Multiple sclerosis (MS) is an autoimmune disease. The etiology and pathogenesis of MS remain unclear. At present, there are substantial evidences to support the hypothesis that genetics plays a crucial role. The people who have genetic predisposing genes easily develop immune-mediated disorder, probably in conjunction with environmental factors. The aim of this review is to describe recent observations regarding the immunologic pathogenesis of MS.
Animals ; Autoantibodies ; immunology ; Humans ; Models, Biological ; Multiple Sclerosis ; etiology ; immunology ; pathology ; Myelin Basic Protein ; metabolism

An experimental allergic encephalomyelitis was induced by bovine myelin basic protein (MBP) and bovine galactocerebroside (GC) on male guinea pigs. Animals were divided into five experimental and one control groups. Among the five experimental groups, three were inoculated with 75 micrograms, 150 micrograms and 300 micrograms of MBP, respectively, to see the dose dependency of demyelination. The fourth group was inoculated with mixture of 75 micrograms of MBP and 180 micrograms of GC and the fifth group with 180 micrograms GC. All inocula was injected intradermally in emulsion state mixed with equal amount of complete Freund adjuvant. Control group was injected with adjuvant only. Clinical symptoms began to appear from 15th day after inoculation and animals were sacrificed on maximum neurologic deficit or 4 to 5 days after the onset of symptoms. Demyelination was observed in 6 out of 8 animals inoculated with MBP/GC mixture, while only 3 out of 24 animals inoculated with various dosage of MBP showed demyelination. The difference was statistically significant. Serum antibodies to MBP and GC were measured by ELISA method. All of the eight animals inoculated with MBP/GC mixture and two animals inoculated with GC had low titer of anti-GC antibodies, while all animals inoculated with MBP, MBP alone or MBP/GC mixture, had high titer of anti-MBP antibodies. Therefor it is concluded that the demyelination is augmented by GC and is not significantly dose-dependent on MBP.
Animals ; Autoantibodies/*immunology ; Central Nervous System/*immunology/pathology ; Cerebrosides/*immunology ; Dose-Response Relationship, Drug ; Encephalomyelitis, Autoimmune, Experimental/*metabolism/pathology ; Galactosylceramides/*immunology ; Guinea Pigs ; Male ; Myelin Basic Protein/*immunology

An experimental allergic encephalomyelitis was induced by bovine myelin basic protein (MBP) and bovine galactocerebroside (GC) on male guinea pigs. Animals were divided into five experimental and one control groups. Among the five experimental groups, three were inoculated with 75 micrograms, 150 micrograms and 300 micrograms of MBP, respectively, to see the dose dependency of demyelination. The fourth group was inoculated with mixture of 75 micrograms of MBP and 180 micrograms of GC and the fifth group with 180 micrograms GC. All inocula was injected intradermally in emulsion state mixed with equal amount of complete Freund adjuvant. Control group was injected with adjuvant only. Clinical symptoms began to appear from 15th day after inoculation and animals were sacrificed on maximum neurologic deficit or 4 to 5 days after the onset of symptoms. Demyelination was observed in 6 out of 8 animals inoculated with MBP/GC mixture, while only 3 out of 24 animals inoculated with various dosage of MBP showed demyelination. The difference was statistically significant. Serum antibodies to MBP and GC were measured by ELISA method. All of the eight animals inoculated with MBP/GC mixture and two animals inoculated with GC had low titer of anti-GC antibodies, while all animals inoculated with MBP, MBP alone or MBP/GC mixture, had high titer of anti-MBP antibodies. Therefor it is concluded that the demyelination is augmented by GC and is not significantly dose-dependent on MBP.
Animals ; Autoantibodies/*immunology ; Central Nervous System/*immunology/pathology ; Cerebrosides/*immunology ; Dose-Response Relationship, Drug ; Encephalomyelitis, Autoimmune, Experimental/*metabolism/pathology ; Galactosylceramides/*immunology ; Guinea Pigs ; Male ; Myelin Basic Protein/*immunology

OBJECTIVETo investigate the relations between anti-myelin basic protein antibody (anti-MBP) variation and myelinoclasis in the brain stem following brain trauma.

METHODSIn rat models of brain trauma, MBP content and anti-MBP titer in the blood were measured using enzyme-linked immunosorbent assay (ELISA) at different time points after brain trauma, and the degree of myelinoclasis in the brain stem slices was assessed with osmic acid staining.

RESULTSEarly after brain trauma, MBP content in the blood increased followed by significant reduction 10 days later. Four days after the trauma, anti-MBP titer was markedly increased, accompanied by obvious exacerbation of myelinoclasis in the brain stem, both reaching the highest levels on day 10, at the point of which anti-MBP titer increased by 4 folds and the number of myelinoclasis by 10 folds compared with the control group. Anti-MBP titer and brain stem myelinolysis both lowered 30 days later. Correlation analysis showed an intimate positive correlation between anti-MBP titer and the degree of myelinoclasis.

CONCLUSIONAfter brain trauma, MBP is released as a specific antigen into the blood to stimulate the immune system for anti-MBP production, and the antibody is intimately related to the brain stem myelinoclasis.

Animals ; Antibodies ; metabolism ; Brain Injuries ; complications ; Brain Stem ; immunology ; pathology ; Demyelinating Autoimmune Diseases, CNS ; etiology ; immunology ; Female ; Male ; Myelin Basic Protein ; Nerve Tissue Proteins ; blood ; immunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; blood ; immunology

We constructed the expression vector by inserting 21.5 KDa MBP human brain full-length cDNA coding sequence digested with restriction enzyme EcoR I and Sal I into downstream of pGEX-5T expression vector. The recombinant vector p5TMP was transformed into E. coli and the positive clonies were selected and incubated in LB medium induced by IPTG (isopropyl- -D-thiogalactoside). A new polypeptide band with apparent molecular weight 42 KDa was detected in transformed cell lysates by SDS-PAGE. Western blotting analysis confirmed that this fusion protein reacted specifically with antibodies to MBP, the expression level of MBP was about 414.6 mg/L medium estimated by immuno-dot blot, ELISA and absorbance scanning. Newzealand rabbits were immunized by subcutaneous injection of the purified recombinant MBP. The titer was obtained at 1:16 after 5 injections. The specificity of the antibody to MBP was confirmed by immuno-blot and Western blotting.
Animals ; Antibody Formation ; Autoantibodies ; Brain ; immunology ; metabolism ; Cloning, Molecular ; DNA, Complementary ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; Humans ; Myelin Basic Protein ; biosynthesis ; genetics ; immunology ; Rabbits ; Recombinant Fusion Proteins ; biosynthesis ; immunology

BACKGROUNDThe interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV-2 microglia cells.

METHODSTotally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 μl MBP (1 mg/ml); Group B: intrathymic injection of 100 μl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [IL]-1β, tumor necrosis factor-α [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis.

RESULTSThe levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3rd to 7th day, with an upward trend from the 7th to 14th day (10.00 ± 0.23%, 5.28 ± 0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The ratio of CD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P < 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45: 83.39 ± 2.56%, 82.74 ± 2.09%, 87.56 ± 2.11%; CD54: 3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P < 0.05). The expressions of TNF-α, IL-1β, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P < 0.05). No significant difference was found between Groups B and C.

CONCLUSIONSIntrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Antigens, Surface ; analysis ; Brain Injuries, Traumatic ; drug therapy ; CD4-CD8 Ratio ; Coculture Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Microglia ; immunology ; Myelin Basic Protein ; administration & dosage ; pharmacology ; T-Lymphocytes ; immunology

OBJECTIVETo explore the immunological pathogenesis of multiple sclerosis (MS) patients of different TCM syndrome types.

METHODSFifty-nine MS patients were assigned to two types by syndrome typing according to their clinical manifestations, the Gan-Shen yin-deficiency (GSYD, 40 cases) type and the both yin-yang deficiency (YYD, 19 cases) type. Difference of patients' age of first attack, times of relapsing, duration of disease, MRI finding and evoked potential between the two groups were compared. The immunology indexes were also compared in part of the patients (26 cases in GSYD type and 12 cases in YYD type).

RESULTSThe age of first attack was later (P < 0.01), level of myelin basic protein in cerebrospinal fluid was higher (P < 0.05), in the YYD type than those in the GSYD type. Besides, the relapsing time in GSYD type, and the blood-brain barrier index and level of myelin basic protein in YYD type showed an ascending trend (P = 0.056, 0.074, 0.093, respectively).

CONCLUSIONImmunological difference exists between the MS patients of GSYD type and those of YYD type.

Adolescent ; Adult ; Child ; Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Multiple Sclerosis ; drug therapy ; immunology ; pathology ; Myelin Basic Protein ; Nerve Tissue Proteins ; cerebrospinal fluid ; immunology ; Phytotherapy ; Syndrome ; Transcription Factors ; cerebrospinal fluid ; immunology ; Yang Deficiency ; drug therapy ; immunology ; pathology ; Yin Deficiency ; drug therapy ; immunology ; pathology ; Young Adult