Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

The dengue virus circulates as four distinct serotypes, where a single serotype infection is typically asymptomatic and leads to acquired immunity against that serotype. However, the developed immunity to one serotype is thought to underlie the severe manifestation of the disease observed in subsequent infections from a different serotype. We developed a stochastic model of the adaptive immune response to dengue infections. We first delineated the mechanisms initiating and sustaining adaptive immune responses during primary infections. We then contrasted these immune responses during secondary infections of either a homotypic or heterotypic serotype to understand the role of pre-existing and reactivated immune pathways on disease severity. Comparison of non-symptomatic and severe cases from heterotypic infections demonstrated that overproduction of specific antibodies during primary infection induces an enhanced population of cross-reactive antibodies during secondary infection, ultimately leading to severe disease manifestations. In addition, the level of disease severity was found to correlate with immune response kinetics, which was dependent on beginning lymphocyte levels. Our results detail the contribution of specific lymphocytes and antibodies to immunity and memory recall that lead to either protective or pathological outcomes, allowing for the understanding and determination of mechanisms of protective immunity.

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Differential Expression of Immunogenic Proteins on VirulentMycobacterium tuberculosisClinical Isolates

BioMed Research International ◽

10.1155/2014/741309 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

Pablo Schierloh ◽

Laura Klepp ◽

Camila Vazquez ◽

Roxana Valeria Rocha ◽

Federico Carlos Blanco ◽

...

Keyword(s):

Immune Response ◽

Latin American ◽

Adaptive Immune Response ◽

Cross Reactivity ◽

Igg Antibodies ◽

Humoral Immune ◽

Adaptive Immune ◽

Humoral Immune Responses ◽

Resistant Tuberculosis ◽

Immunogenic Proteins

Molecular epidemiology has revealed thatMycobacterium tuberculosis(Mtb), formerly regarded as highly conserved species, displays a considerable degree of genetic variability that can influence the outcome of the disease as well as the innate and adaptive immune response. Recent studies have demonstrated thatMtbfamilies found worldwide today differ in pathology, transmissibility, virulence, and development of immune response. By proteomic approaches seven proteins that were differentially expressed between a local clinical isolate from Latin-American-Mediterranean (LAM) and from Haarlem (H) lineages were identified. In order to analyze the immunogenic ability, recombinant Rv2241, Rv0009, Rv0407, and Rv2624c proteins were produced for testing specific antibody responses. We found that these proteins induced humoral immune responses in patients with drug-sensitive and drug-resistant tuberculosis with substantial cross-reactivity among the four proteins. Moreover, such reactivity was also correlated with anti-Mtb-cell surface IgM, but not with anti-ManLAM, anti-PPD, or anti-Mtb-surface IgG antibodies. Therefore, the present results describe newMtbantigens with potential application as biomarkers of TB.

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