SH Lecture - Lymphatic Structure and Organs: Difference between revisions

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[[File:SHsmall.jpg]]
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==Introduction==
==Introduction==
 
[[File:Lymphatic-system-overview.jpg|thumb|400px|Lymphatic system]]
 
--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 14:53, 3 March 2013 (EST) Dear keen medical students, I will be updating the lecture for 2013 from this existing 2012 version. The content wil be similar, but I am reorganising the information to improve clarity in the presentation. I will have the final version up on Sunday evening before lecture.
 
----
 
 
 
[[File:Adult_lymphatic_system.jpg|thumb|400px|Lymphatic system]]
While the structure of the lymphatic system (''lympha'' = clear water) is well described, there is much to still learn about the complex development and function of this "system".
While the structure of the lymphatic system (''lympha'' = clear water) is well described, there is much to still learn about the complex development and function of this "system".


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This lecture will provide an overview of the histology of key lymphoid organs, including the lymph nodes, spleen and thymus, as well as extranodal lymphoid tissues including mucosal associated lymphoid tissues (MALT)
This lecture will provide an overview of the histology of key lymphoid organs, including the lymph nodes, spleen and thymus, as well as extranodal lymphoid tissues including mucosal associated lymphoid tissues (MALT)


Note - Immunity is covered in detail elsewhere in the course, current lecture is limited to Lymphoid Organ structure/location.
===Key Concepts===
===Key Concepts===
# Lymphatic System
# Lymphatic System
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# Extranodal Lymphoid Tissues
# Extranodal Lymphoid Tissues
# Mucosal Associated Lymphoid Tissues (MALT)
# Mucosal Associated Lymphoid Tissues (MALT)
<gallery>
File:Lymphatic-system-tonsil.jpg|Tonsil
File:Lymphatic-system-tonsil-MALT.jpg|Tonsil and MALT
File:Lymphatic-system-thymus.jpg|Thymus
File:Lymphatic-system-spleen.jpg|Spleen
File:Lymphatic-system-bone-marrow.jpg|Bone marrow
</gallery>


==Textbook References==
==Textbook References==
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{{Immune Links}}
{{Immune Links}}


==Two Cellular Systems==
==Two Cellular Systems==
* '''Mononuclear Phagocytic System''' (MPS, also called Lymphoreticular System or Reticuloendothelial System, RES) - circulating monocytes of peripheral blood and non-circulating (fixed) tissue macrophages found throughout the body
* '''Lymphoid System''' - three major types of lymphocytes (T, B, and NK), tissues, organs and vessels
* '''Lymphoid System''' - three major types of lymphocytes (T, B, and NK), tissues, organs and vessels


* '''Mononuclear Phagocytic System''' (MPS, also called Lymphoreticular System or Reticuloendothelial System, RES) - circulating monocytes of peripheral blood and non-circulating (fixed) tissue macrophages found throughout the body
Lymphoid Organs
* Central  - Lymphocytes develop from precursor cells in bone marrow. (see blood marrow image)
* Peripheral - Lymphocytes respond to antigen lymph nodes or spleen.




[http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4423 MBoC Figure 24-3 Human lymphoid organs]


==Lymphatic System==
[[File:Hematopoietic_and_stromal_cell_differentiation.jpg|600px]]
[[File:Lymphatic vasculature 02.jpg|thumb|300px|Lymphatic Development]]
* Connective Tissue Embryonic origin- Mesoderm
* Consists of Cells, tissues and organs


Immune System Note: Immunity is covered in detail elsewhere in the course, current lecture is about Lymphoid Organ structure/location
{| class="wikitable collapsible collapsed"
! Blood Cells
|-
| The blood cell information shown below in the table is shown to identify the relative proportions of different cell types in the circulating blood. This information is provided in the lecture as additional information for reference purposes only.


* Tissues and Organs
{{Blood Cell Number Table}}
** Thymus, spleen, lymph nodes, lymphatic nodules, diffuse lymphatic tissues, bone marrow
|}
** Organs consist also of structural cells and extracellular matrix
* Lymphatic vessels connect system parts
* Cells are '''Lymphocytes'''
* B Lymphocytes and T Lymphocytes
* White blood cells, leukocytes


These are blood cells
===Mononuclear Phagocytic System===


==Blood Cells==
(Mononuclear Phagocytic System MPS, also called Lymphoreticular System or Reticuloendothelial System, RES)


[[File:Hematopoietic_and_stromal_cell_differentiation.jpg|500px]]
[[File:Monocyte 01.jpg|300px]] [[File:Liver- Kupffer cell and reticular fibre.jpg]]


[[SH_Lecture_-_Lymphatic_Structure_and_Organs#Blood_Cell_Numbers|Blood Cell proportions]]
Mononuclear Phagocytes 2 types:
# Circulating '''monocytes''' of peripheral blood (monocytes entering the connective tissue differentiate into '''macrophages''')
# Non-circulating (fixed) tissue '''macrophages''' (MΦ) found throughout the body (Liver (Kuffler cells), spleen and other tissues)
 
 
===Lymphoid System===
Functional cells are the '''lymphocytes''' (B, T, NK) and '''dendritic cells''' (process antigen and present it on their surface).


[[File:lymphocyte 01.jpg|200px]] [[File:Lymphocyte_02.jpg|400px]]
[[File:lymphocyte 01.jpg|200px]] [[File:Lymphocyte_02.jpg|400px]]
===Lymphocyte Electron Micrographs===
 
{|
| '''B Cell Development'''
| '''Germinal Centres'''
| '''Plasma cells'''
|-
| valign=top|
* Bone marrow
* blood
* Lymph node, nodule
* Lymphatic vessel
* Bone marrow
| valign=top|
* Bone Marrow
* Medullary cords contain plasma cells
| valign=top|
* secrete antibody directly into blood for distribution to all body
* in local extrafollicular sites are short lived 2–4 days
* longer-lived plasma cells in bone marrow 3 weeks to 3 months+
|}
 
{| class="wikitable collapsible collapsed"
Lymphocyte Electron Micrographs
|-
| Histologically, there is little difference in appearance between T and B lymphocytes until activated.
 
<gallery>
<gallery>
File:T and B lymphocytes EM10.jpg|T and B Lymphocyte
File:T and B lymphocytes EM10.jpg|T and B Lymphocyte
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File:T2_lymphocyte_EM13.jpg|Cytotoxic (T)
File:T2_lymphocyte_EM13.jpg|Cytotoxic (T)
</gallery>
</gallery>
 
|}
==Central/Peripheral Lymphoid Organs==
 
Central lymphoid organs
* Lymphocytes develop from precursor cells (see blood marrow image)
 
Peripheral lymphoid organs
* Lymphocytes respond to antigen
* lymph nodes or spleen
 
==Mononuclear Phagocytic System==
 
(Mononuclear Phagocytic System MPS, also called Lymphoreticular System or Reticuloendothelial System, RES)
 
[[File:Monocyte 01.jpg|300px]] [[File:Liver- Kupffer cell and reticular fibre.jpg]]
 
Mononuclear Phagocytes 2 types:
# Circulating '''monocytes''' of peripheral blood (monocytes entering the connective tissue differentiate into '''macrophages''')
# Non-circulating (fixed) tissue '''macrophages''' (MΦ) found throughout the body (Liver (Kuffler cells), spleen and other tissues)


==Lymph==
==Lymph==
[[File:Lymphatic_vasculature_04.jpg|thumb|400px|Vasculature]]
[[File:Lymphatic_vasculature_04.jpg|thumb|300px|Vasculature]]


* Fluid portion of lymphatic circulation
* Fluid portion of lymphatic circulation
* blood plasma will leave blood vessels into surrounding tissues
* blood plasma will leave blood vessels into surrounding tissues
* adds to normal tissue interstitial fluid
* adds to normal tissue interstitial fluid
* surplus of liquid needs to be returned to circulation
* surplus of liquid needs to be returned to circulation
* Lymph vessels provide unidirectional flow of this liquid
* Lymph vessels provide unidirectional flow of this liquid
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==Lymph Vessels==
==Lymph Vessels==
[[File:Gray0599.jpg|thumb|Thoracic and right lymphatic ducts]]
[[File:Gray0599.jpg|thumb|Thoracic and right lymphatic ducts]]
Three types based on size and morphology
Three types based on size and morphology


* '''Lymph capillaries''' begin as blind-ending tubes in connective tissue, larger than blood capillaries, very irregularly shaped
* '''Lymph capillaries''' - begin as blind-ending tubes in connective tissue, larger than blood capillaries, very irregularly shaped
* '''Lymph collecting vessels''' larger and form valves, morphology similar to lymph capillaries
* '''Lymph collecting vessels''' - larger and form valves, morphology similar to lymph capillaries
* '''Lymph ducts''' 1 or 2 layers of smooth muscle cells in wall
* '''Lymph ducts''' - 1 or 2 layers of smooth muscle cells in wall


[[File:Lymphatic_vasculature_03.jpg|300px]]
Lymphangion


(Remember anatomy acronym - '''NAVL''' = Nerve, Artery, Vein and Lymph)
(Remember anatomy acronym - '''NAVL''' = Nerve, Artery, Vein and Lymph)
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==Lymphocyte Circulation==
==Lymphocyte Circulation==


[http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4442 MBoC Figure 24-14. The path followed by lymphocytes as they continuously circulate between the lymph and blood]
* Microbial '''antigens''' are carried into the lymph node by '''dendritic cells''', which enter via afferent lymphatic vessels draining an infected tissue.  
* The circulation through a lymph node is shown.
* '''T and B cells''' enter the lymph node via an artery and migrate out of the bloodstream through postcapillary venules.  
* Microbial antigens are carried into the lymph node by dendritic cells, which enter via afferent lymphatic vessels draining an infected tissue.  
** Unless they encounter their antigen, the T and B cells leave the lymph node via efferent lymphatic vessels, which eventually join the thoracic duct.  
* T and B cells, by contrast, enter the lymph node via an artery and migrate out of the bloodstream through postcapillary venules.  
* Unless they encounter their antigen, the T and B cells leave the lymph node via efferent lymphatic vessels, which eventually join the thoracic duct.  
* The thoracic duct empties into a large vein carrying blood to the heart.  
* The thoracic duct empties into a large vein carrying blood to the heart.  
* A typical circulation cycle takes about 12–24 hours.
* A typical circulation cycle takes about 12–24 hours.
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==Diffuse Lymphatic Tissue==
==Diffuse Lymphatic Tissue==
 
[[File:oesophagus MALT.jpg|thumb|300px|'''MALT''' - '''M'''ucosa '''A'''ssociated '''L'''ymphoid '''T'''issue either ('''BALT''' - '''B'''ronchus '''A'''ssociated  '''L'''ymphoid '''T'''issue or '''GALT''' - '''G'''ut '''A'''ssociated '''L'''ymphatic '''T'''issue)]]
Alimentary canal, respiratory passage, urogenital tract
Alimentary canal, respiratory passage, urogenital tract
* '''Not enclosed by a connective tissue capsule'''
* '''Not enclosed by a connective tissue capsule'''
* Located in subepithelial tissue - '''Lamina propria'''
* Located in subepithelial tissue - '''lamina propria'''
* Diffuse lymphatic tissue + nodules
* Reactive - enlarge when activated (by antigen)


'''Lymphocytes'''
'''Lymphocytes'''
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* proliferation and differentiation
* proliferation and differentiation


'''Effector cells'''
'''Adaptive immunity has 2 main classes'''
* B Cell secreting antibody = '''Plasma Cell'''
* T Cell = '''Memory Cell''', Cytotoxic T cells, T helper cell
 
* Diffuse lymphatic tissue + nodules
* Reactive - enlarge when activated (by antigen)
 
==MALT, BALT and GALT==
{|
| [[File:oesophagus MALT.jpg]]
| valign=top|Internal epithelia Associated Lymphoid Tissue - naming based upon the anatomical locations


'''MALT''' - '''M'''ucosa '''A'''ssociated '''L'''ymphoid '''T'''issue
# '''Antibody-mediated''' - B Lymphocyte secreting antibody = '''Plasma Cell'''
* '''BALT''' - '''B'''ronchus '''A'''ssociated  '''L'''ymphoid '''T'''issue
# '''Cell-mediated''' - T Lymphocytes form '''memory cell''', Cytotoxic T cells, T helper cell
* '''GALT''' - '''G'''ut '''A'''ssociated '''L'''ymphatic '''T'''issue
|}


==Immune Responses==
Adaptive immunity has 2 main classes


# '''Antibody-mediated''' - B Lymphocyte
===Lymph Nodules===
# '''Cell-mediated''' - T Lymphocyte
 
==Lymph Nodules==
* Organized concentrations of lymphocytes
* Organized concentrations of lymphocytes
** No capsule, covered by epithelia
** No capsule, covered by epithelia
* Nodules are also the unit structure seen in a node
* Nodules are also the unit structure seen in a node
* Oval concentrations in meshwork of reticular cells
* Oval concentrations in meshwork of reticular cells
===Gastrointestinal Tract===
* Oropharynx - Tonsils
* Distal small intestine (ilieum) - Peyer’s Patches
* Appendix, cecum


===Nodule States===
===Nodule States===
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** Dark outer ring (small lymphocytes)
** Dark outer ring (small lymphocytes)


'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A49 Immnuobiology - Figure 1.10. Organization of typical gut-associated lymphoid tissue]
===Gastrointestinal Tract===
* Oropharynx - Tonsils
* Distal small intestine (ilieum) - Peyer’s Patches
* Appendix, cecum


==Tonsils==
==Tonsils==
[[File:Lymphatic-system-tonsil-MALT.jpg|thumb|400px|Tonsil and MALT]]
Anatomical location -  Palatine  ('''tonsils'''), Lingual  and Pharyngeal ( '''adenoids''' )
Anatomical location -  Palatine  ('''tonsils'''), Lingual  and Pharyngeal ( '''adenoids''' )
Ring of oral adenoid tissue:
* anterior - '''lingual tonsil''' formed by the submucous adenoid collections.
* lateral - '''palatine tonsils''' and adenoid collections near the auditory tubes.
* posterior - '''pharyngeal tonsil''' on the posterior wall of the pharynx.
* between main masses are smaller collections of adenoid tissue.


===Palatine Tonsils===
===Palatine Tonsils===
[[File:Tonsil_histology_01.jpg|300px]] [[File:Tonsil_histology_02.jpg|300px]]
<gallery>
File:Tonsil_histology_01.jpg|Tonsil overview
File:Tonsil_histology_02.jpg|Tonsil detail
</gallery>


* the "tonsils", lateral wall of oropharynx
* the "tonsils", lateral wall of oropharynx
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* covered by a pseudostratified ciliated epithelium with goblet cells
* covered by a pseudostratified ciliated epithelium with goblet cells


==Peyer's Patch==
===Gastrointestinal Tract - Peyer's Patch===


[[File:Peyer's patch 01.jpg|200px]] [[File:Peyer's patch 02.jpg|200px]]
[[File:Peyer's patch 01.jpg|200px]] [[File:Peyer's patch 02.jpg|200px]]
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microfold cells or M-cells
microfold cells or M-cells


==Lymph Nodes==
==Lymph Nodes==
 
[[File:Lymphatic-system-overview.jpg|thumb|400px|]]
[[Quicktime Movie - Mouse Lymph Node 7]] | [[Quicktime_Movies#Immune|more lymph node movies]]
* Location throughout the entire body - Concentrated in axilla, groin, mesenteries
[[File:Lymph_node_structure.jpg|thumb]]
* Encapsulated organ (1 mm - 2 cm)
[[File:Lymph node structure 01.png|thumb|Schematic of lymph node showing lymph sinuses]]
* Antigen transformed lymphocytes from the blood
[[File:Lymph_node_cartoon_01.jpg|thumb|Detailed structure]]
[http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A47 Immunobiology - Figure 1.8. Organization of a lymph node]
 
[http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4444 MBoC Figure 24-16. A simplified drawing of a human lymph node]
 
{|
| * Encapsulated organ (1 mm - 2 cm)
* In lymph vessel pathways “filter”
* In lymph vessel pathways “filter”
* Afferent- towards node
* Afferent- towards node
* Efferent- away from node
* Efferent- away from node
* Location throughout the entire body - Concentrated in axilla, groin, mesenteries
 
* Antigen transformed lymphocytes from the blood
Lymph flow
| [[File:Lymph_node_histology_06.jpg|200px]]
* enters the node through '''afferent vessels'''
|}
* filters through the '''sinuses'''
* leaves through '''efferent vessels'''
===Lymph Node Structure===
===Lymph Node Structure===
[[File:Lymph_node_histology01.jpg|thumb|Lymph node cortex histology]]


Connective Tissue
Connective Tissue
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[[File:Lymph node histology 02.jpg]] [[File:Lymph node histology 03.jpg]]
[[File:Lymph_node_cartoon_01.jpg|Lymph_node_cartoon_01.jpg]]


Lymph
<gallery>
File:Lymph_node_histology01.jpg|Lymph node cortex histology
File:Lymph node histology 02.jpg
File:Lymph node histology
File:Lymph_node_histology_04.jpg|
</gallery>


* enters the node through '''afferent vessels'''
* filters through the '''sinuses'''
* leaves through '''efferent vessels'''


Subcapsular sinus = marginal sinus
Subcapsular sinus = marginal sinus
[[File:Lymph_node_histology_01.jpg]] [[File:Lymph_node_histology_04.jpg]]


Continuation of trabecular sinus
Continuation of trabecular sinus
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'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A47 Immunobiology - Figure 1.8. Organization of a lymph node]
'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A47 Immunobiology - Figure 1.8. Organization of a lymph node]


==Thymus==
==Thymus==
{|
[[File:Lymphatic-system-thymus.jpg|thumb|400px|Thymus]]
| [[File:Thymus_cartoon.jpg|300px]]
| [http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4429 MBoC Figure 24-6. The development and activation of T and B cells]
 
[http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4430/ Figure 24-7. Electron micrographs of nonactivated and activated lymphocytes]
|}
===Development Changes===
[[File:Gray1178.jpg|thumb|Fetal thymus anatomy]]
[[File:Fetal thymus.jpg|thumb|Fetal thymus]]
Changes with age
Overall Size
* birth 10-15 g
* puberty 30-40 g
* after puberty - involution
** Replaced by adipose tissue
** middle-aged 10 g


===Thymus Anatomy===
===Thymus Anatomy===
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** majority of them developing T-lymphocytes (= thymic lymphocytes or thymocytes)
** majority of them developing T-lymphocytes (= thymic lymphocytes or thymocytes)


===Fetal/Young Thymus===
===Development Changes===
{|
{Changes with age
| [[File:Thymus - young 01.jpg‎|300px]]
Overall Size
| [[File:Thymus - young 02.jpg‎|300px]]
* birth 10-15 g
|-
* puberty 30-40 g, after puberty - involution
|Young medulla
* middle-aged 10 g, replaced by adipose tissue
|Young cortex
 
|}
<gallery>
Thymic corpuscle
File:Thymus_cartoon.jpg|
File:Gray1178.jpg|Fetal thymus anatomy
File:Fetal thymus.jpg|Fetal thymus
File:Thymus - young 01.jpg‎|Young medulla
File:Thymus - young 02.jpg‎|Young cortex
</gallery>
 


Hassall’s corpuscle - Mass of concentric epithelioreticular cells
'''Thymic corpuscle''' - (Hassall’s corpuscle) mass of concentric epithelioreticular cells.


===Adult Thymus===
===Adult Thymus===
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==Spleen==
==Spleen==
[[File:Spleen anatomy.jpg]] [[File:Gray1039.jpg|300px]]
[[File:Lymphatic-system-spleen.jpg|thumb|400px|Spleen]]


===Functions===
<gallery>
File:Spleen anatomy.jpg
File:Gray1039.jpg|
</gallery>
===Spleen Function===


'''1. Immune'''
'''1. Immune'''
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===Structure===
===Structure===
[[File:Spleen_histology_01.jpg]] [[File:Spleen_histology_02.jpg]]
* Capsule, trabeculae (dense connective tissue)
* Capsule, trabeculae (dense connective tissue)
* Splenic pulp White pulp, red pulp - based on appearance and cell content
* Splenic pulp white pulp, red pulp - based on appearance and cell content.


[[File:Spleen_histology_05.jpg|thumb|White pulp -periarterial lymphoid sheath (PALS)]]
[[File:Spleen_histology_05.jpg|thumb|White pulp -periarterial lymphoid sheath (PALS)]]
{|
|
'''White Pulp'''
'''White Pulp'''
* lymphocytes surround central arteries
* lymphocytes surround central arteries
* as periarterial lymphoid sheath (PALS)
* as periarterial lymphoid sheath (PALS)
 
|
'''Red Pulp'''
'''Red Pulp'''
* Red blood cells
* Red blood cells
* Splenic sinuses
* Splenic cords and sinuses
* Splenic cords
|}


[[File:Spleen_histology_03.jpg]]
'''Reticular Fibers''' (type III collagen) act as supporting meshwork.


'''Reticular Fibers'''
<gallery>
File:Spleen_histology_01.jpg|Overview Red and White Pulp
File:Spleen_histology_02.jpg|Overview Red and White Pulp
File:Spleen_histology_03.jpg|Cords and Sinuses
File:Spleen_histology_05.jpg|Reticular Fibre overview
File:Spleen_histology_04.jpg|Reticular Fibre detail
File:Spleen_histology_06.jpg|unlabeled red and white pulp
File:Spleen_histology_07.jpg|unlabeled red pulp and macrophages
File:Spleen_histology_08.jpg|unlabeled white pulp germinal centre
File:Spleen_histology_09.jpg|unlabeled reticular fibre
File:Spleen_histology_10.jpg|unlabeled white pulp reticular
File:Spleen_histology_11.jpg|unlabeled red pulp reticular
</gallery>


[[File:Spleen_histology_05.jpg]]
{{Spleen Histology}}
[[File:Spleen_histology_04.jpg]]




{{Spleen Histology}}




'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A48 Immunobiology - Figure 1.9. Organization of the lymphoid tissues of the spleen]
==Additional Information==


==B Cell Development==
''The following is not part of the lecture and is for reference purposes only.''
* Bone marrow
* blood
* Lymph node, nodule
* Lymphatic vessel
* Bone marrow


Germinal Centres
[[File:SHsmall.jpg|left]] [[SH Practical - Lymphatic Structure and Organs|'''SH Practical - Lymphatic Structure and Organs''']] associated practical support page. Note that virtual slides will be used in the associated practical class and this linked page is provided for student self-directed learning of concepts from the virtual slides.
* Bone Marrow
* Medullary cords contain plasma cells


Plasma cells
* secrete antibody directly into blood for distribution to all body
* in local extrafollicular sites are short lived 2–4 days
* longer-lived plasma cells in bone marrow 3 weeks to 3 months+


==Additional Information==
''The following is not part of the lecture and is for reference purposes only.''


{|
{| class="wikitable collapsible collapsed"
| width=300px valign=top|[[SH Practical - Lymphatic Structure and Organs|'''SH Practical - Lymphatic Structure and Organs''']] associated practical support page. Note that virtual slides will be used in the associated practical class and this linked page is provided for student self-directed learning of concepts from the virtual slides.
!  Additional Images
| '''Additional Images'''
|-  
|
<gallery>
<gallery>
File:Adult_lymphatic_system.jpg|Adult lymphatic system
File:Lymph_node_cartoon.jpg|Lymph node cartoon
File:Lymph_node_cartoon.jpg|Lymph node cartoon
File:Lymph_nodes_head_neck_superficial.jpg|Lymph nodes - head neck superficial
File:Lymph_nodes_head_neck_superficial.jpg|Lymph nodes - head neck superficial
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* [http://www.ncbi.nlm.nih.gov/books/NBK27123/#A819 Summary to Chapter 7]
* [http://www.ncbi.nlm.nih.gov/books/NBK27123/#A819 Summary to Chapter 7]
|}
|}
{| class="wikitable collapsible collapsed"
{| class="wikitable collapsible collapsed"
! Blood Cells
! Blood Cells
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</gallery>
</gallery>
|}
|}
:Textbook Links: [http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4429 MBoC Figure 24-6. The development and activation of T and B cells | [http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4430/ Figure 24-7. Electron micrographs of nonactivated and activated lymphocytes] | [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A48 Immunobiology - Figure 1.9. Organization of the lymphoid tissues of the spleen]


== Terms ==
== Terms ==
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* '''cell''' - has a specific cell biology definition, but is often used instead of "lymphocyte" when describing B and T cells.  
* '''cell''' - has a specific cell biology definition, but is often used instead of "lymphocyte" when describing B and T cells.  
* '''Cell-mediated immunity''' - the immune function of T lymphocytes.  
* '''Cell-mediated immunity''' - the immune function of T lymphocytes.  
* '''CD''' - (cluster of differentiation) identifies immunological surface markers on cells.
* '''CD4+''' - (T helper cells) refers to T lymphocytes that express CD4 (glycoprotein of the immunoglobulin superfamily) on their surface.
* '''CD8+''' - (cytotoxic T cells) refers to T lymphocytes that express CD8 (glycoprotein of the immunoglobulin superfamily) on their surface.
* '''"clockface"''' - a term used to describe the appearance of plasma cell nuclei due to the clumping of the chromatin at the nucleus periphery. More clearly seen in tissue plasma cells that the bone marrow smear, where they are sometimes confused with the basophilic erythroblasts.
* '''"clockface"''' - a term used to describe the appearance of plasma cell nuclei due to the clumping of the chromatin at the nucleus periphery. More clearly seen in tissue plasma cells that the bone marrow smear, where they are sometimes confused with the basophilic erythroblasts.
* '''cords of Billroth''' - spleen cellular columns located in red pulp. surrounded by splenic sinusoids. Cords contain reticular cells, macrophages, lymphocytes, plasma cells and erythrocytes.
* '''cords of Billroth''' - spleen cellular columns located in red pulp. surrounded by splenic sinusoids. Cords contain reticular cells, macrophages, lymphocytes, plasma cells and erythrocytes.
* '''cortex''' - outer layer, used in association with medulla (innner layer or core) a general description that can be applied to describing an organ with a layered structure.  
* '''cortex''' - outer layer, used in association with medulla (innner layer or core) a general description that can be applied to describing an organ with a layered structure.  
* '''dendritic cells''' - (DCs) immune cells that function to process antigen and present it on their surface to other immune cells.
* '''Effector cells''' - the immune functioning (active) B and T lymphocytes.  
* '''Effector cells''' - the immune functioning (active) B and T lymphocytes.  
* '''Efferent lymph''' - vessel carrying lymph away from a node.  
* '''Efferent lymph''' - vessel carrying lymph away from a node.  
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* '''medulla''' - inner layer or core, used in association with cortex (outer layer) a general description that can be applied to describing an organ with a layered structure.  
* '''medulla''' - inner layer or core, used in association with cortex (outer layer) a general description that can be applied to describing an organ with a layered structure.  
* '''Memory Cell''' - effector T cell (lymphocyte)
* '''Memory Cell''' - effector T cell (lymphocyte)
* '''NK cell''' - (Natural killer cell, large granular lymphocytes) are a type of cytotoxic lymphocyte, responding rapidly to virally infected and tumor cells.
* '''normoblast''' - seen in bone marrow smear, a developing erythroblast (red blood cell) that still retains a nucleus.
* '''normoblast''' - seen in bone marrow smear, a developing erythroblast (red blood cell) that still retains a nucleus.
* '''parenchyma''' - (Greek = ''enkeim'' "to pour in") cells forming the functional cells of an organ or tissue. These cells carry out the function of the organ at a cellular level, and are not the structural cells, connective tissue, extracellular matrix (stromal).  
* '''parenchyma''' - (Greek = ''enkeim'' "to pour in") cells forming the functional cells of an organ or tissue. These cells carry out the function of the organ at a cellular level, and are not the structural cells, connective tissue, extracellular matrix (stromal).  

Revision as of 17:40, 3 March 2013

SHsmall.jpg

Introduction

Lymphatic system

While the structure of the lymphatic system (lympha = clear water) is well described, there is much to still learn about the complex development and function of this "system".

  1. Immune - “monitor” of body surfaces, internal fluids
  2. Extracellular fluid - returns interstitial fluid to circulation
  3. Gastrointestinal tract - carries fat and fat-soluble vitamins


Aim

This lecture will provide an overview of the histology of key lymphoid organs, including the lymph nodes, spleen and thymus, as well as extranodal lymphoid tissues including mucosal associated lymphoid tissues (MALT)

Note - Immunity is covered in detail elsewhere in the course, current lecture is limited to Lymphoid Organ structure/location.

Key Concepts

  1. Lymphatic System
  2. Organs - Thymus, Spleen
  3. Lymph Nodes and Nodules
  4. Bone Marrow
  5. Extranodal Lymphoid Tissues
  6. Mucosal Associated Lymphoid Tissues (MALT)

Textbook References



Immune Links: immune | blood | spleen | thymus | lymphatic | lymph node | Antibody | Med Lecture - Lymphatic Structure | Med Practical | Immune Movies | vaccination | bacterial infection | Abnormalities | Category:Immune
Historic Embryology  
1909 Lymph glands | 1912 Development of the Lymphatic System | 1918 Gray's Lymphatic Images | 1916 Pig Lymphatics | 1919 Chicken Lymphatic | 1921 Spleen | 1922 Pig Stomach Lymphatics | 1932 Cat Pharyngeal Tonsil | Historic Disclaimer


Two Cellular Systems

  • Mononuclear Phagocytic System (MPS, also called Lymphoreticular System or Reticuloendothelial System, RES) - circulating monocytes of peripheral blood and non-circulating (fixed) tissue macrophages found throughout the body
  • Lymphoid System - three major types of lymphocytes (T, B, and NK), tissues, organs and vessels

Lymphoid Organs

  • Central - Lymphocytes develop from precursor cells in bone marrow. (see blood marrow image)
  • Peripheral - Lymphocytes respond to antigen lymph nodes or spleen.


Hematopoietic and stromal cell differentiation.jpg

Mononuclear Phagocytic System

(Mononuclear Phagocytic System MPS, also called Lymphoreticular System or Reticuloendothelial System, RES)

Monocyte 01.jpg Liver- Kupffer cell and reticular fibre.jpg

Mononuclear Phagocytes 2 types:

  1. Circulating monocytes of peripheral blood (monocytes entering the connective tissue differentiate into macrophages)
  2. Non-circulating (fixed) tissue macrophages (MΦ) found throughout the body (Liver (Kuffler cells), spleen and other tissues)


Lymphoid System

Functional cells are the lymphocytes (B, T, NK) and dendritic cells (process antigen and present it on their surface).

Lymphocyte 01.jpg Lymphocyte 02.jpg

B Cell Development Germinal Centres Plasma cells
  • Bone marrow
  • blood
  • Lymph node, nodule
  • Lymphatic vessel
  • Bone marrow
  • Bone Marrow
  • Medullary cords contain plasma cells
  • secrete antibody directly into blood for distribution to all body
  • in local extrafollicular sites are short lived 2–4 days
  • longer-lived plasma cells in bone marrow 3 weeks to 3 months+

Lymph

Vasculature
  • Fluid portion of lymphatic circulation
  • blood plasma will leave blood vessels into surrounding tissues
  • adds to normal tissue interstitial fluid
  • surplus of liquid needs to be returned to circulation
  • Lymph vessels provide unidirectional flow of this liquid

Lymph Vessels

Thoracic and right lymphatic ducts

Three types based on size and morphology

  • Lymph capillaries - begin as blind-ending tubes in connective tissue, larger than blood capillaries, very irregularly shaped
  • Lymph collecting vessels - larger and form valves, morphology similar to lymph capillaries
  • Lymph ducts - 1 or 2 layers of smooth muscle cells in wall

Lymphatic vasculature 03.jpg

Lymphangion

(Remember anatomy acronym - NAVL = Nerve, Artery, Vein and Lymph)

Lymphocyte Circulation

  • Microbial antigens are carried into the lymph node by dendritic cells, which enter via afferent lymphatic vessels draining an infected tissue.
  • T and B cells enter the lymph node via an artery and migrate out of the bloodstream through postcapillary venules.
    • Unless they encounter their antigen, the T and B cells leave the lymph node via efferent lymphatic vessels, which eventually join the thoracic duct.
  • The thoracic duct empties into a large vein carrying blood to the heart.
  • A typical circulation cycle takes about 12–24 hours.

Links: MBoC Chapter 24 - The Adaptive Immune System | MBoC Figure 24-14. The path followed by lymphocytes as they continuously circulate between the lymph and blood | Immunobiology

Diffuse Lymphatic Tissue

MALT - Mucosa Associated Lymphoid Tissue either (BALT - Bronchus Associated Lymphoid Tissue or GALT - Gut Associated Lymphatic Tissue)

Alimentary canal, respiratory passage, urogenital tract

  • Not enclosed by a connective tissue capsule
  • Located in subepithelial tissue - lamina propria
  • Diffuse lymphatic tissue + nodules
  • Reactive - enlarge when activated (by antigen)

Lymphocytes

  • travel to nodes and back again
  • proliferation and differentiation

Adaptive immunity has 2 main classes

  1. Antibody-mediated - B Lymphocyte secreting antibody = Plasma Cell
  2. Cell-mediated - T Lymphocytes form memory cell, Cytotoxic T cells, T helper cell


Lymph Nodules

  • Organized concentrations of lymphocytes
    • No capsule, covered by epithelia
  • Nodules are also the unit structure seen in a node
  • Oval concentrations in meshwork of reticular cells

Nodule States

  • Primary Nodule - Mainly small lymphocytes
  • Secondary Nodule
    • Central pale region (germinal centre) - Effector cells and macrophages
    • Dark outer ring (small lymphocytes)

Gastrointestinal Tract

  • Oropharynx - Tonsils
  • Distal small intestine (ilieum) - Peyer’s Patches
  • Appendix, cecum

Tonsils

Tonsil and MALT

Anatomical location - Palatine (tonsils), Lingual and Pharyngeal ( adenoids )

Ring of oral adenoid tissue:

  • anterior - lingual tonsil formed by the submucous adenoid collections.
  • lateral - palatine tonsils and adenoid collections near the auditory tubes.
  • posterior - pharyngeal tonsil on the posterior wall of the pharynx.
  • between main masses are smaller collections of adenoid tissue.

Palatine Tonsils

  • the "tonsils", lateral wall of oropharynx
  • covered by stratified squamous epithelium
  • numerous crypts (10-20) infolds of surface epithelium
  • Afferent lymph vessels absent
  • Efferent lymph vessels are present

Lingual Tonsils

  • lamina propria root of tongue
  • covered by stratified squamous epithelium
  • salivary glands and skeletal muscle are directly adjacent

Pharyngeal Tonsils

  • adenoids or nasopharyngeal tonsils, upper posterior part of throat
  • covered by a pseudostratified ciliated epithelium with goblet cells

Gastrointestinal Tract - Peyer's Patch

Peyer's patch 01.jpg Peyer's patch 02.jpg

Peyer's Patch, Ileum

microfold cells or M-cells


Lymph Nodes

Lymphatic-system-overview.jpg
  • Location throughout the entire body - Concentrated in axilla, groin, mesenteries
  • Encapsulated organ (1 mm - 2 cm)
  • Antigen transformed lymphocytes from the blood
  • In lymph vessel pathways “filter”
  • Afferent- towards node
  • Efferent- away from node

Lymph flow

  • enters the node through afferent vessels
  • filters through the sinuses
  • leaves through efferent vessels

Lymph Node Structure

Connective Tissue

  • Capsule - dense connective tissue (irregular CT, some adipocytes))
  • Trabeculae - dense connective tissue
  • Reticular Tissue - Reticular cells and fibers, supporting meshwork (collagen type III)
    • Reticular cell produces reticular fibers (collagen type III) and surrounds the fibers with its cytoplasm
    • reticular fibbers can also be produced by fibroblasts


Lymph_node_cartoon_01.jpg


Subcapsular sinus = marginal sinus

Continuation of trabecular sinus

Lymphocyte (T and B) Traffic

  1. Enter from high endothelial venules (HEVs also called post-capillary venules)
  2. Spend 8 to 24 h in the lymph node interstitium.
  3. Enter a network of medullary sinuses.
  4. Drain from sinuses into efferent lymphatic vessels.


Links: Immunobiology - Figure 1.8. Organization of a lymph node


Thymus

Thymus

Thymus Anatomy

  • Superior mediastinum, anterior to heart
  • Bilobed lymphoepithelial organ
    • Contains reticular cells but no fibers
  • Stem lymphocytes
    • proliferate and differentiate
    • forms long-lived T- lymphocytes

Thymus Cells

  • Reticular cells
    • Abundant, eosinophilic, large, ovoid and light nucleus 1-2 nucleoli
    • sheathe cortical capillaries
    • form an epitheloid layer
    • maintain microenvironment for development of T-lymphocytes in cortex (thymic epitheliocytes)
  • Macrophages
    • cortex and medulla
    • difficult to distinguish from reticular cells in H&E
  • Lymphocytes
    • cortex and medulla - more numerous (denser) in cortex
    • majority of them developing T-lymphocytes (= thymic lymphocytes or thymocytes)

Development Changes

{Changes with age Overall Size

  • birth 10-15 g
  • puberty 30-40 g, after puberty - involution
  • middle-aged 10 g, replaced by adipose tissue


Thymic corpuscle - (Hassall’s corpuscle) mass of concentric epithelioreticular cells.

Adult Thymus

Thymus adult.jpg

  • Cortical lymphoid tissue is replaced by adipose tissue
  • Increase in size of thymic corpuscles
Thymus Histology: Fetal Thymus overview | Fetal Thymus Medulla | Fetal Thymus Cortex | Adult Thymus | unlabeled fetal overview | unlabeled fetal medulla |unlabeled fetal thymic corpuscle |unlabeled fetal cortex | unlabeled adult overview | Category:Thymus | Immune System Development

Spleen

Spleen

Spleen Function

1. Immune

  • filters blood in much the way that the lymph nodes filter lymph.
  • Lymphocytes in the spleen react to pathogens in the blood and attempt to destroy them.
  • Macrophages then engulf the resulting debris, the damaged cells, and the other large particles.

2. Red Blood Cell Removal

  • The spleen (and liver) removes old and damaged erythrocytes from the circulating blood.
  • Like other lymphatic tissue, it produces lymphocytes, especially in response to invading pathogens.

3. Blood Reservoir

  • The sinuses in the spleen also act as a reservoir for blood.
    • In emergencies, such as hemorrhage, smooth muscle in the vessel walls and in the capsule of the spleen contracts.
    • This squeezes the blood out of the spleen into the general circulation.


Structure

  • Capsule, trabeculae (dense connective tissue)
  • Splenic pulp white pulp, red pulp - based on appearance and cell content.
White pulp -periarterial lymphoid sheath (PALS)

White Pulp

  • lymphocytes surround central arteries
  • as periarterial lymphoid sheath (PALS)

Red Pulp

  • Red blood cells
  • Splenic cords and sinuses

Reticular Fibers (type III collagen) act as supporting meshwork.

Spleen Development: SH Lecture Spleen | SH Adult Histology | Overview Red and White Pulp | Overview Red and White Pulp | Cords and Sinuses | Reticular Fibre overview | Reticular Fibre detail | unlabeled red and white pulp | unlabeled red pulp and macrophages | unlabeled white pulp germinal centre | unlabeled reticular fibre | unlabeled white pulp reticular | unlabeled red pulp reticular | Structure cartoon | Cartoon and stain | Category:Spleen | Histology Stains | Immune System Development



Additional Information

The following is not part of the lecture and is for reference purposes only.

SHsmall.jpg

SH Practical - Lymphatic Structure and Organs associated practical support page. Note that virtual slides will be used in the associated practical class and this linked page is provided for student self-directed learning of concepts from the virtual slides.


Textbook Links: MBoC Figure 24-6. The development and activation of T and B cells | [http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4430/ Figure 24-7. Electron micrographs of nonactivated and activated lymphocytes | Immunobiology - Figure 1.9. Organization of the lymphoid tissues of the spleen

Terms

A few key terms associated with the Lymphoid system.

  • adenoid - (Greek " +-oeides = in form of) in the form of a gland, glandular; the pharyngeal tonsil.
  • Afferent lymph - vessel carrying lymph towards a node.
  • Antibody mediated immunity - the immune function of plasma cells (active B lymphocytes) secreting antibody which binds antigen.
  • antibodies - mammals have five classes (IgA, IgD, IgE, IgG, and IgM)
  • antigen - any substance that is recognised by the immune system and stimulates antibody production.
  • appendix - is a gut-associated lymphoid tissue located at the beginning of the colon. The anatomy is as a finger-like structure that arises from the cecum. The length (2.5-13 cm) is longer in both infants and children and also has more abundant lymphatic tissue in early life. The wall structure is similar to the small intestine (though with no villi), nor plicae circularis. Lymph nodules surround the lumen of the gastrointestinal tract and extend from the mucosa into the submucosa.
  • B lymphocyte (cell) - historically named after a structure called the bursa of Fabricius in birds, a source of antibody-producing lymphocytes. These cells develop in the bone marrow. (More? Electron micrographs of nonactivate and activated lymphocytes)
  • BALT - Bronchus Associated Lymphoid Tissue
  • band cell - (band neutrophil or stab cell) seen in bone marrow smear, a cell undergoing granulopoiesis, derived from a metamyelocyte, and leading to a mature granulocyte. Also occasionally seen in circulating blood.
  • cecum - (caecum, Latin, caecus = "blind") within the gastrointestinal tract a pouch that connects the ileum with the ascending colon of the large intestine.
  • cell - has a specific cell biology definition, but is often used instead of "lymphocyte" when describing B and T cells.
  • Cell-mediated immunity - the immune function of T lymphocytes.
  • CD - (cluster of differentiation) identifies immunological surface markers on cells.
  • CD4+ - (T helper cells) refers to T lymphocytes that express CD4 (glycoprotein of the immunoglobulin superfamily) on their surface.
  • CD8+ - (cytotoxic T cells) refers to T lymphocytes that express CD8 (glycoprotein of the immunoglobulin superfamily) on their surface.
  • "clockface" - a term used to describe the appearance of plasma cell nuclei due to the clumping of the chromatin at the nucleus periphery. More clearly seen in tissue plasma cells that the bone marrow smear, where they are sometimes confused with the basophilic erythroblasts.
  • cords of Billroth - spleen cellular columns located in red pulp. surrounded by splenic sinusoids. Cords contain reticular cells, macrophages, lymphocytes, plasma cells and erythrocytes.
  • cortex - outer layer, used in association with medulla (innner layer or core) a general description that can be applied to describing an organ with a layered structure.
  • dendritic cells - (DCs) immune cells that function to process antigen and present it on their surface to other immune cells.
  • Effector cells - the immune functioning (active) B and T lymphocytes.
  • Efferent lymph - vessel carrying lymph away from a node.
  • GALT - Gut Associated Lymphatic Tissue
  • haemopoiesis (hemopoiesis) formation of blood cells.
  • Hassall's corpuscle - thymic corpuscle.
  • IgA - the main class of antibody in secretions (saliva, tears, milk, and respiratory and intestinal secretions).
  • IgD - the immunoglobulin B cell starts to produce as a cell-surface molecule after leaving the bone marrow.
  • IgE - bind Fc receptors (surface of mast cells in tissues and basophils in the blood).
  • IgG - the major class of immunoglobulin in the blood.
  • IgM - the first class of antibody made by a developing B cell, which may switch to making other classes of antibody.
  • immunodeficiency - when one or more components of the immune system is defective. (More? Immunobiology - immunodeficiency)
  • involution - in the Thymus refers to the replacement, mainly in the cortex, of cells by adipose tissue. (More? PubMed- thymus involution) | Cancer Medicine - Thymomas and Thymic Tumors)
  • lamina propria - a layer of loose connective tissue found underneath the epithelium of mucosa.
  • Leukocyte- (Greek, lukos= clear, white) white blood cell.
  • lingual- related to the tongue.
  • lymph node - connective tissue encapsulated lymphoid organ (1mm - 2cm in size), positioned in the pathway of lymph vessels.
  • M cell - (microfold cell) found in the follicle-associated epithelium of the Peyer's patch. Function to transport gut lumen organisms and particles to immune cells across the epithelial barrier.
  • macrophage - a large highly motile white blood cell which engulfs foreign material (bacteria etc) and both degenerating cells and cell fragments. Found in many different tissues and locations. (More? Immunobiology - Defects in phagocytic cells are associated with persistence of bacterial infection)
  • MALT - Mucosa Associated Lymphoid Tissue
  • medulla - inner layer or core, used in association with cortex (outer layer) a general description that can be applied to describing an organ with a layered structure.
  • Memory Cell - effector T cell (lymphocyte)
  • NK cell - (Natural killer cell, large granular lymphocytes) are a type of cytotoxic lymphocyte, responding rapidly to virally infected and tumor cells.
  • normoblast - seen in bone marrow smear, a developing erythroblast (red blood cell) that still retains a nucleus.
  • parenchyma - (Greek = enkeim "to pour in") cells forming the functional cells of an organ or tissue. These cells carry out the function of the organ at a cellular level, and are not the structural cells, connective tissue, extracellular matrix (stromal).
  • periarterial lymphoid sheath - (PALS) in the spleen the white pulp that surrounds the central arteries. (T-lymphocytes,macrophages and plasma cells)
  • Plasma Cell - active B cell (lymphocyte) which is secreting antibody. Located in either bone marrow or peripheral lymphoid tissues, these cells have and increased cytoplasmic volume (due to increase rough endoplasmic reticulum) in comparison to the inactive (non-secreting) lymphocyte.
  • sentinel lymph node - the hypothetical first lymph node or group of nodes reached by metastasizing cancer cells from a primary tumour.
  • splenic sinusoids - enlarged spleen capillary spaces located in red pulp and surrounding cords of Billroth.
  • stroma - (Greek = "a cover, table-cloth, bedding") tissue forming the framework/support of an organ or tissue. That is the structural cells which form connective tissue and secrete extracellular matrix, rather than the functional cells (parenchymal). All organs can therefore be functionally divided into these 2 components, stromal/parenchymal.
  • Subcapsular sinus (=marginal sinus) space lying under the connective tissue capsule which receives lymph from afferent lymphatic vessels.
  • Thymic corpuscle (=Hassall's corpuscle) a mass of concentric epithelioreticular cells found in the thymus. The number present and size tend to increase with thymus age. (see classical description of Hammar, J. A. 1903 Zur Histogenese und Involution der Thymusdriise. Anat. Anz., 27: 1909 Fiinfzig Jahre Thymusforschung. Ergebn. Anat. Entwickl-gesch. 19: 1-274.)
  • thymic epitheliocytes - reticular cells located in the thymus cortex that ensheathe the cortical capillaries, creating and maintain the microenvironment necessary for the development of T-lymphocytes in the cortex.
  • T lymphocyte (cell) - named after thymus, where they develop, the active cell is responsible for cell-mediated immunity. (More? Electron micrographs of nonactivate and activated lymphocytes)
  • thymus - thymus has a key role in the development of an effective immune system as well as an endocrine function. Immune system T cells are essential for responses against infections and research relates to the postnatal development of T cells within the thymus. Thymus Development
  • tonsils - mucosal-associated lymphoid tissues consists of: 2 palatine tonsils (tonsilla palatina), adenoids (tonsilla pharyngealis) and 1 lingual tonsil (tonsilla lingualis)
  • tonsillar ring - ring of lymphoid tissue (tonsils) around where the mouth and nasal cavity meet the throat.
  • vermiform appendix - see appendix, anatomical region containing gut-associated lymphoid tissue located within the gastrointestinal tract at the beginning of the colon. The anatomy is as a finger-like structure that arises from the cecum. The length (2.5-13 cm) is longer in both infants and children and also has more abundant lymphatic tissue in early life. The wall structure is similar to the small intestine (though with no villi), nor plicae circularis. Lymph nodules surround the lumen of the gastrointestinal tract and extend from the mucosa into the submucosa.


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Cite this page: Hill, M.A. (2024, June 2) Embryology SH Lecture - Lymphatic Structure and Organs. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/SH_Lecture_-_Lymphatic_Structure_and_Organs

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