Transcript Immunol-mol-med-5-2010-Prof

Molecular medicine
Immunology 5
Tissues of the Immune system
Role of the thymus
https://medicine.tcd.ie/immunology/st
udent-area/index.php
Learning objectives
• Key role of certain tissues in immune
system (IS)
• The thymus - site of T cell education
• Bone marrow - source of cells of IS
• Lymph nodes - site of immune reactions
• NB - cells of IS operate in tissues, not in
blood
Lymphatic circulation
Lymphatic circulation
Third network of circulation
Function • Collects fluid from tissues
• Lymph passes through chain of lymph
nodes
• Lymphatic vessels drain to large ducts e.g.
thoracic duct
• Ducts drain into subclavian veins
Thoracic duct
Lymphatic circulation
• High content of lymphocytes
• If lymph is drained from animals lymphocyte count drops
• If the lymphatics are blocked - fluid collects
in tissues - “ lymphoedema ”
Also
• Fat is absorbed from intestine via lymphatic
Swelling due to blocked
lymphatics
Damaged caused by radiation therapy, axilla
Antigen delivery to lymph nodes
Lymphatic circulation
Immune response • Antigen brought to lymph nodes - via lymph
draining to nodes
• Carried by antigen presenting cells e.g. dendritic
cells
• Lymphocytes stimulated by antigen in nodes
• stimulated lymphocytes enter blood and circulate
Lymphoid tissues
Lymphoid tissues
Lymphoid tissues
Central
• Bone marrow
• Thymus
• Bursa
Lymphoid tissues
Central
• Bone marrow
• Thymus
• Bursa
Peripheral
• Lymph nodes
• Spleen
• Unencapsulated -appendix, tonsil, adenoids,
Peyer’s patches
Lymph nodes in neck
Cancer - enlarged nodes
Lymph nodes in axilla
Cancer spread to lymph node
Cancer
cells
“secondaries” or metastasis
Lymph nodes in groin
Bone marrow - cell origin
Stem cells now used for bone marrow transplants
Bone marrow - cartoon
Bone marrow biopsy
Bone marrow - what happens ?
• generation of cells of IS and other
cells - RBC, platelets
• location of B cell maturation “bursa” in
humans?
• site of antibody production by plasma cells
Damage due to cancer therapy
• Chemotherapy
• Radiation therapy
Cause damage to bone marrow
• Cell production reduced - neutrophils
• Antibody production impaired
Thymus - human
Thymus - chicken
Thymus 1.
Location
• Behind sternum - over heart
• Bi-lobed
• Lobules - 2 zones
• Outer zone = cortex
• Inner zone = medulla
Thymus structures
Thymus - histology
Thymus - cartoon
Thymus 2.
Cortex
• Immature “pro-T” cells arrive here
• Learn function of T lymphocytes
• Densely cellular
• 90% of cells die - lymphocyte graveyard !
• Surviving cells migrate to medulla
Thymus 3.
Medulla • mature lymphocytes migrate from cortex - cells
then enter into blood circulation
• Hassal’s corpuscles - characteristic structure of
medulla, function unknown
• Thymus atrophies after puberty - BUT continues
to produce lymphocytes to end …..
Thymus - chicken
Bursa in humans
• No identified equivalent of bursa
• Bone marrow may carry out function of
bursa
• Maturation of pro-B cells in this site
Lymph node - cartoon
Alberts et al.
Lymph node - histology
Lymphoid
follicles
Lymph nodes 1.
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Distributed throughout body
Linked by lymphatics
“afferent” lymphatics - drain to nodes
“efferent” lymphatics - drain from nodes
Blood supply - arterial, venous
Capsule
Lymph nodes 2.
Structure - cortex and medulla
• Cortex - distinct T and B cell areas
• B cells found in round structures - lymphoid
follicles
• Follicles enlarge after antigen stimulation
• Stimulated B cells - migrate to medulla antibody producing “plasma cells”
Lymph nodes 3.
T cell area in cortex
• Surround lymphoid follicles
• Stimulated T cells migrate to medulla and
enter circulation
Other cell populations
• Antigen presenting cells - dendritic cells,
macrophages
Spleen
Spleen - cartoon
Spleen - histology
Phagocytic
area
Lymphocyte area
Spleen 1.
Location
• Under left rib cage
• Blood supply - very vascular
• Accidents - splenectomy
Spleen 1b.
Function
1. Phagocytic organ - removal of dying cells
2. Lymph node type function
3. Storage - platelets
Spleen 2.
Lymph node area
• “white pulp” - 20% of spleen
• Distinct T and B follicular areas
• Respond to circulating antigen - important
in response to certain bacteria*
• “Red pulp” area - phagocytic cells, storage
of other cell types
Spleen 3.
“Red pulp” area - phagocytic cells, storage
• remove particulate matter
• graveyard for aged or damaged RBC, white
cells, platelets
• reservoir - rapid source of platelets and
monocytes
Other lymphoid tissues
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Tonsils
Appendix
Adenoids
Peyer’s patch
These tissues have lymph node like
structure and function but no capsule
Lymphocyte collections in organs
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Gut
Lung
Liver
Placenta
Etc.
Gut lymphocyte structures
Events in lymphoid tissue
• Immune response happens here
• Metastasis - cancer cells can spread to
nodes
• Circulating lymphocytes ‘visit’ nodes - to
see if specific antigen has arrived here
• Lymphocytes may rest in nodes - memory
cells
So, back to the thymus …..
Thymic education
cortex
medulla
CD 2
CD8
CD4
CD8
Pro-T cell
CD3
CD4
- acquire T cell molecules
- react with self MHC
Thymic education
cortex
medulla
CD 2
CD8
CD4
CD8
Pro-T cell
CD3
CD4
- express CD2 first
-then CD3, TCR
- then CD4 and CD8
in cortex
T cell rosette - CD2
T cells bind to sheep red cells, forming a flower
type shape: CD2 on T cell binds to sheep cell.
Used to identify T cells, before monoclonal abys
T cells use CD2 to bind targets
CD2
Th
LFA-3
APC
LFA-3 is present on many target cells,
including APC - additional molecule
for T cell adherence
T cell elimination
- 95% of cells die in cortex
cortex
medulla
CD 2
CD8
CD4
CD8
CD3
CD4
THYMUS
T cell maturation – role of IL-7
IL-7
cortex
medulla
CD 2
CD8
CD4
CD8
CD3
CD4
THYMUS
T cell elimination of - cells that over-react with MHC
- cells that under-react with MHC
cortex
medulla
CD 2
CD8
CD4
CD8
CD3
CD4
THYMUS
Over-reaction of T cell in thymus
APC
T cell
self antigen
Results in apoptosis of T cell – clone
eliminated – “negative selection”
Under-reaction of T cell in thymus
APC
T cell
weak self antigen
Results in apoptosis of T cell
T cell elimination
• Prevents self-reactivity [ reactivity with
one’s “self antigens” ]
• Called “self-tolerance”
• Self-tolerance prevents auto-immunity
• Other mechanisms of self-tolerance also
exist
T cells learn to react with self
MHC + antigen in thymus
T cell
APC
T helper cell reacting with antigen and self MHC
in thymus
diGeorge syndrome
DiGeorge syndrome
Genetic defect found on chromosome 22