Talk:SH Lecture - Lymphatic Structure and Organs: Difference between revisions

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Reciprocal interactions of the intestinal microbiota and immune system  
[[File:SHsmall.jpg]]
http://www.nature.com/nature/journal/v489/n7415/full/nature11551.html
==2012 Lecture Introduction==
[[File:Adult_lymphatic_system.jpg|thumb|300px|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".
 
# Immune - “monitor” of body surfaces, internal fluids
# Extracellular fluid - returns interstitial fluid to circulation
# Gastrointestinal tract - carries fat and fat-soluble vitamins
 


==Todays Lecture in the Online Textbooks==
===Aim===
--[[User:Z8600021|Mark Hill]] 10:32, 24 February 2012 (EST) The following link to text and figures that relate to lymphatic structure and organs. Remember the Lecture is about structure/function and not a description of immunity (that will be covered elsewhere in the course).
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)


===Key Concepts===
# Lymphatic System
# Organs - Thymus, Spleen
# Lymph Nodes and Nodules
# Bone Marrow
# Extranodal Lymphoid Tissues
# Mucosal Associated Lymphoid Tissues (MALT)


==Textbook References==
* [[SH_Practical_-_Lymphatic_Structure_and_Organs|SH Laboratory Support]]
* Janeway’s Immunobiology [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=imm.TOC&depth=2 NCBI Bookshelf] | [http://www.garlandscience.co.uk/textbooks/0815341237.asp Publisher page]
* '''Histology and Cell Biology''' - A.L. Kiersenbaum (2001) Chapter 6: Blood,  Chapter 10: Immune-Lymphatic [http://books.google.com.au/books?id=_ElRdXfE0cYC&lpg=PA68&ots=5lZxyJl86x&dq=Histology%20and%20Cell%20Biology%20-%20A.%20L.%20Kierszenbaum&lr&pg=PA147#v=snippet&q=immune&f=false Cover]
* Previous Lectures: [http://php.med.unsw.edu.au/cellbiology/index.php?title=2010_Society_and_Health_-_Lymphatic_organs_histology 2010] | [http://cellbiology.med.unsw.edu.au/units/medicine/SHlymph.htm 2008]


{| class="wikitable collapsible collapsed"
{| class="wikitable collapsible collapsed"
! Immunobiology Textbook
! Janeway’s Immunobiology
|-  
|-  
| [[File:Mark_Hill.jpg|left|50px]] A useful resource textbook for further reading on '''Lymphatic Structure and Organs''' is [http://www.ncbi.nlm.nih.gov/books/NBK10757/ Immunobiology] 5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.
| [[File:Mark_Hill.jpg|left|50px]] A useful resource textbook for further reading on '''Lymphatic Structure and Organs''' is [http://www.ncbi.nlm.nih.gov/books/NBK10757/ Immunobiology] 5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik. Open links in a new tab if you wish to refer back to this lecture page.


I have included some links in this table below to specific notes and there is also available a [[Talk:SH_Lecture_-_Lymphatic_Structure_and_Organs#Immunobiology_3|complete list of contents]].  
I have included some links in this table below to specific notes and there is also available a [[Talk:SH_Lecture_-_Lymphatic_Structure_and_Organs#Immunobiology_3|complete list of contents]].  
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{{Immune Links}}
==Two Cellular Systems==
* '''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
[http://www.ncbi.nlm.nih.gov/books/NBK26921/figure/A4423 MBoC Figure 24-3 Human lymphoid organs]
==Lymphatic System==
[[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
* Tissues and Organs
** 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
==Blood Cells==
[[File:Hematopoietic_and_stromal_cell_differentiation.jpg|500px]]
[[SH_Lecture_-_Lymphatic_Structure_and_Organs#Blood_Cell_Numbers|Blood Cell proportions]]
[[File:lymphocyte 01.jpg|200px]] [[File:Lymphocyte_02.jpg|400px]]
===Lymphocyte Electron Micrographs===
<gallery>
File:T and B lymphocytes EM10.jpg|T and B Lymphocyte
File:T_and_B_lymphocytes_EM09.jpg|T and B Lymphocyte
File:Plasma_cell_EM06.jpg|Plasma cell (B)
File:T2_lymphocyte_EM13.jpg|Cytotoxic (T)
</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==
[[File:Lymphatic_vasculature_04.jpg|thumb|400px|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
<gallery>
File:Lymphatic capillary.jpg|Lymph capillary
File:Lymphatic_vasculature_03.jpg|Lymphangion
File:Intestine_histology_001.jpg|Jejunum lacteal
</gallery>
==Lymph Vessels==
[[File:Gray0599.jpg|thumb|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
(Remember anatomy acronym - '''NAVL''' = Nerve, Artery, Vein and Lymph)
==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]
* The circulation through a lymph node is shown.
* 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, 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.
* A typical circulation cycle takes about 12–24 hours.
'''Links:''' [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A4419 MBoC Chapter 24 - The Adaptive Immune System] | [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] | [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=imm Immunobiology]
==Diffuse Lymphatic Tissue==
Alimentary canal, respiratory passage, urogenital tract
* '''Not enclosed by a connective tissue capsule'''
* Located in subepithelial tissue - '''Lamina propria'''
'''Lymphocytes'''
* travel to nodes and back again
* proliferation and differentiation
'''Effector cells'''
* 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]]
| Internal epithelia Associated Lymphoid Tissue - naming based upon the anatomical locations
* MALT - Mucosa Associated Lymphoid Tissue
** BALT - Bronchus Associated  Lymphoid Tissue
** GALT - Gut Associated Lymphatic Tissue
|}
==Immune Responses==
Adaptive immunity has 2 main classes
# '''Antibody-mediated''' - B Lymphocyte
# '''Cell-mediated''' - T Lymphocyte
==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
===Gastrointestinal Tract===
* Oropharynx - Tonsils
* Distal small intestine (ilieum) - Peyer’s Patches
* Appendix, cecum
===Nodule States===
* '''Primary Nodule''' - Mainly small lymphocytes
* '''Secondary Nodule'''
** Central pale region (germinal centre) - Effector cells and macrophages
** 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]
==Tonsils==
Anatomical location -  Palatine  ('''tonsils'''), Lingual  and Pharyngeal ( '''adenoids''' )
===Palatine Tonsils===
[[File:Tonsil_histology_01.jpg|300px]] [[File:Tonsil_histology_02.jpg|300px]]
* 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
==Peyer's Patch==
[[File:Peyer's patch 01.jpg|200px]] [[File:Peyer's patch 02.jpg|200px]]
Peyer's Patch, Ileum
microfold cells or M-cells
==Lymph Nodes==
[[Quicktime Movie - Mouse Lymph Node 7]] | [[Quicktime_Movies#Immune|more lymph node movies]]
[[File:Lymph_node_structure.jpg|thumb]]
[[File:Lymph node structure 01.png|thumb|Schematic of lymph node showing lymph sinuses]]
[[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”
* Afferent- towards node
* Efferent- away from node
* Location throughout the entire body - Concentrated in axilla, groin, mesenteries
* Antigen transformed lymphocytes from the blood
| [[File:Lymph_node_histology_06.jpg|200px]]
|}
===Lymph Node Structure===
[[File:Lymph_node_histology01.jpg|thumb|Lymph node cortex histology]]
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
[[File:Lymph node histology 02.jpg]] [[File:Lymph node histology 03.jpg]]
Lymph
* enters the node through '''afferent vessels'''
* filters through the '''sinuses'''
* leaves through '''efferent vessels'''
Subcapsular sinus = marginal sinus
[[File:Lymph_node_histology_01.jpg]] [[File:Lymph_node_histology_04.jpg]]
Continuation of trabecular sinus
Lymphocyte (T and B) Traffic
# Enter from high endothelial venules (HEVs also called post-capillary venules)
# Spend 8 to 24 h in the lymph node interstitium.
# Enter a network of medullary sinuses.
# Drain from sinuses into efferent lymphatic vessels.
'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A47 Immunobiology - Figure 1.8. Organization of a lymph node]
==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===
* 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)
===Fetal/Young Thymus===
{|
| [[File:Thymus - young 01.jpg‎|300px]]
| [[File:Thymus - young 02.jpg‎|300px]]
|-
|Young medulla
|Young cortex
|}
Thymic corpuscle
Hassall’s corpuscle - Mass of concentric epithelioreticular cells
===Adult Thymus===
[[File:Thymus adult.jpg]]
* Cortical lymphoid tissue is replaced by adipose tissue
* Increase in size of thymic corpuscles
{{Thymus Histology}}
==Spleen==
[[File:Spleen anatomy.jpg]] [[File:Gray1039.jpg|300px]]
===Functions===
'''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===
[[File:Spleen_histology_01.jpg]] [[File:Spleen_histology_02.jpg]]
* Capsule, trabeculae (dense connective tissue)
* Splenic pulp White pulp, red pulp - based on appearance and cell content
[[File:Spleen_histology_05.jpg|thumb|White pulp -periarterial lymphoid sheath (PALS)]]
'''White Pulp'''
* lymphocytes surround central arteries
* as periarterial lymphoid sheath (PALS)
'''Red Pulp'''
* Red blood cells
* Splenic sinuses
* Splenic cords
[[File:Spleen_histology_03.jpg]]
'''Reticular Fibers'''
[[File:Spleen_histology_05.jpg]]
[[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]
==B Cell Development==
* Bone marrow
* blood
* Lymph node, nodule
* Lymphatic vessel
* Bone marrow
Germinal Centres
* 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.''
===Immunobiology Textbook===
[http://www.ncbi.nlm.nih.gov/books/NBK10757/ Immunobiology] 5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.
====Part I. An Introduction to Immunobiology and Innate Immunity====
* Chapter 1. Basic Concepts in Immunology
** [http://www.ncbi.nlm.nih.gov/books/NBK27092/ The components of the immune system]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A40 Figure 1.3 All the cellular elements of blood, including the lymphocytes of the adaptive immune system, arise from hematopoietic stem cells in the bone marrow]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A41 Figure 1.4 Myeloid cells in innate and adaptive immunity]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A42 Figure 1.5 Lymphocytes are mostly small and inactive cells]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A43 Figure 1.6 Natural killer (NK) cells]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A45 Figure 1.7 The distribution of lymphoid tissues in the body]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A47 Figure 1.8 Organization of a lymph node]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A48 Figure 1.9 Organization of the lymphoid tissues of the spleen]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A49 Figure 1.10 Organization of typical gut-associated lymphoid tissue]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27092/figure/A51 Figure 1.11 Circulating lymphocytes encounter antigen in peripheral lymphoid organs]
** [http://www.ncbi.nlm.nih.gov/books/NBK27092/#A52 Summary to Chapter 1]
====Part III. The Development of Mature Lymphocyte Receptor Repertoires====
* Chapter 7. The Development and Survival of Lymphocytes
** [http://www.ncbi.nlm.nih.gov/books/NBK27123/ Generation of lymphocytes in bone marrow and thymus]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27123/figure/A803 Figure 7.3 The early stages of B-cell development are dependent on bone marrow stromal cells]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27123/figure/A806 Figure 7.5 The development of a B-lineage cell proceeds through several stages marked by the rearrangement and expression of the immunoglobulin genes]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27123/figure/A809 Figure 7.7 The cellular organization of the human thymus]
*** [http://www.ncbi.nlm.nih.gov/books/NBK27123/figure/A818 Figure 7.13Thymocytes at different developmental stages are found in distinct parts of the thymus]
** [http://www.ncbi.nlm.nih.gov/books/NBK27150/ Survival and maturation of lymphocytes in peripheral lymphoid tissues]
** [http://www.ncbi.nlm.nih.gov/books/NBK27123/#A819 Summary to Chapter 7]
* Associated Practical support page - [[SH Practical - Lymphatic Structure and Organs]]
{{Template:Blood Cell Number Table}}
'''Anatomy of the Human Body''' Gray (1918 Historic anatomy is good, there are there are some functional inaccuracies).
* [http://www.bartleby.com/107/175.html The Lymphatic System] | [http://www.bartleby.com/107/176.html The Thoracic Duct] | [http://www.bartleby.com/107/278.html The Spleen] | [http://www.bartleby.com/107/274.html The Thymus] |
==Additional Images==
<gallery>
File:Lymph_node_cartoon.jpg|Lymph node cartoon
File:Lymph_nodes_head_neck_superficial.jpg|Lymph nodes - head neck superficial
File:Gray1192.jpg|Section of the spleen, showing the termination of the small blood vessels
File:Spleen_histology_06.jpg|human spleen histology
File:Spleen_histology_07.jpg|human spleen histology
File:Spleen_histology_08.jpg|human spleen histology
File:Lymph node 05.jpg|rabbit lymph node subcapsular sinus
</gallery>
== Terms ==
A few key terms associated with the Lymphoid system.
* '''adenoid''' - (Greek " +''-oeides ''<nowiki>= in form of) in the form of a gland, glandular; the pharyngeal tonsil. </nowiki>
* '''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 '''b'''ursa of Fabricius in birds, a source of antibody-producing lymphocytes. These cells develop in the bone marrow. (More? [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.4430 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.
* '''"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.
* '''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? [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&rid=imm.section.1494 Immunobiology - immunodeficiency])
* '''involution''' - in the Thymus refers to the replacement, mainly in the cortex, of cells by adipose tissue. (More? [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&term=thymus+involution&doptcmdl=Books PubMed- thymus involution]) | [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&rid=cmed6.section.23856#23857 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? [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=imm.figgrp.1508 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)
* '''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 '''t'''hymus, where they develop, the active cell is responsible for cell-mediated immunity. (More? [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.4430 Electron micrographs of nonactivate and activated lymphocytes])
thymus
tonsils
*''' 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.
Reciprocal interactions of the intestinal microbiota and immune system
http://www.nature.com/nature/journal/v489/n7415/full/nature11551.html
==Todays Lecture in the Online Textbooks==
--[[User:Z8600021|Mark Hill]] 10:32, 24 February 2012 (EST) The following link to text and figures that relate to lymphatic structure and organs. Remember the Lecture is about structure/function and not a description of immunity (that will be covered elsewhere in the course).


===Immunobiology ===
===Immunobiology ===

Revision as of 11:51, 18 February 2013

SHsmall.jpg

2012 Lecture 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)

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

  • 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


MBoC Figure 24-3 Human lymphoid organs

Lymphatic System

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

  • Tissues and Organs
    • 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

Blood Cells

Hematopoietic and stromal cell differentiation.jpg

Blood Cell proportions

Lymphocyte 01.jpg Lymphocyte 02.jpg

Lymphocyte Electron Micrographs

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)

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)

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


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

Lymphocyte Circulation

MBoC Figure 24-14. The path followed by lymphocytes as they continuously circulate between the lymph and blood

  • The circulation through a lymph node is shown.
  • 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, 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.
  • 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

Alimentary canal, respiratory passage, urogenital tract

  • Not enclosed by a connective tissue capsule
  • Located in subepithelial tissue - Lamina propria

Lymphocytes

  • travel to nodes and back again
  • proliferation and differentiation

Effector cells

  • 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

Oesophagus MALT.jpg Internal epithelia Associated Lymphoid Tissue - naming based upon the anatomical locations
  • MALT - Mucosa Associated Lymphoid Tissue
    • BALT - Bronchus Associated Lymphoid Tissue
    • GALT - Gut Associated Lymphatic Tissue

Immune Responses

Adaptive immunity has 2 main classes

  1. Antibody-mediated - B Lymphocyte
  2. Cell-mediated - T Lymphocyte

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

Gastrointestinal Tract

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

Nodule States

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

Links: Immnuobiology - Figure 1.10. Organization of typical gut-associated lymphoid tissue

Tonsils

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

Palatine Tonsils

Tonsil histology 01.jpg Tonsil histology 02.jpg

  • 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

Peyer's Patch

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

Peyer's Patch, Ileum

microfold cells or M-cells

Lymph Nodes

Quicktime Movie - Mouse Lymph Node 7 | more lymph node movies

Lymph node structure.jpg
Schematic of lymph node showing lymph sinuses
Detailed structure

Immunobiology - Figure 1.8. Organization of a lymph node

MBoC Figure 24-16. A simplified drawing of a human lymph node

* Encapsulated organ (1 mm - 2 cm)
  • In lymph vessel pathways “filter”
  • Afferent- towards node
  • Efferent- away from node
  • Location throughout the entire body - Concentrated in axilla, groin, mesenteries
  • Antigen transformed lymphocytes from the blood
Lymph node histology 06.jpg

Lymph Node Structure

Lymph node cortex histology

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 histology 02.jpg Lymph node histology 03.jpg

Lymph

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

Subcapsular sinus = marginal sinus

Lymph node histology 01.jpg Lymph node histology 04.jpg

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 cartoon.jpg MBoC Figure 24-6. The development and activation of T and B cells

Figure 24-7. Electron micrographs of nonactivated and activated lymphocytes

Development Changes

Fetal thymus anatomy
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

  • 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)

Fetal/Young Thymus

Thymus - young 01.jpg Thymus - young 02.jpg
Young medulla Young cortex

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 anatomy.jpg Gray1039.jpg

Functions

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

Spleen histology 01.jpg Spleen histology 02.jpg

  • 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 sinuses
  • Splenic cords

Spleen histology 03.jpg

Reticular Fibers

Spleen histology 05.jpg Spleen histology 04.jpg


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


Links: Immunobiology - Figure 1.9. Organization of the lymphoid tissues of the spleen

B Cell Development

  • Bone marrow
  • blood
  • Lymph node, nodule
  • Lymphatic vessel
  • Bone marrow

Germinal Centres

  • 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.

Immunobiology Textbook

Immunobiology 5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.

Part I. An Introduction to Immunobiology and Innate Immunity

Part III. The Development of Mature Lymphocyte Receptor Repertoires


Blood Cell Numbers

The adult ranges of cells / 1 litre (l), total blood volume is about 4.7 to 5 litres. Blood Development | Blood Histology

Red Blood Cells

  • Male: 4.32 - 5.66 x 1012/l
  • Female: 3.88 - 4.99 x 1012/l

Leukocytes (white blood cells)

  • Male: 3.7 - 9.5 x 109/l
  • Female: 3.9 - 11.1 x 109/l

Granulocytes

  • 1.8 - 8.9 x 109/l
    • Neutrophils: 1.5 - 7.4 x 109/l
    • Eosinophils: 0.02 - 0.67 x 109/l
    • Basophils: 0 - 0.13 x 109/l

Non-Granulocytes

  • Monocytes 0.21 - 0.92 x 109/l

Lymphocytes

  • 1.1 - 3.5 x 109/l
    • B-cells: 0.06 - 0.66 x 109/l
    • T-cells: 0.77 - 2.68 x 109/l
      • CD4+: 0.53 - 1.76 x 109/l
      • CD8+: 0.30 - 1.03 x 109/l
    • NK cells: 0.20 - 0.40 x 109/l

Platelets

  • 140 - 440 x 109/l
    • not a cell, a cell fragment.


Anatomy of the Human Body Gray (1918 Historic anatomy is good, there are there are some functional inaccuracies).

Additional Images

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.
  • "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.
  • 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)
  • 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

tonsils

  • 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.


Reciprocal interactions of the intestinal microbiota and immune system http://www.nature.com/nature/journal/v489/n7415/full/nature11551.html

Todays Lecture in the Online Textbooks

--Mark Hill 10:32, 24 February 2012 (EST) The following link to text and figures that relate to lymphatic structure and organs. Remember the Lecture is about structure/function and not a description of immunity (that will be covered elsewhere in the course).

Immunobiology

Immunobiology 5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.

Part I. An Introduction to Immunobiology and Innate Immunity

Part III. The Development of Mature Lymphocyte Receptor Repertoires

Molecular Biology of the Cell

Medical Microbiology

Pubmed Bookshelf

Immunobiology

5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.

Contents

  • Preface to the Fifth Edition
  • Acknowledgments
  • Icons Used Throughout the Book

Part I. An Introduction to Immunobiology and Innate Immunity

Part II. The Recognition of Antigen

  • Chapter 3. Antigen Recognition by B-cell and T-cell Receptors
    • The structure of a typical antibody molecule
    • The interaction of the antibody molecule with specific antigen
    • Antigen recognition by T cells
    • Summary to Chapter 3
    • General references
    • Section references
  • Chapter 4. The Generation of Lymphocyte Antigen Receptors
    • The generation of diversity in immunoglobulins
    • T-cell receptor gene rearrangement
    • Structural variation in immunoglobulin constant regions
    • Summary to Chapter 4
    • General references
    • Section references
  • Chapter 5. Antigen Presentation to T Lymphocytes
    • The generation of T-cell receptor ligands
    • The major histocompatibility complex and its functions
    • Summary to Chapter 5
    • General references
    • Section references

Part III. The Development of Mature Lymphocyte Receptor Repertoires

Part IV. The Adaptive Immune Response

  • Chapter 8. T Cell-Mediated Immunity
    • The production of armed effector T cells
    • General properties of armed effector T cells
    • T cell-mediated cytotoxicity
    • Macrophage activation by armed CD4 TH1 cells
    • Summary to Chapter 8
    • General references
    • Section references
  • Chapter 9. The Humoral Immune Response
    • B-cell activation by armed helper T cells
    • The distribution and functions of immunoglobulin isotypes
    • The destruction of antibody-coated pathogens via Fc receptors
    • Summary to Chapter 9
    • General references
    • Section references
  • Chapter 10. Adaptive Immunity to Infection
    • Infectious agents and how they cause disease
    • The course of the adaptive response to infection
    • The mucosal immune system
    • Immunological memory
    • Summary to Chapter 10
    • General references
    • Section references

Part V. The Immune System in Health and Disease

  • Chapter 11. Failures of Host Defense Mechanisms
    • Pathogens have evolved various means of evading or subverting normal host defenses
    • Inherited immunodeficiency diseases
    • Acquired immune deficiency syndrome
    • Summary to Chapter 11
    • General references
    • Section references
  • Chapter 12. Allergy and Hypersensitivity
    • The production of IgE
    • Effector mechanisms in allergic reactions
    • Hypersensitivity diseases
    • Summary to Chapter 12
    • General references
    • Section references
  • Chapter 13. Autoimmunity and Transplantation
    • Autoimmune responses are directed against self antigens
    • Responses to alloantigens and transplant rejection
    • Self-tolerance and its loss
    • Summary to Chapter 13
    • General references
    • Section references
  • Chapter 14. Manipulation of the Immune Response
    • Extrinsic regulation of unwanted immune responses
    • Using the immune response to attack tumors
    • Manipulating the immune response to fight infection
    • Summary to Chapter 14
    • General references
    • Section references
  • Chapter 15. Afterword
    • Evolution of the innate immune system
    • Evolution of the adaptive immune response
    • The importance of immunological memory in fixing adaptive immunity in the genome
    • Future directions of research in immunobiology
    • Summary of the Afterword

Appendices

Molecular Biology of the Cell

Medical Microbiology


Search PubMed Databases immune system

2011

Start Time/End Time: 10am to 11am Monday 28 February 2011 Clancy Auditorium eMed Link to Learning Activity - Lymphatic organs histology


Bookshelf links

old - http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A4419&rendertype=figure&id=A4423 MBoC Figure 24-3 Human lymphoid organs

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

Recent Research

Defining the quantitative limits of intravital two-photon lymphocyte tracking

Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12401-6. Epub 2011 Jul 6.

Textor J, Peixoto A, Henrickson SE, Sinn M, von Andrian UH, Westermann J. Source Institute for Theoretical Computer Science, University of Lübeck, 23562 Lübeck, Germany. textor@tcs.uni-luebeck.de

Abstract

Two-photon microscopy has substantially advanced our understanding of cellular dynamics in the immune system. Cell migration can now be imaged in real time in the living animal. Strikingly, the migration of naive lymphocytes in secondary lymphoid tissue appears predominantly random. It is unclear, however, whether directed migration may escape detection in this random background. Using a combination of mathematical modeling and experimental data, we investigate the extent to which modern two-photon imaging can rule out biologically relevant directed migration. For naive T cells migrating in uninfected lymph nodes (LNs) at average 3D speeds of around 18 μm/min, we rule out uniform directed migration of more than 1.7 μm/min at the 95% confidence level, confirming that T cell migration is indeed mostly random on a timescale of minutes. To investigate whether this finding still holds for longer timescales, we use a 3D simulation of the naive T cell LN transit. A pure random walk predicts a transit time of around 16 h, which is in good agreement with experimental results. A directional bias of only 0.5 μm/min-less than 3% of the cell speed-would already accelerate the transit twofold. These results jointly strengthen the random walk analogy for naive T cell migration in LNs, but they also emphasize that very small deviations from random migration can still be important. Our methods are applicable to cells of any type and can be used to reanalyze existing datasets.

PMID 21734152

http://www.pnas.org/content/108/30/12401.full

Stromal cell contributions to the homeostasis and functionality of the immune system

Nat Rev Immunol. 2009 Sep;9(9):618-29. Epub 2009 Jul 31.

Mueller SN, Germain RN. Source Department of Microbiology and Immunology, The University of Melbourne, Parkville, 3010 Victoria, Australia. smue@unimelb.edu.au Abstract A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance and the effective development of adaptive immune responses take place. What has only recently been recognized is the role that non-haematopoietic stromal elements have in many aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immune responses, and highlight how targeting of these elements by some pathogens can influence the host immune response.

PMID 19644499

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785037

http://www.nature.com/nri/journal/v9/n9/abs/nri2588.html

http://www.microbiol.unimelb.edu.au/research/immunology/s_mueller.html

Lymphatic vessels: structure and function

Isr Med Assoc J. 2011 Dec;13(12):762-8.

Rovenská E, Rovenský J. Source National institute of Rheumatic Diseases, Piestany, Slovak Republik. rovensky.jozef@nurch.sk l ymphatic vessels are part of the lymphatic system. The ves- sels evolved phylogenetically only after it became necessary for multicellular organisms to remove fluids and proteins from tissue and return them to the bloodstream. In humans, the lymphatic system begins to develop between the sixth and seventh week of embryonic development, at a time when the cardiovascular system is already functioning.

PMID 22332449

http://www.ima.org.il/imaj/dynamic/web/ArtFromPubmed.asp?year=2011&month=12&page=762