Download Cells, Tissues and Organs of the Immune System

Cells and Organs
of the
Immune System
Oncology for Scientists
December 1, 2011
Maegan Capitano
Department of Immunology
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What is the immune
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Immune System
• Cells (leukocytes)
• Organs
– Primary: bone marrow and thymus
– Secondary: lymph nodes, spleen, tonsils, etc
• Circulatory system- blood
• Lymphatic system- lymph
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Leukocyteswhite blood cells
Plasma
(serum= clotting factors removed)
After centrifugation,
leukocytes are found in
the “buffy coat”
RBCs
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Two Systems of Immunity
Innate immunity- quick response…
• most ancient line of defense
• some form found in all multi cellular plants and
animals.
Adaptive immunity- takes several days…
• more recent development in evolution
• evolved in jawed vertebrates
• complements innate immunity.
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What are the cells that
comprise the immune
system?
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The cells of the immune system arise
from pluripotent hematopoietic stem
cells (HSC) in a process called
hematopoiesis
The two main lineages formed during
hematopoiesis are:
• Myeloid lineage produces granulocytes,
monocytes, platelets, and erythrocytes
• Lymphoid lineage produces lymphocytes
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The cells of the immune system
differentiate in the bone marrow
A.
B.
C.
D.
Hemosiderin
Erythroid
precursor
Band cells
•
Neutrophil
Megakaryocytes
•
platelets
Univ Penn, Vet School, http://
cal.nbc.upenn.edu/histo
(Dog)
Pleuripotent Hematopoietic Stem Cells give rise to second
generation stem cells with restricted lineage potential
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Hematopoesis (1)
Pleuripotent Stem Cell
Myeloid
lineage
Granulocyte
lineage
Eosinophil
Neutrophil
Basophil
(Myeloid= of or
relating to the bone
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marrow)
Blood smears for Peripheral BloodWright’s stain
• acidophilic
“acid loving”
pink dye- eosin
• basophilic
“alkaline
loving” blue
dye
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Neutrophil
• granules “neutral” don’t stain
red or blue
• Most abundant leukocyte in
the blood
• Multilobed nucleus=
polymorphonuclear leukocyte
+ PMN
• Rapidly migrate from blood to
sites of infection (earliest
phagocyte recruited)
• They can kill microbes in
several ways:
• Phagocytosis (eating)
• Release of granules
containing proteases, etc
• Short lived – major component
of pus
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Eosinophil
• granules stain pink
• Bilobed nuclei
• Release highly toxic
granule proteins/
free radicals which
kill microorganisms
and parasites
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Basophil
• granules stain
dark blueobscure nucleus
• rarest of all
leukocytes < 1%
• Possesses
vasoactive
(effecting blood
vessels) and
immunoreactive
substances
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Hematopoesis (2)
Pleuripotent Stem
Cell
Myeloid
lineage
Monocyte
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Monocytes- Tissue macrophages
Monocyte
• Mononuclear
phagocyteBean-shaped
nucleus
• Become fully
mature
macrophages
• Special names in
different organs
e.g. Kupffer
cells in liver
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Hematopoesis (3)
Pleuripotent Stem Cell
Myeloid
lineage
Mega-
Platelets
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Platelets
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Blood Clot
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Hematopoesis (4)
Pleuripotent Stem
Cell
Myeloid
lineage
Eryth-
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Mature RBCs have no nuclei
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Hematopoesis (5)
Pleuripotent Stem
Cell
Lymphoid
lineage
Lymphocytes
NK cells
T cells
B cells
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Lymphocytes: 3 types
• Cannot be distinguished morphologically
• T-cells
– helper CD4+
– cytotoxic CD8+
– T regulatory
• B-cells
– become antibody producing plasma cells
• NK cells
– part of the innate immune response
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T and B
Lymphocytes
• Large nucleus with
dense chromatin
• Thin rim of
cytoplasm
• Recognizes
specific antigenic
determinants
• Therefore are
responsible for
specificity and
memory of the
adaptive immune
response
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Dendritic cells can come from both
myeloid and lymphoid lineages
• Named after it’s
dendrite-like
processes
• It is considered a
“professional
antigen presenting
cell” since it is
constantly sampling
the environment
around it
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Dendritic cells
Macrophage
B-cell
There are 3
types of Antigen
Presenting Cells
that present Ag
to T-cells and Bcells
• Dendritic cells
• Macrophages
• B-cells
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What are the organs of the
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Organs of the Immune System
can be divided into 2 categories
Primary= Central
Secondary= Peripheral
• Thymus
• Bursa or Bone
Marrow
• Diffuse: GALT, MALT,
BALT
• Lymphoid follicle
• Aggregated follicle
– Tonsil
– Appendix
– Peyer’s patches
• Lymph Nodes
• Spleen
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Lymphoid
Organs
•Tonsils
•Lymph nodes
•Spleen
•Peyer’s
Patches
•Appendix
2. Distribution to
peripheral lymphoid
organs where
responses to
foreign antigens
are initiated
T lymphocytes
1. Maturation in
central lymphoid
organs
B lymphocytes
“Bursa”
in birds
Thymus
Stem cell
(in bone marrow)
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The thymus is the site for T-cell
maturation
Thyroid
Heart
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Thymus
Epithelial cell
Immature T-cells
(Thymocytes)
Hassal’s
corpuscle
Capillary
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Thymus: lobes
Cortex- immature cells
Medulla- mature cells
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Nude and SCID mice
• Nude mice lack T cells
– Recessive nude gene, chromosome 11 which causes
the thymus not to develop
• SCID mice are also immunodeficient but for a
different reason (T & B cells do not mature)
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DiGeorge syndrome- human
• Deletion on chromosome 22
• Anlage of the thymus does not form
• Individual has B cells, but produces few T
cells
• (other craniofacial defects due to failure
of Neural Crest migration)
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In birds, the Bursae of Fabricius is the site of Bcell maturation . In humans this occurs in the
bone marrow.
Bursae
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Organs of the
Immune
System
•Tonsils
•Lymph nodes
•Spleen
•Peyer’s
Patches
•Appendix
2. Distribution to
peripheral lymphoid
organs
T lymphocytes
1. Processing in
central lymphoid
organs
B lymphocytes
Thymus
“Bursa”
Stem cell
(in bone marrow)
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Peripheral
Lymphoid organs
Peyer’s patches
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Peripheral
Lymphoid organs
Tonsils
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Peripheral
Lymphoid organs
Lymph Nodes
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Peripheral
Lymphoid organs
Spleen
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Antigen trapping and presentation
• Secondary (peripheral) lymphoid tissue is
specialized to:
– Trap antigen
– Facilitate interactions between cells to initiate
an immune response
• Particular organs highly developed for
this are:
– Spleen…………..
– Lymph node ……
filters blood
filters lymph
• Contain Antigen Presenting Cells
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Schematic
diagrams of
various types of
lymphoid tissue
• Diffuse
• Lymphoid
follicle
• Aggregated
follicle
• Lymph Node
• Spleen
• Thymus
Lymphoid follicle
Diffuse
Peyer’s patch
Tonsil
Spleen
Lymph Node
Thymus
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Diffuse lymphoid tissue in the mucous
membranes and skin
Epithelium
Lymphocytes
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Lymphoid Follicles
• Found in connective tissue underlying
epithelium in respiratory and digestive
tracts
• Drained by lymphatic capillaries
• Do not occupy fixed positions; they come
and go depending on the conditions in a
given organ at a given time.
• Found in the same place as diffuse
lymphoid tissue.
• Particularly abundant in the digestive
(especially the intestine), respiratory and
genital tracts
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Mucosal Immune System
MALT- Mucosal Associated Lymphoid
Tissue
• Mucosal surfaces of mouth, respiratory
and reproductive tracts are colonized by
lymphocytes and accessory cells
• Respond to ingested, inhaled antigens
• BALT (bronchial tube)
• GALT (gut)
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Tonsils: entrance to the GI tract
1.Palatine
3.Pharyngeal
nodes
2.Lingual
Pharyngeal
Tubal
Palatine
4.Tubal
Lingual
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Diagram of the
Tonsil
Pharynx
• Aggregated
lymphoid follicles
• Corrugated surface
with cracks and pits
CRYPTS
• become filled with
sloughed off cells,
dead lymphocytes
and fluid
• good culture
medium for bacteria
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Organization of the Human Gut (Peyer’s patches
& appendix)
Abdominal
location
X-section
Villi
Small int.
inner surface
X-section
of villus
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Peyer’s Patches are found in the ileum (small
intestine) in the wall opposite the mesentary
Each patch is a collection
of many individual
lymphoid follicles (pink)
scattered between the
microvilli “like puffballs
on a lawn”
X-section showing the
follicles in the submucosa
Each patch may have up to 70
follicles: 200 patches, 30-40 big
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ones
Plane of cross section shown in next slide
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Peyer’s patches
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Appendix
Cecum of the
large intestine
with vermiform
appendix- (2-20 cm)
X-section:
follicles
There is a
network of
lymphatics
surrounding
each follicle
"Its major importance would appear to be financial support of the
surgical profession." Alfred Sherwood Romer and Thomas S.
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Parsons The Vertebrate Body (1986) p. 389.
The Lymph Node: filters lymph
• Filtering stations interposed in the
lymphatic vessels
• Varying sizes (pinhead to walnut)
• Present everywhere, but large and
numerous ones are found in certain sites:
axillary, groin (inguinal LNs), near the
abdominal aorta (coeliac LNs), in the neck
(cervical LNs) and in the mesentery
(mesenteric LNs)
• Regional nodes: draining particular
regions or organs
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1. Superficial Cervical Nodes
2. Deep cervical nodes
3. Mediastinal nodes
4. Axillary node
5. Brachial node
A. Thymus
B. Spleen
6. Pancreatic node
7. Renal nodes
8. Mesenteric node
9. Inguinal node
10. Lumbar nodes
11. Sacral Node
12. Sciatic node
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Lymph nodes
filter lymph
Lymphatic vessels
Lymph node
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Structure of a Lymph Node
Afferent Lymphatics
• Cortex
– B-cells
• Paracortex
– T-cells
Subcapsula
r
sinus
Capsule
Trabeculae
• Medulla
– Plasma cells:
mature B
cells which
pump out a
lot of
antibodies
P
C
M
Artery
Vein
Efferent Lymphatic
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Cell Trafficking into and out of lymph nodes:
Lymphocytes and dendritic cells enter lymph nodes by
different routes.
FRC= fibroblastic reticular cells form channels to T-cell zone- guide
DC’s to vicinity of high endothelial venules (site for immune cell
entrance)
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Miyasaka and Tanaka, 2004 Nat Rev Immunol
Metastasis to the Lymph Node
• Most cancers spread via lymphatic
vessels to ipsilateral, regional “draining”
lymph nodes
• Seldom fatal, but since lymph eventually
drains back to blood stream, often source
of hematogenous metastasizing cells=
these tumors disrupt organ function & can
cause death
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Effect of Lymph Node Removal
• If lymph node is negative for metastatic
cells, removal of the entire group of
nodes is avoided
• Side effects: disturbing lymph drainage
causes edema (swelling), pain &
discomfort
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The Spleen: filters blood
• In contrast to lymph nodes, which are
inserted in the lymph circulation, the spleen
is inserted in the blood circulation
• Receives 5% of cardiac output; screens
entire blood volume in 20-30 min
• Oblong, purplish body the size of a fist
• Smooth surfaced except for hilus, where
blood vessels enter and leave
* There are no lymphatics leading to the
spleen.
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The Spleen- a composite organ
combines innate and adaptive immunity
• White Pulp– Small arterioles surrounded by sheaths of
lymphocytes= Peri-Arteriole Lymphoid
Sheaths (PALS)
– Surrounded by marginal zone
• Red Pulp
– “Cords” of cells: Erythrocytes, macrophages,
dendritic cells, few lymphocytes and plasma
cells
– Also contains venous Sinusoids
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Spleen- surface of a fresh cut appears
stippled due to red and white pulp
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Spleen
capsule
trabeculae
Red pulp
Central artery
White pulp
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Localization of cells in the white pulp
B-cells
S
S
Red pulp
∗
S
Artery
T-cells
Depicted with closed circulation (∗)
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Circulation in the spleen...
Penicillar arteries
Depicted with open circulation
Venous
sinuses
Central artery
White pulp
Marginal zone
Trabecular
artery and vein
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Function of the spleen cont.
• Erythrocytes enter the red pulp, push through
the masses of macrophages filling the splenic
cords and enter the sinuses.
– As the red blood cells enter, the macrophages
examine every one and any cells showing age or
defects are engulfed.
– Any particulate matter present in the blood is taken
up by macrophages and destroyed.
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Spleen- Red pulp
Sinusoid
Pulp
Cord
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Spleen- Red pulp
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Summary
• The immune system is composed of many
cells, tissues and organs
• The anatomical arrangement of the
immune system facilitates interactions
between antigens and cells at appropriate
times
• If you understand the anatomy, you will be
able to better understand the context of
these interactions...
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