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Hematology & Immune System
Hematology & Immune System
SYSTEM
By Fentahun A. (MSc.)
Outlines
Outlines of the presentation
Introduction
The Immune System & Lymphoid Organs
The lymphoid organs and main paths of lymphatic vessels
Antigens
Antibodies
Cytokines
Cells of the Immune System
Lymphocytes
Types of Immune Responses
Lymphoid Tissue
INTRODUCTION
2. IgA
It is the main immunoglobulin found in secretions, such as
nasal, bronchial, intestinal, and prostatic, as well as in
tears, colostrum, saliva, and vaginal fluid.
3. IgM
It constitutes about 10% of blood immunoglobulins and
usually exits as a pentamer.
Together with IgD, it is the major immunoglobulin found on
the surface of B lymphocytes. These two classes of
immunoglobulins have both membrane-bound and circulating
forms.
IgM bound to the membrane of a B lymphocyte functions as its
specific receptor for antigens.
The result of this interaction is the proliferation of B
lymphocytes into antibody-secreting plasma cells.
Secreted IgM, when bound to antigen, is very effective in
activating the complement system.
Classes of Antibodies Continued.
4. IgE
It is much less abundant than the other classes and
usually exists as a monomer.
As its Fc region has a great affinity for receptors
present on the surfaces of mast cells and basophils,
it attaches to these cells after being secreted by
plasma cells and only small amounts are found in
the blood.
Classes of Antibodies Continued.
When IgE molecules present on the surface of mast
cells or basophils encounter the antigen that elicited
the production of this specific IgE, the antigen
antibody complex triggers the liberation of several
biologically active substances, such as histamine,
heparin, leukotrienes, and eosinophil-chemotactic
factor of anaphylaxis.
5. IgD
The properties and activities of IgD are not
completely understood.
Definition:-
The functions of cells in the immune system are regulated
by a large number of molecules, mainly cytokines, which
are peptides or glycoproteins usually with low molecular
masses (between 8 and 80 kDa).
After their final maturation, T cells leave the thymus and are
distributed throughout the body in connective tissues and
lymphoid organs.
Thymus 100 0
Bone marrow 10 90
Spleen 45 55
Lymph nodes 60 40
Blood 70 30
Cont
Three important subpopulations of T cells
are the following:
1. 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.
Cont
2. Cytotoxic T cells
Are CD8+ and act directly against foreign cells or
virus-infected cells by two main mechanisms.
In one, 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.
In the other, they attach to a cell and kill it by
triggering mechanisms that induce programmed
cell death, or apoptosis
Cont
3. Regulatory T cells
Are CD4+CD25+ and play crucial roles in
allowing immune tolerance, maintaining
unresponsiveness to self-antigens and
suppressing excessive immune responses.
These cells produce peripheral tolerance, which
backs up the central tolerance emerging in the
thymus.
Types of Immune Responses
The two basic types of immune responses are
The innate response and the adaptive response.
The innate response
Which can include the action of the complement system,
defensins, and cells such as neutrophils, macrophages, mast cells,
and natural killer cells.
is fast, nonspecific, and older from an evolutionary point of view.
It does not produce memory cells.
The adaptive response,
Which depends on the initial recognition of antigens by B and T
cells.
is more complex, is slower and specific, produces memory cells,
and is a more recent evolutionary development.
Lymphoid Tissue
Definition:-
Lymphoid tissue is connective tissue characterized by a rich supply
of lymphocytes.
It exists free within the regular connective tissue or is surrounded by
capsules, forming the lymphoid organs.
Because lymphocytes have very little cytoplasm, lymphoid tissue
filled densely with such cells stains dark blue in H&E-stained
sections.
Lymphoid tissues are basically made up of free cells, typically with a
rich network of reticular fibers of type III collagen supporting the
cells.
In most lymphoid organs, the reticular fibers are produced by a
fibroblastic cell called a reticular cell, whose many processes rest on
the fibers.
Cont
The thymus is an exception in that its cells are
supported by a reticulum of unusual epithelial
cells.
The network of reticular fibers of the lymphoid
tissue may be relatively dense and thus able to hold
many free lymphocytes, macrophages, and plasma
cells.
Areas of more loosely organized lymphoid tissue,
with fewer and larger spaces, allow easy movement
of these cells.
Thymus
The thymus is a bilateral
bilateralorgan
organlocated
locatedininthe
the
mediastinum; it attains its peak
peak development
development during
during
youth.
Thymus
Like bone marrow and B cells, the thymus is
considered a central or primary lymphoid organ
because T lymphocytes form there.
Whereas all other lymphoid organs originate
exclusively from mesenchyme (mesoderm), the
thymus has a dual embryonic origin.
Its precursor lymphoblasts originate in the bone
marrow, but then move to invade a unique
epithelium that developed from the endoderm of
the embryo's third and fourth pharyngeal
pouches.
Cont
The thymus has a connective tissue capsule that
penetrates the parenchyma and divides it into
incomplete lobules, with continuity between the
cortex and medulla of adjoining 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 is The thymic cortex.
Cont
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 euchromatic
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.
Cytoplasmic bundles of intermediate keratin filaments
(tonofilaments) give evidence of these cells' epithelial origin.
Occluding junctions between flattened epithelial reticular cells
at the boundary between cortex and medulla help to separate these
two regions.
Cont
The thymic medulla also contains;
a cytoreticulum of 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.
The thymus, an encapsulated, bilateral organ in the mediastinum, is subdivided by connective tissue (CT) septa into connected
lobes. Lobes of an active thymus shown have peripheral regions of cortex (C), where basophilic lymphocytes are fairly dense, and
more central medulla (M) regions with fewer lymphocytes. Besides the differences in location and cell density, the medulla region is
characterized by the scattered presence of distinct thymic corpuscles (arrow). X140. H&E.
The thymic medulla contains fewer
lymphocytes than the cortex and the
epithelial reticular cells (arrowheads)
have different morphology and
function. The most characteristic
feature of the medulla in humans is
the presence of thymic (Hassall's)
corpuscles (H). These are of variable
size and contain layers of epithelial
reticular cells undergoing
keratinization and degeneration.
X200. H&E.
Cont
Arterioles and capillaries in the thymic cortex are
sheathed by flattened epithelial reticular cells with
tight junctions.
These features create a blood-thymus barrier and
prevent most circulating antigens from leaving the
microvasculature and entering the thymus cortex.
No such barrier is present in the medulla and
mature T lymphocytes exit the thymus via venules
in this zone.
The capillary endothelium has a thick basal
lamina.
Cont
The thymus has no afferent lymphatic vessels and
does not constitute a lymph filter, as do lymph
nodes.
The few lymphatic vessels of the thymus are in the
connective tissue of the capsule, septa and blood
vessel walls and are all efferent.
Role of the Thymus in T Cell Maturation
65
The Spleen
Spleen is found In left
hypochondria thus,
cant be palpated.
surface projection of
the longitudinal axis
of the spleen is the
tenth rib.
It is concealed
anteriorly by the
greater curvature of
stomach & left colic
(splenic) flexure.
66
Spleen
The spleen has: 2 ends medial
and lateral
2 borders upper and lower
2 surfaces parietal
(diaphragmatic) in relation to
diaphragm & visceral surface in
relation to stomach, left kidney,
left colic flexure and tail of
pancreas.
Superior extremity:
directed toward the vertebral column
Inferior extremity:
rests on the left colic flexure and phrenicocolic ligament
Associated ligaments of the spleen (double layers of
peritoneum):
phrenicocolic ligament (from Lt Colic Flexure to Diaphragm)
gastrolienal ligament: from stomach to spleen
lienorenal ligament: from spleen to Lt kidney 68
Spleen
The spleen is the largest single accumulation of
lymphoid tissue in the body and the only one involved
in filtration of blood, making it an important organ in
defense against blood-borne antigens.
It is also the main site of destruction of aged
erythrocytes.
As is true of other secondary lymphoid organs, the
spleen is a production site of antibodies and activated
lymphocytes, which are delivered to the blood.
Any inert particles in blood are actively phagocytosed
by spleen macrophages.
Cont
The spleen is surrounded by a capsule of dense connective
tissue from which emerge trabeculae, which partially
subdivide the parenchyma or splenic pulp.
Large trabeculae originate at the hilum, on the medial
surface of the spleen;
these trabeculae carry nerves and arteries into the splenic
pulp as well as veins that bring blood back into the
circulation.
Lymphatic vessels that arise in the splenic pulp also leave
through the hilum via the trabeculae.
Spleen
Clinical Considerations: