PART 1
CHAPTER 4: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM:
LYMPHOCYTES AND PLASMA CELLS
Turgeon, Immunology and Serology
5 th Ed
LYMPHOCYTES AND PLASMA CELLS
 Adaptive immune system is
comprised of the humoral and
cellular system
 Immunologically specific
cellular component of the
immune system is organized
around two 2 classes of
specialized cell T and B
lymphocytes
 Lymphocytes recognize foreign
antigens, directly destroys some
cells, or produce antibodies as
plasma cells.
 T cells subsets, including NK
cells, together with classic
innate immune cells, contribute
significantly to the
development and
establishment of acute and
chronic inflammatory diseases.
LYMPHOID AND NONLYMPHOID SURFACE
MEBRANE MARKERS
 T-lymphocytes have a relatively smooth
surface compared with the rough
pattern of B lymphocytes.
 Introduction of monoclonal antibody
(Mab) testing led to the present
identification of surface membrane
markers of lymphocytes and other cells.
 Surface markers are used to identify
and enumerate various lymphocytes
subsets, establish lymphocyte maturity,
classify leukemias, and monitor patients
on immunosuppressive theraphy.
 Cell surface molecules recognized by
MAbs are called anitgens.
 Surface markers were named according
to the antibodies that reacted with
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them, but a uniform nomenclature
system has now been adopted.
 A surface marker that identifies a
particular lineage or differentiation
stage with a defined structure, and that
can be identified with a group or cluster
of MAbs, is called a member of a cluster
of differentiation CD
 Markers can be categorized as follows:
1. Some markers are specific for
cells of a particular lineage or
maturational pathway.
2. Some markers vary in
expression, depending on the
state of activation or
differentiation of the same
cells-for example: CD Ag
identification used to classify
lymphocytes subsets
3. In addition CD classification for
the identification and
separation of lymphocytes, CD
antigens are involved
4. CD Ag are involved in various
lymphocyte functions, usually
the ff.
a. Promotion of cell to cell
interactions and adhesion
b. Transduction of signals that
lead to lymphocyte activation.
SITES OF LYMPHOCYTE DEVELOPMENT
 In fetal development, and throughout
the life cycle, the bone marrow
becomes the sole provider of
undifferentiated progenitor cells, which
can further develop into lymphoblasts.
 Continued cellular development and
proliferation of lymphoid precursors
occur as the cells travel to the primary
and secondary lymphoid tissues.
PART 1
CHAPTER 4: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM:
LYMPHOCYTES AND PLASMA CELLS
Turgeon, Immunology and Serology
5 th Ed
PRIMARY LYMPHOID TISSUE  In postnatal life, the thymus is the
primary organ that produces naïve
 THYMUS- early in embryonic
T cells for the peripheral T cell pool
development, the stroma and non-
but production of cells declines as
lymphoid epithelium of the thymus
early as 3 months of age.
are derived from the third and
 Most changes in immune function,
fourth pharyngeal pouches.
such as dysfunctional of T and B
 Older persons are immunogically
lymphocytes, elevated levels of
challenge because of aging causes a
circulating immune complexes,
reduction in the production of naïve
increase in autoantibodies, and
T cells by the thymus.
monoclonal gammopathies are
 The thymus, located in the
correlated with involution of the
mediastinum, exercises control over
thymus.
the immune system.
 Immune senescence may account
 Progenitor cells that migrate to the
for the increased susceptibility of
thymus proliferate and differentiate
older adults to infections,
under the influence of the humoral
autoimmune disease and
factor, thymosin.
neoplasms.
 Lymphocyte precursors with
acquired surface membrane
BONE MARROW
antigens are referred to as
 Bone marrow is the source of
thymocytes.
progenitor cells.
 The reticular structure of the
 Can differentiate into lymphocytes
thymus allows significant number of
and other hematopoietic cells
lymphocytes to pass through it to
(granulocytes, erythrocytes,
become fully immunocompetent
megakaryocytes populations).
(able to function in the immune
 It is believed that the bone marrow
response), thymus-derived T cells.
and gut-associated lymphoid tissue
The thymus also regulates immune
(GALT) may also play a role in the
function by the secretion of
differentiation of progenitor cells
multiple soluble hormones.
into B lymphocytes
 Cells die in the thymus and
apparently are phagocytized, a
SECONDARY LYMPHOID ORGANS
mechanism to eliminate
 Secondary lymphoid tissues include
lymphocyte clones reactive against
lymph nodes, spleen, GALT, thoracic
self.
duct, bronchus-associated lymphoid
 97% die in the thymus before
tissue BALT, skin-associated
becoming mature T cells
lymphoid tissue, and blood.
 Viable cells migrate to the
 Mature lymphocytes and accessory
secondary tissues.
cells (antigen-presenting cells) are
 The absence or abnormal
found throughout the body
development of the thymus results
 Allows migration and interactions
in a T lymphocyte deficiency.
between antigen-presenting cells, T

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PART 1
CHAPTER 4: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM:
LYMPHOCYTES AND PLASMA CELLS
Turgeon, Immunology and Serology
5 th Ed
and B lymphocytes, and follicular
dendritic cells (FDCs) and other
stromal cells.
 Tumor necrosis factor (TNF) and
lymphotoxin are essential to the
formation and maintenance of
secondary organs.
 Cytokines are produced by B and T
lymphocytes.
 Proliferation of the T and B
lymphocytes in the secondary or
peripheral lymphoid tissues is
primarily dependent on antigenic
stimulation.
 The T lymphocytes of T cells
populate the following:
a. Perifollicular and paracortical
regions of the lymph nodes
b. Medullary cords of the lymph
nodes
c. Periarteriolar regions of the
spleen
d. thoracic duct of the circulatory
system
 The B lymphocytes or B cells
multiply and populate the
following:
a. Follicular and medullary
(germinal centers) of the lymph
nodes
b. Primary follicles and red pulp of
the spleen
c. Follicular regions of GALT
d. Medullary cords of the lymph
nodes
LYMPH NODES
 Lymph nodes act as lymphoid filters
in the lymphatic system.
 Lymph nodes respond to antigens
introduced distally and routed to
them by afferent lymphatics.
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 Lymph node reactivity can occur
after systemic antigen challenge
(serum sickness)
SPLEEN
 Spleen acts as a lymphatic filter
within the blood vascular tree.
 Important site of antibody
production in response to IV
particulate antigens (bacteria).
 Also major organ for the clearance
particles
GUT-ASSOCIATED LYMPHOID TISSUE
 GALT includes lymphoid tissue in
the intestines (Peyer’s patches) and
the liver.
 Features IgA production and
involves a unique pattern of
lymphocyte recirculation.
 Pre-B cells develop in Peyer’s
patches and, after meeting antigen
from the gut, many enter the
general circulation and then return
back to the gut.
 GALT is also important for the
development of tolerance to
ingested antigens.
THORACIC DUCT
 Thoracic duct lymph is a rich source
of mature T cells.
 Chronic thoracic duct drainage can
cause T cell depletion and has been
used as a method of
immunosuppression.
BRONCHUS-ASSOCIATED LYMPHOID TISSUE
(BALT)
 Includes lymphoid tissue in the lower
respiratory tract and hilar lymph nodes.
 Mainly associated with IgA production
in response to inhaled antigens
SKIN-ASSOCIATED LYMPHOID TISSUE
 Antigens introduced through the skin
are presented by the epidermal
PART 1
CHAPTER 4: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM:
LYMPHOCYTES AND PLASMA CELLS
Turgeon, Immunology and Serology
5 th Ed
Langerhans cells, which are bone
marrow-derived accessory cells.
 Interacts in the skin and in draining
lymph nodes.
BLOOD
 Important lymphoid organ and
immunologic effector tissue.
 Circulating blood has enough mature T
cells to produce a graft vs host reaction
 Blood transfusions have been
responsible inducing acquired
immunologic tolerance in kidney
allograft patients
 Most frequently sampled lymphoid
organ.
CIRCULATION OF LYMPHOCYTES
 Mature T lymphocytes survive for
several months or years, whereas the
average life span of B lymphocytes is
only B lymphocytes is only few days.
 Lymphocytes move freely between the
blood and lymphoid tissues.
 Lymphocyte recirculation- enables
lymphocytes to come into contact with
processed foreign antigens and
disseminate antigen-sensitized memory
cells throughout the lymphoid system.
 Clonal expansion may occur regionally,
and excluded from returning to the
thymus
 Pool of T cells clonal elements is
developed by a combination of positive
selection of clones able to recognize
and react to foreign antigens, and
negative selection (purging) of clones
able to interact with self-antigens in a
damaging way.
VIRGIN OR NAÏVE LYMPHOCYTES
 Cells that have not encountered their
specific antigens
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 Express high-molecular weight
 Memory cells- long-lived T or B cells
that have been stimulated by Antigen
and can make quick response to a
previously encountered antigen
 Memory B cells-carry surface IgG and
increased level of cell-adhesion
molecule (CAMs), chemical mediators.
DEVELOPMENT OF T LYMPHOCYTES
 T Cells derived from Bone marrow
progenitor cells that mature in the
thymus glands.
EARLY CELLULAR DIFFERENTIATION AND
DEVELOPMENT
 Differentiation of lymphocytes begins in
the thymus as thymocytes.
 CD44 and CD55 are surface membrane.
 Maturation period is 3 weeks
 Filter through the cortex to medulla of
thymus
 Thymic stromal cells include fibroblast,
macrophages, epithelial cells, dendritic
cell: all of these cell types play a role in
T cell development
DOUBLE NEGATIVE THYMOCYTES
 Thymocytes lacking CD4 and CD8
surface membrane markers referred as
double-negative thymocytes
 Proliferate in outer cortex of thymus
under the influence of IL7 (critical for
growth and differentiation)
 TCR (T cell receptor) begin development
stage for rearrangement of gene that
code for the receptors
 CD3 constitutes the main part of T cell
antigen receptor
 Combination of B chain with CD3 forms
the pre-T cell antigen receptor (TCR)
PART 1
CHAPTER 4: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM:
LYMPHOCYTES AND PLASMA CELLS
Turgeon, Immunology and Serology
5 th Ed
 Signaling by the B chain promotes
development of CD4+ and CD8+ Example: CD4 = both CD3 and CD4
thymocyte CD45RA= naïve helper T cell
CD8+ lymphocytes = CD3 and
CD8

Phases of Adaptive immune response

1. Antigen recognition
2. Lymphocyte activation
3. Antigen elimination
4. Contraction (Homeostasis)
5. Memory

DOUBLE POSITIVE THYMOCYTES

 CD4+ and CD8+ or double positive

surface markers represent second stage
of thymocyte development
 Rearrange genes coding for alpha
chains
 T cells must recognize foreign antigen in
association with class I and II MHC
molecules
 Any thymocyte that unable to recognize
self-MHC dies withut leaving the
thymus
 Double negative may act as NK cells
because of capability of binding to
many natural, unprocessed cell surface
molecule

LATER CELLULAR DIFFERENTIATION AND

DEVELOPMENT OF T LYMPHOCYTES

 Mature T cells leave the thymus their T

cell receptor are CD4+ or CD8+ only
one type of marker and migrate to
medulla

T LYMPHOCYTES SUBSETS
 CD4+ subset- helper inducer T cell
 CD8+ subset –suppresor cytotoxic T cell

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