Cells and Organs of the Immune System

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Chapter 2 Cells and Organs of the Immune System
Sept 26,28 Oct 3, 2006
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• ?? (secondary) ???????? ??????
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Outline 1. Hematopoiesis (??) 2.
Cells of the Immune System 3. Organs of the
Immune System 4. Lymphoid Cells and Organs
Evolutionary Comparisons
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Hematopoiesis
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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
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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.
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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.
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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.
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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.
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Cells of the Immune System
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Total leukocytes ()
1 2 3 4
3.7 5.1 x 103 1.5 3.0 x 103 1 4.4 x 102 1
2.2 x 102 lt 1.3 x 102
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• 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

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Lymphoid Cells - 20 - 40 of the
bodys 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
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B Lymphocytes Bursa of Fabricius (???)
or Bone Marrow T Lymphocytes
Thymus
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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).
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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
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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
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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 21 in human peripheral
blood.
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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.
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Fate of Antigen-activated Small B Lymphocytes
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• 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

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Mononuclear Phagocytes - Monocytes circulating
in the blood - Macrophages in the tissues
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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
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• 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

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• 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

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Phagocytosis is Followed by Digestion and
Presentation of Ag
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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.
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Granulocytic Cells (granulocytes) - Neutrophils
(polymorphonuclear leukocytes, PMN) -
Eosinophils - Basophils
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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
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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
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• 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).

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Dendritic cells (DC) and their origins
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• 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

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Organs of the Immune System
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The Human Lymphoid System
secondary lymphoid organs
primary lymphoid organs
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• 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
• Peyers patches

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Various lymphoid organs (primary secondary)
are connected by blood vessels and lymphatic
systems.
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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.
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The Thymus
stromal cells
maturation
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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
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Changes in the Thymus with Age
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• 35-yr-old 20
• 65-yr-old 2
• ???????

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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.
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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.
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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.
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Lymphatic Vessels
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Secondary Lymphoid Organs 1. Organized lymphoid
organs lymph nodes spleen 2. Less
organized lymphoid tissues, collectively called
mucosa-associated lymphoid tissue (MALT)
- Peyers patches - tonsils -
appendix - numerous lymphoid follicles
(within intestines, upper airways,
bronchi and genitourinary tract)
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• 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.

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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.
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A Secondary Lymphoid Follicle
germinal center (B cells, TH cells, M?,
follicular DC)
dense mantle of small B lymphocytes
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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
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A Lymph Node
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The Spleen
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Tonsils
?
??
?
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Peyers Patch
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Structure of M Cells
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Production of IgA Ab in the Gut
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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.
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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?