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Chapter 11 : Adaptive Immune Responses to Infection and Opportunities for Vaccine Development ()

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Abstract:

The critical interface between the host immune system and the pathogen in large part determines the outcome of an infection. In this chapter, the author presents a discussion on immunity to enable the readers understand how a pathogen is able to establish infection and how the immune system is able to control or clear infection. The adaptive immune response is of particular interest because under the appropriate conditions it can lead to long-lasting, pathogen-specific immunity, which is the basis for vaccine development. One of the challenges when considering , , , and is the extent and variety of ways in which many of these organisms modulate the host immune response. and modulate the host immune response, though in a somewhat different fashion. Importantly, most animals that survive acute disease are able to control but not clear the infection. In a study conducted, both immunized and infected animals had comparable antibody repertoires to major surface protein 2 (MSP2) in terms of breadth of response and titer. Among the immunized animals, there was no association between either breadth or magnitude of the anti-MSP2 response and either complete protection from infection or control of bacteremia. Together, these data argue that protection afforded with the outer membrane vaccine is due to immune responses directed at outer membrane proteins (OMPs) other than the immunodominant and antigenically variable MSP2. Virulence factors are targets for some of the most effective vaccines currently in use.

Citation: Noh S, Brown W. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 330-365. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch11

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Bacterial Proteins
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Immune Systems
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Major Histocompatibility Complex
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Infection and Immunity
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FIGURE 1

Surface complex immunization recapitulates the protection induced by whole outer membrane immunization. (A) Protection against high-level bacteremia. (B) Protection against severe anemia. (Reprinted from with permission.) doi:10.1128/9781555817336.ch11.f1

Citation: Noh S, Brown W. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 330-365. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch11
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Image of FIGURE 2
FIGURE 2

OMPs separated by two-dimensional electrophoresis. One gel (B) was stained with SYPRO Ruby for total protein detection, while proteins from the other gel (A) were transferred to a nitrocellulose membrane for immunoblotting with serum (IgG2) from immunized animals. (A) A representative immunoblot from one of three animals tested. To identify spots of interest for mass spectroscopy, images from the SYPRO Ruby-stained gel and immunoblot were overlaid. Block a represents proteins identified as MSP2. Spots 60 and 61 represent MSP3, and spot 17 represents MSP5. Spots 12 and 70 were not immunoreactive but were used as two of several reference spots to determine reproducibility of outer membrane-separated two-dimensional gels. Spots 6, 63, and 17 were used to align two-dimensional immunoblots. (Reprinted from ) doi:10.1128/9781555817336.ch11.f2

Citation: Noh S, Brown W. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 330-365. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch11
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Image of FIGURE 3
FIGURE 3

IVTT is a high-throughput method that allows rapid expression and identification of T-lymphocyte antigens for any pathogen for which the genome sequence is available. (A) Candidate antigens identified from the genome were expressed from transcriptionally active PCR products, which included C-terminal FLAG and N-terminal six-His tags, using an -based IVTT system. Purification of the target antigen was accomplished using antibodies to six-His and FLAG epitope tags and protein G bead-affinity purification. (B) Purified IVTT-expressed, bead-bound antigens were processed and presented by APCs to T lymphocytes from immunized animals and evaluated for immunogenicity in proliferation assays. doi:10.1128/9781555817336.ch11.f3

Citation: Noh S, Brown W. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 330-365. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch11
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Image of FIGURE 4
FIGURE 4

The physical association between a T-cell epitope (∆) and B-cell epitope (⬢) can enhance the antibody response to the B-cell epitope. Upon exposure to the conjugated antigens, dendritic cells take up, process, and present the T-cell epitope on MHC class II molecules. Helper CD4 T cells that recognize and bind the peptide become primed by the APC. Concurrently, B cells bind the B-cell epitope, internalize the entire construct, and process the antigen via the MHC class II pathway. The T-cell epitope is then displayed in the context of MHC class II molecules on the surface of the B cell. The previously primed T cell can recognize and bind this antigen and thus provide help to the B cell, resulting in B-cell activation, isotype switching, and production of high-affinity antibodies targeting the B-cell epitope. doi:10.1128/9781555817336.ch11.f4

Citation: Noh S, Brown W. 2012. Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (), p 330-365. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch11
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