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Prof.

Mukund Vats
Senior Scientist & Head of Department
Virology, VSBT (University Of Pune)
Baramati,, Pune
Baramati
Prof. Mukund Vats
Senior Scientist & Head of Department
Virology, VSBT (University Of Pune)
Baramati,, Pune
Baramati
 Lymphoid Organs are sites where cells of the immune system
originate and develop and where acquired immune responses are
initiated.
 Primary lymphoid organs are the sites where lymphocytes
originate or mature. There are two primary lymphoid organs in
mammals, the bone marrow and the thymus.
 The bone marrow (B) is also the site of B cell development and
maturation.
 Although T cell precursors originate in the bone marrow, their
maturation occurs in the thymus (T).
 Secondary lymphoid organs are the sites where acquired
immune responses are initiated and are scattered throughout the
body, but are concentrated in areas that are most likely to be
invaded by pathogens (i.e. the gastrointestinal tract, the respiratory
tract, & the genitourinary tract).

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 Secondary lymphoid organs are lymph nodes, spleen, and
mucosal-associated lymphoid tissues (MALT), which includes gut-
associated lymphoid tissues (GALT), and bronchial-associated
lymphoid tissues (BALT).
 Lymphatic fluid circulates through the tissues in lymphatic vessels
(called simply "lymphatics").

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Primary Lymphoid Organs
(bone marrow, thymus) are sites
where lymphocytes originate or
mature
Secondary Lymphoid Organs
(shown in blue) are sites where
acquired immune responses are
initiated.
Lymphatic Fluid is extracellular
fluid that circulates through tissues
Lymphatic Vessels (lymphatics)
deliver lymphatic fluid and white
blood cells from sites of infection
to secondary lymphoid tissues
where acquired immunity is
developed.
Lymphoid tissue organization
Maximizes interactions between
T and B cells, T cells and
Macrophages. These interactions
Are essential for antibody
Contact: mukundvats@gmail.com Production.
 T cell precursors leave bone marrow and migrate to the thymus where they mature.
The immature cells are called thymocytes and enter the cortex of the thymus.
1. Resident cells in the cortex interact with thymocytes and induce T- Cell Receptor (TCR)
expression, which consists of the antigen binding unit and the CD3 complex.
2. Mature T cells departing the thymus can be classified into, helper cells that express CD4
(often called CD4+ T cells) and cytotoxic T cells that express CD8 (called CD8+ T cells).

3. Thymocyte Selection – positive and negative selection


a) Resident cells in the thymus express the MHC ligand for the T cell receptor. Once the T cell
receptor is expressed on developing thymocytes, it can interact with its ligand (MHC) on the
resident cells.
b) Positive Selection identifies those T cell precursors that express receptors capable of binding self-
MHC. These cells are given a positive signal, which induces them to proliferate and survive. Cells
unable to recognize self-MHC die in the cortex.
c) Once T cells have been positively selected, they undergo negative selection. Precursors with
TCRs that bind well to MHC with self-antigens (and hence induce autoimmunity) are deleted or
inactivated in the medulla. Less than 5% of T cell precursors that enter the thymus survive
selection. Survivors move through the medulla and exit as mature CD4+ or CD8+ T cells.

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+ Selection

- Selection

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Secondary Lymphoid Organs

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 Lymph nodes are scattered throughout the body and filter out microbes or damaged
tissue.
 Lymph nodes are responsible for the acquired immune response against antigens
encountered in the skin or connective tissues.
 Afferent lymphatic deliver fluid from the tissues to the sub-capsular sinus of the lymph
node. This fluid contains cells that have encountered pathogens and hence is the source
of the antigens that stimulate the acquired immune system.
 From the sub-capsular sinus, the lymph drains into the cortex of the lymph node. The
cortex contains B cell-rich areas called follicles. The B cell follicles are in contact with T
cell-rich regions, which facilitate the interactions between these two lymphocytes that are
necessary for antibody production. Some follicles contain germinal centers; these are
areas where B cells proliferate and differentiate after they have encountered antigen.
Activated B cells mature into plasma cells, which secrete large amounts of antibody, and
are located in the medulla of the lymph node. Lymphoid fluid leaves the lymph node
through the efferent lymphatic. In addition, activated B and T cells and antibody molecules
leave the lymph nodes and enter the peripheral blood.

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 Lymph nodes are the sites where
immune responses are mounted to
antigens in lymph.
 They are encapsulated beanshaped
structures containing a reticular network
packed with lymphocytes, macrophages,
and dendritic cells.
 Clustered at junctions of the lymphatic
vessels, lymph nodes are the first
organized lymphoid structure to
encounter antigens that enter the tissue
spaces.
 As lymph percolates through a node,
any particulate antigen that is brought in
with the lymph will be trapped by the
cellular network of phagocytic cells and
dendritic cells.

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 Morphologically, a lymph node can be divided into three roughly
concentric regions:
1. The outermost layer, the cortex, contains lymphocytes (mostly B
cells), macro-phages, and follicular dendritic cells arranged in primary
follicles. After antigenic challenge, the primary follicles enlarge into
secondary follicles, each containing a germinal center. In children
with B-cell deficiencies, the cortex lacks primary follicles and
germinal centers.
2. Beneath the cortex is the paracortex, which is populated largely by T
lymphocytes and also contains interdigitating dendritic cells thought
to have migrated from tissues to the node. These interdigitating
dendritic cells express high levels of class II MHC molecules, which
are necessary for presenting antigen to TH cells.
3. The innermost layer of a lymph node, the medulla, is more sparsely
populated with lymphoid-lineage cells; of those present, many are
plasma cells actively secreting antibody molecules

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 As antigen is carried into a regional node by the lymph, it is
trapped, processed, and presented together with class II MHC
molecules by dendritic cells resulting in the activation of TH cells.
 The initial activation of B cells is also thought to take place within
the T-cell-rich paracortex.
 Once activated, TH and B cells form small foci consisting largely of
proliferating B cells at the edges of the paracortex. Some B cells
within the foci differentiate into plasma cells secreting IgM and IgG
within 4–6 days of antigen challenge.
 A few B cells and TH cells migrate to the primary follicles of the
cortex.
 Within a primary follicle, development of a secondary follicle
takesplace with a central germinal center.
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Contact: mukundvats@gmail.com
 While lymph nodes are
specialized for trapping antigen
from local tissues, the spleen
plays a major role in mounting
immune responses to antigens in
the blood stream.
 It is a large, ovoid secondary
lymphoid organ situated high in
the left abdominal cavity.
 It can respond to systemic infections. Unlike the lymph nodes, the
spleen is not supplied by lymphatic vessels. Instead, bloodborne
antigens and lymphocytes are carried into the spleen through the
splenic artery.

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 The spleen is surrounded by a capsule that extends a number of
projections (trabeculae) into the interior to form a
compartmentalized structure.
 The compartments are of two types, the red pulp and white pulp

1. Red pulp consists of a network of sinusoids populated by


macrophages and numerous red blood cells (erythrocytes) and few
lymphocytes; it is the site where old and defective red blood cells are
destroyed and removed. Many of the macrophages within the red pulp
contain engulfed red blood cells or iron pigments from degraded
hemoglobin.
2. White pulp surrounds the branches of the splenic artery, forming a
periarteriolar lymphoid sheath (PALS) populated mainly by T
lymphocytes. Primary lymphoid follicles are attached to PALS. These
follicles are rich in B cells and some of them contain germinal centers.
The marginal zone, located peripheral to the PALS, is populated by
lymphocytes and macrophages.

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 Blood-borne antigens and
lymphocytes enter the spleen
through the splenic artery, which
empties into the marginal zone.
 In the marginal zone, antigen is
trapped by dendritic cells, which
carry it to the PALS.
Lymphocytes in the blood also
enter sinuses in the marginal
zone and migrate to the PALS.  The activated B cells, together with some
 The initial activation of B and T TH cells, then migrate to primary
cells takes place in the Tcell-rich follicles in the marginal zone.
PALS. Here dendritic cells  Upon antigenic challenge, these primary
capture antigen and present it follicles develop into characteristic
combined with class II MHC secondary follicles containing germinal
molecules to TH cells. Once centers, where rapidly dividing B cells
activated, these TH cells can then
activate B cells. (centroblasts) and plasma cells are
surrounded by dense clusters of
Contact: mukundvats@gmail.com
concentrically arranged lymphocytes.
Mucosal-Associated
Lymphoid Tissues
(MALT)

"MALT" refers to a diffuse


collection of lymphoid tissues that
line the respiratory, alimentary,
and genitourinary tracts.
MALT produce the immune
responses against pathogens that
invade the mucosa that line these
tracts. Like the spleen and lymph
nodes, the MALT contains B cell
follicles and distinct T cell-rich
regions. In the intestine we find
Peyer's Patches and the tonsils
are similar structures in the upper
alimentary tract.
Although its organization is similar
to the spleen and lymph node, the
mucosal immune system is
different in several ways:
(1) unlike the spleen and lymph
node, MALT tissue is not
surrounded by a fibrous
capsule,
(2) IgA is the predominant class
of immunoglobulin produced
in MALT.
(3) It is not filtering Ag delivered
by vessels like the blood
vessels or lymphatic vessels.

Contact: mukundvats@gmail.com

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