LYMPHOPOIESIS
LYMPHOPOIESIS
• Lymphocytes are the smallest and the second
most abundant type of white blood cell.
• They are known as the cells of immunity.
• Lymphocytes have large round/oval nuclei
that occupies most of the cell with little
cytoplasm.
• The nucleus will stain dark purple or blue
when it is exposed to certain stains.
• Lymphocytes include subpopulations of cells with
various origins, life spans, and function.
• These cells show more morphologic variation than
other WBCs.
• The lymphocyte’s life can span several years to days
or even hours.
• The primary functions of lymphocytes are to
recognize and react with specific antigens, work with
macrophages to eliminate pathogens, and provide
long-lasting immunity to previously encountered
pathogens.
TYPES OF LYMPHOCYTES:
• T cells (Thymus-dependent cells), B cells (bone
marrow–derived cells) and NK cells (natural killer
cells or Null cells)
• T, B and Null cells are morphologically similar.
• They are distinguished functionally and by
immunological markers.
• B cells (matures in the bursa or bone marrow),
mediate humoral or antibody-mediated immunity.
• T cells (matures in the thymus), mediate
cell mediated immunity.
• Most lymphocytes are short-lived, with an
average life span of a week to a few
months, but a few live for years, providing
a pool of long-lived T and B cells.
• These cells account for immunologic
“memory,” a more rapid, vigorous
response to a second encounter with the
same antigen.
• Of all lymphocytes about 70-80% are T-
cells,
• 15-30% are B-cells
• And approx. 5% are NK cells.
• Plasma cells are not normally seen in the
peripheral blood but are present in the
bone marrow and other tissues
Natural killer (NK) cells
• NK cells are neither T nor B cells, though are
often CD8+. They characteristically have
prominent granules and are often large
granular lymphocytes.
• These are lymphocytes which can kill virus
infected cells (and tumour cells) without
antigenic stimulation although antibody
enhances their activity.
• They destroy cells by secreting cytotoxins and
direct adhesion. They have no immunological
memory.
• Lymphocytes are derived from the
hematopoietic stem cell (HSC)
• As we already know, HSC can develop into
common lymphoid progenitor (CLP) or
common myeloid progenitor (CMP).
• CLP produce committed B-, T-, or NK
progenitor cells.
• The committed progenitor cells will generate T,
B and NK lymphocytes
Sites of Lymphopoiesis
• The bone marrow and thymus are the primary
lymphoid organs in which lymphocytes develop from
progenitor cells.
• The secondary lymphoid organs in which specific
immune responses are generated are the lymph nodes,
spleen and lymphoid tissues of the alimentary (Peyer’s
patches) and respiratory tracts.
• In the secondary sites, lymphocytes undergo
activation, proliferation and additional maturation
• Proliferation of the T and B lymphocytes in
the secondary or peripheral lymphoid tissues
is primarily dependent on antigenic
stimulation.
• Stem cells that migrate to the thymus
proliferate and differentiate under the
influence of specific cytokines.
• These cells acquire thymus-dependent
characteristics to become immunocompetent
(able to function in the immune response) T
lymphocytes.
PROCESS
• 1. Pluripotential cell
• 2. Lymphoid multipotential cells : migrate to lymphoid
organs
• 3. Lymphocyte colony forming cell
• 4. Lymphoblast :
• 5. Prolymphocyte :
• 6. B and T lymphocytes : in the thymus or bone marrow,
these cells synthesize cell surface receptors
The lymphoblast
• This is the first morphologically identifiable cell of the
lymphocytic maturational series in the bone marrow.
• The overall size ranges from 15 to 20 µm, with a
nuclear-cytoplasmic (N:C) ratio of 4:1.
• The nuclear shape is either round or oval. One or two
nucleoli may be present.
• The small amount of cytoplasm is medium blue and
may have a darker-blue border. No granules are
present.
The Prolymphocyte
• The second stage in the maturational development of
the lymphocyte
• This cell may be seen in the bone marrow, thymus,
and secondary lymphoid tissues. The overall size is
usually about the same (15 to 18 µm) as the
lymphoblast.
• The N:C ratio ranges from 4:1 to 3:1.
• No cell surface receptor that mark them as T or B
lymphocyte.
• The nuclear shape is usually oval or slightly
indented.
• The number of nucleoli varies from none to
one.
• The small amount of cytoplasm is medium blue
with a thin, darker blue rim.
• A few azurophilic granules may be present.
Mature lymphocytes
• Mature lymphocytes range in size from large (17 to 20
µm) in younger cells to small (6 to 9 µm) in older cells.
• The N:C ratio ranges from 2:1 in younger cells to 4:1
to 3:1 in older cells.
• The nucleus is round or oval and may have an
indentation (cleft). Nucleoli are not visible. The
chromatin pattern is dense and appears clumped.
• The cytoplasm is light sky blue and very scanty. A few
azurophilic granules may be present.
T-CELL DEVELOPMENT
• T- Lymphocyte development begins with CLP
cells that migrate into to the thymus where
they will differentiate and mature into T cells.
• It is associated with the movement of the cells
through the cortex and medulla of the thymus.
• Maturing begins in the cortex, and as the cells
develop more they move towards the medulla.
• The T cells in the thymus stay in an
antigen-free environment for almost 1
week.
• Only 2 to 4% of the original population of
T cells is able to survive in this
environment.
• Other T cells either undergo apoptosis or
are eaten and destroyed by macrophages.
• The death of this large amount of T-
lymphocytes ensures that the surviving
lymphocytes can recognize self-major
histocompatibility complexes (MHCs).
• Recognition of this complex prevents the
autoimmune destruction of the body’s own
cells.
• T cells or thymocytes may differentiate into
helper T (Th) cells, cytotoxic T (Tc) cells,
memory T cells, and suppressor or regulatory T
cells.
• Once stimulated by the appropriate antigen, helper T
cells secrete chemical messengers called cytokines,
which stimulate the differentiation of B cells into
plasma cells, thereby promoting antibody production.
• Therefore T-helper cells are believed to initiate and
oversee the immune response.
• Regulatory T cells act to control immune reactions,
hence their name.
• Cytotoxic T cells, which are activated by various
cytokines, bind to and kill infected cells and cancer
cells.
B-LYMPHOCYTE DEVELOPMENT
• B lymphocytes arise from lymphoid stem cells
in bone marrow.
• Initial development occurs in primary
lymphoid organ (BM) from where B cells
migrate to the secondary lymphoid organs (LN
& spleen) and further differentiation occurs on
antigenic stimulation
• There are various stages in the development of
B lymphocytes:
• Stem Cell (HSC)
↓
• Committed Lymphoid Progenitor
↓
• Pro-B cell
↓
• Pre-B cell
↓
• Immature B cell
↓
• Mature B cell
• B-cell development is altered by cytokines.
• Interleukin-7 interacts with stem cell factor to
begin the process.
• In order for the cells to function, they will
express immunoglobulin (Ig) on their surface.
• B cells mature in the bone marrow and
circulate in the peripheral blood until they
undergo recognition of antigen
• At this point they mature into memory B cells
or plasma cells.
• When naïve B cells encounter antigens in the
secondary lymphoid tissues, they are
induced to proliferate,
• resulting in clonal expansion producing large
numbers of B cells with the same B-Cell
Receptor capable of recognizing that
particular antigen.
• This process is followed by differentiation of
the antigen-activated B cell into memory B
cells and antibody-secreting plasma cells
• The plasma cell is the fully differentiated B cell
• Plasma cells have a characteristic morphology
with an eccentric round nucleus with a
'clockface‘ or ‘cartwheel’ chromatin pattern
and strongly basophilic cytoplasm
• The plasma cells are capable of producing and
releasing antibodies, while the memory cells
remember antigens that they were once
exposed to in the past.
• B-Lymphocytes make up about 15–30%
of body lymphocytes
• They contain antigen receptors to only
one antigen and produce
immunoglobulins or antibodies to that
single antigen.
• B-lymphocytes become activated when
presented with an antigen from a helper
T-lymphocyte
• The pool of peripheral lymphocytes is
closely regulated and remains relatively
constant in the absence of disease
• The numbers of T lymphocytes both in
secondary lymphoid organs and in the
circulation are kept under strict control.
• Lymphocytes move freely between the blood
and lymphoid tissues.
• This activity, referred to as lymphocyte
recirculation, enables lymphocytes to come in
contact with processed foreign antigens and to
disseminate antigen-sensitized memory cells
throughout the lymphoid system.
• Lymphocytes recirculate back to the blood via
the major lymphatic ducts
Regulation
• Lymphopoiesis is stimulated and
regulated by:
• Specific microenvironment
• Thymic hormones
• Antigens
• IL-1 and IL-3
• Lymphocyte interleukins such as IL-2, B-cell
growth factor, B-cell differentiation factor.
