A rapid blood test to monitor immunity shift during pregnancy and potential application for animal health management.

The immune health of a farm animal can have significant impact on its overall health, welfare and productivity. One of the most vulnerable physiological states for both humans and animals is pregnancy. Many systemic changes correlate with the gravid state, including shifts in the immune system that may impact the ability to respond optimally to pathogen challenge. Because of this, it would be beneficial to be able to monitor the immune health of the pregnant animals closely. Recently, we developed a new nanoparticle-enabled rapid blood test that can detect ongoing immune responses from both laboratory and farm animals. Here, we report that this novel test reveals highly repeatable and acute changes associated with pregnancy and peri-parturition period in laboratory mice and in cattle. We hypothesize that the test score change reflects changes in the immune status of the gravid females related to the humoral immune response. The test is easy to conduct, of low cost, with results obtained in less than 20 min. This rapid test could be potentially used as an onsite test in local farms and small clinics for animal health management.

A Single-Step Gold Nanoparticle-Blood Serum Interaction Assay Reveals Humoral Immunity Development and Immune Status of Animals from Neonates to Adults.

A well-developed, functional immune system is paramount to combat harmful attacks from pathogenic organisms and prevent infectious diseases. Newborn animals and humans have only limited immunity upon birth, but their immune functions are expected to develop within weeks to months and eventually to reach a maturity that will provide full protection. Despite the importance of immune activity in animal and human health management, there is no convenient test available that allows for rapid assessment of the state of immune function in nonlaboratory settings. Here we report an extremely simple and rapid blood test that may be used in point-of-care clinics or field settings to evaluate the humoral immune status of animals. The test detects a cooperative interaction between a gold nanoparticle and arguably the three most important proteins involved in the immune system: immunoglobulin M (IgM), immunoglobulin G (IgG), and at least one complement protein, C3, in the blood serum. Such interactions cause the gold nanoparticles to form clusters and aggregates. The average particle size of the gold nanoparticle-serum mixture, measured by dynamic light scattering, corresponds positively to the immune status and activity of the subject. Our study demonstrates that the test may be used not only for monitoring the immune function development from neonates to adults, but also for detecting active immune responses during infection. Although data reported here are largely based on murine and bovine models, it is likely that this test will be applicable to humans as well.

A Rapid Blood Test To Determine the Active Status and Duration of Acute Viral Infection.

The ability to rapidly detect and diagnose acute viral infections is crucial for infectious disease control and management. Serology testing for the presence of virus-elicited antibodies in blood is one of the methods used commonly for clinical diagnosis of viral infections. However, standard serology-based tests have a significant limitation: they cannot easily distinguish active from past, historical infections. As a result, it is difficult to determine whether a patient is currently infected with a virus or not, and on an optimal course of action, based off of positive serology testing responses. Here, we report a nanoparticle-enabled blood test that can help overcome this major challenge. The new test is based on the analysis of virus-elicited immunoglobulin G (IgG) antibody present in the protein corona of a gold nanoparticle surface upon mixing the gold nanoparticles with blood sera. Studies conducted on mouse models of influenza A virus infection show that the test gives positive responses only in the presence of a recent acute viral infection, approximately between day 14 and day 21 following the infection, and becomes negative thereafter. When used together with the traditional serology testing, the nanoparticle test can determine clearly whether a positive serology response is due to a recent or historical viral infection. This new blood test can provide critical clinical information needed to optimize further treatment and/or to determine if further quarantining should be continued.

Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC.

We examine here the in vitro requirements to activate immunocompetent T cells, present among thymocytes, to give rise to CTL, CD4+ T cells producing IL-2 and CD8+ T cells producing IFN-gamma. These thymocytes are naive in not having received antigen-dependent signals characteristic of the periphery. Their activation, upon stimulation with allogeneic spleen cells depleted of T cells, referred to here as allogeneic antigen-presenting cells (APCs), to produce allo-MHC-specific effector T cells, requires activated (radiation resistant) CD4+ T cells, syngeneic with the responding thymocytes. We refer here to these T cells as 'help'. Furthermore, optimal T cell activation requires an Ig+ B220+ cell in the allogeneic APC population, most probably a B cell. The allogeneic APCs cannot be replaced by conventional bone marrow (BM)-derived dendritic cells (DCs) activated by CD40 ligation or exposure to LPS. The requirements for both help and allogeneic B cells in the activation of thymocytes contrast with the requirements to generate substantial responses from splenic T cell populations. Activated, BM-derived DCs stimulate substantial splenic responses without help. These different requirements for activation could reflect the fact that thymocytes have not received an exit-thymus signal and/or that splenic T cells are heterogeneous, containing naive, memory and partially-activated T cells.