Lymph node – an organ for T‐cell activation and pathogen defense

Abstract

The immune system is a multicentered organ that is characterized by intimate interactions between its cellular components to efficiently ward off invading pathogens. A key constituent of this organ system is the distinct migratory activity of its cellular elements. The lymph node represents a pivotal meeting point of immune cells where adaptive immunity is induced and regulated. Additionally, besides barrier tissues, the lymph node is a critical organ where invading pathogens need to be eliminated in order to prevent systemic distribution of virulent microbes. Here, we explain how the lymph node is structurally and functionally organized to fulfill these two critical functions - pathogen defense and orchestration of adaptive immunity. We will discuss spatio-temporal aspects of cellular immune responses focusing on CD8 T cells and review how and where these cells are activated in the context of viral infections, as well as how viral antigen expression kinetics and different antigen presentation pathways are involved. Finally, we will describe how such responses are regulated and 'helped', and discuss how this relates to intranodal positioning and cellular migration of the various cellular components that are involved in these processes.

Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses

“…Our data show that not only T cells migrate to the lymph node in a circadian manner but that also dendritic cells, the major APCs, are present more prominently around night onset, peaking at the same time as lymphocytes. Both cell types need to interact to produce a functional adaptive immune response (Gasteiger et al., 2016). It therefore appears likely that having them present at the same time in the confined environment of the lymph node enhances the likelihood of antigen encounter by the very few specific T cell clones, as opposed to cells entering and exiting at random times.…”

“…After LN entry, lymphocytes interact with dendritic cells in order to scan presented antigen (Gasteiger et al., 2016), and finally emigrate into efferent lymphatic vessels. For this egress, expression of the sphingosine-1-phosphate-receptor 1 (S1P1, encoded by S1pr1 ) on lymphocytes is critical, recognizing the chemoattractant phospholipid sphingosine-1-phosphate (S1P) (Matloubian et al., 2004).…”

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

“…Draining LNs are located near the tumor nodule in many kinds of malignant tumors, and the LN sinus is filled with lymphatic fluid in which a large number of macrophages are found. 1,2 Under normal conditions, LN sinus macrophages capture pathogens, however, they also capture abnormal antigens and debris derived from tumor tissues that flow into the lymphatic fluid in patients with malignant tumors. As such, the LN sinus is proactively associated with the induction of antigen-specific immune responses.…”

High CD169 expression in lymph node macrophages predicts a favorable clinical course in patients with esophageal cancer

“…Subcapsular and medullary sinus macrophages express CD169, which mediates the capture of exosomes and is associated with immune responses to exosome antigens . CD169‐positive LN sinus macrophages (LySMs) are thought to block tumor‐promoting humoral immune responses by capturing tumor‐derived extracellular vesicles .…”