Chapter 2

Cells and
Organs of the
Immune System
 Outline

1. Hematopoiesis

2. Cells of the Immune System

3. Organs of the Immune System

4. Lymphoid Cells and Organs –

Evolutionary Comparisons
Hematopoiesis
All blood cell arise from the hematopoietic
stem cell (HSC).

Locations of Hematopoiesis (humans):

embryo yolk sac (first weeks)

® fetal liver & spleen
(3rd to 7th mo of gestation)
® bone marrow
Properties of hematopoietic
stem cells (HSC):

1. Capability to give rise to all

differentiated blood cells
2. Self-renewing; each division of
a stem cell creates at least one
stem cell.
Hematopoiesis

Progenitor cells
proliferate and
differentiate into
various cell types
through the action of
growth factors,
cytokines and
stromal cells.
Stromal cells: fat cells,
endothelial cells, fibroblasts,
macrophages.
[Clinical Focus]
Stem Cells - Clinical Uses and Potential
Providing a functional immune system to individuals with:

1. a genetically determined immunodeficiency, such

as severe combined immunodeficiency (SCID).
2. life-threatening genetic disorder in hematopoiesis, such
as sickle-cell anemia or thalassemia.
3. treatment of high-dose chemotherapeutic agents or
radiation, such as cancer patients.
 Transplantation

Autologous : The recipient is also the donor.

Syngeneic : The donor is genetically identical,
i.e., an identical twin of the recipient .
Allogeneic : The donor and the recipient are
not genetically identical within
the same species.
Xenogeneic : The donor and the recipient are
from different species.
 Cells of the
Immune System
 Total leukocytes (%)

1
2

3 3.7 – 5.1 x 103

4 1.5 – 3.0 x 103
1 – 4.4 x 102
1 – 2.2 x 102
< 1.3 x 102
 Cells of the Immune System

- Lymphoid cells
B lymphocytes, T lymphocytes – bearing antigen receptors
Natural killer cells (NK cells)

- Mononuclear phagocytes
Monocytes, Macrophages

- Granulocytic cells
Neutrophils, Eosinophils, Basophils, Mast cells, Dendritic cells
 Lymphoid Cells

- 20% - 40% of the body’s white blood cells

- 99% of the cells in the lymph
- ~ 1010 - 1012 in the human body
- Circulate in the blood and lymph
- Migrate into the tissue spaces and lymphoid
organs
B Lymphocytes:
Bursa of Fabricius
or
Bone Marrow

T Lymphocytes:
Thymus
 Cluster of Differentiation (CD)

All of the monoclonal antibodies (mAb) that

react with a particular membrane molecule on
the cell are grouped together as a cluster of
differentiation (CD).
 B Lymphocyte Markers

Immunoglobulin (Ig, Ab) as receptors for Ag

B220 (CD45R)
MHC Class II
CR1 (CD35) & CR2 (CD21)
FcgRII (CD32)
B7-1 (CD80) & B7-2 (CD86)
CD40
 T Lymphocyte Markers

T cell receptor (TCR) as Ag receptors

CD3
CD4 or CD8
CD28; a receptor for B7 on B cells and APC
CD45
 Two Major Subpopulations of
T Lymphocytes
CD4+ T cells: only recognize Ag bound to class II
MHC molecules (also called class-II
restricted)
: generally function as T helper (TH) cells
CD8+ T cells: only recognize Ag bound to class I
MHC molecules (also called class-I
restricted)
: generally function as T cytotoxic (TC) cells

The ratio of CD4+/CD8+ T cells is ~ 2:1 in human peripheral blood.

TH cells (usually CD4+) : proliferate and secrete
various cytokines
TH1 response – produces a cytokine profile that
supports inflammation and
activates mainly T cells and
macrophages.
TH2 response – activates mainly B cells and
immune responses that depend
upon antibodies.

TC cells (usually CD8+): proliferate and differentiate

into cytotoxic T lymphocytes
(CTL) which can eliminate
altered self-cells.
Fate of Antigen-activated
Small B Lymphocytes
 Natural Killer (NK) Cells
- large, granular lymphoid cells
- cytotoxic against certain tumor cells and virus-
infected cells with no previous immunization
- Part of the innate immune system
- constitute 5 - 10% of the lymphocytes in human
peripheral blood
- using NK cell receptors or CD16 (FcgRIII) as
recognition molecules
- NK T cells: possessing both TCR and NK cell receptors
 Mononuclear Phagocytes

- Monocytes: circulating in the blood

- Macrophages: in the tissues

 Macrophages
1. 5- to 10-fold larger than monocytes
2. contain more and complex organelles, especially lysosomes
3. increased phagocytic ability
4. produce higher levels of hydrolytic enzymes
5. increased ability to kill ingested microbes
6. increased secretion of inflammatory mediators, and
7. increased ability to activate T cells
 Tissue Macrophages

Alveolar macrophages in the lung

Histiocytes in connective tissues
Kupffer cells in the liver
Mesangial cells in the kidney
Microglial cells in the brain
Osteoclasts in bone
Macrophages can be activated by:

- components of bacterial cell walls

- phagocytosis of particulate Ag
- cytokines secreted by TH cells (the most
potent one is interferon-g, IFN-g)
- mediators of the inflammatory response
Phagocytosis is Followed by Digestion and
Presentation of Ag
Opsonin: A substance (e.g., Ab) that binds to both
Ag and phagocytes, thereby enhancing
phagocytosis.

The process by which opsonins render

particulate Ags more susceptible to
phagocytosis is called opsonization.
Granulocytic Cells (granulocytes)

- Neutrophils
(polymorphonuclear leukocytes, PMN)
- Eosinophils
- Basophils
Neutrophils :
- phagocytic and microbicidal (similar to macrophages)
- extravasation: movement of circulating neutrophils
into tissues

Eosinophils:
- less phagocytic
- defend parasitic organisms

Basophils:
- nonphagocytic
- release pharmacologically active substances
- play a major role in certain allergic responses
Mast Cells:
- not differentiated until leaving the blood and
entering the tissues, such as the skin,
connective tissues, and mucosal epithelial
tissues
- release histamine and other pharmacologically
active substances
- play an important role in the development of
allergies
 Dendritic Cells
- Langerhans dendritic cells in the epidermal layer of skin
- Interstitial dendritic cells in the interstitial space of all
organs except the brain

- Monocyte-derived dendritic cells arise from

monocytes that have migrated from the bloodstream into
tissues.
- Plasmacytoid dendritic cells arise from plasmacytoid cells

They play roles in innate immune defense and act as

antigen-presenting cells (APC).
Dendritic cells (DC) and their origins
All DCs constitutively express high levels of
class I & class II MHC molecules,
costimulatory molecules B7 (CD80,CD86)
and CD40 molecules, which can interact with
T cells.
major functions of DC:
- immature DC in periphery:
sense of invasion
capture of foreign Ag
- mature DC migrate into lymphoid organs:
presentation of Ag to T cells
 Organs of the
Immune System
The Human Lymphoid System
secondary
lymphoid
organs

primary
lymphoid
organs
Primary (central) lymphoid organs
- Provide appropriate microenvironments for the
development and maturation of lymphocytes.
- thymus and bone marrow

Secondary (peripheral) lymphoid organs

- Trap antigen from tissues or vascular spaces and are
sites where mature lymphocytes can interact
effectively with that antigen.
- lymph nodes, spleen and various mucosal-associated
lymphoid tissues (MALT), e.g., tonsil, appendix and
Peyer’s patches
Various lymphoid organs (primary
& secondary) are connected by blood
vessels and lymphatic systems.
Lymphatic System

- Once mature lymphocytes have been generated

in the primary lymphoid organs, they circulate
in the blood and lymphatic system, a network
of vessels that collect fluid that has escaped into
the tissues from capillaries of the circulatory
system and ultimately return it to the blood.
 The Thymus
stromal cells:
maturation
 The Function of the Thymus

The function of the thymus is to

generate and select a repertoire of T cells
that will protect the body from infection.
Those T cells which do not recognize
Ag-MHC or react with self-Ag-MHC will
undergo apoptosis in the thymus.
Changes in the Thymus with Age
 Bone Marrow
In mice and humans, immature B cells
proliferate and differentiate within the bone
marrow, and the stromal cells interact with the
B cells and secrete various cytokines that are
required for development.
Like thymic selection during T-cell
maturation, a selection process within the bone
marrow eliminates B cells with self-reactive
antibody receptors.
 Lymphatic System

The lymphatic system serves as a means

of transporting lymphocytes and Ag from
tissues to organized lymphoid organs, where
the lymphocytes may interact with the
trapped Ag and undergo activation.
Lymph – Interstitial fluid derived from blood
plasma that contains a variety of
small and large molecules,
lymphocytes and some other cells.
It circulates through the lymphatic
vessels.
The largest lymphatic vessel, the thoracic duct,
empties into the left subclavian vein near the
heart.
Lymphatic Vessels
 Secondary Lymphoid Organs
1. Organized lymphoid organs :
lymph nodes & spleen
2. Less organized lymphoid tissues, collectively called
mucosa-associated lymphoid tissue (MALT) :
- Peyer’s patches
- tonsils
- appendix
- numerous lymphoid follicles (within intestines,
upper airways, bronchi and genitourinary tract)
Lymph nodes are the sites where immune
responses are mounted to antigens in lymph
and the spleen plays a major role in mounting
immune responses to antigens in the blood.
 Lymphoid organs contain primary follicles
which comprise a network of follicular dendritic
cells and small resting B cells. After an antigenic
challenge, a primary follicle becomes a larger
secondary follicle – a ring of concentrically
packed B lymphocytes surrounding a center (the
germinal center) in which proliferating B
lymphocytes and some TH cells intersperse with
macrophages and follicular dendritic cells.
A Secondary Lymphoid Follicle

germinal center
(B cells, TH cells, Mf,
follicular DC)

dense mantle of
small B
lymphocytes
 Follicular dendritic cells
- different from other Ag-presenting dendritic cells
- do not express class II MHC molecules
- do not function as Ag-pesenting cells for TH cell
activation
- exclusively located in lymphoid follicles (in
organized secondary lymphoid organs)
- express high levels of receptors for Ab
- play an important role in the maturation of B cells
A Lymph Node
The Spleen
Tonsils
Peyer’s Patch
Structure of M Cells
Production of IgA Ab in the Gut
 Evolutionary Distribution of
Lymphoid Tissues

Adaptive immunity only evolved in the subphylum Vertebrata.

However, neither T nor B lymphocytes have been found in the
jawless fishes.
Questions:

1. What can activate macrophages? How does the

activity of macrophages change after activation?
2. What are the functions of dendritic cells?
3. What are the surface molecules characteristic for T
and B lymphocytes?
4. What are the primary and secondary lymphoid
organs? What are their functions?