pendekatan imunodefisiensi
DESCRIPTION
imuodefisiensiTRANSCRIPT
Imunodefisiensi Imunodefisiensi
Evy YunihastutiEvy Yunihastuti
Immunodeficiency andImmunodeficiency andAutoimmunityAutoimmunity
Evy YunihastutiEvy Yunihastuti
ImmunodeficiencyImmunodeficiency
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ImmunodeficiencyImmunodeficiency
• Primary Primary ImmunodeficiencyImmunodeficiency– Neutrophil defectsNeutrophil defects– Humoral: B cell Humoral: B cell
defectsdefects– Humoral: ComplementHumoral: Complement– Cell-mediatedCell-mediated:: T cells T cells– Severe combined Severe combined
immunodeficiencyimmunodeficiency
• Secondary Secondary ImmunodeficiencyImmunodeficiency– AIDSAIDS– NeutropeniaNeutropenia
• Post-transplantPost-transplant• BMTBMT• chemotherapychemotherapy
– Splenectomised Splenectomised patientpatient
Immunodeficiency in adultsImmunodeficiency in adults
Infectious disease: HIV
Infectious disease: HIV
Environmental stress
Environmental stress
Age extremes: old age
Age extremes: old age
Surgery & trauma, splenectomy
Surgery & trauma, splenectomy
Immunosuppresive drugs *
Immunosuppresive drugs *
malnutritionmalnutrition
Genetic and metabolic disease
Genetic and metabolic disease
Adaptive & innate
IMMUNITY
Adaptive & innate
IMMUNITYIMMUNODEFICIENCY
IMMUNODEFICIENCY
INFECTIONINFECTION
TUMORTUMOR
*20 mg or more per day of prednisone, 14 days or longerNOT aerosols, alternate day, short courses, topical
Chinen J, Shearer.WT. Secondary immunodeficiency. J Allergy Clin Immunol 2010; 125: S195-202 , Epidemiology and Prevention of Vaccine-Preventable Diseases. National Center for Immunization and Respiratory Diseases. CDC. Revised April 2009.
Body surfaces and their resident Body surfaces and their resident microbial floramicrobial flora
The immunodeficient hostThe immunodeficient host
• Virulent infection with common Virulent infection with common organism (e.g. TB)organism (e.g. TB)
• Infection with opportunistic pathogenInfection with opportunistic pathogen– virus (cytomegalovirus - CMV)virus (cytomegalovirus - CMV)– bacteria (bacteria (Mycobacterium avium Mycobacterium avium
intracellulare)intracellulare)– fungi (aspergillus, candida, pneumocystis)fungi (aspergillus, candida, pneumocystis)– protozoa (cryptosporidia, toxoplasma)protozoa (cryptosporidia, toxoplasma)
Immunodeficient patients Immunodeficient patients are…are…• More susceptible to infection and diseaseMore susceptible to infection and disease
• More likely to develop persistent infectionMore likely to develop persistent infection
• More likely to develop multiple infectionsMore likely to develop multiple infections
• may develop unusual clinical may develop unusual clinical manifestations, i.e. which are not seen in manifestations, i.e. which are not seen in immunocompetent patientsimmunocompetent patients
Acquired Immunodeficiency Acquired Immunodeficiency NeutropeniaNeutropenia
• Timely admission in cyclical chemotherapyTimely admission in cyclical chemotherapy– <0.5 x 10<0.5 x 1099/l risk of infection/l risk of infection– <0.1 x 10<0.1 x 1099/l high risk of septicaemia/l high risk of septicaemia
NeutrophilsX 109/l
Time (days)
Cytotoxic
0.50.1
Onset maximum risk
2 4 6 8 10 12
Major clue Major clue categories in categories in suspected suspected infection in infection in patients who patients who areareimmunocomprimmunocompromised.omised.
Opportunistic Infection Percentage (%)
Candidiasis oral 50
Pulmonary TB 37
Pneumonia 16.5
Extra pulmonary TB 13.8
Toxoplasma encephalitis 12.1
Chronic Diarrhea 11.2
Seborrheic dermatitis. 5.3
CMV retinitis 3.4
Candidiasis esophageal 3.3
Persistent Fever 3.2
Herpes zoster 3.2
EPP 1.6
Wasting syndrome 1.2
Herpes simplex 0.6
Cryptococcal Meningitis 0.4
ITP 0.2
Toxocariasis 0.1
PCP 0
Pattern of opportunistic infections of newly diagnosed HIV-infected patients in Ciptomangunkusumo hospital 2008-2009
Karjadi TH, Yunihastuti E , Pramundita R, Aziza S, Lie S, Imran D, et al.Presented at 2010 PDPAI Clinical Research Meeting
Defects in immunity suggested by Defects in immunity suggested by infectioninfection
Phagocytes
Non Specific immunity
LymphadenitisSkin infectionLiver, lung abscessGI disease, UTI
BacteriaStaphylococci, E colliKlebsiellaFungi: candida, aspergillus
Bacteria: salmonella, proteus
ComplementClassic-alternate
Systemic bacterial infectionAutoimmune disease
Pyogenic bacteria: StaphylococciNeisseria
Virus: CMV, HSV
Defence system
Infectious complication
Common microorganism
Less common
Defects in immunity suggested by Defects in immunity suggested by infectioninfection
B cells antibody
Specific immunity
Respiratory tract sespisGI tract sepsis
Pyogenic bacteriaStaphylococciStreptococciHaemophilus
EnterovirusOther bacteria: salmonella
T cells cellular immunity
Viral infectionGastroenteritisLymphoproliferation
Virus: CMV, adeno, HSVPyogenic bacteriaFungi: candida, aspergilus, PCPProtozoa: cryptospora
Other bacteria
Defence system
Infectious complication
Common microorganism
Less common
Opportunistic infection and CD4 cell Opportunistic infection and CD4 cell countcount
Temporal relationship of stem-Temporal relationship of stem-cell transplantation with cell transplantation with complicationscomplications
Timeline of posttransplant infections Timeline of posttransplant infections following solid organ transplantationfollowing solid organ transplantation
Management of Management of immunodeficiencyimmunodeficiency
• Managing the causeManaging the cause
• Treatment and prevention of infectionTreatment and prevention of infection
• SupportiveSupportive
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HIV preferentially infect CD4+ T HIV preferentially infect CD4+ T cellscells
HIV
RNARNA
DNA
ds DNAds DNA
RT
Integrase
TranscriptionTranscription
Proviral DNAProviral DNA
Spliced mRNASpliced mRNA
mRNAmRNA
Genomic RNA
PolyproteinProtein
Protease
1 2233
44
55vpr
HIV replicates in CD4HIV replicates in CD4
Type of HIV progressionType of HIV progression
A model of HIV pathogenesisA model of HIV pathogenesis
HIV-1 infection and replication
Main target CCR5+ activated CD4+ T cell
HIV-1 infection and replication
Main target CCR5+ activated CD4+ T cell
Systemic immune activationAdaptive and innate
Systemic immune activationAdaptive and innate
Massive CD4+ T cell depletion
In particular mucosal CD4+ T cell
Massive CD4+ T cell depletion
In particular mucosal CD4+ T cell
Bacterial Translocati
onIncl. TLR ligand
Bacterial Translocati
onIncl. TLR ligand
Viral reactivation
In particular CMV
Viral reactivation
In particular CMV
Anti-HIV immune responseCellular and
humoral
Anti-HIV immune responseCellular and
humoral
Production of HIV proteins
Gp120, nef
Production of HIV proteins
Gp120, nef
Exhaustion of immune responseDecline of regenerative
capacity loss of effective anti-HIV immunity
= Immunosenescence?
Exhaustion of immune responseDecline of regenerative
capacity loss of effective anti-HIV immunity
= Immunosenescence?
Inflammation-related disordersOsteoporosis
AtherosclerosisNeurocognity deterioration
Frailty
= inflammation-ageing?
Inflammation-related disordersOsteoporosis
AtherosclerosisNeurocognity deterioration
Frailty
= inflammation-ageing?
Sustained T-cell apoptosis
Turn over and senescence
Sustained T-cell apoptosis
Turn over and senescence
Secretion of proinflammatory
cytokinese.g. IL-6, TNFα, IL-1β
Secretion of proinflammatory
cytokinese.g. IL-6, TNFα, IL-1β
Persistence of this process
=> Collapse of immune system / AIDSPersistence of this process
=> Collapse of immune system / AIDS
Systemic immune activationAdaptive and innate
Systemic immune activationAdaptive and innate
Homeostatic mechanism
Cellular renewalhematopoesis
Homeostatic mechanism
Cellular renewalhematopoesis
DamageToLymphoidtissue
HIVreplication
HIVreplication
Prinsip penatalaksanaanPrinsip penatalaksanaan HIVHIV
SupoSuportifrtif
Infeksi Infeksi oportuoportunistiknistik
AntiretAntiretroviralroviral(ARV)(ARV)
02-200702-2007 LSU SVM PBSLSU SVM PBS 2525