Re: how does the embryological immune system develop

Ben, Thank you for your very interesting and challenging question. My expertise is in the immune systems of Rat, Mice and Rabbits. All three of these mammals have immune systems that begin to develop during embryogenesis but are not completely developed at birth and require additional development as the first exposure to environmental antigens occurs. There are primary lymphoid organs that develop in various embryonal locations but move to others as development proceeds. The bone marrow starts with hematopoietic cells near the aorta above the mesonephros, moves to the yolk sac and then the spleen. Later in intrauterine development the bone marrow function moves to the marrow cavities of bone as blood vessels invade and begin to remodel the cartilage models into bone. The thymus develops from two arches of branchial cleft epithelium which migrates down into the mediastinum. Then this knot of epithelium attracts hematopoietic cell precursors to infiltrate the epithelium which begins the development of the thymus. There is substantial cross-talk between the potential residents of these tissues and the stromal elements that support them and allow for their migration and compartmentalization. I am aware the more primitive organisms such as sea sponges and corals have cells that can recognize related species that derived from different clones. contact of different clones of sponges or corals can result in cell killing not unlike what happens between a killer t-cell and its virally infected (or cancerous) target. A lot of the genes lymphoid cells use to recognize and respond to antigens are highly concerved in nature even to non-vertebrate animals like the ones I just mentioned. Sea stars have totipotential amoebacytes that act like lymphoid cells, monocytes and neutrophils all at once. These cells serve as a primitive or innate immune system and such a primitive system persists in vertebrates and man, responding to the same limited set of environmental antigens. Here is a link to my lecture notes on the immune system. There are also links to other lecture notes contained in these. Further, you may find this list of references interesting to read. I hope this answer helps you in your search for useful information. http://www.geocities.com/artnscience/art-notes.html

Journal References:

1. Anderson, A.O. 1990. "Structure and organization of the lymphatic system." In Immunophysiology. The role of cells and cytokines in immunity and inflammation. Oppenheim, J.J. and E. Shevach (eds.), pp. 14- 45, Oxford University Press, NY.

2. Fu, Y.X. and D. Chaplin. 1999. Development and Maturation of Secondary Lymphoid Tissues. An nu. Rev. Immunol. 17:399-433.

3. Anderson, A.O. and S. Shaw. 1993. T cell adhesion to endothelium: the FRC conduit system and other anatomic and molecular features which facilitate the adhesion cascade in lymph node. Sem. Immunol. 5:271-282.

4. Anderson, A.O., and S. Shaw. 1995. "Lymphocyte Trafficking." Chapter 3, In Clinical Immunology, Principles and Practice. R.R. Rich, T.A. Fleisher, B.D. Schwartz, W.T. Shearer, and W. Strober (eds.), pp 39-49, Mosby-Year Book, Inc., St. Louis, MO.

5. Ebnet, K., E.P. Kaldjian, A.O. Anderson, and S. Shaw. 1995. Orchestrated information transfer underlying leukocyte endothelial interactions. Ann. Rev. Immunol. 14:155-177.

6. Gretz, E.J., E.P. Kaldjian, A.O. Anderson, and S. Shaw. 1996. Sophisticated strategies for information encounter in the lymph node: The reticular network as a conduit of soluble information and a highway for cell traffic. ("Cutting Edge") J. Immunol. 157:495-499.

7. Butcher, E.C. and L.J. Picker. 1996. Lymphocyte Homing and Homeostasis. Science 272:60-66.

8. Gretz, J.E., A.O. Anderson, and S. Shaw. 1997. Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol. Rev. 156:11-24.

9. Anderson, A.O. 1997. New Technologies for Producing Systemic and Mucosal Immunity by Oral Immunization: Immunoprophylaxis in Meals, Ready-to-Eat. In Emerging Technologies for Nutrition Research, National Academy Press, Washington, DC, pp. 451-500.

10. Immunological Reviews Vol 156. Table of Contents lists multiple relevant topics, 1997.

11. Sehgal, D., E. Schiaffella, A.O. Anderson, and R.G. Mage. (1998) Analysis of single B cells by Polymerase Chain Reaction reveal rearranged VH with germline sequences in spleens of immunized rabbits: Implications for B cell repertoire maintentance and renewal. J. Immunol. 161:5347-5356.

12. Mage RG, Sehgal D, Schiaffella E, Anderson AO. 1999. Gene- conversion in rabbit B-cell ontogeny and during immune responses in splenic germinal centers. Vet Immunol Immunopathol 72:7-15

13. Kuprash, D.V., M.B. Alimzhanov, A.V. Tumanov, A.O. Anderson, K. Pfeffer, and S.A. Nedospasov. 1999. TNF and Lymphotoxin beta Cooperate in the Maintenance of Secondary Lymphoid Tissue Microarchitecture But Not in the Development of Lymph Nodes. J. Immunol 163: 6575-6580.

14. Seghal, D., E. Schiaffella, A.O. Anderson and R.G. Mage. 2000. Generation of heterogeneous rabbit anti-DNP antibodies by gene conversion and hypermutation of rearranged VL and VH genes during clonal expansion of B-cells in splenic germinal centers. Eur. J. Immunol. 30:3634-3644.

15. Gretz, J.E., C.C. Norbury, A.O. Anderson, A.E.I. Proudfoot, and S. Shaw. 2000. Lymph-borne Chemokines and Other Low Molecular Weight Molecules Reach High Endothelial Venules via Specialized Conduits While a Functional Barrier Isolates the Lymphocyte Microenvironments in Lymph Node Cortex. J. Exp. Med. 192:1425-1440.

16. Kaldjian, E.P., J.E Gretz, A.O Anderson, Y. Shi, S. Shaw. 2001. Spatial and molecular organization of lymph node T cell cortex: A labyrinthine cavity bounded by an epithelial sheet of fibroblastic reticular cells anchored to basement membrane-like extracellular matrix. Intl. Immunology 13:1243-1253.

17. Kuprash, D.V., M.B. Alimzhanov, A.V. Tumanov, S.I. Grivennikov, A.N. Shakkov, L.N. Drutskaya, M.W. Marino, R.L. Turetskaya, A.O. Anderson, K. Rajewsky, K. Pfeffer and S. A. Nedospasov. 2002. Redundancy in TNF and LT signaling in vivo: mice with inactivation of the entire TNF/LT locus versus single knockout mice. Mol. Cell. Biol. 22:8626-8634.

18. Nolte, M.A., J.A.M. Belien, I. Schadee-Eestermans, W. Jansen, W.W.J. Unger, N. van Rooijen, G. Kraal and R.E. Mebius. 2003. A Conduit System Distributes Chemokines and Small Blood-borne Molecules through the Splenic White Pulp. J. Exp. Med 198:505-512

19. Bejenoff, M., S. Granjeaud and S. Guerder. 2003. The Strategy of T Cell Antigen-presenting Cell Encounter in Antigen-draining Lymph Nodes Revealed by Imaging of Initial T Cell Activation. J. Exp. Med. 198:715-724

20. von Andrian, U.H. and T. Mempel. 2003. Homing and Cellular Traffic in Lymph Nodes. Nature Reviews Immunology 3: 867-878. [PubMed]

21. Mempel, T.R., S.E. Henrickson, and U.H. von Andrian. 2004. T cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427: 154-159. [PubMed]

22. Pribila JT, AA Itano, KL Mueller, Y Shimizu. 2004. The alpha1beta1 and alphaEbeta7 integrins define a subset of dendritic cells in peripheral lymph nodes with unique adhesive and antigen uptake properties. J Immunol. 172: 282-91