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IMUNNODEFICIENCY M. Sjabaroeddin Loebis, Lily Irsa, Rita Evalina Allergy Immunology Division Pediatrics Departement Medical Faculty Sumatera Utara University
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4. DEFISIENSI IMUN new.ppt [Read-Only] - ocw.usu.ac.idocw.usu.ac.id/...alergy-immunology-anak/mk_aia_slide_imunnodeficiency.pdf · •Defect immune system defense immune mechanism

Aug 15, 2019

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Page 1: 4. DEFISIENSI IMUN new.ppt [Read-Only] - ocw.usu.ac.idocw.usu.ac.id/...alergy-immunology-anak/mk_aia_slide_imunnodeficiency.pdf · •Defect immune system defense immune mechanism

IMUNNODEFICIENCY

M. Sjabaroeddin Loebis, Lily Irsa, Rita Evalina

Allergy Immunology Division

Pediatrics Departement

Medical Faculty Sumatera Utara University

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• Defect immune system � defense

immune mechanism and homeostasis

• Immune system unable to respond appropriately and effectively to infectious microorganisms

Introduction

infectious microorganisms

• Main consequence :

- infection

- incidence autoimmune disease

increase

- malignancy increase

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• Typical : SPUR ( Serious, Persistence, Unusual or Recurrent )

Introduction……….

• 1952, Burton : hipogamaglobulinemia in 8 yo boy with sepsis and arthritis since 4 yo

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Introduction………

SPUR Example Comment

Serious Meningococcal

septicemia

Life-threatening

infections

Persistent Oral candidiasis,

resistent to local

Persist despite

appropriate AB

Infections suggesting underlying immunodeficiency

resistent to local

therapy

appropriate AB

Unusual PCP, M. avium

intracellulare

infection

Maybe unusual in

terma of iether site

or organism

involved

Recurrent Upper or lower

respiratory

infection

Dificult to define

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Introduction ………..

• Until now > 100 IP

• Variation in severity

• US : 1 million, world : 10 million

• Man, woman, all age• Man, woman, all age

• Child : severe type

• Important : early diagnosis and early management

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Classification of immunodeficiency

1. Underlying cause

- primary � genetic

- secondary � drugs, infection (HIV,

Epstein-Barr, malaria, etc), malignancy,

malnutrition, systemic disease (DM,liver / renal malnutrition, systemic disease (DM,liver / renal

failure), splenectomy

� The immunological mechanisms underlying

secondary immune defects are often multiple

and difficult to demonstrated by routine

immunological laboratory testing

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Typical clinical features of PI

Deficient Bacteria Viruses Fungi GvH Abscesses Neisserial infc.

Antibody Common Uncom Uncom No Yes May occur

T cells No Comm Comm Rare No Rare

B and T

cells

Commom Comm Comm com

m

Rare Rare

Neutrophils Common Comm Comm No Comm Rare

Compleme

nt (clasical)

Common Rare Rare No Uncomm Rare

Compleme

nt (terminal

and

alternative)

Uncomm No No No No Comm

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The 10 Warning Signs of PI

1. Eight or more new ear infections within a year.

2. Two or more serious sinus infections within a year.

3. Two or more months on antibiotics with little or without effect.

4. Two or more pneumonias within a year.

5. Failure of an infant to gain weight or grow normally.6. Recurrent deep skin or organ abscesses �Surgical

intervention for chronic infection, e.g. lobectomy, recurrent intervention for chronic infection, e.g. lobectomy, recurrent

incision of boils

7. Persistent thrush in mouth or elsewhere on skin, after

age 1.

8. Need for intravenous antibiotics to clear infections.

9. Two or more deep-seated infections such as

meningitis, osteomyelitis, cellulitis, or sepsis.

10. A family history of PI

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Classification of……………

2. Deficient component in innate system

- may occur both primary and secondary � patients with breaches of the normal physical defenses against infection physical defenses against infection (severe burns, skin loss) extremely vulnerable to infection and have secondary immunodeficiency

- PI may also affect the innate system (complement, phagocyte system)

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Classification of……………

3. Deficient component in adaptive system

- main component : antibody production

or T cell function

- HIV infection AIDS specific- HIV infection � AIDS � specific

cellular defect

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ETIOLOGY• Genetic defect

• Drugs / toxin (immunosupressan, anticonvulsan)

• Metabolic and nutritional disorder (malnutrition, vit. And mineral deficiency)

• Chromosome abnormality (deletion 22q11, trisomi 18)

• Infection (transient, permanent)• Infection (transient, permanent)

• Type, location and the organisms causes infection � help to know where the defect

• 4 main area :

- T cell

- B cell

- PMN cell

- complement

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GANGGUAN FUNGSI SISTEM IMUN YANG SERING

DEFISIENSI

• Defisiensi sel B : infeksi bakteri rekuren seperti otitis media, pnemonia rekuren

• Defisiensi sel T : kerentanan meningkat terhadap virus, jamur dan protozoa

• Defisiensi fagosit : infeksi bakteri, autoimunitas

FUNGSI BERLEBIHANFUNGSI BERLEBIHAN

• Sel B : gamopati monolonal

• Sel T : kelebihan sel Ts yang menimbulkan infeksi dan penyakit limfoproliferatif

• Fagosit : hipersensitivitas, beberapa penyakit autoimun

• Komplemen : edem angioneurotik akibat tidak adanya inhibitor esterase C1

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Serum Ig levels and age

100

Seru

m Ig levels

(%

adult v

alu

es)

Maternal

Transfer IgG

IgM

IgG

IgA

birth

Age (years)

0 20 30

Gestation (weeks)

1 10

50

Seru

m Ig levels

(%

adult v

alu

es)

IgA

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Presenting symptoms PI100

Perc

enta

ge o

f patients

80

90

90%

respirato

ry

0

30

Perc

enta

ge o

f patients

10

20

21%

15%13%

6% 6% 6%

respirato

ry

skin

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PEMBAGIAN DEFISIENSI IMUNDEFISIENSI IMUN NONSPESIFIK

A. Defisiensi komplemen ; kongenital, fisiologik, didapat

B. Defisiensi interferon dan lisozim ; kongenital, didapat

C. Defisiensi sel NK ; kongenital, didapat

D. Defisiensi sistem fagosit : kuantitatif, kualitatif

DEFISIENSI IMUN SPESIFIK

A. Defisiensi kongenital atau primerA. Defisiensi kongenital atau primer

B. Defisiensi imun fisiologik ; kehamilan, usia tahun pertama, usia lanjut

C. Defisiensi didapat / sekunder : malnutrisi, infeksi, obat, trauma, tindakan kateterisasi dan bedah, penyinaran, penyakit berat, kehilangan Ig/lekosit, stres, agamaglobulinemia dengan timoma

D. AIDS

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A. DEFISIENSI IMUN NONSPESIFIK1. DEFISIENSI KOMPLEMEN

- berhubungan dengan infeksi dan LES

- fungsi komplemen : bunuh kuman, opsonisasi, kemotaksis,

cegah peny.autoimun, eliminasi kompleks Ag-Ab

- kebanyakan herediter

a. Defisiensi komplemen kongenital

- defisiensi inhibitor esterase C1 � angioedema herediter

- aktivitas C1 tidak terkontrol, produksi kinin � permebilitas

kapiler ↑.

- C2a dan C4a dilepas �sel mast lepas histamin didaerahdekat trauma

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- defisiensi C2 dan C4 � peny.serupa LES

- defisiensiC3 � fragmen C5 kemotaktik tidak diproduksi

�kompleks Ag-Ab tidak dapat diendapkan dimembran �

gangguan opsonisasi �infeksi berat dan fatal

- defisiensi C5 � gangguan kemotaksis �rentan thdp

infeksi bakteri

- defisiensi C6, C7 dan C8 � rentan thd septikemia

meningokok dan gonokok, derajat infeksi berat thdp

Neiseria, sepsis, dan artritis, juga meningkatkan DIC

b. Defisiensi komplemen fisiologik : hanya pada neonatus,

karena kadar C3, C5, dan faktor B masih rendah

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c. Defisiensi komplemen didapat :

- def. C1q,r,s � autoimun / LES, rentan infeksi

- def. C4 � LES

- def. C2 � sering, gejala (-), LES

- def. C3 � infeksi rekuren, GN kronik

- def. C5-8 � rentan infeksi terutama Neiseria

_ def. C9 � jarang, infeksi rekuren (-)

2. DEFISIENSI INTERFERON DAN LISOZIM

a. Kongenital � infeksi mononukleosis yang fatal

b. Didapat � pada malnutrisi protein / kalori

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3. DEFISIENSI SEL NKa. Kongenital � penderita osteopetrosis, IgG, IgA dan

kekerapan autoantibodi ↑b. Didapat � akibat imunosupresi / radiasi

4. DEFISIENSI SISTEM FAGOSIT- Risiko infeksi berulang

- berhubungan dengan jumlah netrofil ↓- berhubungan dengan jumlah netrofil ↓- risiko meningkat bila jumlah fagosit < 500/mm3

- defisiensi ditekankan terhadap sel PMN

a. defisiensi kuantitatif : produksi ↓ atau destruksi ↑- produksi netrofil ↓ : kemoterapi, lekemia, disgenesisretikuler

- destruksi ↑ : fenomena autoimun akibat obat tertentu

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b. defisiensi kualitatif

- Chronic Granulomatous Disease (CGD) : infeksi rekuren, X

linked resesif, 2 tahun pertama, defek netrofil, tidak mampu

membentuk peroksid hidrogen / metabolit oksigen toksik

lainnya

- Def. Glucose-6-phosphate dehydrogenase (G-6-PD) : X- Def. Glucose-6-phosphate dehydrogenase (G-6-PD) : X

linked, klinis spt CGD, anemia hemolitik, gejala mulai usia <

2 thn, limfadenopati, hepatosplenomegali, KGB terus

menerus keluar cairan

- Def. mieloperoksidase (DMP) : kemampuan bunuh netrofil ↓

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- Sindrom Chediak-Higashi (SCH) : jarang, infeksi rekuren,

piogenik, prognosis buruk, netrofil mengandung lisosom

besar abnormal � bersatu dgn fagosom � melepas isi

terganggu � telan & hancurkan mikroba terlambat

- Sindrom Job : pilek berulang (tidak terjadi inflamasi

normal, abses stafilokok, eksim kronis, otitis media,

kemotaksis terganggu, IgE sangat tinggi, eosinofiliakemotaksis terganggu, IgE sangat tinggi, eosinofilia

- Sindrom lekosit malas (lazy leucocyte) : rentan infeksi,

jumlah netrofil ↓, respon kemotaksis dan inflamasi

terganggu

- Def. adhesi leukosit : infeksi bakteri dan jamur rekuren,

gangguan penyembuhan luka

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B. DEFISIENSI IMUN SPESIFIK1. DEFISIENSI KONGENITAL / PRIMER

a. Def. imun primer sel B (hipogamagobulinemia)�gangguan

perkembangan sel B, semua Ig / kelas / subkelas tidak ada

- X-linked hipogammaglobulinemia : Bruton 1952, hanya

pada bayi ♂, tampak usia 5-6 bulan saat IgG ibu mulai ↓, jaringan limpoid mengecil

- hipogammaglobulinemia sementara : sintesis terlambat,- hipogammaglobulinemia sementara : sintesis terlambat,

sebab tidak jelas, def. sementara sel Th

- common variable hypogammaglobulinemia (CVH) ; mirip

Bruton, insiden autoimun tinggi, jumlah sel B & Ig normal

tapi kemampuan produksi dan melepas terganggu, bisa

♂/♀, biasanya mulai usia 15-35 tahun, semua Ig kurang- def. Ig selektif (disgama-globulinemia) : satu atau lebih

kadar Ig ↓, yang lain normal

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b. Def. imun primer sel T � rentan infeksi, disertai gangguan

produksi Ig, tidak ada respons terhadap imunisasi

- aplasi timus kongenital (sindroma DiGeorge) : sebab (?),

kelenjar paratiroid terkena, hipokalsemia 24 jam pertama

diikuti kelainan jantung dan ginjal, tidak diturunkan,

pengobatan dengan transplantasi timus fetal, prognosis

buruk bila tidak diobati

- kandidiasis mukokutan kronik (KMK) : gangguan fungsi- kandidiasis mukokutan kronik (KMK) : gangguan fungsi

sel T selektif, biasanya disertai disfungsi berbagai

kelenjar endokrin, transplantasi tmus memberikan hasil

bervariasi

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c. Def. kombinasi sel B dan sel T yang berat

- severe combined immunodeficiency disease (SCID)

- sindrom Nezelof

- sindrom Wiskott-Aldrich (WAS) : tidak mampu respon

terhadap Ag polisakarida, rentan thdp lekemia,

trombositopeni, infeksi rekuren, IgM ↓, IgG normal, IgAdan IgE ↑, terapi dgn antibiotik dan transplantasi sutul

- ataksia teleangiektasi : autosomal resesif, mengenai- ataksia teleangiektasi : autosomal resesif, mengenai

saraf, endokrin dan vaskuler. Gerakan otot tidak

terkoordinasi, dilatasi pembuluh darah kecil, limfopenia,

IgA/IgE/IgG ↓, timbul pada usia < 2 tahun

- defisiensi adenosin deaminase

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2. DEFISIENSI IMUN SPESIFIK FISIOLOGIK

- Kehamilan

- Usia tahun pertama

- Usia lanjut

3. DEFISIENSI IMUN DIDAPAT / SEKUNDER

- Malnutrisi

- Infeksi / Obat, trauma, tindakan kateterisasi dan bedah- Infeksi / Obat, trauma, tindakan kateterisasi dan bedah

- Penyinaran

- Penyakit berat

- Kehilangan imunoglobulin

- Stres

- Agamaglobulinemia dengan timoma

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Def.komplemen 2%Def. granulosit 18%

Def. sel B & T 20% Def. sel T 10% Def. sel B 50%

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DIAGNOSIS• Pemeriksaan darah menunjukkan bagian dari sistem imun yang

tidak ada atau tidak bekerja semestinya � evaluasi fungsi sel B

- kuantitatif : IgG, IgA, IgM, IgE, kuantitatif IgG subkelas

- Ab spesifik :

- isohemaglutinasi IgM thd golongan darah ABO

- Ab tetanus toxoid- Ab tetanus toxoid

- Ag pnemokokal polisakarida

- Ab thd Ag vaksin varisela, HBV, measles

- Ab thd agen respirasi : RSV, mikoplasma, para influensa,

influensa A / B

- kuantitatif sel B dan fenotip : CD20, CD21, Ig permukaan sel B

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COMMON VARIABLE IMMUNODEFICIENCY (CVID)

• Sel B dan T

• Predominan : hipogamaglobulinemia

• Infeksi berulang

• Ig berkurang, respons terhadap antibiotik jelek

• Berhubungan dengan limpoma, artritis

• Jaringan limpoid hipertropi• Jaringan limpoid hipertropi

• Hepatosplenomegali � trombositopeni sekunder

• Gangguan autoimun sering � hematologi, neurologi, CAH, endokrinopati

• Antibodi spesifik tidak ada / kurang

• Anggota keluarga mempunyai insidens tinggi terhadap defisiensi IgA, penyakit autoimun, autoantibodi, keganasan

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ISOLATED IgA DEFISIENSI

• Defisiensi Ab yang sering

• 1 : 400 s/d 1 : 3000

• IgA < 7 mg/dl dengan IgG dan IgM normal

• Berhubungan dengan ataxia-telengiaktase

• Autosomal• Autosomal

• Berhubungan dengan atopi

• Prekwensi tinggi terhadap penyakit autoimun

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TRANSIENT HYPOGAMAGLOBULINEMIA OF INFANCY

• Sintesis Ig terlambat

• Fisiologis terjadi pada usia 2 – 4 bulan

• Kadang berlanjut sampai usia 2 – 3 tahun

• Infeksi saluran nafas berulang

• IgG dan IgA rendah, tapi IgM normal/tinggi• IgG dan IgA rendah, tapi IgM normal/tinggi

• Ig spesifik surface limfosit normal

• Self limited

• Perbaikan pada usia 18 – 36 bulan

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TERAPI• Antibiotik• Pengganti antibodi � IVIG

• Alternatif : bone marrow transplantation, enzyme replacement, or gene therapy

• Dengan intervensi, pasien IP diharapkan bisa tumbuh kembang secara normal :

- bisa berpartisipasi dalam kegiatan kerja, belajar, - bisa berpartisipasi dalam kegiatan kerja, belajar,

keluarga aktivitas sosial

- kejadian dan beratnya infeksi berkurang

- sedikit efek samping dari pengobatan

- merasa nyaman dengan dirinya sendiri dan

program pengobatan