Koen Gerritse - Academia.edu (original) (raw)
Papers by Koen Gerritse
: Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant B... more : Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant Biological warefare agents (bacteriophage MS-2 and bacteria Erwinia herbicola) could be detected in a direct fashion without the use of labelled antibodies. The detection device is incorporated into a ruggedized suit-case together with an aerosol sampler and sample handling system and can be used in the field for military monitoring purposes.
Eur J Cancer, 1995
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). It is wid... more Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). It is widely assumed that the pathology is a result of autoimmune responses directed against CNS antigens, possibly triggered by an environmental factor, in a genetically susceptible individual. This thesis describes investigations concerning the role of antibodies and antibody forming cells in immunopathogenesis and immunomodulation in MS. In this chapter we introduce some basic understandings with regard to the central nervous system, the pathogenesis and etiology of MS and the presently best available animal model for MS, experimental autoimmune encephalomyelitis (EAE). The aim of the study and experiments are described in "Outline of the thesis" (1.8). 1.2 The central nel"VOUS system Most body functions are actively controlled by the CNS. The CNS receives information from sensory organs. Upon processing of this information, the eNS generates and controls body responses. In addition, the information may also be stored in the CNS for future use. The information to and from the CNS is transported via the peripheral nervous system. The major compartments within the CNS are the brain and the spinal cord, which are surrounded by the cerebrospinal fluid (CSF) and protected by the skull and vertebral column, respectively. CNS tissues are a complex of nerve cells (neurons), supporting cells (glia cells or neuroglia) and blood vessels. Three basic types of glia cells can be identified: astrocytes and microglia, both contributing to the structure and function of nervous tissue, and oligodendrocytes. Nerve fibres are protected by an isolating myelin sheath. The myelin around the axons in the CNS, is formed by layers of oligodendrocyte cell cytoplasm and membranes, which are wrapped many times around one or more axons (figure 1). The myelin sheaths in the peripheral nervous system are formed, in a similar way, by Schwann cells (England and Wakely, 1991). Demyelination is associated with an impaired conductivity, which leads to a vadety of neurological signs and symptoms. Several demyelinating diseases are known of both the peripheral nervous system, e.g. Guillain Barre syndrome, and CNS, e.g. acute demyelinating encephalomyelitis, subacute sclerosing panencephalitis. MS is characterized by multi-focal demyelination of CNS white matter, accompanied with perivascular infiltrates of mononuclear cells. Since demyelination in MS-patients is restricted to the CNS, it is possible that remains to be established. Myelin proteolipid protein (PLP) can induce a T-cell-mediated demyelinating disease in the Hartley guinea pig (Yoshimura et aI., 1985), the Lewis rat (Yamamura et aI., 1986) and in rabbits (van der Veen et aI., 1986). Therefore, PLP is considered to be an important putative autoantigen in the pathogenesis of MS as well. T-cells reactive with PLP have been isolated from patients with early relapsing remitting MS (Trotter et aI., 1991). PLP reactive T-cells were also detected in blood and CSF from control patients, but these cells were detected in much lower numbers as compared to the frequency in MS patients (Sun et al., 1991). No difference in reactivity to PLP peptide 139-151, a peptide which can induce demyelination in SILII mice, was measured between T-cells from peripheral blood from MS patients as compared to T-cells from normal subjects and from patients with other neurological diseases. These data indicate that the presence of T-cells reactive with putative CNS antigens in sera by itself is not leading to CNS demyelination. Possibly, the autoreactive T-cells are recruited specifically to the site of immune attack, i.e. the CNS tissues, in MS patients and not in healthy subjects or in patients with other neurological diseases.
Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant Bio... more Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant Biological warefare agents (bacteriophage MS-2 and bacteria Erwinia herbicola) could be detected in a direct fashion without the use of labelled antibodies. The detection device is incorporated into a ruggedized suit-case together with an aerosol sampler and sample handling system and can be used in the field for military monitoring purposes.
Proceedings of the National Academy of Sciences of the United States of America, Jan 19, 1996
We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and ... more We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological disease. CD40L-positive cells were co-localized with CD40-bearing cells in active lesions (perivascular infiltrates). Most of these CD40-bearing cells proved to be of the monocytic lineage (macrophages or microglial cells), and relatively few were B cells. To functionally evaluate CD40-CD40L interactions, EAE was elicited in mice by means of proteolipid-peptide immunization. Treatment with anti-CD40L monoclonal antibody completely prevented the development of disease. Furthermore, administration of anti-CD40L monoclonal antibody, even after disease onset, shortly before maximum disability score was reached led to dramatic disease reduction. The presen...
Journal of Immunological Methods, 1992
Journal of Immunological Methods, 1990
Coupling of peptides to immunogenic protein carriers is required for the generation of anti-pepti... more Coupling of peptides to immunogenic protein carriers is required for the generation of anti-peptide antibody responses. Carbodiimides are hetero bi-functional coupling reagents that are utilized for coupling reactions through carboxyl and amino groups. The procedures generally used for carbodiimide coupling of peptides and proteins result in conjugates which generate immunodominant antibody responses directed against the neodeterminants on the carrier protein. These determinants are induced by the reaction of carrier and/or peptide with the coupling agent. We have investigated the potential inhibiting effect of an imidazole intermediary on the formation of unwanted neodeterminants during carbodiimide coupling. The serum antibody responses elicited with the peptide-protein conjugates produced were evaluated in ELISA. We have modified and improved the coupling with a watersoluble carbodiimide (EDC) in such a way that a high response to the coupled peptide is obtained in association with negligible levels of anti-neodeterminant antibodies.
Journal of Immunological Methods, 1990
Controlled and efficient conjugation of synthetic peptides to proteins, for use in immunization o... more Controlled and efficient conjugation of synthetic peptides to proteins, for use in immunization or in assay procedures, is a prerequisite for the immunological applications of synthetic peptides. This study describes a new method of conjugating synthetic peptides to proteins in such a way that no homopolymers of synthetic peptides or proteins occur. To achieve this, the protein is first activated with glutaraldehyde and subsequently excess glutaraldehyde is removed. Then coupling of the synthetic peptide to the activated protein occurs while subsequently the surplus reactive glutaraldehyde groups on the protein are blocked with lysine. Excess free peptide and lysine is then removed by dialysis. This improvement not only results in better defined conjugates when compared to classical glutaraldehyde couphng, but also in the consumption of smaller amounts of synthetic peptide during conjugate formation. When used for immunization we obtained similar and sometimes even better responses with the glutaraldehyde based conjugates than with succinimidyl (MBS) conjugates of the same peptides. The performance of the modified conjugates in ELISA procedures, immunization and immunocytochemistry suggests that they are superior to conjugates formed by classical glutaraldehyde coupling.
As a model system for the industrial use of fungal cells in the enzymatic conversion of chemicals... more As a model system for the industrial use of fungal cells in the enzymatic conversion of chemicals, the parahydroxylation of benzoate was studied. To increase the amount of benzoate-para-hydroxylase (BPH, EC 1.14.13.12.) in the cell the gene coding for the enzyme (bphA) was cloned and expressed in Aspergillus niger. Detection of the enzymatic activity of the protein was not reproducible. It was decided to raise an antiserum for immuno-detection purposes. Sufficient benzoate-para-hydroxylase for immunization could not be obtained; therefore the synthetic-peptide strategy was used. We demonstrate that synthesis of antigenic determinants, can be useful in the production of highly specific reagents for the detection of proteins. The availability of monospecific polyclonal sera opens new possibilities in functional studies and purification of benzoate-para-hydroxylase.
: Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant B... more : Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant Biological warefare agents (bacteriophage MS-2 and bacteria Erwinia herbicola) could be detected in a direct fashion without the use of labelled antibodies. The detection device is incorporated into a ruggedized suit-case together with an aerosol sampler and sample handling system and can be used in the field for military monitoring purposes.
Eur J Cancer, 1995
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). It is wid... more Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). It is widely assumed that the pathology is a result of autoimmune responses directed against CNS antigens, possibly triggered by an environmental factor, in a genetically susceptible individual. This thesis describes investigations concerning the role of antibodies and antibody forming cells in immunopathogenesis and immunomodulation in MS. In this chapter we introduce some basic understandings with regard to the central nervous system, the pathogenesis and etiology of MS and the presently best available animal model for MS, experimental autoimmune encephalomyelitis (EAE). The aim of the study and experiments are described in "Outline of the thesis" (1.8). 1.2 The central nel"VOUS system Most body functions are actively controlled by the CNS. The CNS receives information from sensory organs. Upon processing of this information, the eNS generates and controls body responses. In addition, the information may also be stored in the CNS for future use. The information to and from the CNS is transported via the peripheral nervous system. The major compartments within the CNS are the brain and the spinal cord, which are surrounded by the cerebrospinal fluid (CSF) and protected by the skull and vertebral column, respectively. CNS tissues are a complex of nerve cells (neurons), supporting cells (glia cells or neuroglia) and blood vessels. Three basic types of glia cells can be identified: astrocytes and microglia, both contributing to the structure and function of nervous tissue, and oligodendrocytes. Nerve fibres are protected by an isolating myelin sheath. The myelin around the axons in the CNS, is formed by layers of oligodendrocyte cell cytoplasm and membranes, which are wrapped many times around one or more axons (figure 1). The myelin sheaths in the peripheral nervous system are formed, in a similar way, by Schwann cells (England and Wakely, 1991). Demyelination is associated with an impaired conductivity, which leads to a vadety of neurological signs and symptoms. Several demyelinating diseases are known of both the peripheral nervous system, e.g. Guillain Barre syndrome, and CNS, e.g. acute demyelinating encephalomyelitis, subacute sclerosing panencephalitis. MS is characterized by multi-focal demyelination of CNS white matter, accompanied with perivascular infiltrates of mononuclear cells. Since demyelination in MS-patients is restricted to the CNS, it is possible that remains to be established. Myelin proteolipid protein (PLP) can induce a T-cell-mediated demyelinating disease in the Hartley guinea pig (Yoshimura et aI., 1985), the Lewis rat (Yamamura et aI., 1986) and in rabbits (van der Veen et aI., 1986). Therefore, PLP is considered to be an important putative autoantigen in the pathogenesis of MS as well. T-cells reactive with PLP have been isolated from patients with early relapsing remitting MS (Trotter et aI., 1991). PLP reactive T-cells were also detected in blood and CSF from control patients, but these cells were detected in much lower numbers as compared to the frequency in MS patients (Sun et al., 1991). No difference in reactivity to PLP peptide 139-151, a peptide which can induce demyelination in SILII mice, was measured between T-cells from peripheral blood from MS patients as compared to T-cells from normal subjects and from patients with other neurological diseases. These data indicate that the presence of T-cells reactive with putative CNS antigens in sera by itself is not leading to CNS demyelination. Possibly, the autoreactive T-cells are recruited specifically to the site of immune attack, i.e. the CNS tissues, in MS patients and not in healthy subjects or in patients with other neurological diseases.
Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant Bio... more Using a bulk acoustic wave immunosensor device, Staphylococcus enterotoxin B and two simulant Biological warefare agents (bacteriophage MS-2 and bacteria Erwinia herbicola) could be detected in a direct fashion without the use of labelled antibodies. The detection device is incorporated into a ruggedized suit-case together with an aerosol sampler and sample handling system and can be used in the field for military monitoring purposes.
Proceedings of the National Academy of Sciences of the United States of America, Jan 19, 1996
We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and ... more We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological disease. CD40L-positive cells were co-localized with CD40-bearing cells in active lesions (perivascular infiltrates). Most of these CD40-bearing cells proved to be of the monocytic lineage (macrophages or microglial cells), and relatively few were B cells. To functionally evaluate CD40-CD40L interactions, EAE was elicited in mice by means of proteolipid-peptide immunization. Treatment with anti-CD40L monoclonal antibody completely prevented the development of disease. Furthermore, administration of anti-CD40L monoclonal antibody, even after disease onset, shortly before maximum disability score was reached led to dramatic disease reduction. The presen...
Journal of Immunological Methods, 1992
Journal of Immunological Methods, 1990
Coupling of peptides to immunogenic protein carriers is required for the generation of anti-pepti... more Coupling of peptides to immunogenic protein carriers is required for the generation of anti-peptide antibody responses. Carbodiimides are hetero bi-functional coupling reagents that are utilized for coupling reactions through carboxyl and amino groups. The procedures generally used for carbodiimide coupling of peptides and proteins result in conjugates which generate immunodominant antibody responses directed against the neodeterminants on the carrier protein. These determinants are induced by the reaction of carrier and/or peptide with the coupling agent. We have investigated the potential inhibiting effect of an imidazole intermediary on the formation of unwanted neodeterminants during carbodiimide coupling. The serum antibody responses elicited with the peptide-protein conjugates produced were evaluated in ELISA. We have modified and improved the coupling with a watersoluble carbodiimide (EDC) in such a way that a high response to the coupled peptide is obtained in association with negligible levels of anti-neodeterminant antibodies.
Journal of Immunological Methods, 1990
Controlled and efficient conjugation of synthetic peptides to proteins, for use in immunization o... more Controlled and efficient conjugation of synthetic peptides to proteins, for use in immunization or in assay procedures, is a prerequisite for the immunological applications of synthetic peptides. This study describes a new method of conjugating synthetic peptides to proteins in such a way that no homopolymers of synthetic peptides or proteins occur. To achieve this, the protein is first activated with glutaraldehyde and subsequently excess glutaraldehyde is removed. Then coupling of the synthetic peptide to the activated protein occurs while subsequently the surplus reactive glutaraldehyde groups on the protein are blocked with lysine. Excess free peptide and lysine is then removed by dialysis. This improvement not only results in better defined conjugates when compared to classical glutaraldehyde couphng, but also in the consumption of smaller amounts of synthetic peptide during conjugate formation. When used for immunization we obtained similar and sometimes even better responses with the glutaraldehyde based conjugates than with succinimidyl (MBS) conjugates of the same peptides. The performance of the modified conjugates in ELISA procedures, immunization and immunocytochemistry suggests that they are superior to conjugates formed by classical glutaraldehyde coupling.
As a model system for the industrial use of fungal cells in the enzymatic conversion of chemicals... more As a model system for the industrial use of fungal cells in the enzymatic conversion of chemicals, the parahydroxylation of benzoate was studied. To increase the amount of benzoate-para-hydroxylase (BPH, EC 1.14.13.12.) in the cell the gene coding for the enzyme (bphA) was cloned and expressed in Aspergillus niger. Detection of the enzymatic activity of the protein was not reproducible. It was decided to raise an antiserum for immuno-detection purposes. Sufficient benzoate-para-hydroxylase for immunization could not be obtained; therefore the synthetic-peptide strategy was used. We demonstrate that synthesis of antigenic determinants, can be useful in the production of highly specific reagents for the detection of proteins. The availability of monospecific polyclonal sera opens new possibilities in functional studies and purification of benzoate-para-hydroxylase.