Infections and the immune system

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Mol Immunol 2002 Jan;38(8):567-80 Related Articles, Books, LinkOut

Regulation of cytokine gene transcription in the immune system.

Holloway AF, Rao S, MF.

Division of Biochemistry and Molecular Biology, Curtin School of

Medical Research, Australian National University, Canberra ACT 2601,

Australia.

The controlled expression of cytokine genes is an essential component of an

immune response. The specific types of cytokines as well as the time and

place of their production is important in generating an appropriate immune

response to an infectious agent. Aberrant expression is associated with

pathological conditions of the immune system such as autoimmunity, atopy and

chronic inflammation. Cytokine gene transcription is generally induced in a

cell-specific manner. Over the last 15 years, a large amount of information

has been generated describing the transcriptional controls that are exerted

on cytokine genes. Recently, efforts have been directed at understanding how

these genes are transcribed in a chromatin context. This review will discuss

the mechanisms by which cytokine genes become available for transcription in

a cell-restricted manner as well as the mechanisms by which these genes

sense their environment and activate high level transcription in a transient

manner. Particular attention will be paid to the role of chromatin in

allowing transcription factor access to appropriate genes.

PMID: 11792425 [PubMed - indexed for MEDLINE]

Adv Exp Med Biol 2001;490:99-107 Related Articles, Books, LinkOut

Functional role of epitope spreading in the chronic pathogenesis of

autoimmune and virus-induced demyelinating diseases.

SD, Eagar TN.

Department of Microbiology-Immunology and Interdepartmental Immunobiology

Center, Northwestern University Medical School, Chicago, IL 60611, USA.

These results support a model of epitope spreading (Figure 4) wherein

localized virus-specific T cell-mediated inflammatory processes lead to the

recruitment/activation of CNS-resident APCs which can serve both as effector

cells for myelin destruction and as APCs which efficiently process/present

endogenous self epitopes to autoreactive T cells. Thus, inflammatory

responses induced by viruses which trigger pro-inflammatory Th1 responses

and have the ability to persist in genetically susceptible hosts, may lead

to chronic organ-specific autoimmune disease via epitope spreading.

Regardless of the specificity of the T cells (myelin peptides in R-EAE or

TMEV epitopes in TMEV-IDD) responsible for initiating myelin destruction,

epitope spreading plays an important contributory role in the chronic

disease process in genetically susceptible SJL mice. Epitope spreading has

obvious important implications to the design of antigen-specific therapies

for the potential treatment of MS and other autoimmune diseases. This

process indicates that autoimmune diseases are evolving pathologies and that

the specificity of the effector autoantigen-specific T cells varies during

the chronic disease process.

Publication Types:

Review

Review, Tutorial

PMID: 11505979 [PubMed - indexed for MEDLINE]

J Neurovirol 2001 Apr;7(2):117-24 Related Articles, Books, LinkOut

Persistence of the influenza A/WSN/33 virus RNA at midbrain levels of

immunodefective mice.

Aronsson F, Karlsson H, Ljunggren HG, sson K.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Strains of influenza A virus are known to infect specific subpopulations of

neurons in the mouse brain. Here we report that all segments of the genome

of the neurotropic influenza A virus, strain WSN/33, can persist in the

brains of immunodefective transporter associated with Antigen Processing 1

(TAP1) mutant mice. Ten to 17 months after injection of virus into the

olfactory bulbs, viral RNA encoding the nonstructural NS1 protein was

detected in sections from the brain at midbrain levels by RT-PCR in almost

all animals. Both negative-strand genomic RNA (vRNA) and positive-strand

RNA, including mRNA, were found. RNA encoding nucleoprotein and polymerases,

which form the replicative complex of the virus, were detected in fewer

brains. RNA encoding envelope proteins were found only in occasional brains.

No viral cDNA could be identified. This observation shows that certain

regions of the brain in immunodefective mice may harbor the genome of

influenza A virus including the NS1 gene, the products of which may play a

regulatory role in host-cell metabolism.

PMID: 11517384 [PubMed - indexed for MEDLINE]

J Immunol 2001 Sep 15;167(6):3470-7 Related Articles, Books, LinkOut

The central nervous system inflammatory response to neurotropic virus

infection is peroxynitrite dependent.

Hooper DC, Kean RB, GS, Spitsin SV, Mikheeva T, Morimoto K, Bette M,

Rohrenbeck AM, Dietzschold B, Weihe E.

Department of Microbiology and Immunology, Jefferson University,

Philadelphia, PA 19107, USA. douglas.c.hooper@...

We have recently demonstrated that increased blood-CNS barrier permeability

and CNS inflammation in a conventional mouse model of experimental allergic

encephalomyelitis are dependent upon the production of peroxynitrite

(ONOO(-)), a product of the free radicals NO* and superoxide (O2*(-)). To

determine whether this is a reflection of the physiological contribution of

ONOO(-) to an immune response against a neurotropic pathogen, we have

assessed the effects on adult rats acutely infected with Borna disease virus

(BDV) of administration of uric acid (UA), an inhibitor of select chemical

reactions associated with ONOO(-). The pathogenesis of acute Borna disease

in immunocompetent adult rats results from the immune response to the

neurotropic BDV, rather than the direct effects of BDV infection of neurons.

An important stage in the BDV-specific neuroimmune response is the invasion

of inflammatory cells into the CNS. UA treatment inhibited the onset of

clinical disease, and prevented the elevated blood-brain barrier

permeability as well as CNS inflammation seen in control-treated

BDV-infected rats. The replication and spread of BDV in the CNS were

unchanged by the administration of UA, and only minimal effects on the

immune response to BDV Ags were observed. These results indicate that the

CNS inflammatory response to neurotropic virus infection is likely to be

dependent upon the activity of ONOO(-) or its products on the blood-brain

barrier.

PMID: 11544340 [PubMed - indexed for MEDLINE]

Nihon Kokyuki Gakkai Zasshi 2001 Oct;39(10):763-9 Related Articles, Books,

LinkOut

[A case of lymphocytic interstitial pneumonia with Sjogren's syndrome and

systemic lupus erythematosus in which human herpes virus-6 infection was the

suspected pathogen]

[Article in Japanese]

Totani Y, Demura Y, Ameshima S, Miyamori I, Ishizaki T.

Third Department of Internal Medicine, Fukui Medical University,

Matsuoka-town, Fukui 910-1193, Japan.

A 47-year-old-woman was admitted to our hospital complaining of thirst and

dry cough after catching cold. Sjogren's syndrome (SjS) and systemic lupus

erythematosus (SLE) were diagnosed. Chest X-P and CT findings suggested

strongly that she had interstitial pneumonia. Thoracoscopic lung biopsy was

therefore performed, and the biopsy specimens showed marked infiltration of

small lymphocytes and of plasma cells into the alveolar walls and

interlobular septa. Since the infiltrating cells were not atypical and gene

analysis did not show mono-clonality, we made a diagnosis of lymphocytic

interstitial pneumonia (LIP). Because the patient's symptoms appeared only

after she caught cold, we suspected that virus infections were somewhat

involved in the etiology of these diseases. The level of human herpesvirus-6

(HHV-6) antibody was high, and furthermore, HHV-6 was detected using the

polymerase chain reaction from lung biopsy specimens. We suspected in this

case that LIP, SjS, and SLE had appeared concomitantly after an active HHV-6

infection.

PMID: 11828732 [PubMed - indexed for MEDLINE]

Semin Arthritis Rheum 2002 Feb;31(4):256-63 Related Articles, Books, LinkOut

Viral infections and antiphospholipid antibodies.

Uthman IW, Gharavi AE.

Department of Internal Medicine, Faculty of Medicine, American University of

Beirut, Beirut, Lebanon; and the Morehouse School of Medicine, Atlanta, GA.

OBJECTIVE: To study the relationship between viral infections and the

induction of antiphospholipid (aPL) antibodies. METHODS: We reviewed the

medical literature from 1968 until 2000 using MEDLINE and the key words

virus, infection, antiphospholipid, and anticardiolipin. RESULTS:

Anticardiolipin antibodies and/or lupus anticoagulant were associated with a

number of viral infections, including hepatitis C virus, human

immunodeficiency virus, cytomegalovirus, varicella zoster, Epstein-Barr

virus, adenovirus, and parvovirus B. In many instances, the presence of

these antibodies was associated with thrombosis. CONCLUSION: The clinical

significance of finding aPL antibodies in patients with viral infections

remains unknown. In some patients, these antibodies may be transient and

disappear within 2 or 3 months. In other susceptible individuals, they may

persist and raise the question of whether infections may trigger the

development of aPL antibodies in autoimmune diseases. Semin Arthritis Rheum

31:256-263. Copyright 2002, Elsevier Science (USA). All rights reserved.

PMID: 11836658 [PubMed - in process]

Z Naturforsch [C] 2001 Nov-Dec;56(11-12):1135-43 Related Articles, Books,

LinkOut

Cross--reactivity of the V3-speciflc antibodies with the human C1q.

Petkovic M, Metlas R.

Institute of Medical Physics and Biophysics, Medical Faculty, University of

Leipzig, Germany. petm@...

It has been previously shown that the sequence similarity between a portion

of the envelope glycoprotein 120 (gp120) from the human immunodeficiency

virus type-1 (HIV-1) and several types of human collagen and collagen-like

molecules exists. That observation led to the suggestion that the antibodies

against the third hypervariable region (V3) of HIV-1 gp120 (V3-specific

antibodies) might have a role in the autoimmune phenomena observed in

HIV-infected persons. In this study we have examined the cross-reactivity of

the V3-specific antibodies purified from sera of HIV-infected individuals,

sera obtained from the rheumatoid arthritis and systemic lupus crythematosus

patients, as well as from the sera of healthy volunteers with the separate

chains of a subcomponent of the first component of the human complement

system, Clq. Our results show that the V3-specific antibodies are present in

the sera of the HIV-infected individuals, patients suffering of the systemic

autoimmune diseases as well as in the sera of healthy volunteers. Whereas

these antibodies appeared in the HIV+-sera after antigen challenge, those

present in the HIV- -sera probably represent the antibodies that are

cross-reactive with the antigen. V3-reactive antibodies can be purified by

affinity chromatography and they were highly specific for the V3-peptide.

Additionally, they showed cross-reactivity with the separate chains of the

human Clq as well as with the chicken collagen type VI. Possible

physiological implications are discussed.

PMID: 11837669 [PubMed - in process]

Clin Immunol 2002 Feb;102(2):107-116 Related Articles, Books, LinkOut

Endogenous Retroviruses in Systemic Lupus Erythematosus: Candidate Lupus

Viruses.

Adelman MK, Marchalonis JJ.

Microbiology and Immunology, The University of Arizona, Tucson, Arizona,

85724

Although the etiology of systemic lupus erythematosus (SLE) remains unclear,

there is substantial circumstantial evidence that the development of SLE is

dependent on environmental, genetic, and retroviral factors. SLE patients

produce high titer antibodies to various retroviral proteins, including Gag,

Env, and Nef of HIV and HTLV, in the absence of overt retroviral infection.

We review the factors linking HERVs to SLE and consider the various

processes utilized by endogenous retroviruses in the etiopathogenesis of

SLE. In particular, we consider the role of HTLV-1-related endogenous

sequence (HRES-1) in SLE. We propose that molecular mimicry between HRES-1

and the small ribonucleoprotein complex initiates the production of

autoantibodies, leading to immune complex formation, complement fixation,

and pathological tissue deposition. [copyright]2002 Elsevier Science (USA).

PMID: 11846452 [PubMed - as supplied by publisher]

Microbes Infect 2001 Nov;3(14-15):1249-59 Related Articles, Books, LinkOut

The involvement of class Ib molecules in the host response to infection with

Salmonella and its relevance to autoimmunity.

Soloski MJ, Metcalf ES.

Division of Rheumatology, Department of Medicine and The Graduate Program in

Immunology, The s Hopkins University School of Medicine, MD 21218,

Baltimore, USA

Class I molecules with limited polymorphism have been implicated in the host

response to infectious agents. Following infection with Salmonella

typhimurium, mice develop a CD8(+) CTL response that specifically recognizes

bacteria infected cells. An immunodominant component of the CTL response

recognizes a peptide epitope derived from the Salmonella GroEL molecule that

is presented by the non-polymorphic MHC class Ib molecule Qa-1. T cells

recognizing the bacterial peptide also cross-recognize a homologous peptide

from the mammalian hsp60 molecule. Since Qa-1 has a functional equivalent in

humans, this observation may be relevant not only to the host response

involved in clearing infection but also in understanding the link between

infection with Gram-negative pathogens and autoimmune disease.

PMID: 11755413 [PubMed - in process]

Eur Respir J 2001 Dec;18(6):1013-25 Related Articles, Books, LinkOut

The immunology of virus infection in asthma.

Message SD, ston SL.

National Heart and Lung Institute, Dept of Respiratory Medicine, Imperial

College School of Medicine at St 's, London, UK.

The respiratory tract is commonly infected by a range of viruses with

overlapping pathologies. The majority of episodic exacerbations of asthma

are associated with viral infection, in particular with rhinovirus

infections. Experimental rhinovirus infection in human volunteers provides a

useful model of natural virus-induced asthma. The asthmatic airway is

characterized by an infiltrate of eosinophils and T-lymphocytes expressing

the type 2 cytokines interleukin (IL)-4, IL-5 and IL-13. An effective

antiviral immune response requires early viral clearance and appropriate

termination of the immune response to minimize associated immunopathology

and tissue damage. The antiviral immune response is made up of innate

(nonspecific) and specific components, and requires the coordinated actions

of many different cell types including neutrophils, macrophages,

eosinophils, dendritic cells, epithelial cells, mast cells, natural killer

cells and B- and T-lymphocytes. Coordination of this response involves

numerous cytokines and chemokines. T-lymphocytes expressing type 1 cytokines

including interferon-gamma play a key role. Pre-existing asthmatic

inflammation in the lower airway may modify the immune response to viral

infection by altering the balance of T-cell cytokine expression from type 1

towards a type 2 in what is always a mixed response. The consequence is

delayed viral clearance, persistent virus-induced inflammation and

amplification of the allergic inflammation.

PMID: 11829084 [PubMed - in process]

J Clin Endocrinol Metab 2002 Feb;87(2):752-7 Related Articles, Books,

LinkOut

Identification of the 49-kDa autoantigen associated with lymphocytic

hypophysitis as alpha-enolase.

O'Dwyer DT, AI, ML, Andronicos NM, Ranson M, PJ,

Crock PA.

Pediatric Endocrine Unit, Hunter Children's Hospital, University of

Newcastle, Newcastle, New South Wales 2310, Australia.

Lymphocytic hypophysitis is part of the spectrum of organ-specific

autoimmune diseases, and although its histopathology is well documented, its

pathogenesis is unclear. Serum autoantibodies directed against a 49-kDa

cytosolic protein are detected by immunoblotting in 70% of patients with

biopsy-proven lymphocytic hypophysitis. Here we report the purification and

identification of this first target autoantigen in lymphocytic hypophysitis.

The autoantigen has a molecular mass of 49 kDa, a cytosolic localization,

and a ubiquitous tissue distribution. The 49-kDa protein was purified from

monkey brain and human placental cytosol. Limited amino acid sequencing

after proteolytic digestion of the human placental protein showed identity

with alpha-enolase. The identification was confirmed using sera from

patients with pituitary autoimmunity, which strongly reacted with

recombinant human alpha-enolase and yeast enolase, but not with rabbit

muscle beta- enolase. This indicates that the immunoreactive epitopes are

largely conserved from yeast to human, but are not present in beta-enolase.

alpha-Enolase autoantibodies are not specific to pituitary autoimmune

disease and have been reported in other autoimmune diseases. However, this

study is the first to indicate a role for alpha-enolase as an autoantigen in

lymphocytic hypophysitis.

PMID: 11836316 [PubMed - in process]

J Clin Invest 2002 Jan;109(1):79-87 Related Articles, Books, LinkOut

Presented antigen from damaged pancreatic beta cells activates autoreactive

T cells in virus-mediated autoimmune diabetes.

Horwitz MS, Ilic A, Fine C, E, Sarvetnick N.

Department of Immunology, The Scripps Research Institute, La Jolla,

California 92037, USA.

The induction of autoimmunity by viruses has been attributed to numerous

mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent

diabetes mellitus (IDDM) resembling the final step of disease progression in

humans. The immune response following the viral insult clearly precipitates

IDDM. However, the molecular pathway between viral infection and the

subsequent activation of T cells specific for islet antigen has not been

elucidated. These T cells could become activated through exposure to

sequestered antigens released by damaged beta cells, or they could have

responded to factors secreted by the inflammatory response itself. To

distinguish between these possibilities, we treated mice harboring a

diabetogenic T cell repertoire with either the islet-damaging agent

streptozotocin (STZ) or poly I:C, which nonspecifically activates T cells.

Significantly, only treatment of mice with STZ resulted in IDDM and mimicked

the effects observed following CB4 infection. Furthermore,

antigen-presenting cells from STZ-treated mice were shown to directly

activate autoreactive T cells and induce diabetes. Therefore, the primary

role of CB4 in the precipitation of IDDM is to damage tissue, causing

release and presentation of sequestered islet antigen. These events

stimulate autoreactive T cells and thereby initiate disease.

PMID: 11781353 [PubMed - indexed for MEDLINE]

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