Download Immune system

IMMUNE SYSTEM
LECTURE FOR MEDICAL STUDENTS
DEPARTMENT OF HISTOLOGY,
CYTOLOGY AND EMBRYOLOGY KhNMU
2012
An Immune system is a collection of biological processes
within an organism that protects against disease by identifying
and killing pathogens and tumour cells. It detects a wide
variety of agents, from viruses to parasitic worms, and needs
to distinguish them from the organism's own healthy cells and
tissues in order to function properly.
Antigen is substance that stimulates the production of an
antibody when introduced into the organism. Antigens include
toxins, bacteria, viruses, and other foreign substances.
Antibodies (also known as immunoglobulins, abbreviated Ig)
are gamma globulin proteins that are found in blood or other
bodily fluids and are used by the immune system to identify
and neutralize foreign objects, such as bacteria and viruses.
The major components
of the immune system are:
•Immunocompetent cells
•Antibodies
•Complement system
•Bone marrow
•Thymus
•Spleen
•Lymph nodes
•Tonsils
Immunocompetent cells:
1.T-lymphocytes {T-helper,T-suppressor,T-cytotoxic
(killer cells),T-memory cells}
2.Natural killer cells(NK-cells)
3. B-lymphocytes
4.Plasma cells
5.Macrophages
6.Granulocytes of the blood(Neutrophilic, Eosinophilic,
Basophilic Leucocytes)
7.Monocytes
8.Mesenhymal reticular cells
9.Epithelial reticular cells
10.Antigen Presenting Cells (APC) {Dendritic cells,
Langerhans’ cells of the skin, Kupffer’s cells of the
Liver, Dust cells of the Lung etc.)
BONE MARROW
The marrow of all bones begins as active hematopoietic tissue
or red marrow(RBM). During growth, development, and
aging, portions of the active red marrow are replaced by
adipocytes to form yellow marrow(YBM).
1. Stroma consists of adipocytes (up to 75% of
red marrow), macrophages, and reticular
connective tissue composed of reticular
cells,adventitial cells and the reticular fibers (type
III collagen). Adventitial cells are highly branched,
poorly differentiated mesenchymal derivatives
resembling fibroblasts. Their processes separate
the developing blood cells from the endothelium
of the bone marrow sinusoids.
2.Hematopoietic cords fill the interstices of the
stroma and are crowded with overlapping blood cells of
all types and at all stages of differentiation.
RBM is composed of interdigitating masses of stroma
and hematopoietic cords.
3.Abundant sinusoids lie between the cords and have
openings in their walls through which maturing blood
cells and platelets enter the circulation. In histologic
section, the dense packing of the cells makes
identification of individual cell types difficult. Thus,
differentiating blood cells are commonly studied in
smears.
4.Erythroblastic islands are clusters of developing
erythrocytes surrounding macrophages and receiving
iron from them.
Bone marrow functions
1.Hematopoiesis.
2.Bone marrow helps destroy old red blood cells.
Macrophages in the bone marrow, spleen, and liver
break down hemoglobin to form (1) globin, which is
quickly hydrolyzed; (2) porphyrin rings, which are
coverted to bilirubin; and (3) iron, which is complexed
with and transported by the plasma protein transferrin to
the bone marrow for reuse by developing erythrocytes.It
is located in cytoplasmic vacuoles termed siderosomes.
3.Recirculation of the blood and immunocompetent
cells.
4.Depot of the blood
5.Immune protection(defence)
Hematopoietic Bone Marrow Stem Cells
Stem cells
can differentiate
into many
different cell types
How does it
decide what
to become?
Bone Marrow
• Bone marrow is a general term for the
soft tissue occupying the medullary
cavity of a long bone, the spaces amid
the trabeculae of spongy bone, and the
larger haversian canals.
• There are 2 main types: red & yellow.
• Red bone marrow = blood cell forming
tissue = hematopoietic tissue
• Red bone marrow looks like blood
but with a thicker consistency.
• It consists of a delicate mesh of
reticular tissue saturated with
immature red blood cells and
scattered adipocytes.
Notice the red marrow
and the compact bone
Distribution of Marrow
• In a child, the medullary cavity
of nearly every bone is filled
with red bone marrow.
• In young to middle-aged adults,
the shafts of the long bones are
filled with fatty yellow bone
marrow.
– Yellow marrow no longer
produces blood, although in
the event of severe or
chronic anemia, it can
transform back into red
marrow
• In adults, red marrow is limited
to the axial skeleton, pectoral
girdle, pelvic girdle, and
proximal heads of the humerus
and the femur.
Classification of Lymphoid Tissues and Organs:
In peripheral lymphoid organs (lymph nodes, spleen,
tonsils) and unencapsulated lymphatic aggregates, lymphocyte
production is antigen-dependent and provides committed
immunocompetent cells that respond to specific antigens.
In central lymphoid organs (thymus, bone marrow, bursa
of Fabricius [in birds]), lymphocyte production is antigenindependent and supplies uncommitted T lymphocyte
(thymus) or B lymphocyte (bone marrow, bursa) precursors
that later move to peripheral organs and tissues. Mounting
effective immune responses to new antigens requires ongoing
production of uncommitted lymphocytes by the central
lymphoid organs.
Lymphoid Nodules (Follicles): These occur in all
lymphatic aggregates except the thymus. Active
(lymphocyte-producing) nodules each have a darkstaining periphery, or mantle zone, that contains
tightly packed small lymphocytes, and a light-staining
core, or germinal center, that contains numerous
immunoblasts (lymphoblasts), ie, lymphocytes
stimulated by antigens to enlarge and proliferate.The
lighter staining reflects the increased cytoplasmic
volume and decreased nuclear heterochromatin that
accompany lymphocyte activation.
Lymph Nodules
Ileum, Nodule
Lymphatic Nodule




“Non-capsulated”
Single or aggregated
Independent
OR
parts of lymphoid
organs
Outer dark zone


(Corona or cap)
Germinal centre
Peyer’s Patches
Smaller aggregates present under many mucous
membranes :“Mucosa Associated Lymphoid Tissue” or
MALT
Lymph node
Lymphatic nodule
Fig. 22.12a(TECapsule
Art)
Afferent
lymphatic
vessel
Trabecula
Efferent
lymphatic
vessel
Lymph Node
Fig. 21.12 a and b
23
Lymph Node
•
•
•
•
•
Capsulated
Afferent lymphatics  “subcapsular sinus”
Hilum – blood vessels, efferent lymphatic
Cortex and medulla
Cortex
– Lymphatic nodules, germinal centres
– “Paracortex” T-dependent zone
• Medulla
– Medullary cords and sinusoids
M
C
C
M
LYMPH NODES
These are the smallest but most numerous encapsulated lymphoid organs.
Scattered in groups along lymphatic vessels , they act as in-line filters of
the lymph, removing antigens and cellular debris and adding Igs. Lymph
nodes are bean-shaped structures with convex and concave surfaces.
The parenchyma consists of a peripheral cortex, adjacent to the convex
surface, and a central medulla lying near the depression (hilum) in the
concave surface. The connective tissue capsule gives off trabeculae that
penetrate between the cortical nodules and subdivide the cortex.
Cortex. The cortex is dark-staining owing to the presence of tightly
packed lymphocytes. These are suspended in a reticular connective tissue
network and arranged as a layer of typical secondary lymphoid nodules
(containing primarily B lymphocytes) with germinal centers. The cortex
also contains reticular cells, antigen-presenting follicular dendritic cells,
macrophages, a few plasma cells, and some helper T cells.
Medulla. Lighter staining than the cortex, the medulla is composed of
cords of lymphoid tissue (medullary cords) separated by medullary
sinuses. The lymphocytes are mainly small, less numerous than in the
cortex. The cords are also rich in reticular cells and fibers and contain
many plasma cells that have migrated from the cortex.
Paracortical zone. This is the T-dependent region, lying between the
cortical lymphoid nodules and the medulla. It contains mainly T
lymphocytes suspended in a reticular connective tissue . B lymphocytes,
plasma cells, macrophages, and antigen-presenting interdigitating
dendritic cells may also be present.
Lymphatic vessels.
Sinuses (subcapsular, peritrabecular, medullary).
Functions:
1.Filtration of lymph
2.Lymphocyte production (lymphopoiesis).
3. Immunoglobulin production.
Lymph Node
Lymph Node
SPLEEN
The largest of the lymphoid organs. Splenic pulp is composed of
many erythrocytes, leukocytes, and macrophages, as well as a
variety of blood vessels, all suspended within a meshwork of
mesenchymal reticular cells and fibers.
White pulp consists of the lymphoid tissue surrounding each of
the many central arteries; it has 2 major components. The sleeves
of lymphoid tissue immediately surrounding each central artery
are called periarterial lymphatic sheaths (PALS). These contain
mainly T lymphocytes and constitute the T-dependent regions of
the spleen.
Surrounding each PALS, or appended to one side, is the second
component, the peripheral white pulp (PWP). PWP contains
mainly B lymphocytes and usually includes a typical secondary
lymphoid nodule with a germinal center.
Red pulp makes up most of the spleen and also has 2 major
components: the red pulp cords and the splenic sinusoids that lie
between them.
The red pulp (Billroth’s) cords are irregular sheets of reticular
connective tissue that branch and anastomose to surround the
sinuses. In addition to reticular cells and fibers, the cords contain
many cell types, including all the formed elements of blood,
dendritic cells, macrophages, plasma cells, and lymphocytes.
Splenic sinusoids differ from common capillaries: the lumen is
wider and more irregular; there are 2-3-m spaces between the
lining endothelial cells; and there is a sparse, discontinuous basal
lamina that is composed largely of reticular fibers arranged in
bands that run roughly perpendicular to the length of the vessel.
The marginal zone forms a border between the white and red
pulp; it consists of a moatlike arrangement of blood sinuses and
loose lymphoid tissue containing few lymphocytes.
Spleen
35
Open and closed theories of splenic circulation. Blood in
the capillaries reaches the sinusoid lumens by two ways. The
closed theory holds that the capillary walls are continuous
with the walls of the sinusoids and that the capillaries empty
directly into the sinusoid lumens. The open theory holds that
the capillaries end abruptly in the red pulp cords and that
blood reaches the sinusoid lumens by percolating through
the cords and passing through openings in the sinusoid walls.
For humans, current evidence favors the open theory.
Central arteries and open blood circulation are unique
feature for the spleen.
Functions:
1.Filtration of blood. 2.Lymphocyte production
(lymphopoiesis). 3.Destruction of worn red blood cells
4.Extramedullary hematopoiesis.
Thymus is the only discrete central lymphoid organ in
humans. It produces only T lymphocyte precursors and
has no lymphoid nodules. Its reticular cells derive from
endoderm and produce no reticular fibers.
It is the only organ containing Hassall’s corpuscles.
Its age-dependent structural atrophy or involution is
also unique among lymphoid organs.
2 lobes are joined and covered by a thin loose
connective tissue capsule that penetrates the lobes as
septa, dividing each lobe into incomplete lobules.
Cortex. This is the dark-staining periphery of each
lobule . Small lymphocytes predominate
Medulla. In effect, each thymic lobe has a single medulla that
extends into the core of each of the lobules. The light staining
of the medulla reflects the presence of more epithelial reticular
cells and fewer lymphocytes than in the cortex.
The spheric Hassall’s corpuscles (30-150 m in diameter)
are composed of concentric layers of flattened epithelial
reticular cells. With age, cells in the core of the corpuscles
may die and calcify.
Functions:
1.T lymphocyte production.
2.Blood -thymus barrier.
3. Production hormone - thymosin
Histology of Thymus
40
Thymus
•
•
•
•

Hassal’s Corpuscles
Capsule
Lobules
Cortex
Medulla
Differentiation
Figure 5-3 part 1 of 2
Immature
thymocytes are
here
More mature
thymocytes are
here
Figure 5-3 part 2 of 2
The Human Thymus Involutes With Age
Fetal Thymus
Adult Thymus
INVOLUTION OF THE THYMUS
Two types:1. Age dependent 2. Accidental involution
due to some exogenous agent, such as chemical or
radiation insult or severe chronic infections
TONSILS
These incompletely encapsulated lymphoid aggregates
contain many lymphoid nodules; they underlie the mucous
membranes (epithelial lining) of the mouth and pharynx.
Together with the diffuse subepithelial lymphoid tissue that
connects them to form a ring, they guard the common
entrance to the digestive and respiratory tracts.
The 3 types, palatine tonsils, the pharyngeal tonsil, and
lingual tonsils, differ in number, epithelial covering,
presence (or absence) and number of epithelial invaginations
or crypts, and presence (or absence) of a definitive partial
capsule.
Most specific structures: epithelial linings, lymphatic
nodules under the epithelium with lymphatic infiltration
and crypts.
Tonsils
Tonsil
Palatine Tonsil