ORGANS OF THE IMMUNE

SYSTEM
Quiz
Which are considered as organs of the immune
system?
A. Bone marrow
B. Thymus
C. Lymph nodes
D. Spleen
E. All of the above
Primary Lymphoid Organs
Responsible for development of stem cells into
mature immune cells
Primary Lymphoid Organs
• Bone Marrow
HSCs reside and give rise to all cell types
• Thymus
T-cells complete their maturation
Secondary Lymphoid Organs
Cells encounter antigen and initiate an immune
response
• Spleen
• Lymph nodes
• Specialized sites in gut and other mucosal tissues
• Skin
Quiz
Which are considered as producer of cells of the
immune system?
A. Bone marrow
B. Thymus
C. Lymph nodes
D. Spleen
E. Only A and B
Quiz
Which are considered as the place where immune
cells counter antigens?
A. Bone marrow
B. Thymus
C. Lymph nodes
D. Spleen
E. Only C and D
Primary Lymphoid Organs
• Bone Marrow
• Thymus
Bone Marrow
Supports self-renewal and differentiation of
• HSCs into mature blood cells

All bones contain marrow

Bone Marrow
The most active sites of haematopoiesis are
• Long bones (femur, humerus)
• Hip bones (ileum)
• Sternum
Bone Marrow
Bone Marrow: Endosteal Niche
Directly surrounding the bone and
• In contact with bone-producing osteoblasts
Bone Marrow: Vascular Niche
Area directly surrounding the blood vessels and
• In contact with endothelial cells
Bone Marrow Cells
• Osteoblasts: Make bones
• Endothelial cells: Line the blood vessels
• Reticular Cells: Connecting cell to bone and blood
vessels
• Sympathetic Neurons: Control the release of HSCs
Quiz
All cells produced from HSC are matured in bone
marrow
True
False
Thymus
Thymic microenvironment nourishes thymocytes
(Immature T-cells) to mature T-cells
T-cells complete their development
• Develop TCRs (T-cell receptors) here
Thymus
Thymic Selection
Thymocytes are selected on basis of
Their reactivity to self MHC-peptide complexes
• Expressed on the surface of thymic stromal cells
Positive Thymic selection
Those thymocytes that bind
Self MHC-peptides undergo
• Positive selection
 Positive Selection
Permits the survival of only those T cells whose
• TCRs are capable of recognizing self-MHC
molecules
Responsible for the creation of a self-MHC-
restricted repertoire of T cells
Positive Thymic Selection
Results in T-cell
• Survival
• Maturation and
• Migration
To the thymic medulla
Negative Thymic selection
Those thymocytes whose
TCR bind self MHC-peptide complexes
With too high affinity are
• Induced to die
 Negative Selection
Eliminates T cells that react too strongly with
• Self-MHC or with
• Self-MHC plus self-peptides
Extremely important factor in generating
Primary T-cell repertoire that is
• Self-tolerant
Thymic Selection
Most thymocytes (95%) do not navigate the journey
through the thymus successfully
Quiz
Positive Selection is
A. Selection of cells responsive to Ag
B. Elimination of cells non responsive to Ag
C. Elimination of high affinity cells
D. Selection of low affinity cells
E. Only A and B
Quiz
Negative Selection is
A. Selection of cells responsive to Ag
B. Elimination of cells non responsive to Ag
C. Elimination of high affinity cells
D. Selection of low affinity cells
E. Only C and D
Secondary Lymphoid Organs
Encounter of cells with antigens
• Lymphatic system and Lymph Node
• Spleen
• MALT
• Skin
Lymphatic System: Lymph
Lymph vessels are filled with
A protein-rich fluid (lymph)
• Derived from fluid component of blood (plasma)
Lymphatic System: Lymph
Seeps through thin walls of capillaries into
surrounding tissue
Lymph: Surrounding Tissues
Called interstitial fluid
• Permeates all tissues and
• Bathes all cells

If not returned it swells the location

• Causes edema that may be life threatening
Lymph
Much of fluid is returned to blood through walls of
venules
Remainder of interstitial fluid enters delicate
network of
• Primary lymphatic vessels
Lymph: Walls of Primary Vessels
Consist of a single layer of loosely apposed
endothelial cells

• Allows fluids and cells to enter lymphatic

network
Lymph: Walls of Primary Vessels
Within these vessels, the fluid, (now called lymph)

Flows into a series of progressively larger

collecting vessels called
• Lymphatic vessels
Lymphatic System: Lymph
All cells and fluid circulating in the lymph are
ultimately returned to the blood system
Lymphatic System: During Infection
When a foreign antigen enters the tissues
• It is picked up by the lymphatic system (which
drains all the tissues of the body)
Lymphatic System: During Infection
Antigen is carried to various organized lymphoid
tissues such as
• Lymph nodes, which trap the foreign antigen
Lymphatic System: During Infection
APCs that engulf and process the antigen
• Can gain access to lymph
Lymphatic System
As lymph passes from the tissues to lymphatic
vessels, becomes enriched in specific leukocytes,
including
• Lymphocytes
• Dendritic cells
• Macrophages
Quiz
Correct statement about lymph is
A. It is derived from liquid part of blood
B. It has all types of blood cells
C. Both A and B
D. None of the above
Lymph Node
It has three parts
Cortex
Paracortex
Medulla
Lymph Node
Lymph Node: Cortex
• Lymphocytes (Mostly B-Cells)
• Macrophages
• Follicular dendritic cells (arranged in follicles)
Lymph Node: Paracortex
• T-lymphocytes
• Migrated dendritic cells
Lymph Node: Medulla (Innermost)
• Lymphocytes exit through efferent lymphatics
• It has plasma cells actively secreting antibody
Quiz
B-cell rich zone of Lymph node is
A. Cortex
B. Paracortex
C. Medulla
Quiz
T-cell rich zone of Lymph node is
A. Cortex
B. Paracortex
C. Medulla
T Cells in the Lymph Node
It takes every naïve T lymphocyte about 16 to 24
hours to
• Browse all the MHC-peptide combinations
presented by the
• APCs in a single lymph node
T Cells in the Lymph Node
Naïve lymphocytes enter the cortex of the lymph
node by passing between
• Specialized endothelial cells of high endothelial
venules (HEV)
T Cells in the Lymph Node
Once naïve T cells enter the lymph node
• They browse MHC-peptide antigen complexes on
• Surfaces of DCs present in
• Paracortex
T Cells in the Lymph Node
Paracortex is traversed by stromal cells called
• Fibroblast reticular cells (FRCs)
T Cells in the Lymph Node
This network is referred to as
• Fibroblast reticular cell conduit system (FRCC)
and

Guides T-cell movements via associated

• Adhesion molecules and
• Chemokines
B Cells in the Lymph Node
In LN, B cells are activated and differentiate into
• High-affinity antibody-secreting plasma cells
B Cells in the Lymph Node
B-cell activation requires both
• Antigen engagement by the B-cell receptor (BCR)
• Direct contact with an activated CD4+TH cell
B Cells in the Lymph Node
B cells circulate through the blood and lymph
• Visit the lymph nodes on a daily basis
• Entering via the HEV
B Cells in the Lymph Node
Specific signals and chemokines draw them
• Not to paracortex, but to
• Lymph node follicle

Ultimately depend upon follicular dendritic cells

(FDCs) for guidance
Not on FRCC
The Generation of Memory T and B Cells
in the Lymph Node
The interactions between
• TH cells and APCs, and
• Activated TH cells and activated B cells

Results proliferation and differentiation

Also in the generation of memory T and B cells

The Generation of Memory T and B Cells
in the Lymph Node
Memory T and B cells can
• Take up residence in secondary lymphoid tissues or
• Can exit the lymph node

Travel to and among tissues that first encountered

the pathogen.
The Generation of Memory T and B Cells
in the Lymph Node
• Memory T cells that reside in secondary lymphoid
organs are referred to as central memory cells
and
• are distinct in phenotype and functional potential
from effector memory T cells that circulate among
tissues.
Spleen
• Situated high in the left side of the abdominal
cavity, is a large, ovoid organ
• It has important role in mounting immune
response for antigens in blood
• Not supplied by lymphatic vessel
• Has Splenic artery and splenic vein
Spleen
Spleen
It has
• Red pulp
• White pulp
• Separated by marginal zones
Spleen: Red Pulp
• The splenic red pulp consists of a network of
sinusoids populated by red blood cells,
macrophages, and some lymphocytes.
• It is the site where old and defective red blood
cells are destroyed and removed
Spleen: Red Pulp
Many of the macrophages within the red pulp
contain engulfed red blood cells or iron-containing
pigments from degraded hemoglobin
Spleen: White Pulp
• It is the site where pathogens first gain access to
the lymphoid-rich regions of the spleen.

Surrounds the branches of the splenic artery

Consists of the periarteriolar lymphoid sheath
(PALS) populated by
• T lymphocytes as well as B-cell follicles
Spleen: White Pulp
As in lymph nodes, germinal centers are generated
within these follicles during an immune response.
Spleen: Marginal Zone
The marginal zone, which borders the white pulp,
is populated by unique and specialized
macrophages and B cells, which are the first line
of defense against certain blood-borne pathogens.
Spleen: Function during Infection
Blood-borne antigens and lymphocytes enter the
spleen through the splenic artery
• Interact first with cells at the marginal zone.

In the marginal zone, antigen is trapped and

processed by dendritic cells, which travel to the
PALS
Spleen: Function during Infection
• Specialized, resident marginal zone B cells also
bind antigen via complement receptors and
convey it to the follicles.
Spleen: Function during Infection
Migrating B cells in the blood enter sinuses in the
marginal zone and
• Migrate to the follicles

Migrating T lymphocytes in the blood enter sinuses

in the marginal zone and
• Migrate to the PALS
Spleen: Function during Infection
The events that initiate the adaptive immune
response in the spleen are analogous to those that
occur in the lymph node.
Spleen: Function during Infection
Circulating naïve B cells encounter antigen in the
follicles
Spleen: Function during Infection
Circulating naïve CD8 and CD4 T cells meet
antigen as MHC-peptide complexes on
• Surface of dendritic cells in the T-cell zone (PALS)
Spleen: Function during Infection
• Once activated, CD4+TH cells then provide help to
B cells and CD8+T cells that have also encountered
antigen.
• Some activated B cells, together with some TH
cells, migrate back into follicles and
• generate germinal centers.
Additional Reading
MALT
• mucosa-associated lymphoid tissue (MALT)
• T- and B-cell zones and lymphoid follicles are also
found in mucosal membranes that line
• the digestive,
• respiratory, and
• urogenital systems, as well as
• in the skin
MALT
• bronchus-associated lymphoid tissue (BALT)
• nasal-associated lymphoid tissue (NALT)
• gut-associated lymphoid tissue (GALT)
MALT
• mucosal epithelial layer contains intraepithelial
lymphocytes (IELs), many of which are T cells
• lamina propria, which lies under the epithelial
layer, contains large numbers of
• B cells,
• plasma cells,
• activated T cells, and
• macrophages in loose clusters
MALT
• Peyer’s patches, nodules of 30 to 40 lymphoid
follicles, extend into the muscle layers that are just
below the lamina propria
• In the digestive tract, specialized M cells transport
antigen across the epithelium
MALT
Skin
• The skin is the largest organ in the body and a
critical anatomic barrier against pathogens.
• It also plays an important role in nonspecific
(innate) defences
Skin: Cells in Epidermis
• Keratinocytes present in epidermal layer secrete
a number of cytokines that may function to induce
a local inflammatory reaction.
• Langerhans cells, skin-resident dendritic cells that
internalize antigen by phagocytosis or endocytosis.
Skin: Cells in Epidermis
• Intra-epidermal Lymphocytes; which are
predominantly T cells; believed to play a role in
combating infections that enter through the skin,
Skin: Cells in Dermal Layer
• Scattered lymphocytes,
• dendritic cells,
• monocytes,
• macrophages,
• HSC