Bythe end of this

The Lymphoid System chapter you should be

able to:
1.Write the different organs and
functions of primary and
seconday lymphoid sysem
2.Organize the step by step
maturation of B cells and T
cells
3. Summarize the role and
function of B cells and T cells

Lymphoid organs and tissues

• What are the circulatory

systems found in human?

Organs of primary and • The lymphatics serve as a

drainage system to remove
secondary lymphoid cellular debris and
microbes from the body's
system tissues to the lymph nodes.

• Lymphoid organs are

classified as primary or
Diagram Adopted from Lippincott's secondary
Illustrated Reviews: Immunology, 2nd ED
 Lymphoid organ classification Lymphoid organs and tissues
• Lymphocytes develop within the primary
Primary Secondary lymphatic lymphatic organs and the secondary lymphoid organs
trap and concentrate immunogens
organ organ/ tissue
• This provide sites where large
numbers of circulating immune cells
Thymus Simple Intermediate can make contact with each other.
• Specific immune reactions takes
To nsil
Organs Bone • Diffuse LT place and immune response follows.
Marrow 1
• Solitary LN2
Lymph
• Aggregate LN3 Nodes
1
Mucosa-associated lymphoid tissue (MALT)- various part of thebody

Spleen
2 Mucous membrane of intestines
3 Peyer's patches (ileum)

Primary lymphoid organs

The functions and

importance of lymphoid
organs
 Primary lymphoid organs
• Lymphocyte educational centers.

• All lymphocytes originate within the bone

marrow, Tcells are sent at an early age to
the thymus for "advanced education“.

• Other lymphocytic lineage, Bcells are "home

Advanced education Tcells
schooled“ and remain within the bone
marrow.

• Stromal cells within the thymus and bone

marrow closely regulate the development of Home school Bcells
T and Blymphocytes respectively.

Thymus
• Thymus is a bi-lobed organ.

• Stem cells (prothymocytesT‘ cells’) in bone

marrow will migrate to thymus.
• Cortical thymocytes in thymus will
acquire a nascent TCR,as well
as both CD4 and CD8 surface
molecules. Positive
Negative
selection
selection
 T-cel Maturation
• Cells fated to become immunoglobulin- producing
lymphocytes- develop in BM.

• They develop their BCRsby DNArearrangement.

• Express auxiliary molecules (lgα and lgβ), and

begin todisplay lgM on their surfaces prior to
leaving the bone marrow. Positive
• Like Tcells, these cells undergoes extensive
Negative
“exams” to scrutinize self-reactive cellsand
exclude them before graduations.
selection
selection

Double Negative Selection

• These large double-negative thymocytes actively
proliferate in the outer cortex under the influence of
interleukin-7.
 Pre- T cel s Double Positive Selection
•
• At this second stage, when
thymocytes express both CD4
and CD8 antigens, they are called
double-positive

Double_x0002_positive thymocytes
proliferate and then begin to
rearrange the genes coding for the
alpha chain

Double Positive Selection

• At this second stage, when thymocytes
express both CD4
and CD8 antigens, they are called double-
positive
Mature T cel s
The two separate mature T-cell populations created
• differ greatly in function. T cells bearing the CD4 receptor
are termed helper, or inducer, cells, while the CD8-
positive (CD8) population consists of cytotoxic T cells
 Subset of T-cel s Regulatory T cel s
• Th1 and Th 2 • they possess the CD4 antigen and
CD25 and produce IL-10

• Th1 cells produce interferon gamma • play an important role in suppressing

(IFN-γ) and tumor necrosis factor-beta (TNF-β), the immune response to self-
which protect cells against intracellular pathogens. antigens.

Th2 cells produce a variety of

interleukins,
• including IL- 4 , IL- 5 , IL- 10 , and IL- 13 .
The essential role of the Th2 cells is to help B
cells produce antibody against extracellular
pathogens.

Antigen Activation Bone marrow (BM)

• • Cells fated to become immunoglobulin-
producing lymphocytes- develop in BM.

• • They develop their BCRsby

DNArearrangement.

• Express auxiliary molecules (lgα and lgβ), and

begin to display lgM on their surfaces prior
to leaving the bone marrow.
•
• Like T cells, these cells undergoes extensive
“exams” to scrutinize self-reactive cells
and exclude them before graduations.
 B cell development B cell development
• B cells are generated in the bone marrow • Early B cell development
• Takes 1-2 weeks to develop from hematopoietic stem constitutes the steps that lead
cells to mature B cells to B cell commitment and
• Sequence of expression of cell surface receptor and expression of surface
adhesion molecules which allows for differentiation of immunoglobulin, production of
B cells, proliferation at various stages, and movement mature B cells
within the bone marrow microenvironment
• Immature B cell leaves the bone marrow and • Mature B cells leave the
undergoes further differentiation bone marrow and migrate to
• Immune system must create a repertoire of receptors secondary lymphoid tissues
capable of recognizing a large array of antigens while • B cells then interact with
at the same time eliminating self-reactive B cells exogenous antigen and/or T
helper cells = antigen-
dependent phase

B cell development
Pro-B cells
• earliest B-cell
precursor can be
recognized by the
presence of a surface
molecule called CD45R
 Pre-B cells Immature B cells
• T h e f i r s t h e a v y
• Have functional IgM but no other Ig expression
chainssynthesized are the μ
chains, which belong to the class
of immunoglobulins called IgM
• Completion of light chain rearrangement commits a cell
to produce an antibody mol_x0002_ecule with specificity
for a particular antigen or group of related antigens

Mature B cells Activated B cells and Plasma cells

• Complete IgM molecule on cell surface

• Exit bone marrow, migrate to secondary lymphoid

organs, then express both surface IgM and IgD as
well as other molecules that mediate cell-cell and
cell-ECM adhesive interactions
 Plasma B cells Secondary lymphoid tissues &
• Secrete antibodies, have few surface antibodies organs
• Those that arise from follicular B cells are found
mainly in the bone marrow and are long-lived
(months)
• Those that arise from non-follicular B cells are short
lived (days to weeks)
• Plasma cell differentiation involves
– loss of Bcl6, Pax-5, CD19, CD20, and B cell
activation antigens
– Appearance of XBP-1, BLIMP-1, CD38,
CD138, cytoplasmic Ig

Secondary lymphoid tissues & Secondary lymphoid tissues &

organs
• Secondary lymphoid tissues function as
filtration devices removing
• Foreign matter
• Dead cells
• Protein aggregates from the circulation.
• Secondary lymphoid organs are rich in
supply of blood vessels and lymphatic
vessels.
organs
• Secondary lymphoid provides a condition
which accommodate leukocyte-rich nature.
• These facilitates Cellular interaction providing
leukocytes an environment in which they
can
• Exchange regulatory signals

• These facilitate the movement of • Undergo further development

lymphocytes, monocytes, and
dendritic cells into and out of these • Proliferate before reentering the circulatory
organs. sys.
Secondary lymphoid tissues & organs Secondary lymphoid tissues &
• Leukocyte- and debris-rich
organs
lymph percolates through
the body of the lymph node.
• Here they encounter

• Phagocytic cells
(macrophages and dendritic
cells) that remove dead and √
dying cells
• Cellular debris
Diagram Adopted from Lippincott's
• Microorganisms from the
Illustrated Reviews: Immunology, 2nd ED lymph. √ √

a. Spleen b. Lymph nodes

• The largest lymphoid organ homes: • Small round or oval-shaped
• Blymphocytes secondary lymphoid organs.
• Tlymphocytes
• Other leukocytes • Their function:
om
• Spleen clears particulate matter fr • Filters to purify lymph, the fluid and
-
the blood and concentrates blood cellular content of the lymphatic
borne antigens and microbes. circulatory system.
D
i
a
g
r
• Provide sites for mingling of lymphocytes,
a
m
monocytes, and dendritic cells for
A
initiation of immune responses.
d
o
p
t
e
d
f
r
o
m
 b. Lymph nodes c. Mucosa-associated
T-cell-rich area
lymphoid tissues
• Forming nodules
• The secondary lymphoid tissues that
or follicles. defend the mucosa surfaces are:
• Tonsils in the nasopharynx.
• Thymus
independent area • Peyer's patches in the submucosal surfaces
and contains of the small intestine.
mostly Bcells

• Follicles develop • Peyer's patches function similarly

a central area,
with large to lymph nodes and the spleen.
proliferating cells
during immune
response
• They are located at potential portals
of microbial entry.

c. Mucosa-associated c. Mucosa-associated
lymphoid tissues lymphoid tissues

Tonsils are located as a defensive ring around
the
• nasopharynx at the portal of
entry for both the respiratory
and gastrointestinal
systems.
Peyer's patches are lymphoid
• accumulations lying
underneath the villi of the
small bowel (within the area
delineated by the dotted
line).
 c. Mucosa-associated
tissue lymphoid
s
Lymphatic circulatory system

Intestinal villi contain intraepithelial lymphocytes,

•
interstitial leukocytes, and raining lymphatics (lacteals)
that serve to both sample the intestinal environment
and defend the bowel frommicrobial invasion.

Lymphatic circulatory system Lymphatic circulatory system

• Leukocytes and their products use
two circulatory systems:
• Cardiovascular system (Humoral and • How does the lymph fluid forms?
cellular)
• lymphatic circulatory system (Lymph,
leukocytes and cellular debris).

• The lymphatic capillaries drain into large

lymphatic vessels that drain into lymph • How does the lymph fluid return
nodesfor filtration. to blood?

• Ultimately, the lymphatic trunk vessels

join to form the thoracic duct that
conveys lymph into the subclavian
artery.
Reference:
 Stevens, C. D. (2010). Clinical Immunology and Serology A
Laboratory Perspective Third Edition. F.A. Davis Company.
 Turgeon, Mary Louise, IMMUNOLOGY AND SEROLOGY IN
LABORATORY MEDICINE, 2nd edition, Mosby-Year Book, Inc., St.
Louis, Missouri, l996
 Abbas, Abul K.. (2014). Basic immunology: functions and


disorders of the immune system, 4th ed.. Philadelphia
Olson, Kate Rittenhouse. (2013). Contemporary clinical
Thank You
immunology and serology. Boston
 Hall, Angela. (2010). Immunology. Oxford
 Playfair, J.H.L. (2013). Immunology at a Glance, 10th ed.. UK :
Wiley-Blackwell