• Decreased T-cell recognition: DNA viruses (e.g., HSV, CMV, and EBV) can bind to or alter the localization of major histocompatibility complex (MHC) class I proteins, impairing peptide presentation to CD8+ cytotoxic T cells. Although downregulation of MHC class I molecules might cause virus-infected cells to be targets for NK cells, herpesviruses also express MHC class I homologuess that act as decoys that engage inhibitory receptors of NK cells. Herpesviruses can target MHC class II molecules for degradation, impairing antigen presentation to CD4+ helper T cells. Viruses also can infect leukocytes to directly compromise their function (e.g., HIV infects CD4+ T cells, macrophages, and dendritic cells).
Afterbypassinghosttissuebarriers,infectiousmicroorganismsmustalsoevadehostinnateandadaptiveimmunitymechanismstosuccessfullyproliferateandbetransmittedtothenexthost.Strategiesincludethefollowing:
Resistingphagocytosis(e.g.,byproducingacapsule)
Suppressingthehostadaptiveimmuneresponse(e.g.,byinhibitingantigenpresentationanddisruptinginterferonpathways)
In contrast with the vast molecular diversity of microbes, the morphologic patterns of tissue responses to microbes are limited, as are the mechanisms directing these responses. Therefore, many pathogens produce similar reaction patterns, and few features are unique to or pathognomonic for a particular microorganism, adding to the challenge in histopathologic diagnosis.
The interaction between the microbe and the host determines the histologic features of the response to the microbes. There are five major histologic patterns of tissue reaction in infections: suppurative, mononuclear/ granulomatous, cytopathic-cytoproliferative, necrosis, and chronic inflammation/scarring. Suppurative inflammation is discussed in Chapter 3.
Diffuse, predominantly mononuclear, interstitial infiltrates are a common feature of all chronic inflammatory processes, but sometimes they appear acutely in response to viruses, intracellular bacteria, or intracellular parasites. In addition, spirochetes and some helminths also provoke chronic inflammation. Eosinophilia can be prominent with some helminthic infections.
MORPHOLOGYWhichmononuclearcellpredominateswithintheinflammatorylesiondependsonthehostimmuneresponsetotheorganism.Thus,lymphocytespredominateinHBVinfection (Fig.
9.10A ),whereasplasmacellsarecommonintheprimaryandsecondarylesionsofsyphilis(see
Fig.9.10B).The presenceoftheselymphoidcellsreflectscell-mediatedimmuneresponsesagainstthepathogenorpathogen-infectedcells.Granulomatousinflammationisadistinctiveformofmononuclearinflammationusuallyevokedbyinfectiousagentsthatresisteradication,butneverthelessarecapableofstimulatingstrongT-cell–mediatedimmunity(e.g.,M. tuberculosis, Histoplasma capsulatum, schistosomeeggs).Granulomatousinflammation(Chapter3)ischaracterizedbyaccumulationofactivatedmacrophagescalledepithelioidcells,whichmayfusetoformgiantcells.Insomecases,thereisacentralareaofcaseousnecrosis(see
Fig.9.10C
Cytopathic-cytoproliferative reactions usually are produced by viruses. The lesions are characterized by cell necrosis or cellular proliferation, usually with sparse inflammatory cells.