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Immunodynamics

Interactions between pathogens and host immune systems.

Overview

The transmission and evolutionary dynamics of pathogens in populations are fundamentally linked to the cellular and molecular interactions that occur within an infected individual.  These interactions invariably involve the host innate and (in vertebrates) the adaptive immune system. CIDD researchers combine empirical approaches with dynamic modeling and statistical analysis to unravel the complex interactions between pathogens and the host immune system. This research complements CIDD studies of host-parasite co-evolution, interactions between parasites, and system heterogeneities.

Within host dynamics

Infectious organisms must transit multiple tissue types to locate susceptible regions or cells for replication. Simultaneously they must avoid intra- and extra-cellular host defenses. Many pathogens have evolved intricate mechanisms to manipulate host immunity to their advantage. CIDD researchers study the kinetics and patterns of within host pathogen dispersal and host response to link molecular and cellular mechanisms that occur within individuals with transmission and adaptation in populations.

Pathogenesis

Disease can result from infection as a consequence of pathogen virulence factors or the host response to the organism. CIDD researchers integrate experimental systems with statistical methods and network analysis to gain insight into pathological processes and to explore potential intervention strategies.

Cross-species infections

During adaptation to a new host species, a pathogen must locate a permissive cell and circumvent the innate response of the host in order to replicate. The mechanisms by which pathogens gain fitness in a new host –and ultimately in new host populations -are the subject of study by both empirical and computational CIDD researchers.

Polymicrobial infections

The presence of an existing infection can change the within host dynamics, pathogenesis, infectious period, and susceptibility of a host to infection with a second organism. CIDD researchers use in vivo and in vitro study systems and multiple computational approaches to address the increase complexity of polymicrobial infections.

Study systems include

Bordetella in mice, rabbits and guinea pigs (Harvil, Chiaromonte, & Hudson)

Helminths in rabbits (Cattadori)

FIV in cats (Poss & Chiaromonte)

Respiratory Syncytial Virus and Parainfluenza Virus in vitro (Poss, Reluga, Chiaromonte)

 

 

 

 

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Sample papers

Roy, S, J Lavine, F. Chiaromonte,J Terwee, S VandeWoude, O Bjornstad, M Poss. 2009. Multivariate statistical analysis of host immunological response to simultaneous infection with a host adapted and a novel feline lentivirus. Plos One.doi:10.1371/journal.pone.0007359

Long GH, Chan BHK, Allen JE, Read AF, & Graham AL (2008) Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites. BMC Evolutionary Biology 8:128

Gopinathan L, Kirimanjeswara GS, Wolfe DN, Kelly ML & Harvill ET (2007) Different mechanisms of vaccine-induced and infection-induced immunity to Bordetella bronchiseptica. Microbes and Infection 9(4):442-8

Thakar J, Pilione M, Kirimanjeswara G, Harvill ET & Albert R (2007) Modeling systems-level regulation of host immune responses. PLoS Computational Biology 8:e109.


 
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