Download Free Medical Neonatal and paediatric immunology relevant to HIV persistence PowerPoint Presentation

Neonatal and paediatric immunology relevant to HIV persistence PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Neonatal and paediatric immunology relevant to HIV persistence.

Tags : Pediatrics, Child Health, pediatric practice, pediatrician, health providers, HIV-infected infants, Adolescent Transition, HIV-infected adolescents, paediatric immunology, Neonatal

Published on : Jul 18, 2020 | Views : 1732 | Downloads : 2

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

IAS 2016 Towards an HIV Cure Symposium Durban, South Africa www.iasociety.org Neonatal and paediatric immunology relevant to HIV persistence Deena Gibbons PhD Peter Gorer Department of Immunobiology Kings College London & Nigel Klein MD PhD Institute for Child Health University College London
Slide 2-

Neonatal Immunology and HIV Infant immunology qualitatively/ quantitatively different from that in the adult. Different immune response to HIV Different HIV susceptibility Different HIV persistence unique aspects towards cure. www.iasociety.org
Slide 3-

So what is different in infants? Innate immunity Monocytes DCs PMNs TLRs Levy et al, Blood 108:1284 (2006); Smed-Sorenson et al, J Virol 79:8861 (2005) Impaired response to TLR7 (detects ss RNA of HIV) in neonatal monocytes pDC: mDC in adult 1:2 pDC: mDC in infant 3:1 www.iasociety.org
Slide 4-

So what is different in infants? Adaptive immunity T follicular helper cells T cells B cells Development of TFH in newborn mice defective compared to adults -major reservoir of HIV T memory stem cell (TSCM)? -HIV reservoir Majority are naïve in infant (less susceptible to HIV?) Much higher CD4:CD8 ratio Banga et al, Nat Med 22:754 (2016); Bamford et al, Clin Exp Immunol 181:110 (2014) Debock et al, JI 191:1231 (2013); Buzon et al, Nat Med 20:139 (2014). www.iasociety.org
Slide 5-

Sundaravaradan et al PNAS 103: 11701 (2006) 3x increased replication of HIV in cord blood T cells 9x increased replication of HIV in cord blood monocytes Differential expression of host factors determine this susceptibility Contributes to faster disease progression in neonates Increased replication of HIV in CB mononuclear cells Sundaravaradan et al Virology 400:32 (2010) www.iasociety.org
Slide 6-

Although under optimal circumstances, lymphocytes from neonates can mount robust responses, the responses in neonates, particularly Th1 responses, are sub-optimal / almost non-existent, conventionally explained as a way to maintain tolerance. Birkholz et al, Human Immunology 75 584 (2014) www.iasociety.org Zaghouani and Adkins, Trends Immunol 30:.585 (2009). Neonatal T cell Function
Slide 7-

Infants do make immune responses to HIV Thobakgale et al, J Virol. 81:12775 (2007) www.iasociety.org
Slide 8-

Tolerogenic environment Decreased type 1 IFNs Decreased levels of Th1 cytokines (IL12/IFN), some bias towards Th2 and extracellular pathogen clearance Low magnitude (or non existent) CD4 and CD8 responses with narrow specificity Contributes to faster disease progression in neonates? Prendergast et al, Nat Rev Immunol 12:636 (2012) Lohman-Payne et al, Clin Exp Immunol178:86 (2014), Wang et al J. Leuk Biol 97:391 (2015) Does the T cell function influence HIV viraemia in children? www.iasociety.org
Slide 9-

Log10 HIV-1 RNA plotted against age in untreated HIV-infected children Log10 RNA copies/ml 0 2 4 6 8 Age in years 10 3 www.iasociety.org 4 5 6 PENTA, AIDS 12:F1-F8 (1998)
Slide 10-

But… neonatal CD4 are not inert.. just different Adult Baby IL-17 IFN …..they make CXCL8 www.iasociety.org CXCL8 CD4
Slide 11-

% of CD4 making CXCL8 decreases with age www.iasociety.org
Slide 12-

Mainly produced by epithelia, macrophages, fibroblasts Two forms 77aa/72aa .Recruits neutrophils to phagocytose antigen Human PMNs can’t respond to IL17 Binds CXCR1 & CXCR2 Levels of receptors are tightly controlled www.iasociety.org CXCL8
Slide 13-

CXCR1+ve CD8 defines a highly cytotoxic CD8 T cell Does CXCR1 define a “rapid-responder” subset of CD8 T cells that bridges the gap between the innate and acquired immune responses. Interestingly, significant expression of CXCR1 on HIV-1–specific CD8 T cells in individuals on HAART was restricted to persons who were able to control HIV-1 replication when taken off HAART. Takata et al. Blood 119:1390 (2012) Hess et al Blood 104:3463-3471 (2004) www.iasociety.org CXCL8 receptors
Slide 14-

Summary I www.iasociety.org Human neonatal immune system is not just an immature version of the adult Neonates have different responses - not sub-optimal. Classic adult HIV reservoirs may not be the same in infants
Slide 15-

Thymic Output is a key difference Vital for a diverse T-cell repertoire High thymopoesis in infancy, declining with age Difficult to measure / complex interplay Bains et al Blood 2009 Sangaard et al AIDS 28.209 2014 www.iasociety.org
Slide 16-

Increased Thymic output leads to a different pattern of Immune Reconstitution Sefe et al Paeds and Child Health 17:121. 2007 Pakker et al Nat Med 4.208. 1998 Bunupuradah et al AIDS 27:579 2013 www.iasociety.org
Slide 17-

The decline in Thymic Output has an important influence on eventual CD4 count www.iasociety.org
Slide 18-

The decline in Thymic Output has an important influence on eventual CD4 count Robbins et al CID 48.350 2009 Walker AS Manuscript in preparation from Arrow Trial www.iasociety.org
Slide 19-

age THYMUS EFFECTOR MEMORY T CELLS CD45RO+ NAÏVE T CELL POOL CD45RA+ antigen antigen death ✟ death ✟ death ✟ HIV Reservoirs may be different in children and can be influenced by the balance between tolerogenic environment and drivers of immune activation www.iasociety.org
Slide 20-

Cells more permissive to HIV infection are present in newborns and early childhood Bunders et al Immunobiology 120:4383 2012 Lawrie et al SAMJ 105:589 2015 Targets in Gut and LNs found in neonates More memory cells and activation in Africa www.iasociety.org
Slide 21-

Drivers of immune activation may exceed immune tolerance Doyle et al submitted Prendergast et al et al. AIDS Res. and Hum Retr. 28:465 (2012) Mold et al Science 322:1562 2008 www.iasociety.org
Slide 22-

Majority of infants treated early don’t seroconvert www.iasociety.org Payne et al Lancet ID 15:803 2015 Butler et al PIDJ 34:3 2015
Slide 23-

New initiatives to understand immunological responses associated with viral control time HIV RNA Birth/perinat al HIV infection On ART (acute phase) Off-ART (interruption/low adherence) 50 cp/mL slow suppressor rapid suppressor rapid rebounder slow rebounder EPPICC IMPAACT 1115 CHER CHERUB-UK NEVEREST CHANGES Thai Cohort www.iasociety.org IMPAACT 1115 CHER PENTA11 Elite controllers Palma P. et al. J. Viral Eradic 2015
Slide 24-

Summary II www.iasociety.org Children have much higher Thymic Output with better immune reconstitution Infants do not seroconvert to HIV if ART started early which affords unique opportunities for immune modulation to HIV The balance between immune tolerance and activation may be key to the future Cure agenda for children

User Presentation
Related Presentations

High HIV prevalence in infants attending nutrition and inpatient entry points

By: MarieAltmann
Views: 1830

High-Resource Perspective on Adolescent Transition and Research Priorities

By: MarieAltmann
Views: 2172

OUTCOMES OF HIV EXPOSED INFANTS BEFORE AND AFTER IMPLEMENTING OPTION B Plus PMTCT GUIDELINE IN KAMPALA

By: MarieAltmann
Views: 1718

Impact of the frequency of plasma viral load monitoring on treatment outcome among perinatally HIV-infected Asian children stable on first-line cART

By: MarieAltmann
Views: 2243

Pediatric Drug Pipeline: New Drugs, New Strategies

By: MarieAltmann
Views: 1756

Growth and Development

By: medhelp
Views: 2182

Neonatal Hypoglycemia and Hypocalcemia

By: medhelp
Views: 2153

Pediatrics

By: drdwayn
Views: 2119

Its A Gut Feeling: Abdominal Pain in Children

By: JenniferDwayne
Views: 2141

Birth Defects

By: medhelp
Views: 1750

MarieAltmann

About : I am a passionate Pediatrician with experience of working in world-renowned hospital systems as well as community-based clinics. I have skills like Advocacy, Team Building, Event Planning, and Public Speaking. A dedicated and worthy healthcare services professional with a MPH focused in International studies from Tulane School of Public Health and Tropical Medicine.
Occupation : Medical Professional
Specialty : MD
Country : United States of America
Website :

HEALTH A TO Z