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1-Organization of the lymphoid tissues of the

spleen .
2- Organization of typical Gut-associated lymphoid
tissue

‫ ايه جمعه بشير محمد‬/ ‫االسم‬

Code : 88
Spleen
The spleen is a secondary lymphoid organ present in
allvertebrates. Its most primitive version is found in
cyclostomes,where the splenic tissue is part of the gut
wall. Inhigher vertebrates the organ parenchyma is divided
intotwo large compartments, the white pulp and the red
pulp,which are distinguished by colour in fresh organ
sections at low magnification.
The white pulp harbours dense and highly organized
accumulations of B and T lymphocytes around arterioles,
while most of the red pulp consists of blood-filled spaces.
These red pulp spaces are composed of two different
structures. First, the splenic sinuses represent a specialized
part of the vasculature connecting arterioles and veins.
They are not present in all species. Second, the splenic
cords are strands of loose connective tissue without
endothelium filled with all types of blood cells,
macrophages and plasma cells.
The spleen is located between an artery and a vein, and it
functions as a blood filter. As with Peyer's patches, there
are no lymphatics that bring lymph into the spleen.
However, in contrast to lymph nodes and Peyer's patches,
where entry of B can T cells from the blood occurs only via
high endothelial venules, the spleen is like an "open-house
party" in which everything in the blood is invited to enter.
The following diagram figure 13 shows one of the filter
units that make up the spleen.
When blood enters from the splenic artery, it is diverted
out to the marginal sinuses from which it percolates
through the body of the spleen before it is collected into
the splenic vein. The marginal sinuses are lined with
macrophages that clean up the blood by phagocytosing
cell debris and foreign invaders. As they ride along with
the blood, B cells and T cells are temporarily retained in
different areas, T cells I n a region called the periarteriolar
lymphocyte sheath (PALS) that surround the central
arteriole, and B cells in the region between the PALS and
the marginal sinuses. Once activated by APCs in the PALS,
T cells move into the lymphoid follicles, and give help to B
cells that have recognized their cognate antigen.

Histology The microscopic structure of the spleen

has been most thoroughly investigated in mice and rats.
The nomenclature for different microanatomical
compartments and different splenic macrophage
populations was coined in rats. Thus, in the following
paragraphs splenic microanatomy is first described in this
species and then in humans. The overall morphology of
mouse spleens is similar to that of rats. With respect to
the so-called ‘compartments’ of the spleen, it has to be
kept in mind that a large proportion of lymphocytes are
migratory cells. Lymphocytes arrive via the blood, migrate
into a compartment to settle down for some time and
leave again into the blood. This process is called
lymphocyte recirculation. It supports the detection of
antigens and the spreading of immune responses in the
body. Thus, the spleen is an organ of variable cellular
composition. See also: Lymphocytes; Lymphocytes:
recirculation

White pulp of rat spleen

The splenic white pulp is divided into three
compartments, where either T or B lymphocytes
predominate. The T-cell zone is called the periarteriolar
lymphatic sheath (PALS). There are two further
compartments primarily inhabited by B lymphocytes, the
follicles and the marginal zone (MZ). See also: B
lymphocytes; T lymphocytes: helpers

Red pulp of rat spleen

 The splenic red pulp consists of the splenic cords and the
splenic sinuses (also named sinusoids). The cords
represent the ‘open’ part of the splenic circulation, which
is formed by strands of loose connective tissue occupied
by lymphocytes, plasma cells, macrophages, granulocytes,
red cells and thrombocytes. Terminal arterioles of the red
pulp arising from the central arterioles, directly open into
the splenic cords. In the cords the blood moves in highly
irregular spaces, which lack endothelial cells, to finally
enter the splenic sinuses from the outside. A proportion of
the blood may also directly enter the open beginnings of
red pulp veins. The facts mentioned for the splenic red
pulp of rats also apply to humans. In humans, the
phenotype of the sinus endothelial cells is also very
special. For example, these cells express the a chain of
CD8. The functional significance of this phenomenon,
which is not found in rats, is unknown. “To make things
even more complicated, the spleen receives 10-15% of the
body’s blood supply all on its own. That means that if you
bruise it, lacerate it, or, in the worst case scenario, rupture
it, the amount of internal bleeding that may result can
immediately turn life-threatening. That is not all. Even
though it was initially confirmed that Jason Witten had
only a laceration, it has been well documented that spleen
injuries can worsen, and possibly progress to outright
rupture, 10 days or more after the initial injury even when
appropriate precautions are taken. In other words, the
Cowboy doctors had to make absolutely sure Witten’s
spleen laceration had completely healed before letting him
do what tight ends do. A re-injury or rupture of a still
injured spleen would have been catastrophic; it is fair to
say that the Cowboys were not going to put Witten on the
field without medical clearance, signed medical waiver or
not. Does any of this sound familiar? It might. If you or any
of your friends ever suffered from the dreaded kissing
disease infectious mononucleosis, or “mono,” your doctor
probably told you that you had to avoid contact sports.
The reason is that your spleen helps your body fight
certain kinds of infections, such as ones caused by the
EpsteinBarr Virus, the virus responsible for mono. To do
so, it goes into overdrive and swells. Just as a balloon gets
more and more fragile as it grows, so does the spleen,
along with its massive blood supply. “If Witten’s spleen did
rupture with his original injury or thereafter, surgery
would have been necessary to repair the spleen or remove
it altogether, as while the spleen is helpful in fighting
certain infections, it is not an essential organ. That was not
the case, and Witten is off to the races for the Cowboys
and fantasy football players everywhere. Unlike a dreaded
hamstring strain that can persist all season long, this was a
finite injury that has completely healed.

Gut associated lymphoid tissue the gut associated

immune system fences off potentially harmful intestinal
antigens from the systemic circulation and induces
systemic tolerance against luminal antigens. Intestinal
immune responses against luminal antigens include IgA
secretion and induction of regulatory cells. Unlike few
other cytokines, lymphotoxin a/b regulates the
development of intestinal lymphoid organs.
The embryonic development of Peyer’s patches, postnatal
lamina propria B cell development, and isolated lymphoid
follicle development all depend on lymphotoxin b receptor
interactions. Lymphotoxin a/b signalling also contributes
to the development of mesenteric lymph nodes. In
addition, intestinal inflammation is suppressed by
inhibition of lymphotoxin b signalling, an observation
which has initiated clinical studies using this treatment
principal. Intestinal follicular lymphoid organs are sites of
antigen presentation. Antigen presenting cells tune the
delicate balance between intestinal immune tolerance and
inflammation. Therefore, gut associated lymphatic organs
and factors regulating their development are critical for
the prevention of adverse immune reactions to intestinal
antigens. This review provides an overview on the role of
lymphotoxin and the gut associated lymphatic organs in
the regulation of oral tolerance and intestinal
inflammation . Intestinal mucosal surfaces are exposed to
alimentary and bacterial antigens of the intestinal flora.
The physiological immune response towards intestinal
antigens is non-harmful to the entire organism and
includes induction of systemic immune tolerance and IgA
secretion. Inflammatory bowel disease (IBD) is associated
with activation of the local intestinal and systemic immune
responses. In various animal models of IBD, uncontrolled
immune responses following intestinal injury result in
mucosal insult. Colitis is associated with loss of tolerance
against intestinal antigens, which also contributes to
perpetuation of local and systemic inflammatory immune
responses. Characterisation of intestinal inflammatory
cytokine pathways has provided valuable tools to
modulate the activity of IBD. While inhibition of tumour
necrosis factor receptor (TNFR) interactions is effective in
controlling IBD, inhibition of interactions between the TNF
family molecule lymphotoxin b (LTb, bound in LTa1b2)
with its receptor (LTbR) is currently being investigated as a
potential IBD treatment. LTa1b2-LTbR interactions control
the development and function of the intestina immune
system. During embryonic development, LTbR ligation is
critical for the formation of gut associated lymphoid tissue
(GALT). Postnatal LTa1b2- LTbR ligation controls the
development of amina propria (Lp) B cells. In adult mice,
experimental colitis can be suppressed by inhibition of
LTa1b2-LTbR signalling. Presentation of antigens to
immune effector cells is concentrated at sites of organised
mucosal lymphoid follicles. The hallmark of organised
GALT is the presence of lymphoid follicles. Therefore, GALT
is the intestinal frontier of the systemic immune response.

INTESTINAL IMMUNE TOLERANCE: MLN ARE

CRITICAL AND PP MIGHT BE REDUNDANT FOR ORAL
TOLERANCE THE ROLE OF LYMPHOTOXIN AND GALT
ORGANS IN
Immune tolerance is defined as induction of any
mechanism by which a potentially injurious immune
response is prevented, suppressed, or shifted to a non-
injurious class of immune response’’.67 OT is a mechanism
of tolerance induction, and OT has been demonstrated by
the specific suppression of cellular and/or humoral
immune responses to an antigen by prior administration of
the antigen by the oral route. OT probably serves as a
mechanism to prevent the development of adverse
immune reactions against intestinal and nutritional
antigens.