Virulence factors and pathogenesis of other Bacillus species
The state of knowledge on virulence factors of Bacillus species other than B. anthracis is less advanced owing to the relatively spasmodic association between these species and infections and to the absence of adequate models for analyzing the candidate factors and determining their actions in the laboratory. Bacillus species characteristically produce a host of enzymes and other extracellular metabolites. Among those of B. cereus, four groups of what are broadly described as toxins have been...
Further reading Fbx
Berczi I, Baragar FD, Chalmers IM, Keystone EC, Nagy E and Warrington RJ 1993 Hormones in self tolerance and autoimmunity a role in pathogenesis of rheumatoid arthritis Autoimmunity 16 45-56. Cornacchia E, Golbus J, Maybaum J, Strahler J, Hanash S and Richardson B 1988 Hydralazine and procaina- mide inhibit T cell DNA methylation and induce auto-reactivity. Journal of Immunology 140 2197-2200. Hala K, Malin G, Dietrich H et al 1996 Analysis of the initiation period of spontaneous autoimmune...
Effect of iron deficiency on susceptibility to infection
Decreases in response to infection have been demonstrated in iron-deficient humans and animal models. The first study of the effects of iron deficiency on susceptibility to infection in infants was conducted in the late 1920s by Mackay, who recommended the use of iron fortified cow's milk. Iron fortification resulted in increased hemoglobin concentration and a 50 reduction in respiratory and gastrointestinal infections. In the multitude of studies conducted over the past 70 years, children with...
Hypergammaglobulinemia
Philip R Greipp, Divisions of Hematology and Hematopathology, Mayo Clinic, Rochester, Minnesota, USA Hypergammaglobulinemia results from an overproduction of immunoglobulin by plasma cells, most commonly including an increase in plasma cells in the bone marrow. The plasma cell increase and the associated increase in immunoglobulin may be polyclonal or monoclonal. In polyclonal hypergammaglobulinemia, nonneoplastic plasma cells increase in number in response to an antigenic stimulus such as...
Functional consequences of IgG glycosylation
The oligosaccharides of the Fc do not appear to be involved in binding of antigen, protein A, or recognition by rheumatoid factor. This has been shown by several authors who have compared aglycosyl IgG produced by culturing cells in the presence of tunicamycin, with native IgG. Proteolytic susceptibility and those interactions between IgG and Clq or cellular-bound receptors are, however, critically affected by Fc oligosaccharides. For example, binding to monocyte and macrophage Fc receptors,...
Conclusions Pip
Human histocompatibility class I molecules consist of a MHC-encoded heavy chain and an invariant 32m. In the HLA gene complex, there are 17-20 class I heavy chain genes including various pseudogenes and gene fragments. Only six genes HLA-A, -B, -C, -E, -F and -G are known to encode 3,m-associated molecules. HLA-A, -B and -C molecules are present on virtually all nucleated cells. HLA-F. and -F transcripts have been detected on almost all cell lines and tissues examined. In contrast, HLA-G...
Approaches to immunotherapy with LAK or ANK cells
Adoptive transfers of LAK cells and IL-2 to tumor-bearing animals were effective in inducing the regression of established lung, liver and subcutaneous metastases of immunogenic and nonimmuno-genic sarcomas or adenocarcinomas. To achieve therapeutic effects with LAK cells plus IL-2, it was necessary to administer sufficient numbers of LAK cells and high enough concentrations of IL-2 and to reduce tumor burden by previous surgery or by-including chemotherapy. Therapy with LAK cells of IL-2...
B cell epitopes
B cell epitopes interact directly with mlgs on the surfaces of B cells and no processing of the antigen is required for these interactions. As a result, B cell receptors can bind antigens in their native conformations. This is why antibodies raised against native proteins often recognize 'discontinuous epitopes', antigenic determinants composed of amino acids that are far apart in primary sequences but are in close proximity in the folded structures. By the same token, antibodies raised against...
Fascioliasis
Karen S Ovington, Division of Biochemistry and Microbiology, Faculty of Science, Australian National University, Canberra, Australia Fascioliasis is a geographically widespread parasitic disease which is of economic importance because it lowers the productivity of livestock. Recently the disease has also been shown to be prevalent and clinically significant in humans in Latin America. The flat, leaf-shaped worms which cause this disease are digenean trematodes of the genera Fasciola or...
Uses of antisera
A final word about the use of antisera. They are used in medicine both for diagnostic purposes and for patient treatment, and in the laboratory they are used as analytical and preparatory tools. Thus the injection of antisera against toxins such as diphtheria and tetanus, against the venoms of snakes, and against rabies still remains a mainstay of treatment. Equally, the use of specific antiserum allows for the detection and quantitation of minute quantities of telltale antigens such as...
Further reading Fsw
Anderson MT, Tjioe IM, Lorincz MC et al 1996 Simultaneous FACS analysis of two distinct transcriptional elements within a single cell using engineered green fluorescent proteins. Proceedings of the National Academy of Sciences of the USA 93 8508-8511. Hayakawa K and Hardy RR 1988 Normal, autoimmune, and malignant CD5 B cells the Ly-1 B lineage Annual Review of Immunology 6 197-218. Herzenberg I.A and Stall AiVl 1989 Conventional and Ly-l B-cell lineages in normal and mu transgenic micc. Cold...
Factors influencing reactions to drugs
Clearly the structures, metabolism and chemical properties of specific drugs and their metabolites have important influences on human immune responses and the expression of clinical allergic reactions. The dose, route, duration and frequency of therapy also can influence the expression of allergic reactions to drugs. In addition, active disease processes, such as infections, and a variety of individual patient factors influence responses. The presentation of drug antigens during an infection...
Application and interpretation of the assay
The CF test is often used for the screening of antibodies against a variety of possible pathogenic microbes especially viruses for this a pool of 1520 different antigens can be used. Most antigens are commercially available and reasonably priced. Relatively crude antigens infected cell lysates are mostly sufficient for the test. Test sera need to be screened in at least two dilutions because in high titer sera an excess of antibody may fail to generate complement-activating immune complexes the...
Bare lymphocyte syndrome type III
Patients with BLS type III display no cell surface class II antigens as well as little or no class I proteins. The phenotype of these patients is most variable and many of these patients are classified as BLS type II due to their residual class I antigen expression. The immunodeficiency of these individuals mirrors that of BLS type II patients including susceptibility to chronic infections and early death without intervention. Peripheral blood levels of CD4 T cells are low and antibody...
Chromosomal translocations in hematological malignancies
In several neoplastic entities, the development of a malignant phenotype has been intimately related to the gain of abnormal chromosomal patterns. Chronic myelogenous leukemia is the first disease in which an association with a consistent chromosomal abnormality chromosome Philadelphia was established. This results from a reciprocal translocation involving chromosomes 9 and 22. Subsequently, this translocation was also shown to occur in acute lymphoblastic leukemia ALL and acute myelogenous...
Examples of determinant spreading
Determinant spreading during the course of experimental autoimmune encephalomyelitis The term, determinant spreading, was first applied by Lehmann and colleagues to the phenomenon observed in experimental autoimmune encephalomyelitis EAE , a model of human multiple sclerosis MS . EAE is an inflammatory demyelinating disease of the central nervous system mediated by CD4 T cells specific for myelin autoantigens. liAF can be induced in susceptible mouse strains by immunization with myelin basic...
Fibroblasts
Ifor R Williams, Department of Dermatology, Harvard Medical School, Massachusetts, USA Fibroblasts are cells of mesodermal origin present in all forms of connective tissue. They are the least specialized of the connective tissue cell types. The primary role of fibroblasts is the production of proteins and polysaccharides that are secreted into the extracellular space of connective tissues to form the extracellular matrix. Appropriate combinations of these fibroblast-derived synthetic products...
Fungi Immunity To
Thomas S Harrison and Stuart M Levitz, The Evans Memorial Department of Clinical Research and the Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA The fungi are nonmotile eukaryotes that possess a cell wall and reproduce by means of spores. Over 100 000 species of fungi have been described, but only 100-200 regularly cause disease in humans. Most fungi are saprophytes rather than obligate parasites, human infection being an incidental event in the life...
J Kyq
Figure 1 Serum protein electrophoresis. On the left is a normal pattern. Note the gamma globulin band is wide and the densito-metric tracing is broad-based. On the right is a monoclonal gammopathy pattern. The gamma region contains a narrow band and the densitometric tracing shows a tall narrow spike' cause of the IgE increase is not known. Hyper-IgD syndrome has also been described. These patients may present with constitutional symptoms including fever and headaches, and they may have...
Biological properties
Endotoxins represent the pyrogens fever-inducing agents of gram-negative bacteria, pyrogenicity being probably the first activity of endotoxin recognized. Endotoxins are endowed with a large spectrum of biological activities that may be demonstrated in vivo and in vitro. Of these, pyrogenicity, leukopenia and leukocytosis, induction of the local, generalized Schwartzman phenomenon, and lethal shock arc-examples of classical endotoxic activities. A summary of the more important biological...
Nonspecific immunity
A number of nonspecific host factors form an important first line of defense against fungal invasion. These include the mechanical barrier provided by the skin and mucous membranes, competition for nutrients from the normal indigenous bacterial flora, and the mucociliary clearance system of the respiratory tract. The importance of these factors is illustrated by the association of disseminated candidiasis with the disruption of mechanical barriers by burns, surgical wounds or intravenous...
Further reading Cmi
Behr T, Fischer W, Peter-Katalinic J and Egge H 1992 The structure of lipoteichoic acid, improved preparation, chemical and mass spectrometric studies. European Journal of Biochemistry 207 1063-1075. Gronberg G, Nilsson U, Bock K and Magnusson G 1994 Nuclear magnetic resonance and conformational investigations of the pentasaccharide of the Forssman antigen and overlapping di-, tri-, and tetra-saccharide sequences. Carbohydrate Research 257 35-54. Hakomori SI 1984 Tumor-associated carbohydrate...
Immunodeficiency Secondary
A David B Webster, Department of Clinical Immunology, Royal Free Hospital School of Medicine, University of London, London, UK Copyright 1998 Elsevier Ltd. All Rights Reserved. Although the term 'secondary' is unsatisfactory and in the future is likely to be replaced by a more descriptive classification, secondary immunodeficiency is used to describe most of the immunodeficiency disorders that are not due to inherited single gene defects of lymphocyte function, with the important exception of...
Nonspecific mechanisms
Active nonspecific immunopotentiation Immunomodulators of biological origin A summary of the different categories of substances that have been used is shown in Table 2. This represents a small sample of a vast array, with an attempt made to select the more promising. In general terms, these agents have been used both as adjuvants in vaccination procedures and as immunotherapeutic tools for neoplasms and to a lesser extent infectious disease. Little is known about the specific mechanism s by...
CD28 Structure and expression
CD28 was first detected and characterized with a monoclonal antibody mAb 9.3 made by Paul Martin and John Hansen at the Fred Hutchinson Cancer Research Center in 1981. Studies with this mAb showed that CD28 is a differentiation antigen expressed on thymocytes and most mature T cells, including all CD4 T cells and CD 8 T cells with cytolytic activity. A subpopulation of CD8 T cells with suppressor activity are CD28 negative. The CD28 molecule was shown to be a homodimeric glycoprotein composed...
Cadherins
Cadherins have been implicated in Ca2 -dependent homotypic aggregation of nonlymphoid cells and play an important structural role in cell-cell junctions. Although there are several different cadherins, to date only E-cadherin has been implicated in regulating immunological function. Intraepithelial lymphocytes express the aK 37-integrin, which binds to E-cadherin expressed on epithelial cells. This adhesive interaction has been proposed to play a role in retaining Ep7-expressing T cells at...
Pcna
Proliferating cell nuclear antigen PCNA , also named cyclin, is a protein of 29 kDa that is primarily present in dividing cells. It has been identified as an auxiliary protein of DNA polymerase 8, a particle involved in DNA replication. Several nuclear enzymes serve as antigen for autoantibodies. Topoisomerase I is the most important of these. It is an enzyme of 100 kDa which is involved in the relaxation of supercoiled DNA, by nicking and releasing one strand of the DNA duplex.
Cellular and humoral immune responses
While some leukocytes in protochordate invertebrates close relatives of the vertebrates have been termed 'lymphocyte-like cells', evidence that these are homologs of vertebrate lymphocytes remains tenuous these animals lack the rearranging genes and clonal expansion that characterize the vertebrate lymphoid receptors for antigen. Among both primitive acoelomate taxa, such as the sponges and the corals, and more derived coelomate, with blood circulatory systems taxa such as the tunicates sea...
CD45 ligands
As yet it is not clear how the extracellular domain regulates the defined biology of CD45. While a number of candidate ligands have emerged, it has been difficult to identify specific interactions that modulate the biological function of CD45. Due to its extensive modification with carbohydrate, it is likely that lectins will be important CD45 ligands. CD22 is a cell surface cation-independent lectin with a specificity for a2,6-linked sialic acid moieties and is expressed specifically on mature...
Info Arx
Figure 1 Computer graphic model of the structure of the VH component of NEWM human antibody. The CDRs loop out from the scaffold structure of the framework regions blue to provide the antigen binding surface at one end of the molecule. The framework residues marked are those most commonly involved in maintaining the correct conformation of the CDR loops. Reproduced with permission from Harris and Cunningham 1995 . See also color Plate 9. Figure 1 Computer graphic model of the structure of the...
Efferent phase
Because congenitally athymic nude and adult thy-mectomized, irradiated and bone marrow-restored ATXBM animals do not reject incompatible grafts, it is clear that T cells are required for graft rejection. It is also clear from adoptive transfer experiments that helper cells are essential for the initiation of the immune response to a graft. Thus, in most experimental models of transplantation, CD4 but not CD8 T cells are able to reconstitute ATXBM or nude animals with the ability to reject an...
Annexins Lipocortins
Fusao Hirata, Departments of Pharmaceutical Science, Pharmacology amp Institute of Chemical Toxicology, Wayne State University, Michigan, USA The annexin lipocortin family of proteins possess a highly conserved core region, consisting of four or eight repeats of approximately 70 amino acid residues, and a highly variable N-terminal region. The core region mediates Ca2 -dependent binding to phospholipid membranes and forms a Ca2 channellike structure. The physical and structural properties of...
Local vasoconstriction
A number of physiologically derived compounds appear to induce vasoconstriction of a transient nature at the site of vascular injury. These include participation of endothelin, a very potent vasoconstrictor which is synthesized by endothelial cells, thromboxane A2 TXA2 , serotonin and the a-adre-nergic system. Thrombin, interleukin 1 IL-1 , transforming growth factor 3 TGF 3 , angiotensin II and epinephrine promote the expression of endothelin mRNA, whereas shear stress, atrial natriuretic...
Functions of IL6 Immune response
Interleukin 6 was originally identified as a T cell-derived lymphokine that induces final maturation of B cells into antibody-producing cells. Recombinant human IL-6 acts on B cells activated with Staphylococcus aureus Cowan I or pokeweed mitogen PWM to induce immunoglobulin M IgM , IgG and IgA production, but not on resting B cells. Anti-IL-6 antibody was found to inhibit PWM-induced Ig production, indicating that IL-6 is one of the essential factors in PWM-induced Ig production. Furthermore,...
Hemolytic Disease Of The Newborn
Cyril A Clarke, formerly at Department of Genetics and Microbiology, University of Liverpool, Liverpool, UK For this article, hemolytic disease of the newborn HDN is taken to be the condition resulting from blood group incompatibility between mother and fetus, and clinically 'rhesus' Rh disease is the most important example. During pregnancy, and particularly during the trauma of delivery, some fetal red cells may cross the placenta and enter the maternal circulation. When the mother is Rh...
Virotypes diarrheaproducing E coli
Recently, E. coli strains have been categorized on the basis of certain virulence factors i.e. virotyping . This classification scheme is based on the production of certain E. coli toxins, patterns of E. coli adherence to particular host cells, the abilities of E. coli strains to invade the intestinal epithelium, and the patterns of intestinal mucosal pathology produced by E. coli. Virotyping therefore more directly relates various E. coli strains to the actual disease process than does...
Historical background Jls
The early studies on responses to protein antigens established a relationship between the degree of uptake of the antigen by the 'reticuloendothelial system' and its immunogenicity. This was most evident in the responses to foreign albumins or gamma globulins where the antigenic preparations differed in their content of polymeric molecules. Albumin or gamma globulins with a heavy content of polymers or aggregates were strongly immunogenic while, in contrast, preparations made mostly of monomers...
Immunoselection techniques
These techniques make use of antibodies either polyclonal antisera or preferably mAbs directed to surface antigens expressed by given lymphocyte subsets. Both direct and indirect immunoselection procedures have been applied. Direct methods require a single step i.e. only the antibody directed to a relevant antigen is needed , while indirect methods require a second reagent i.e. an antiserum directed to the first antibody . The advantages of direct methods include a greater speed and a better...
Strategies of infection and host defense mechanisms
Pathogens reach the eye by two routes. They infect the eye directly through the conjunctiva and cornea, or they reach the eye through the vascular, lymphatic or nervous systems following infection elsewhere. The front of the eye protects itself from infection in many ways, and few organisms can infect the intact front surface. An eye with a damaged front surface is, however, far more susceptible to infection. Pathogens which reach the avascular tissues of the eye are partially isolated from...
Agglutination
Abram B Stavitsky, Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA A variety of particles bearing either natural or conjugated epitopes on their surfaces are specifically agglutinated by polyclonal or monoclonal antibodies to these epitopes. These particles can be inert but bearing these epitopes on their surfaces. They can also be large viruses, eukaryotic cells, or a variety of other cells, including bacteria, yeasts,...
Granular leukocytes
Granular leukocytes include neutrophils, eosinophils and basophils. The number of neutrophils increases during infections to provide one of the first lines of defense against invading foreign material and microorganisms. In allergies and parasitic infestations, the number of eosinophils increases. Basophils are important for the production of histamine, the primary cause of skin reactions in allergic responses. The most actively phagocytic of leukocytes are neutrophils and macrophages, a...
HEV function in lymphocyte extravasation
To select sufficient antigen-specific lymphocytes for the initiation of immune responses, as many naive lymphocytes as possible should be sampled by antigen-presenting cells within lymphoid tissues. The clearly identifiable function of HEVs in this process is to recognize and sort lymphocytes from other leukocytes in the bloodstream and deliver them into lymph nodes. It is reasonable to assume that all of the HEV-associated properties described above may, in some way, regulate the selective...
Effects of IL13 on monocytes and endothelial cells
The effects of IL-13 on monocytes macrophages and endothelial cells are similar to those of IL-4. IL-1 modulates the phenotype of both human and murine monocytes macrophages and it inhibits production of proinflammatory cytokines, chemokines and nitric-oxide by these cells. IL-13 inhibits synthesis of IL-la, IL-1 p, IL-6, IL-12, tumor necrosis factor a TNE-a and the chemokines IL-8, macrophage inflammatory protein MlP-la and MIP-1 3 by monocytes. In addition, it enhances production of the IL-1...
Further reading Qup
Bacon KB and Schall TJ 1996 Chemokines as mediators of allergic inflammation. International Archives of Allergy and Immunology 109 97-109. Baggiolini M and Dahinden CA 1994 CC chemokines in allergic inflammation. Immunology Today 15 127-133. Baggiolini M, Dewald B and Moser B 1994 lnterleukin-8 and related chemotactic cytokines - CXC and CC chemokines. Advances in Immunology 55 97-179. Baggiolini M, Dewald B, Moser B 1997 Human chemokines an update. Annual Review of Immunology 15 675-705....
Basis of atopy
The incidence of atopy is closely related to the serum IgE concentration, with less than 5 of the individuals with levels less than 60 iu ml 1 iu 2.4 xg being affected, but over 95 of those with values over 450 iu ml. There is also an obvious genetic influence, with over 50 of individuals having two allergic parents being atopic, compared with 15 in the normal population. There are several genetic influences determining IgE production an autosomal dominant gene codes for low IgE levels,...
Susceptibility to endotoxin
Sensitivity towards endotoxin is genetically determined - different animals showing an enormous variation in endotoxin susceptibility. Rabbits, dogs and swine are very sensitive, while mice, rats and guinea pigs are, in comparison, much less sensitive. Humans belong to the most endotoxin-sensitive mammals, an amount of 0.03 xg per 70 kg body weight of pure endotoxin administered intravenously sufficing to cause a marked leukopenia after 1 h, which is followed by leukocytosis 3 h later. Higher...
Bystander suppression
It was initially thought that a major problem of all the tolerance regimes designed to inhibit the dominant autoimmune response would be the fact that they would block only a fraction of the autoimmune responses, and with time, weaker residual responses would amplify to restore the pathologic status quo. However, there is increasing evidence that this may not be the case, and that 'bystander suppression' may develop. The phenomenon of bystander suppression is that during 'tolerization' with a...
Purine nucleoside Phosphorylase deficiency
Deficiency of the enzyme purine nucleoside Phosphorylase PNP usually results in the appearance of signs and symptoms of immunodeficiency between the ages of 3 and 18 months. There is a striking dichotomy between T and B cell immunity in these patients. Humoral immunity, B cells, B memory cells, and plasma cell differentiation are generally intact. Indeed, the presence of autoantibodies and elevated immunoglobulin levels are usually present. In contrast, T cell immunity is markedly affected....
Fetal Calf Serum
Hinnak Nonhoff, Abteilung Transfusionsmedizin, Eberhard-Karls-Universit t, T bingen, Germany Willy A Flegel, Abteilung Transfusionsmedizin, Universit t Ulm, Ulm, Germany Copyright 1998 Elsevier Ltd. All Rights Reserved. The beginning of cell culture techniques during the first decade of this century was marked by the finding that biologically derived fluids are required to maintain cells in vitro. Various supplements were used successfully, varying widely from tissue extracts, spinal and...
Affinity measurement in solution by competition ELISA
In the competition ELISA the monoclonal antibody at a fixed concentration and the antigen at varying concentrations are first incubated in solution until the equilibrium is reached. Then, the concentration of the free i.e. not associated with antigen monoclonal antibody at equilibrium is determined by a classical indirect ELISA using antigen-coated plates. For correct determination of the free antibody concentration at equilibrium, several requirements must be fulfilled 1 The absorbance...