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Category: Viruses and Viral Pathogenesis
Innate Immune Responses in HIV Infection, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815653/9781555813932_Chap09-1.gif /docserver/preview/fulltext/10.1128/9781555815653/9781555813932_Chap09-2.gifAbstract:
The role of various innate immune cells and soluble factors in HIV infection is covered in this chapter. The innate immune system recognizes incoming pathogens through pattern recognition receptors (PRRs). Among these are Toll-like receptors (TLRs), nucleotidebinding oligomerization domain (NOD)-like receptors (NLRs), and RIG-1-like receptors (RLRs). C-type lectin-like receptors (CLRs) also interact with carbohydrate containing organisms. Dendritic cells (DCs) DCs in the blood are the myeloid dendritic cells (MDCs) and plasmacytoid dendritic cells (PDCs). The majority of DCs are MDCs. PDCs represent <1% of the blood DCs. HIV infects DCs and usually shows low-level virus replication. MDCs are more susceptible than PDCs to virus infection and replication. The DCs can pass infectious virus to CD4+ cells. Natural killer (NK) cells function through the interaction of cell surface inhibitory or activating molecules. They respond against virus-infected cells having decreased MHC class I expression. γ δ T cells differ from the conventional α β T cells in that their T-cell receptor is encoded by different gene segments. These cells, which can be infected by HIV, are present in several body tissues, but particularly in mucosae. Like NK and NK-T cells, γ δ T cells have effector functions, including cytotoxic activity and cytokine production. Innate immunity plays a role in controlling HIV infection in the central nervous system. HIV has many interactions with the innate immune system and affects immune cell number and function as well as the production of innate cytokines and soluble components.
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Interaction of the innate and adaptive immune systems. Following acute infection by a microorganism, the components of the innate immune system respond rapidly, releasing cytokines that induce fever and initiating antimicrobial activity by innate immune cells (e.g., neutrophils and natural killer cells). The cytokines and the antimicrobial activity also elicit the subsequent responses of T and B cells of the adaptive immune system. Thus, a close interaction between the innate and adaptive immune systems exists, and the early activity of innate immune cells can have influence on both innate and adaptive immune responses. Adapted from reference 2528 with permission from Elsevier.
Dendritic cells, uninfected and infected with HIV-1. (A) Purified dendritic cells were obtained from PBMC cultured for 6 days in GM-CSF and TNF-α. Magnification, x9,000. (B) CD4+ cord blood cells were cultured with GM-CSF, TNF-α, and stem cell factor. After 7 days, the derived cells were infected with HIV-1BAL, washed, and cultured for a further 8 days. A mature dendritic cell with a very indented nucleus and HIV on the surface (arrowhead) is shown. Magnification, x4,500. (C) Further magnification of the dendritic cell in panel B, showing HIV-1BAL particles on the cell surface. Magnification, x60,000. All panels provided by S. Knight and R. English.
T-lymphocyte surface markers and their corresponding ligands on the antigen-presenting cell. Cell-to-cell contact between a CD8+ (MHC class I-restricted) or a CD4+(MHC class II-restricted) T lymphocyte and an APC involves the binding of several surface molecules with their specific ligands on the APC surface. Figure provided by S. Stranford.
Morphology of PDCs and MDCs. By electron microscopy (a), PDCs appear as lymphoblasts with a medium to large diameter; a lightly eccentric, indented, round or oval nucleus; lightly stained perinuclear areas; and well developed rough endoplasmic reticulum. By scanning electron microscopy, resting PDCs have a spherical shape (b), whereas CD40L-activated PDCs have a dendritic cell-like morphology (c). Original magnifications, ×7,000 (a) and ×3,000 (b, c). By Giemsa staining, the PDC have a plasmacytoid morphology (d). The CD11c+ blood MDCs display dendrites by Giemsa staining (e) and electron microscopy (f). Reproduced from references 1642 and 4133 with permission.
Relationship of plasmacytoid dendritic cell (PDC) number to clinical state. Each circle represents a value for a different study subject. Horizontal bars indicate the median. The number of blood PDCs is increased in long-term survivors (LTS) (P< 0.05 for all group comparisons versus LTS) and decreased in AIDS patients (P< 0.01 for all group comparisons versus AIDS). Most of the progressors had received antiretroviral therapy for several months; no substantial difference in PDC number was observed between these subjects and those who were untreated. Reprinted from reference 4215 with permission.
Regulation of NK cell activation and function during viral infections. Soon after many acute viral infections, IFN-α/β is induced by infected cells to activate NK cell-mediated cytotoxicity and blastogenesis (open arrows pointing to the right in the top pathway). Some, but not all, viral infections also spontaneously elicit detectable IL-12 production (broken arrows pointing to the right in the bottom pathway). If IL-12 is present, NK cell production of IFN-γ is induced. The IFN-γ response has been conclusively shown to contribute to antiviral defense primarily by activating cell-mediated immune responses. IFN-a/ p acts to block or inhibit IL-12 expression and can cause a lack of detectable IL-12 during certain viral infections. This process, by reducing IFN-γ, could affect the extent of cell-mediated response induced by IFN-γ. Once T-cell responses are activated, they can then act to turn off the NK cell response. Reprinted from reference 374 with permission.
Gene arrangement at the TCR-γ and TCR-δ loci of γδ T cells. Approximate location of V, (D), J, and C segments are illustrated. Pseudo-genes are indicated by empty boxes. Adapted from the International Immunogenetics Information System (http://imgt.cines.fr). Provided by D. Pauza.
Functional network of innate immunity elements in the brain. Reprinted from reference 4229 with permission from Elsevier. MNGC, multinucleated giant cells.
Components of the innate and adaptive immune systems
Comparison of immune systems a
Pattern recognition receptors a
Distribution of dendritic cells a
Comparison of blood dendritic cells a
Characteristics of dendritic cells a
Characteristics of plasmacytoid dendritic cells a
Roles of type 1 interferons
Effect of HIV infection on dendritic cells a
Natural killer (NK) cell receptors and their ligands a
NK cell function a
Effects of HIV on NK cell function
Official and alternative nomenclatures for common TCR-γ and TCR-δ genes of γδ T cells
Potential role of complement in HIV infection
Features of innate immunity in the central nervous system
Potential role of complement in HIV neuropathogenesis
Interactions of HIV with the innate immune system