1953: Abilene Christian College Bible Lectures - Full Text

Delivered in the Auditorium of Abilene Christian College, February, 1953 ABILENE, TEXAS PRICE: $3.00 firm foundation publishing house Box 77 Austin 01, Texa

Modeling lymphocyte homing and encounters in lymph nodes

International audienceBackgroundThe efficiency of lymph nodes depends on tissue structure and organization, which allow the coordination of lymphocyte traffic. Despite their essential role, our understanding of lymph node specific mechanisms is still incomplete and currently a topic of intense research.ResultsIn this paper, we present a hybrid discrete/continuous model of the lymph node, accounting for differences in cell velocity and chemotactic response, influenced by the spatial compartmentalization of the lymph node and the regulation of cells migration, encounter, and antigen presentation during the inflammation process.ConclusionOur model reproduces the correct timing of an immune response, including the observed time delay between duplication of T helper cells and duplication of B cells in response to antigen exposure. Furthermore, we investigate the consequences of the absence of dendritic cells at different times during infection, and the dependence of system dynamics on the regulation of lymphocyte exit from lymph nodes. In both cases, the model predicts the emergence of an impaired immune response, i.e., the response is significantly reduced in magnitude. Dendritic cell removal is also shown to delay the response time with respect to normal conditions

Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse

International audienceMemory CD8(+) T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m). Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+) T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs) fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m) as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+) T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+) T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+) T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+) T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells

Splenic clearance of heated red blood cells: Congestion, sequestration, erythrophagocytosis and erythropoiesis and the role of the splenic lobule

The mechanism by which the spleen clears damaged red blood cells (RBC) from the blood is based on the unique open circulation of the spleen which allows blood to leave the confines of the closed vascular system and enter the filtration beds, or pulp cords. Damaged RBC are sequestered in these specialized vascular beds and then destroyed by resident macrophages. Neither the open circulation nor the clearance process are well understood. The aim of this thesis was to provide fundamental information on the structure and function of the spleen and its behavior during the clearance process. Heated RBC (HRBC) were used as a simplified model of damaged RBC. This model avoided complicating factors such as anemia, infection and chronicity and so could be used to identify those aspects of clearance that are specific responses to damaged RBC. A single bolus of isologous donor HRBC was injected into a series of mice and the onset, progression and resolution of a discrete episode of HRBC destruction in the spleen was studied by transmission electron microscopy, light microscopy and tissue culture. Within minutes of injection, vascular changes including hyperemia and changes in interendothelial slit patency congested the filtration beds, creating a low shear environment in which large numbers of RBC came in direct contact with macrophages and reticular cells. While RBC were temporarily trapped in congested filtration beds, HRBC adhered to reticular cells and thus became sequestered there. Macrophages culled most HRBC within two hours with the assistance of reticular cells and barrier cells. HRBC clearance stimulated splenic erythropoiesis and monocytopoiesis. Erythropoiesis occurred in the absence of anemia and elevated serum erythropoietin and was ultimately ineffective. The splenic lobule was central to the clearance process and its anatomy was explored in detail. The vascular, cellular and proliferative responses to damaged RBC were strikingly similar to those of inflammation and tissue repair. We hypothesize that clearance is a modified form of inflammation and show how inflammatory processes are modified by the complex anatomy of the splenic lobule to remove damaged cells from the blood, thereby sparing the circulation from harmful effects of intravascular inflammation