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Chapter 2
Cells and
Organs of the
Immune System
Sept 26,28 & Oct 3, 2006
你需要學習的課題:
1. 「淋巴器官」 (lymphoid organ) 分為哪兩大類?
2. 初級 (primary) 淋巴器官有哪些? 有什麼功能?
3. 次級 (secondary) 淋巴器官有哪些? 有什麼功能?
4. 免疫系統包含哪些細胞、器官及組織? 各有什
麼特色及功能?
Outline
1. Hematopoiesis (造血)
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
骨髓系
淋巴系
Progenitor cells
proliferate and
differentiate into
various cell types
through the action of
growth factors,
cytokines and
stromal (基質) cells.
Stromal cells: fat cells,
endothelial cells, fibroblasts,
macrophages.
[Clinical Focus]
Stem Cells (幹細胞)
- 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.
儲存臍帶血的意義是什麼?
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 (黏液囊)
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 virusinfected 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
(調理素) 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 (淋巴系統)
- 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.
*repertoire
: 總目錄 (即對抗外物的所有T 細胞)
Changes in the Thymus with Age
• 想一想:
胸腺的重量自出生到青春期直線上升，
青春期以後胸腺就逐漸萎縮
35-yr-old: 20%
65-yr-old: 2%
有無特殊意義？
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
(胸管),empties into the left subclavian (鎖骨下)
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, M,
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
血管神經
出入口
Tonsils
上顎
舌
咽
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?