BASIC IMMUNOLOGY

LECTURE 4
LYMPHOID TISSUES AND ORGANS
(ANATOMY AND FUNCTIONS)

N. Gachechiladzde
2020 East European University (EEU)
 TYPES OF LYMPHOID TISSUES AND
ORGANS
The primary lymphoid organs are the
sites where pre-B and pre-T
lymphocytes mature into naïve B and T
cells in the absence of foreign antigen.
The secondary lymphoid organs are
the sites in which naïve, antigen
specific T and B lymphocytes
encounter invaders to generate an
adaptive response and long-lived
protective immunity.
• Primary/central/generative organs are – Bone marrow and
Thymus
• Peripheral/secondary organs are - lymph nodes, the spleen and
the mucosal-associated lymphoid tissues (MALTs)
 BONE MARROW
The bone marrow is the site of generation of all
circulating blood cells in the adult from hematopoietic
stem cells (HSC), called hematopoiesis;

Initially, during fetal development, hematopoiesis occurs

in blood islands of the yolk sac, then shifts to the liver
between the third and fourth months of gestation.

Liver remains the major site of fetal hematopoiesis until

shortly before birth and then shifts to bone marrow (BM).

The bone marrow remains the primary site of

hematopoiesis in adult until death.
 FUNCTIONS OF BONE MARROW
The bone marrow is a source of self-renewing populations of

stem cells.

Red blood cells, granulocytes, monocytes, dendritic cells,

platelets,B and T lymphocytes, and NK cells all originate from

a common hematopoietic stem cell (HSC) in the bone marrow.

Normally, only mature cells are released from the marrow into the bloodstream.

It is a site of B cells differentiation and development(in birds, B cells differentiate into the
bursa of Fabricious, hence the term of B cells).

It is a home for antibody secreting cells. It is a reservoir for differentiated plasma cells.
 LOCATION OF BONE MARROW
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
B CELL DEVELOPMENT IN THE BONE
MARROW
 THYMUS
The thymus is a bilobed organ situated in the anterior mediastinum. Each lobe is divided into multiple
lobules by fibrous septa, and each lobule consists of an outer cortex and an inner medulla.
 It is composed of cortical and medullary

epithelial cells, stromal cells, interdigitating

cells and macrophages. These ‘accessory’
cells are important in the differentiation
of the immigrating T cell precursors and
their ‘education’ (positive and negative
selection) prior to their migration into
the secondary lymphoid tissues.
 THYMUS
The thymus has an interactive role with the endocrine system as thymectomy
leads to a reduction in pituitary hormone levels as well as atrophy of the gonads.
Conversely, neonatal hypophysectomy (removal of the pituitary gland) results in
thymic atrophy.
Thymic epithelial cells produce the hormones thymosin and thymopoietin and
in concert with cytokines (such as IL-7) probably important for the development
and maturation of thymocytes into mature T cells.
 THYMUS
Both the cortex and medulla
of the thymus are crossed
by a three-dimensional
stromal-cell network composed
of epithelial cells, dendritic
cells, and macrophages,
which make up the framework
of the organ and contribute to
the growth and maturation of
the thymocytes
 FUNCTION OF THYMUS
 The thymus is the
site of T cell
maturation.

 It is the site of T cell

education.

 T cell learn to
recognize self as self
(central tolerance)
 MATURATION OF T CELLS IN THE
THYMUS
Precursors of T cells travel from the
bone marrow through the blood to the
thymus. In the thymic cortex,
progenitors of αβT cells express TCRs
and CD4 and CD8 co-receptors.
Selection processes eliminate self-
reactive T cells in the cortex at the
double-positive (DP) stage and also
single-positive (SP) medullary
thymocytes.
They promote survival of thymocytes
whose TCRs bind self MHC molecules
with low affinity. Functional and
phenotypic differentiation into
CD4+CD8−or CD8+CD4−T cells occurs
in the medulla, and mature T cells are
released into the circulation.
 TERMINOLOGY: CLUSTER OF
DIFFERENTIATION (CD)
Unique cell surface molecules (markers),
which are recognized by antibodies - CD
antigens do not belong to any particular
class of molecules.
CD specific antibodies are used for:
Determining of functions of CD molecules.
Identifying the distribution of CD antigens

in different cell populations in normal

individuals;
Diagnosis of various health conditions.
STAGES OF T CELL MATURATION IN
THYMUS
 THYMIC INVOLUTION
The Thymus undergoes a process called THYMIC INVOLUTION, as T cells
leave the thymus to populate other lymphoid effector organs, the organ
shrinks, leaving only the epithelia-retucular cells
 THE LYMPH NODES
 Lymph nodes are encapsulated,
vascularized secondary lymphoid
organs with anatomic features that
favor the initiation of adaptive immune
responses to antigens carried from
tissues by lymphatics.
 Lymph nodes are situated along
lymphatic channels throughout the
body and therefore have access to
antigens encountered at epithelia and
originating in interstitial fluid in most
tissues.
 MORPHOLOGY OF A LYMPH NODE

The anatomic segregation of B and T cells

ensures that each lymphocyte population is
in close contact with the appropriate APCs,
that is, B cells with FDCs and T cells with
dendritic cells.
LYMPH NODE STRUCTURE AND FUNCTIONAL
REGIONS
 The cortex includes B cells and
follicular dendritic cells. The
paracortical region includes T
cells and dendritic cells.

 Macrophages are found in the

subcapsular sinus and medullary
cord.

 Lymphocytes enter into the

lymph node through an artery at
the hilus region, and into the
parenchyma through high
endothelial venules (HEVs)
expressing peripheral node
addressins
SPLEEN STRUCTURE
Largest lymphoid organ (weighs about 150g in
adults)
The splenic parenchyma is anatomically and
functionally divided into red pulp and white pulp.
The white pulp is circular in structure and is made
up mainly of lymphocytes. It functions in a manner
similar to the nodules of the lymph node.
The red pulp surrounds the white pulp and
contains mainly red blood cells and macrophages.
The main function of the red pulp is to phagocytize
old red blood cells.
A region of specialized cells surrounding the
marginal sinus, called the marginal zone, forms the
boundary between the red pulp and white pulp.
 SPLEEN: FUNCTIONS
The spleen’s major functions are to remove aging and damaged blood cells and
particles (such as immune complexes and opsonized microbes) from the
circulation and to initiate adaptive immune responses to blood-borne antigens.
The white pulp contains the cells that mediate adaptive immune responses to
blood-borne antigens.
 SPLEEN
The architecture of the white pulp is analogous to the
organization of lymph nodes, with segregated T cell and B
cell zones.
 In the mouse spleen, the central arteries are surrounded by
cuffs of lymphocytes, most of which are T cells. Because of
their anatomic location, morphologists call these T cell zones
periarteriolar lymphoid sheaths.
B cell–rich follicles occupy the space between the marginal
sinus and the periarteriolar sheath.
The marginal zone just outside the marginal sinus is a distinct
region populated by B cells and specialized macrophages. The
B cells in the marginal zone, known as marginal zone B cells,
are functionally distinct from follicular B cells and have a
limited repertoire of antigen specificities.
 MUCOSAL ASSOCIATED LYMPHOID TISSUE
(MALT)
The MALT covers all mucosal surfaces not only in the gut, but also the
oropharyngeal and lacrimal mucosae, the nasal and bronchial airways, and the
genitourinary tracts. MALT protects a huge surface area and contains approximately
half of the lymphocytes of the entire immune system.
The mucosal epithelium that surrounds MALT is populated by a dense network of
DCs, plasma cells, and intraepithelial lymphocytes that helps to maintain the
epithelial barrier.
 MUCOSAL ASSOCIATED LYMPHOID TISSUE
(MALT)
In addition to the epithelial
cells characteristic of the host
tissue, the epithelial surface
contains modified epithelial
cells called M cells, so called for
the microfolds of the surface
cell membrane.
A sequence: M cell (antigen
transport), dendritic cell
(antigen presentation) and
lymphocyte (the response cell)
is established.
MUCOSAL ASSOCIATED LYMPHOID TISSUE
(MALT)
 REFERENCES
Abul K. Abbas, Andrew Lichtman – Basic Immunology (3rd edition)
P.14-18

Roit’s Essential Immunology (13th Edition)

P. 172 - 185