Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Reviews
Year : 2011 | Month : February | Volume : 5 | Issue : 1 | Page : 131 - 133 Full Version

Immune Mediated Containment And The Consequences Of The Human Immunodeficiency Virus Infection


Published: February 1, 2011 | DOI: https://doi.org/10.7860/JCDR/2011/.1108
GAYATHREE NAIK* , SRINIVAS R DESHPANDE**

*MD, Assistant Professor in Microbiology, Hassan Institute of Medical Sciences, Hassan, Karnataka Pin 573201, E mail:gaya3doc@yahoo.com.Ph: +91-9480158773; **MD, Associate Professor in Biochemistry, Malabar Medical College, Modakallur, Atholi, Calicut Dist, Kerala 670001

Correspondence Address :
Dr Srinivas R Deshpande
Professor and HOD Biochemistry,
Malabar Medical College, Modakallur, Atholi, Calicut Dist, Kerala 670001
E mail:sriradesh1971@yahoo.com.Ph:+91-9480158750

Abstract

The Human immunodeficiency virus infection is essentially an infection of the immune system, with progressive and profound defects in the cell mediated immune response. The pathogenesis of the Human immunodeficiency virus infection is a multi-factorial process, consisting of aberrant cellular activation and the disregulation of nearly every aspect of the immune system. The lentivirus subverts the immune system by infecting the CD4+Tcells that normally orchestrate immune responses and by activating the immune system and inducing a cytokine milieu that the virus uses to its own replication advantage. The disease outcome depends on the innate immune response, the adaptive immune response, the host genetic factors and the differences in viral pathogenicity.

Keywords

Human immunodeficiency (HIV) virus, chemokines, innate immunity, adaptive immunity.

Acquired immune deficiency syndrome (AIDS), (1) is a condition in which the human immune system begins to fail, leading to life-threatening opportunistic infections. (1) On exposure to the Human immunodeficiency virus (HIV), most individuals develop an early immune response that limits, but does not stop the virus from spreading throughout the body and destroying the host immune defenses. (1) Many recent studies have shed light on some of the potentially important factors of protective immune responses and have provided further insight into the viral kinetics, which determine the immune control, the viral adaptation and the immune escape. (1),(2) Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical in defining the time of origin and the timescale of the virus evolution. (2) The global HIV epidemic is due to a cross-species infection of humans by a chimpanzee lentivirus, called the simian immunodeficiency virus (SIVcpz), which occurred in West Central Africa.(3) Chimpanzees, are supposed to have acquired the SIVcpz sometime after their divergence into multiple sub-species viz. Pan troglodytes and P.t.schweinfurthii which are naturally infected.(4) SIVcpz is mostly an asymptomatic infection in chimpanzees and the experimental transmission of these viruses to susceptible non-natural hosts results however, in progressive and profound immunodeficiency and Acquired Immune Deficiency Syndrome (AIDS). Acquired Immune Deficiency Syndrome is defined by the development of serious opportunistic infections, neoplasms, or life threatening manifestations resulting from progressive HIV-induced immunosuppression. AIDS was first recognized in mid-1981, when unusual clusters of Pneumocystis jirovecii pneumonia and Kaposi’s sarcoma were reported in young, previously healthy, homosexual men in North America. (5) In 1983, two years after the first reports of AIDS, a cytopathic retrovirus was isolated from persons who were suffering with AIDS and associated conditions such as chronic lymphadenopathy.(6), (7)

MECHANISMS OF HIV TRANSMISSION Most cases of HIV infections worldwide are the result of sexual transmission across a mucosal surface, but the important modes also include parenteral transmission or transmission from mother to infant. For sexual transmission, the risk of male to male transmission is greater than the risk of heterosexual transmission, and it is highest in persons practicing receptive anal intercourse.(7)(8) Other factors that are hypothesized to possibly amplify transmission, include other co-infections (eg, malaria and tuberculosis, sexually transmitted diseases(STD), or in particular, the co-transmission of STD and HIV.(9)

THE IMMUNOLOGY OF HIV INFECTION(10) HIV induces the dysfunction of nearly all elements of the immune system and the pathogenesis of HIV disease is multifactorial. (10) .The immune response against HIV-1 is modulated by multiple host genetic determinants, many of which are directly or indirectly implicated in recognition of the virus [includes chemokine receptors, human leukocyte antigen (HLA), T-cell receptor (TCR), antibodies, Toll-like receptors (TLRs)], immune cell trafficking (includes chemokines and receptors, adhesion molecules), and immune response amplification (includes the molecules which are involved in signaling pathways and in the cytokine genes) (10) The immune response which is generated by the host and the selection pressure which is exerted on the virus, particularly at the time of early infection, direct the emergence of adaptive escape mutants. Accordingly, some mutations reduce the viral fitness and make it either revert to the wild-type or gradually wane out, whereas others might rescue the virus from host surveillance. (11) Thus, viruses have the ability to adapt and evolve differentially at varying rates in different individuals, depending on their host genetic architecture and their concordance in the immunome. In general, greater the immune concordance between the virus donor and the recipient, the easier it is for the virus to transcend and re-establish itself in the new host.(11)-(12)

HIV ENTRY AND DISSEMINATION: The first step in HIV and SIV infections involves the interaction between the gp120 and the CD4+T cells. (11) The two major chemokine co-receptors for HIV/SIV infections are the C-X-C chemokine receptor types 4 and 5 (CXCR4 &CCR5).(12), (13) A number of other chemokine receptors and related proteins can serve as co-receptors for the HIV/SIV fusion and the infection in cultured cells. These include CCR2b, CCR3, CCR8, APJ, Bonzo (STRL33).BOB (GPR15), and US28.(14) The primary function of the viral Env glycoproteins is to promote a fusion reaction between the viral and the target cell membranes. This membrane fusion enables the viral core to gain entry into the host cell cytoplasm.

IMMUNE MEDIATED CONTAINEMENT: Retroviruses possess the ability to convert their single- stranded RNA (ssRNA) genomes into dsDNA during the early stages of the infection process.(15),(16) This reaction is catalysed by the enzyme, reverse transcriptase, in conjunction with its associated ribonuclease (RNAase H) activity. The retroviral genome is packaged into the virion as two copies of ssRNA. (15),(16) A distinguishing feature of the retrovirus replication is the insertion of a DNA copy of the viral genome into the host cell chromosome after reverse transcription. The integrated viral DNA (the provirus) serves as a template for the synthesis of viral RNA and is maintained as a part of the host cell genome for the lifetime of the infected cell. (17) The recovery from many human viral infections is not associated with the eradication of infection, but rather with immune mediated containment. Although HIV infection is associated with progressive and ultimately profound immunosuppression, a highly variable course of disease has been seen among the infected persons. The disease outcome depends on the innate immune response, the adaptive immune response, the host genetic factors and the differences in viral pathogenicity.

INNATE IMMUNE RESPONSES The initial immune response to HIV involves innate immune mechanisms.

A) DENDRITIC CELLS (DC’s): Plasmacytoid dendritic cells (pDCs) are important mediators of innate immunity that act mainly through the secretion of interferon –α (IFN-α) . (18)DCs are among the first cells to encounter HIV after mucosal exposure and are probably responsible for transporting the virus to the lymphoid organs, thus facilitating the infection of the CD4+T cells and viral dissemination. DCs express several different chemokine receptors that can be used as HIV co-receptors for entry.(18),(19) Beignon et al showed that toll like receptors(TLR) on plasmacytoid dendritic cells(pDCs) are activated by HIV-1 RNA via TLR-7, resulting in high levels of interferon alpha (IFN-α) ,interleukin-12, tumour necrosis factor alpha(TNF- α ), and IL-6( Interleukin-6), which together result in a profound activation of the immune system. (20),(21) These plasmacytoid dendritic cells are also infectable with HIV, and may contribute to impaired dendritic cell functions in infected persons.(22) ; additionally, pDCs have been shown to be severely reduced in number in the peripheral blood of HIV-infected individuals. (18)-(21)

B) NATURAL KILLER CELLS: Natural killer cells (NK) are also a part of the innate immune response to HIV. The presumed role of the Natural killer cells is to provide immunesurveillance against the virus-infected cells, certain tumour cells, and the allogeneic cells. Abnormalities of NK cells are observed throughout the course of the HIV disease and these abnormalities increase with disease progression. NK cells from HIV- infected individuals are defective in their ability to kill typical NK target cells, as well as the gp160-expressing cells. HIV viraemia is inversely correlated with the ability of the Natural killer cells and the NK- derived cell supernatants to suppress virus replication.(23) The abnormality in NK cell lysis is thought to occur after the binding of the NK cell to its target.(24) Natural killer cells from HIV-infected individuals are able to mediate ADCC (Antibody-Dependent Cell-mediated Cytotoxicity) (25) and are an important source of HIV inhibitory chemokines in HIV- infected individuals. NK cells which are isolated from HIV-infected individuals produce high constitutive levels of Macrophage Inflammatory Protein -1α (MIP -1α), Macrophage Inflammatory Protein 1β (MIP -1 β), and RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted).(26),(27) Thus, NK cells, like CD8+T cells, may inhibit HIV replication by cell- mediated killing, as well as by the secretion of soluble HIV inhibitory factors.

(C) NEUTROPHILS: Dysregulation of neutrophil function occurs at all stages of the HIV infection. The oxidative capacity of neutrophils, after priming with the granulocyte-macrophage colony stimulating factor, is also increased in HIV-infected individuals. (27)The opsonising activity of neutrophils is significantly impaired. Neutrophils from AIDS patients undergo apoptosis at an increased rate, as compared with those from the normal controls.(28) The dysfunction of neutrophils in HIV-infected individuals, especially in women, is characterized by an increased incidence and the severity of candida infection, due to a defective non-oxidative killing.(29)

(D) MONOCYTES-MACROPHAGES: Cells of the monocyte-macrophage lineage play key roles in the immunopathogenesis of the HIV disease. These cells serve as reservoirs of viral infection. The dysfunction of these cells contributes to CD4+T cell dysfunction and to the impaired host defense against intracellular pathogens.(30) Monocytes express CD4 and numerous HIV co-receptors on their surface, including CCR5,CXCR4,and CCR3, and serve as targets for HIV infection. (31),(32) HIV is relatively non-cytopathic for cells of the monocyte-macrophage lineage than the CD4+Tcells, and HIV can replicate extensively in these cells.(33) Cells of the monocyte-macrophage lineage are central, even to the pathogenesis of the HIV-induced central nervous system disease. The HIV infection of the brain microglial cells, derived from the monocyte lineage, may lead to encephalopathy, neuropathy, astrocytocis, and cerebral vasculitis.(34) The levels of monocyte chemotactic protein type 1(MCP-1) are markedly elevated in the cerebrospinal fluid of AIDS patients. HIV infected macrophages are likely to be a major source of these high levels of MCP-1. MCP-1 in turn, recruits and activates monocytes, which elaborate pro-inflammatory cytokines and thereby enhance HIV replication and induce neuropathological diseases.(35) Impaired accessory cell function may result from decreased MHC (Major Histocompatibility complex) class II expression, decreased interleukin-12 secretion, and from increased IL-10 secretion. HIV- induced dysregulation of antigen presentation can in turn cause the hypo-responsiveness of the CD4+T cells. HIV-associated abnormalities in antigen uptake, oxidative burst, and chemotaxis have been described in monocyte-macrophages (36) as a consequence of the poor intracellular killing of the Candida species yeast forms, (37) Toxoplasma gondii, (38) and Histoplasma capsulatum(39).

ADAPTIVE IMMUNE RESPONSES

(A) HUMORAL IMMUNE RESPONSES: Human immunodeficiency virus infection is associated with the development of antibodies that appear within one week of the initial infection. A subset of these can neutralize the virus, either by binding directly to the envelope glycoprotein trimer on the surface of the free virions, or following CD4-gp120 binding after virus attachment, thus preventing the fusion of the viral and the cell membranes, which is essential for viral entry.(40) The viral envelope is highly glycosylated, and these sugars prevent antibody binding to the underlying peptidic structure. These neutralizing antibody responses are sufficiently strong to influence viral evolution, thus leading to mutant viruses that escape recognition. New antibodies develop to neutralize the mutant virus that escapes again. (41)
(B) CELLULAR IMMUNE RESPONSES

(1) CD8+T CELL RESPONSES: Adaptive immunity generally involves the rapid expansion of the CD8+T cells which recognize foreign proteins on the infected cell surface, which are presented by the HLA antigen class I molecules. Direct cytolysis by the CD8+T cells occurs, which recognizes the viral oligo-peptides at the cell surface, thereby eliminating the production of the virus from that cell. In the early weeks following HIV infection, the viral load was found to decrease from an average of 1Ă—106 copies/ml to an average of 30,000 copies/ml.(42) The CD8+T cells of HIV –infected patients secrete soluble factors that are able to inhibit viral replication in the absence of cell killing. Suppressive activity is mediated by chemokines, MIP-1α, MIP-1β, and RANTES. These chemokines are natural ligands for CCR5, a co-receptor for the R5 strain of HIV-1 and inhibit viral replication primarily by blocking virus entry. In addition, after the entry of the virus, the chemokines suppress HIV transcription in the infected cells.(43)
(2) CD4+T CELL RESPONSES: The optimal function of the CD8+T cells depends on the presence of virus- specific CD4+T cells which help to co-ordinate an effective cytotoxic T-lymphocyte(CTL) response that mediates the restriction of virus replication by the production of Interferon-γ.(44)

HOST GENETICS AND VIRAL CONTROL One of the strongest predictors of disease progression is the HLA type of the host. The HLA class I alleles, B*27 and B*57 are associated with a low viral load and prolonged asymptomatic infection.(45) Other HLA alleles which are associated with a more rapid disease progression, include the subtype HLA B35 allele, which is referred to as HLA B35px.(46)

Conclusion

HIV has the capability to subvert the activation of the human immune system to its own replication advantage. The immune control of HIV often fails due to viral escape from the cellular and the humoral host immune responses. (47) Many viral factors and host genetic characteristics play a crucial role in the control of the HIV disease by delaying the progression to AIDS or even by preventing infection.48 Further, the HIV disease progression is intimately related to virus replication, and the net amount of virus replication reflects a balance among the factors that either induce or downregulate the virus expression (49),(50) Chemokine receptors function as the necessary cofactors for HIV entry into the target cells and represent new potential targets of therapeutic intervention. (51),(52) Elements of both humoral and cell mediated immune responses against HIV have been implicated in the partial control of virus replication. A near complete understanding about the virus –host interactions that lead to the dysfunction and the depletion of the immune system, can only aid in the development of prevention and effective therapeutic strategies.

References

1.
Kuritzkes DR and Walker BD. Field’s Virology. 5th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins; . Chapter 58, HIV-1: Pathogenesis, clinical manifestations, and treatment;2007; p. 2187-97.
2.
Worobey M, Gemmel M, Teuwen DE, Haselkorn T, Kuntsman K, Bunce M et al. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960. Nature 2008; 455 (7213): 661-4.
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