Lymphoid Functional Anatomy

1. Lymphoid Functional Anatomy The role of secondary lymphoid organs in trapping antigens For Tuesday Week 6 Practical Workshop, Dunnbook Chapter 10 Comments and Feedback please to the Author, simon.hunt@path.ox.ac.uk Start/help

2. Left-click anywhere to continue Left-click anywhere to continue Left-click anywhere to continue Using This Presentation – Help! • Navigate by clicking the Left mouse button • Some items within a page continue automatically to the next item, with never longer than a 3-second delay. Others need a manual mouse-click, including when the page ends to go to the next page. Hence you control the rate of presentation. • Don’t use the PageUp or PageDown keyboard buttons unless you want to skip through pages – you may miss things. • The Right mouse button provides a menu to allow you to skip and shortcut and repeat pages • Use this presentation in association with your Dunnbook • Comments in yellow boxes in this presentation have equivalent spaces on paper for you to complete, flagged by a • Here’s a good online medical dictionary if you need one… • …and some aids to find research papers and reviews..…. Help for this presentation

3. Purposes of this presentation • To show how the siting of lymph nodes in the body, interconnected by lymphatic vessels, serves to trap pathogens at the local draining nodes • Examples are of material • inoculated through the skin: plague • injected to a muscle: an antigenic adjuvant • inhaled to the lungs: anthrax • To encourage you to explore areas you find interesting by following hyperlinks • To encourage you to keep your eyes open for features of interest and for the physical dimensions, especially of images Presentation objectives

4. Lymphatics and Lymphoid organs, overview From http://www.pedisurg.com4/ImagesPtEduc/lymph_nodes.gif The lymphatics shown here are the superficial ones draining the skin. If all the lymphatics that drain organs were also shown, she would be green all over. Check that you know the difference between “lymphatic” and “lymphoid”.  Why is it important to know the routes of lymphatics in cancer patients? From http://www.newhopehealthclinic.com/symptoms_lymphoma_lymph_glands_swollen.htm Here is a more detailed view in a child. Note the chains of nodes Lymphatics and Lymphoid organs, overview

5. Head & neck Groin Underarm Lymph Node Chains in Three Body Regions Try palpating an accessible node: see http://home.teleport.com/~bobh/Nodes.htm ) especially if you or your practical partner has an infection which has caused one to swell From http://www.jdaross.mcmail.com/lymphatics4.htm#Lymph%20nodes Lymphnode chains in three regions

6. From http://medicine.ucsd.edu/clinicalmed/head.htm 1 mm Compare scale with next slide Here’s a chance to revise your knowledge of:  Anterior, Posterior, Pre-, Supra-, Sub-…. Surface Locations of Lymph Node Chainsin Head and Neck A typical active lymph node, e.g. in an infection  Write a description of the immediate surroundings of the lymph node. The material in which it is embedded here is very typical. Surface Locations of Lymph Node Chains

7. It’s pretty important for clinicians to get it right between lymph node enlargement due to an immune response, and to a tumour. That’s part of clinical training, but you could start thinking now how a scientific approach could assist in making the distinction Cancer: enlarged Lymph Node with lymphoma Pathologists are fond of food metaphors for the very inedible specimens they study. Can you think of other examples? Compare scale with previous slide Cut sections of this enlarged lymph node involved with high-grade non-Hodgkin's lymphoma in AIDS reveal a "strawberry sundae" appearance with swirls and globs of red in white. From http://medlib.med.utah.edu/WebPath/TUTORIAL/AIDS/AIDS088.html An enlarged lymphomatous lymph node

8.  Sketch a stick-man schematic to make it clear from which view this X-ray was taken • Common Iliac Lymph Nodes Abdominal lymphangiogram This illustrates the connections between chains of lymph nodes by lymphatics From http://www.med.umich.edu/lrc/coursepages/M1/anatomy/html/radiology/xray/lymphangiogram.html  What might be the likely biological purpose of arranging lymph nodes in a series of chains like this?  Anything odd in this image? Lymphangiogram

9. The Black DeathNecrosis (gangrene) of the tissue caused by plaguefromhttp://www.historique.net/microbes/pestis.html Plague If the history and current status of plague epidemiology interest you, see the recent WHO report Fleas transfer the bacterial infection (Yersinia Pestis) from rodents by subcutaneous inoculation to various animals and topeople. Initial signs and symptoms may be nonspecific with fever, chills,malaise, myalgia (muscular pain or tenderness), nausea, prostration, sore throat and headache. Commonly a lymphadenitis (inflammation of the nodes) develops in those lymph nodes that drain the site ofthe flea bite, where there may be an initial lesion. This is bubonic plague,and it occurs more often in lymph nodes in the inguinal area and less commonly in the axillary and cervical areas. The involved nodes (“buboes”) become swollen, inflamed and tender and may suppurate (i.e. form or discharge pus). Once it has spilled into the bloodstream, the infection is systemic. Fromhttp://www.ph.ucla.edu/epi/bioter/plagueapha_id_a.html Plague

10. The cells that have taken up the antigen are dendritic cells, shown in green in this higher-power view Within the inguinal (draining) node the antigen is quite deep below the surface – the arrows mark the border. More on this next class ------------ in leg muscle at injection site ---------- in draining LN 100 mm 100 mm 10 mm 200 mm 3 hrs 48 hrs 48 hrs 48 hrs Antigen (adjuvant) – red/orange Dendritic cell marker (DEC205)- green In the first couple of hours the antigen is not yet cell associated, but after two days most of it is internalised Antigen transport by dendritic cells following intramuscular inoculation Note the scale bar!  What is an “adjuvant”? Data from Dupuis et al, “Dendritic Cells Internalize Vaccine Adjuvant after Intramuscular Injection“ Cellular Immunology 186: 18 (1998) Antigen fate after i.m. injection

11. Knowledge of functional lung anatomy is essential for clinicians to deal with infections that overwhelm the normal non-specifc immune defences which keep the alveoli normally sterile. Write a checklist of these defences. Abstract schematic Actual radiograph From http://anthrax.radpath.org/Pathogen9.html Inhaled Antigens: the Lung Pulmonary Lymphoid System comprises • Lymphatics- Originate in the pleura- Have valves- Drain towards hilum- Follow interlobular septa- Accompany blood vessels • Draining lymph nodes (shown yellow) • intrapulmonary • mediastinal The bacterial disease anthrax is in the news as an inhaled pathogen. It is a toxigenic bacillus whose details you are not required to know. However, the next two pages make the point that the radiology of the lymph nodes can often give the quickest diagnosis, and reveal the role of the lymphoid organs when non-specific defences have been breached Pulmonary lymphoid system 1

12. The infection begins with the inhalation of the anthrax spore. The ability to reach the pulmonary alveolus requires a spore size of less than 5 microns. The spore is engulfed by alveolar macrophages, and is transported through the pulmonary lymphatics to hilar and mediastinal lymph nodes. Spiral CT through chest. Shows enlarged blood-filled lymph nodes (blue arrows) and fluid surrounding both lungs (red arrows). From http://jol.rsna.org/pr/target.cfm?ID=55 Anthrax bacilli after the spores have germinated, completely filling a pulmonary lymphatic (arrow) Anthrax in a postal worker, USA 2001 With a lymphatic vessel filled like that, it isn’t surprising the outcome sadly was fatal Anthrax

13. early advanced Pulmonary lymphoid system in anthrax CT imaging demonstrates bulky high-attenuation hilar and mediastinal lymphadenopathy which may produce bronchial and vascular narrowing. Large rapidly-progressive pleural effusions are characteristic. The portal of entry is the airway and the organisms are rapidly transmitted via the lymphatics to the intrathoracic lymph nodes and ultimately to the blood stream. Despite the inhalational acquisition of the disease, the lung parenchyma remains relatively uninvolved.From http://anthrax.radpath.org/Summary2.html Pulmonary lymphoid system 2

14. Pathologies of lymph nodes • If you have some time to spare you may like to visit http://home.teleport.com/~bobh/CommonPathofLymphNodes.htm which shows diseases involving lymph nodes of the head and neck, including: • Infectious Mononucleosis (“Glandular fever”) • Non-Hodgkin's Lymphoma • Persistent Generalized Lymphadenopathy • Cat Scratch Disease • Metastatic Carcinoma You have probably by now mastered the meaning of “lymphadenopathy” since that has appeared a number of times, but  what about “lymphadenectomy”? Pathologies of lymph noders

15. Summary • Pathogens at first encounter innate immune defences, e.g. • Skin epithelial barriers • Airway filtration and epithelial secretions • Phagocytosis, perhaps aided by opsonisation by Complement • If the defences are overwhelmed or bypassed, the pathogens travel via afferent lymph • in fluid phase or cell-associated • to draining lymph nodes • usually a chain of nodes are arranged in series • The adaptive immune response starts in the draining node