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Biomedical subjects

A Getahun

Publications and source records attributed to A Getahun.

8 recordsLinked to original sources
PubMed2006

Antibody-mediated regulation of the immune response.

Antibodies administered in vivo together with the antigen they are specific for can regulate the immune response to that antigen. This phenomenon is called antibody-mediated feedback regulation and has been known for over 100 years. Both passively administered and actively produced antibodies exert immunoregulatory functions. Feedback regulation can be either positive or negative, resulting in >1000-fold enhancement or >99% suppression of the specific antibody response. Usually, the response to the entire antigen is up- or downregulated, regardless of which epitope the regulating antibody recognizes. IgG of all isotypes can suppress responses to large particulate antigens like erythrocytes, a phenomenon used clinically in Rhesus prophylaxis. IgG suppression works in mice lacking the known Fc-gamma receptors (FcgammaR) and a likely mechanism of action is epitope masking. IgG1, IgG2a and IgG2b administered together with soluble protein antigens will enhance antibody and CD4+ T-cell responses via activating FcgammaR, probably via increased antigen presentation by dendritic cells. IgG3 as well as IgM also enhance antibody responses but their effects are dependent on their ability to activate complement. A possible mechanism is increased B-cell activation caused by immune complexes co-crosslinking the B-cell receptor with the complement-receptor 2/CD19 receptor complex, known to lower the threshold for B-cell activation. IgE-antibodies enhance antibody and CD4+ T-cell responses to small soluble proteins. This effect is entirely dependent on the low-affinity receptor for IgE, CD23, the mechanism probably being increased antigen presentation by CD23+ B cells.

Animals↗
PubMed2001

FcgammaRIIB in IgG-mediated suppression of antibody responses: different impact in vivo and in vitro.

The suppressive effect of IgG on Ab responses to particulate Ags such as erythrocytes is well documented. IgG-mediated suppression is used clinically in rhesus prophylaxis to prevent RhD-negative mothers from becoming immunized against their Rh D-positive fetuses. We have recently shown that IgG anti-SRBC, passively administered together with SRBC, can induce efficient suppression of primary Ab responses to SRBC in mice lacking the known FcRs for IgG (FcgammaRI, FcgammaIII, and FcgammaRIIB or the neonatal FcR). The lack of a demonstrable effect of the inhibitory FcgammaRIIB was particularly surprising, and, in this study, the involvement of this receptor is further investigated during broader experimental conditions. The data show that SRBC-specific IgG administered up to 5 days after SRBC can induce suppression both in wild-type and FcgammaRIIB-deficient mice. Suppression of secondary Ab responses to SRBC in vivo was similar in the two strains. In contrast, IgG-mediated suppression of Ab responses in vitro was impaired in cultures with primed FcgammaRIIB-deficient spleen cells. In conclusion, inhibition of in vivo Ab responses to SRBC by passively administered IgG can take place via an FcgammaRIIB-independent pathway. This pathway causes >99% suppression and operates during all experimental conditions studied so far. The nature of the mechanism can at present only be hypothesized. Masking of epitopes and/or rapid elimination of IgG-Ag complexes would both be compatible with the observations.

Adoptive Transfer↗
PubMed2000

The major histocompatibility class II alpha chain in salmonid fishes.

In this study the characterisation of the Atlantic salmon (MhcSasa-DAA) and rainbow trout (MhcOnmy-DAA) class II alpha chain cDNA sequences is presented. The DAA sequences from these two salmonid species showed a high degree of similarity, although the Onmy-DAA(*)03 cDNA sequence differed in the cytoplasmic region. Interestingly, the Onmy-DAA(*)02 sequence has lost the second cysteine in the alpha-1 domain. However, another cysteine is present in this sequence 7 positions downstream of the cysteine which is substituted for a leucine. Despite a thorough search, only a single locus of expressed class II alpha chain sequences was identified in both salmonid species. Amplification by PCR and sequencing of the alpha-1 domain from genomic DNA of three Atlantic salmon, identified four different variants assumed to have derived from this single locus. Two of these variants originated from one individual and are likely functional alleles.

Amino Acid Sequence↗
PubMed1999

Influence of the mu-chain C-terminal sequence on polymerization of immunoglobulin M.

Immunoglobulin (IgM) is found in various states of covalent polymerization (microL)n, where n is typically 8, 10, or 12. The usual form of IgM of bony fish is tetrameric (8 microL units) as compared to the pentameric form (10 microL units) observed in cartilaginous fish and mammals. Two hypotheses were tested in this study. First, that the length of the mu-chain C terminus following Cys575 determines whether an IgM polymerizes as a tetramer or as a pentamer. This was tested by examining the covalent polymerization state of mouse IgM mutated to contain a series of mu-chain C-termini from bony and cartilaginous fish. The results proved this hypothesis wrong: mouse IgM bearing the C-terminal sequence of shark, salmon and cod mu-chain behaved identically to native mouse IgM, forming predominantly (microL)10 and (microL)12 forms. The second hypothesis was that an additional Cys residue near the C terminus of the mu-chain is responsible for the multiple covalent structures seen in IgM of the channel catfish. The addition of a catfish C terminus to the mouse mu-chain resulted, as predicted, in the production of a series of covalently bonded forms, with the major species being (microL)4. When a Ser-Cys unit was removed from the catfish C terminus added to the mouse mu-chain, this resulted in production of IgM indistinguishable in structure from that of wild-type mouse IgM.

Animals↗
PubMed1998

Graded retinoid responses in the developing hindbrain.

The purpose of this study was to make an explicit test of the idea that a retinoid could act as a morphogen, differentially activating genes and specifying anteroposterior (a-p) level in the developing vertebrate central nervous system (CNS). Our approach was to characterize the concentration-dependent effects of retinoic acid (RA) on the neural expression of a set of a-p patterning genes, both in vivo and in an in vitro system for neural patterning. Our results indicate that a retinoid is unlikely to specify a-p level along the entire CNS. Instead, our data support the idea that the developing hindbrain may be patterned by a retinoid gradient. Sequentially more posterior hindbrain patterning genes were induced effectively by sequentially higher RA concentration windows. The most posterior CNS level induced under our RA treatment conditions corresponded to the most posterior part of the hindbrain.

Animals↗
PubMed1988

Prevalence of paralytic poliomyelitis in rural and urban populations in Ethiopia: report of a house-to-house survey.

A house-to-house survey was carried out to determine the prevalence of poliomyelitis. During the survey 37,219 households were visited and 17,941 children 5-9 years old were found. Of 231 lame children, lameness compatible with paralytic poliomyelitis was found in 131, of these 91% had their condition before the age of 3 years. Nineteen percent needed a stick support for walking while 12% were unable to walk even with support. This problem was more common in rural populations. The prevalence of paralytic poliomyelitis was 7.3/1,000 children 5-9 years old.

Cerebral Palsy↗
PubMed1988

A house-to-house survey of neonatal tetanus in urban and rural areas in the Gondar region, Ethiopia.

A house-to-house survey of neonatal tetanus was performed in 30 population clusters in Gondar, Northwestern Ethiopia. At the end of the survey 37,219 households were visited and 2010 live births were recalled. Out of the 2010 live-born children 127 had died. Eighty died during the neonatal period. Nine of the neonatal deaths were due to tetanus, giving a neonatal tetanus mortality rate of 4.5/1000 live births. The problem of neonatal tetanus in developing countries, particularly that of Ethiopia, is discussed.

Ethiopia↗