Chapter 10 : Adaptive Immune Responses to Infection and Opportunities for Vaccine Development ()

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Genera belonging to the family , and , include human pathogens. The diseases they cause are referred to as rickettsioses in this chapter. They share three critical factors with implications in pathogenesis and immunity: (i) they are transmitted by arthropod vectors; (ii) they are obligate intracellular bacteria that inhabit the cell cytoplasm; and (iii) the predominant target is the endothelium. The only exception is , the agent of rickettsial-pox, which predominantly infects monocytes and macrophages. The chapter emphasizes on some findings and suggests a framework for a modern conceptualization of the field of rickettsiology at the interface with immunology. The development of the adaptive immune response is conditioned by the innate immune mechanisms activated during early events of the infection. The study of the endothelium in the context of true endothelium-target infections offers new opportunities to explore the role of the endothelium in orchestrating or modifying immune responses. The study of the response to two of the most successful human vaccines in history, the yellow fever vaccine and the smallpox vaccine, is likely to yield relevant paradigms that we could use as guideposts in rickettsiology. Development of a modern vaccine against or should aim at mimicking a physiological immune response in the sense that all branches of adaptive immunity should be stimulated. This implies the identification of a combination of antigens that together can stimulate protective responses mediated by CD8 T cells, CD4 T cells, and B cells (antibodies).

Citation: Valbuena G. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 304-329. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch10
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Image of FIGURE 1

Immunohistochemical detection of (original magnification, ×400). The red precipitate, a product of the alkaline phosphatase tag on the secondary antibody, marks the predominant location of rickettsiae in the capillaries of lung alveolar walls as well as larger vessels. The hematoxylin contrast allows the visualization of abundant macrophages in the alveolar spaces and infiltrating interstitial mononuclear leukocytes. doi:10.1128/9781555817336.ch10.f1

Citation: Valbuena G. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 304-329. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch10
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Image of FIGURE 2

Immunohistochemical detection of in the testis of a mouse infected with a sublethal inoculum (original magnification, ×400). The red precipitate, a product of the alkaline phosphatase tag on the secondary antibody, reveals the endothelial location of rickettsiae in a vein. doi:10.1128/9781555817336.ch10.f2

Citation: Valbuena G. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 304-329. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch10
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Image of FIGURE 3

Immunohistochemical detection of and CD8 T cells in the lung of a mouse infected with a sublethal inoculum (original magnification, ×400). The red precipitate, a product of the alkaline phosphatase tag on the secondary antibody, shows the rickettsiae in a capillary of an alveolar wall infiltrated by mononuclear leukocytes. The brown precipitate, a product of the horseradish peroxidase tag on a different secondary antibody, marks the location of CD8 T cells. doi:10.1128/9781555817336.ch10.f3

Citation: Valbuena G. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 304-329. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch10
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Image of FIGURE 4

Immunohistochemical detection of and the chemokine CXCL9 in the liver of a mouse infected with a sublethal inoculum 5 days earlier (original magnification, ×400). The red precipitate, a product of the alkaline phosphatase tag on the secondary antibody, shows the rickettsiae in focal areas infiltrated by mononuclear leukocytes. The brown precipitate, a product of the horseradish peroxidase tag on a different secondary antibody, marks the location of the chemokine (CXCL9); it outlines the sinusoidal endothelium. doi:10.1128/9781555817336.ch10.f4

Citation: Valbuena G. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 304-329. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch10
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Image of FIGURE 5

Immunohistochemical detection of CD8 T cells in the brain of a child who died of Rocky Mountain spotted fever (original magnification, ×400). The brown precipitate, a product of the horseradish peroxidase tag on the secondary antibody, marks the location of CD8 T cells around two small vessels. doi:10.1128/9781555817336.ch10.f5

Citation: Valbuena G. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 304-329. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch10
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Image of FIGURE 6

Immunohistochemical detection of VCAM-1 in the brain of a mouse infected with a lethal inoculum of (original magnification, ×400). The brown precipitate, a product of the horseradish peroxidase tag on the secondary antibody, marks the endothelial location of the adhesion molecule VCAM-1. doi:10.1128/9781555817336.ch10.f6

Citation: Valbuena G. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 304-329. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch10
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