Secondary lymphoid tissues

In the specialized environment of secondary lymphoid tissues such as lymph nodes or spleen, dendritic cells provide the requirements for naive T-lymphocytes to become activated and to proliferate. The professional antigen-presenting cells present peptides in MHC II, express costimulatory molecules, and release cytokines into the immunological synapse, which is formed by the antigen-presenting cell and the naive T-lymphocyte. Thus, cells of innate immunity initiate and facilitate the activation of naive lymphocytes, and it is easily conceivable that their cytokines and adhesion molecules will instruct the naive T-lymphocyte during activation and differentiation to T-effector cells. 

This experimental drug is a derivative of myriocin. After phosphorylation FTY720 modulates chemotactic responses and lymphocyte trafficking, leading to reversible lymphocyte sequestration in secondary lymphoid tissues. It is in clinical trials for the treatment of multiple sclerosis. 

Biber K, Sauter A, Brouwer N, et al. Ischemia-induced neuronal expression of the microglia attracting chemokine secondary lymphoid-tissue chemokine (SLC). Glia 2001 34 121-133. 

Rappert A, Biber K, Nolte C, et al. Secondary lymphoid tissue chemokine (CCL21) activates CXCR3 to trigger a Cl-current and chemotaxis in murine microglia. J Immunol 2002 168 3221-3226. 

With the exception of whole-animal host resistance assays, the actual testing approach can be described as ex vivo-in vitro in that exposure of the immune system to potential immunotoxicants takes place in vivo, with subsequent immunological evaluation taking place in vitro. Although this approach obviates many uncertainties (effect of xenobiotics on primary or secondary lymphoid tissue, potential requirements for metabolism/bio-transformation, etc.), the use of whole animals presents many secondary issues, such... 

In summary, although numerous AhR-dependent changes in the bone marrow and thymus have been found in TCDD-treated mice, it appears that these effects are self-limiting in adult mice, as T and B cell numbers are not reduced in secondary lymphoid tissue except after exposure to high doses of TCDD or in the context of an adaptive immune response. More subtle effects, such as changes in the antigenic specificity of peripheral T and B lymphocyte populations, have not been documented. 

Psychological stress may influence the immune system by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary axis (SAM). The well-described innervation of primary and secondary lymphoid tissues by the autonomic nervous system also has been implicated in stress-related modulation of the immune response. These pathways operate by producing biological mediators that interact with and affect cellular components of the immune system.13... 

Chiba, K. 2005. FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by antagonistic activity at sphingosine 1-phosphate receptors. Pharmacology and Therapeutics, 108 308-319. 

The immune system functions to protect the organism against infection, foreign proteins, and neoplastic cells. It is organized into primary lymphoid tissue such as bone marrow and thymus and secondary lymphoid tissues such as spleen and lymph nodes. The cells of the immune system are leukocytes and a specific type produces immunoglobulins. 

Circulating dendritic cells Langerhans cells Interdigitating dendritic cells Interstitial dendritic cells Blood, lymph Skin, mucous membrane Secondary lymphoid tissue (with T cells), thymus Gastrointestinal tract, heart, liver, lungs, kidney... 

Fig. 7.1 Phases of tissue transplant rejection. The transplanted tissue sheds antigens. These antigens undergo uptake, processing and presentation to the T cells in the secondary lymphoid tissue by APCs, which include macrophages, B cells, Langerhans cells or dendritic cells. This phase results in the production of antibodies and antigen-specific TH and Tc cells. The antibodies and effector cells then migrate to the grafted tissue where TH cells secrete cytokines and which in combination with the antibodies and Tc cells destroy the grafted tissue (see Color Insert)...

Chiba K, Matsuyuki H, Maeda Y, Sugahara K. Role of sphin- 189. gosine 1-phosphate receptor type 1 in lymphocyte egress from secondary lymphoid tissues and thymus. Cell Mol. Immunol. 2006 3 11-19. 

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