Pierre Youinou

Monoclonal antibody analysis of blood and cornea T lymphocyte subpopulations in herpes simplex keratitis

There is now a great deal of evidence in favor of cell-mediated immunopathogenesis in herpes simplex (HS) keratitis. We used monoclonal antibodies specific for different cell subsets to analyze the blood and cornea-eluded lymphocyte subpopulations in HSV keratitis. There was a significant decrease in the proportion of cells expressing UCHT 1, OKT 4, and MID 4 antigens in the peripheral blood of patients as a whole, as opposed to sex- and age-matched controls. There was a slight decrease in OKT 4 cells in patients with herpetic keratouveitis when compared with patients with herpetic superficial keratitis, and a slight decrease in recurrent herpetic patients. Three corneal buttons showed a marked infiltration by suppressor/cytotoxic T cells, supporting the recent suggestion that lymphocytes might be cytotoxic for keratocytes.

Dissociated impairment of neutrophil functions and recurrent infections

SummaryThis report concerns the study of a 43-year-old woman with a four-year history of recurrent infection caused primarily by staphylococci. The patient was treated with various antibiotic combinations without long-term success. We found phagocytosis, directed migration and the capacity to killStaphylococcus aureus to be impaired; the capacity to adhere to nylon fibre was normal, the non-quantitative NBT reduction test was unaffected and we were unable to detect any humoral abnormality (e. g. in complement or immunoglobulins). The dissociated impairment of neutrophil functions was clearly improved by levamisole.ZusammenfassungWir berichten über eine 43jährige Frau, bei der seit vier Jahren rezidivierende Infektionen, vorwiegend durch Staphylokokken, auftraten. Die Behandlung mit verschiedenen Antibiotikakombinationen blieb ohne anhaltenden Erfolg. Wir stellten eine Störung der Phagozytose und der gerichteten Migration sowie auch eine Beeinträchtigung der Fähigkeit,Staphylococcus aureus abzutöten, fest. Dabei war hingegen die Adhärenz an Nylonfasern normal und der nichtquantitative NBT Reduktionstest unbeeinträchtigt. Im humoralen System konnten wir keine pathologischen Veränderungen feststellen (z. B. Komplement oder Immunglobuline). Die dissoziierte Störung der Neutrophilenfunktion ließ sich durch Levamisol eindeutig bessern.

Perinuclear Factor (Profilaggrin) Autoantibodies

Publisher Summary This chapter provides an overview of methods for detecting antiperinuclear factor (APF) antibodies and characterizes antigenic and biological properties of these antibodies. APF binds to cytoplasmic aggregates encircling the nucleus of buccal epithelial cells and termed “keratohyalin granules,” on the basis of their rough resemblance to the keratohyalin bodies in the stratum granulosum of human epidermis. The chapter states that Epstein-Barr virus infection, APF production by the patients, and perinuclear antigen (PNA) expression by the cell donors, are related by serum APF in over half of the patients with infectious mononucleosis. With the simple indirect immunofluorescence assay, the prevalence of the autoantibody has been evaluated in RA and other connective tissue diseases.

CD5-Expressing B-1 Cells and Infection

The 67 kDa T cell marker CD5 was originally identified on malignant human B cells and subsequently shown to act as a coreceptor on a proportion of normal B lymphocytes in humans and mice. These have been classified into B-2, representing the conventional cells, and B-l, predominating in serous cavities. The latter population comprises B-la, which expresses CD5. The B-lb subpopulations do not express CD5; however, they share all the other attributes of B-1 cells—such as the presence of mRNA for CD5, the expression of the myelomonocytic marker Mac-1, and the reduced density of the high molecular weight isoform of the common leukocyte antigen (Ag) CD45RA. Over the past decade, evidence has been accumulating to suggest that such B-1 lymphocytes are key in the defense from infectious agents. For example, they produce much of the immunoglobulin (Ig), almost all natural antibody (Ab) reactive with lipopolysaccharide, and most of the innate Ab in serum, although constituting only a minor fraction of the B compartment. Furthermore, they contribute significantly to the IgA-producing plasma cells in the lamina propria of the gut.

Heat Shock Protein Autoantibodies

Abstract Heat shock proteins (HSPs) are a wide family of molecular chaperones. The first members of HSPs were observed in cellular stress reactions, especially in thermic changes ascribing their generic names. HSPs can be induced not only following temperature shift but also after other stress pressures such as shear force, cellular injury, and heavy metal intoxication, which all upregulate their expression. In fact, any changes of cellular microenvironment leading to a disturbance of protein integrity will trigger an increased expression of HSPs. Many of them, such as HSP70 and HSP60 subfamilies, are expressed in basal condition as actors of synthesis, protection, and transport of proteins. In all these processes, HSPs will conduct, restore, or maintain the proper folding of proteins to preserve or help to acquire their functions. These purposes make most of them ubiquitously expressed in a similar way to housekeeping proteins. Indeed, knockout animals for HSP60 or GRP75 develop trouble during embryogenesis and are barely viable. Most HSP classifications sort them according to their molecular weights, including subfamilies of HSP90, HSP70, HSP60, HSP40, HSP27, and HSP10. Unfortunately, this classification is not physiologically relevant, especially regarding their implication in autoimmune processes. All HSPs do not derive from the same phylogenic origins. Eukaryotic cells derived from a fusion of eukaryote and mitochondria ancestors. During evolution, both pools of genes mixed with each other to be located either in mitochondria or in the nucleus. Nevertheless, the protein structures of HSPs overall preserve the characteristics of their source. Moreover, HSPs gather proteins from both eukaryotic and bacterial origin, which will later determine their structure and their potential immunogenicity. This feature enlightens the capacity of many HSPs to stimulate pathogen recognition receptors (PRR), which are key elements of innate immunity to detect pathogens during infection.