such as the
femur and humerus.
Structure of bone marrow.
There are two types of bone marrow:
1. red marrow (consisting mainly of with proliferating and differentiating blood
cells in connective tissue matrices bordered by venous sinuses, Red blood
cells, platelets and most white blood cells (Plasma cells and macrophages) arise in
red marrow)
2. yellow marrow (consisting mainly of fat cells)..
Both types of bone marrow contain numerous blood vessels and capillaries the vascular
compartment comprises, thin veins-vascular sinuses that drains into a central vein. The
central vein exist the marrow and drains into the general blood circulation.
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Main function of bone Marrow.
1.It is the site of origin of all T and B cells, Phagocytes, platelets, erythrocytes and
other leukocytes in adults. All the cells of the blood, including lymphocytes, are
produced from hemopoiteic stem cells (HSC) to give rise all elements of the blood.
2. In addition to hematopoiesis. Bone marrow is the site of removal of aged and
defective erythrocyte.
3. Site of differentiation and maturation of B-lymphocytes. In bone marrow, the B-cells
develop their receptors during different stages in bone marrow. The mature B-cell with
IgM+/IgD receptors leaves the bone marrow and circulates in the blood , but it is
considered a "primary" B-cell until it "switches" its membrane immunoglobulin to
another isotype. In addition B-cells in bone marrow undergo gene rearrangement, where
the germline genes encoding the variable and hypervariable regions of the
immunoglobulin light and heavy chains take place in the bone marrow. In addition selfreactive B-cells may be deleted in bone marrow. The deletion of B-cells in bone marrow
involves the B-cell clones with a high affinity for self –antigen during the phase of
transient from pro-B to mature B-cells, and this process is known as negative selection.
This process will maintain the self-tolerence and prevent the autoimmune reaction and
subsequently prevent the occurrence of autoimmune disease
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A. Thymus
gland.
Thymus gland is a very important primary lymphoid organ. It is an important site of Tlymphocyte growth and maturation. Loss of the thymus at an early age as in DiGeorge
Syndrome or surgical removal will results in severs immunodeficiency and a high
susceptibility to infection.
Location of Thymus gland...
It located in the upper anterior portion of the chest cavity, just behind the sternum,
superior to heart.
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DEVELOPMENT OF THE THYMUS.
It develops from ectoderm derived from the third and fourth pharyngeal pouch, Reach its
maximum size just prior to birth, Continuous to grow till age of puberty around 12th year.
Structure of Thymus gland.
It is formed of two lobes, each lobes is surrounded by capsule and is divided into lobules.
Lobules are separated from each other by connective tissues. Each lobule is divided into
outer cortex and inner medulla. Outer cortex contains numerous immature lymphocytes
(thymocytes). Inner medulla contains mature T lymphocytes.
The cortex is stain more densely with haematoxylin and eosin. Where the medulla is
less densely stained with haematoxylin and eosin. The thymus reaches is peak size
around puberty, after which it shrinks or involutes. In adults it is composed mostly of fat
cells and connective tissue.
Numerous different cell types can be found in the thymus:
1. Epithelial cell
A. Cortical epithelial cells. They provide structure and secrete factors that are
essential for T cell development.
B. Nurse cells. These are another type of cortical epithelial cell and can be seen in
close contact surrounding developing thymocytes. They express class I and class
II MHC on their surface.
C. Medullary epithelial cells. Theses provide structure for the medulla and recent
evidence suggests they play an important part in T cell tolerance.
Deep in the medulla they are also aggregated into Hassall's corpuscles (of unknown
function), they appear very early in life and contain debris, nonfunctional degenerative
material.
2. Macrophages. These are found in both the cortex and medulla, although they are
more numerous in the medulla. They are class II MHC negative and play an
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important role in phagocytosis of thymocytes that have died by apoptosis during
development.
3. Dendritic cells. These are another type of bone-marrow derived cells. They
express class II MHC as well as class I MHC.
4. Thymocytes. These are the most abundant cells in the thymus and consist of T
cells in various stages of development.
Function of Thymus gland.
1. Primary function of thymus is the production of thymic lymphocytes.
2. It is the major site for lymphocyte proliferation in the body.
3. Maturation and selection of T cell takes place in thymus.
A. maturation of T-cell. In thymus gland the T-cell develop their specific T cell
markers, including TCR, CD3, CD4 or CD8 and CD2. during this Maturation stage
the T-cells must be successfully rearrange pairs of genes that encode a heterodimeric
T-cell receptor (α β or γ δ).
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B. Thymic education and T-cell selection. T-cells education take place within thymus
gland through two important process of selection 1) positive selection of T
lymphocytes: T cell precursors that express receptors capable of binding with selfMHC. These cells are allowed to proliferate and survive. 2) Negative selection of T
lymphocytes. Any developing thymocytes that have high affinity for self-antigen in
association with MHC molecules will die within the thymus gland. This process the
body will maintain the self-tolerence and prevent the autoimmune reaction and
subsequently prevent the occurrence of autoimmune disease.
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