IMUNO DEFISIENSI

Oleh

Harsoyo Notoatmojo
Bagian Ilmu Kesehatan Anak
FK UNDIP / RSUP Dr.Kariadi
Semarang
Introduction
Defects in immunity may arise at any age
Primary immunodeficiencies :
single gene defects multifactorial
aetiology
childhood at any age

Secondary immunodeficiencies :
may be caused by a wide range of factors
IMUNO DEFISIENSI

Definisi Respon imun yang tidak bekerja

secara efisien dan/adekuat,
ditandai dengan kerentanan terhadap
mikroorganime

infeksi yang bersifat serius, persisten,

unusual ( tidak umum), dan
rekuren (SPUR)
 DEFISIENSI IMUN
(KEKEBALAN YANG
MENURUN)

Mudah terjadi infeksi

Mudah terjadi kanker
Terjadi gangguan dalam kematangan
atau aktifitas sel limfosit

Abbas et al. 2000 Cellular and Molecular Immunology

Infections suggesting underlying
immunodeficiency
SPUR Example Comment
Serious Meningococcal Life-threatening
septicaemia infections
Persiste Oral candidiasis resistant Infections that persist
nt of local therapy despite appropriate
antimicrobial therapy

Unusual Pneumocystis carinii Infections may be

pneumonia : unusual in terms of
Mycobacteria avium either site or
intracellulare infection organism involved
Recurre Recurrent upper or lower Recurrent infection
nt respiratory infection can be difficult to
define
Warning signs of immunodeficiency
10 signs that should alert to the possibility of
immunodeficiency
1. Eight or more new ear infections in a year
2. Two or more serious sinus infections in a year
3. Antibiotics for 2 months without effect
4. Two or more pneumonias in a year
5. Recurrent, deep skin or organ abscesses
6. Two or more deep-seated infections such as osteomyelitis,
cellulitis or sepsis
7. Surgical intervention for chronic infection, e.g. Lobectomy,
recurrent incision of boils
8. Persistent thrush in mouth or elsewhere on the skin after age
1 year
9. Failure to thrive
10. Family history of primary immunodeficiency
Typical clinical features of primary
immunodeficiency states
Deficient Bacteria Virus Fungi Graft Abscess Neisser
immunologi versus es ial
-cal host infectio
component n
Antibody common uncomm uncomm no yes May
on on occur

T cells no common Commo rarely no rare

n
Combined B common common common common rare rare
and T cells

Neutrophils common rare common no common rare

Complement common rare rare No uncomm rare

(classical on
pathway)

Complement uncommo no no no no commo

(terminal and n n
alternate p)
 Clues :
Antibody-deficient syndromes tend to
present with recurrent bacterial infection
of the upper or lower respiratory tract
T cell deficiency causes specific
susceptibility to viral and fungal disease
Neutrophil disorder shows recurrent
abscess formation
Complement defect associates with
recurrent neisserial infection
 PEMBAGIAN IMUNODEFISIENSI
Defective
immunity
Primary Secondary
i.e. Intrinsic defect i.e. Underlying
disease
Missing enzyme Lymphoid malignancy
Missing cell type Infection e.g. HIV
Nonfunctioning compenent Malnutrition
Immunosuppresive
drugs
Congenital/acquired Always acquired
 SPECIFIC IMMUNITY
DEFENCE SYSTEM B CELLS ANTIBODY T CELLS CELLULAR IMMUNITY
Infectious Respiratory tract Viral infections (systemic)
complications when sepsis Gastroenteritis
impaired GI tract sepsis Lymphoproliferation

Common Pyogenic Intracellular organisms :

microorganisms bacteria : Viruses : cytomegalovirus,
Staphylococci adenovirus, HSV, measles,
Streptococci molluscum contagiosum
Haemophillus Pyogenic bacteria
Fungi : candida,
aspergillus, Pneumocystis
carinii
Protozoa :
cryptosporidium
Less common Enteroviruses : Bacteria : campylobacter,
polio, ECHO mycobacteria, listeria
Other bacteria :
salmonella,
campylobacter
 Non-specific immunity
DEFENCE SYSTEM PHAGOCYTES COMPLEMENT CLASSIC-
ALTERNATE
Infectious Lymphadenitis Systemic bacterial
complications when Skin infections infections
impaired Liver, lung Autoimmune diseases
abcesses
GI Disease
Urinary tract
problems
Common Bacteria : Pyogenic bacteria :
microorganisms Staphylococci Streptococci
(catalase positive) Neisseria
Serratia
marcescens
Klebsiella, E. Coli
Fungi : candida,
aspergillus

Less common Bacteria : Viruses : CMV, HSV

TYPES OF
IMMUNODEFICIENCIES
Defective antibody responses
Defective cell-mediated immunity
Hereditary complement component
defects
Hereditary complement deficiencies
Defect in the oxygen reduction pathway of
phagocytes
Leucocyte adhesion deficiency

Roitt et al. 1998, Immunology

REAKSI IMUN
Pertumbuhan Kelenjar Thymus
Akademi Sel Limposit T
 DEFISIENSI IMUN PRIMER PADA PROSES
PERKEMBANGAN DARI SEL STEM SAMPAI SEL
MATUR
1. Defective antibody
responses
Increase susceptibility to pyogenic
infection
B-cell function fails
X-linked agammaglobulinemia, IgA
and IgG subclass deficiency
Failure of proper T-cell signals to B-
cell
Hyper-IgM syndrome, CVID, transient
hypogammaglobulinemia
 2. Defective cell mediated
immunity
T cell deficiency
susceptible for
opportunistic
infection and
humoral
immunodeficiency
Severe combined
immunodeficiency
(SCID)
lymphocyte
deficiency,
Roitt et all.1998 Immunology thymus
does not develop
http://student.biology.arizona.edu/honors2000/group08/images/babybubble.jpg
Adenosine deaminase deficiency and purine
nucleoside phosphorylase deficiency
accumulation of toxic metabolite to lymphoid stem
cell dATP and dGTP inhibition of Ribonucleotide
reductase Inhibition of DNA synthesis and cell
replication
MHC Class II deficiency deficiency CD4 Th
cells and deficiency in antibody

DiGeorge anomaly
congenital defect
of 3rd and 4th
pharyngeal pouches
defect in lymphocyte
maturation and T-cell
Roitt et al. 1998. Immunology
Hereditary ataxia-
teleangiectasia (AT)
chromosomal breaks occur in TCR
and IG genes. They develop wobbly
gait, dilated capilaaries, IgA or IgG
deficiency. T cell is diminished
severe sinus and lung syndrome
 X-LINKED
AGAMMAGLOBULINEMIA
Penderita adalah laki-laki
Defek pada gen B cell cytoplasmic tyrosine
kinase (btk) yang terletak pada lengan
panjang kromosom X.
 DEFISIENSI Ig A
Imunodefisiensi yang
sering ditemui

Kegagalan
perkembangan pada
fase akhir
differensiasi sel B

Penderita rentan
terhadap infeksi
piogenik
 HYPER Ig M
Defisiensi terhadap
IgG dan IgA namun
mensintesis IgM
poliklonal dalam
jumlah besar
(>200mg/dl)

70% diturunkan
secara X-linked
recessive
 A B

Wiskott-Aldrich syndrome. A, Eczematoid lesions in a four year old boy.

B, Purpuric lesions in a six year old boy
Photograph of a four year old boy with neutrophil leukotactic defect.
Note the Facial asymmetry resulting from a seventh nerve palsy
secondary to a brain abscess
Photograph of a nine year old boy with chronic mucocutaneous
candidiasis who was found to be deficient in cell-mediated immunity.
(From Schlegel, R. J. et al.: Severe candidiasis associated with thymic
dysplasia, IgA deficiency, and plasma anti-lymphocyte effects.
Pediatrics 45:926, 1970)
 PENDEKATAN DIAGNOSIS

PEMERIKSAA
AANAMNESIS N FISIK

PEMERIKSAAN
PENUNJANG
Suatu Sindroma Imunodefisiensi
Spesifik
 DEFISIENSI IMUN
PRIMER
1. Defek Imunitas Humoral
2. Defek Imunitas Seluler
3. Defek Komponen Komplemen Herediter
4. Deficiensi Komplemen Herediter
5. Defek Reduksi Oksigen pada
Phagocyt
6. Deficiensi Adhesi Lekosit

Roitt et al. 1998, Immunology

DEFISIENSI IMUNITAS HUMORAL

A.Defisiensi Imunitas Humoral

Hipogamaglobulinemia x-linked
(hipogamaglobulinemia kongenital)
Hipogamaglobulinemia transien (pada bayi)
Defisiensi imun tak terklasifikasi, umum,
bervariasi (hipogamaglobulinemia didapat)
Defisiensi imun dengan hiperIgM
Defisiensi IgA selektif
TANDA-TANDA DEFISIENSI IMUNITAS
HUMORAL
Mudah Terjadi Infeksi Piogenik
Gangguan Fungsi Antibodi :
Agamma Globulinemia,
Defisiensi Subklas IgA dan IgG
Gangguan Sel T dan Sel B :
Hyper-IgM , Hypogamma
Globulinemia Sementara
B.Defisiensi imun selular (sel T)
Aplasia timus kongenital (sindrom DiGeorge)
 2. DEFEK IMUNITAS SELULER

Defisiensi sel T
Kemungkinan
infeksi
oportunistik dan
defisiensi imunitas
humoral

Roitt et all.1998 Immunology

http://student.biology.arizona.edu/honors2000/group08/images/babybubble.jpg
C. Defisiensi Kombinasi Imunitas
Humoral dan Imunitas selular

Defisiensi imun berat gabungan (autosom resesif,

x-linked, sporadik)Defisiensi imun selular dengan
gangguan sintesis imunoglobulin (sindrom
Nezelof)
Defisiensi imun dengan ataksia teleangiektasis
Defisiensi imun dengan eksim dengan
trombositopenia (sindrom Wiskott-Aldrich)
Defisiensi imun dengan timoma
Defisiensi imun dengan short-limbed dwarfism
Defisiensi imun dengan defisiensi adenosin
deaminase
Defisiensi imun dengan defisiensi nukleosid
 C. Defisiensi Kombinasi Imunitas
Humoral dan Imunitas Seluler(lanjt)

Defisiensi karboksilase multipel yang tergantung

biotin
Penyakit graft-versus-host
Sindrom defisiensi imun didapat (AIDS)
Disfungsi fagositPenyakit granulomatosis
kronikDefisiensi glukosa-6-fosfat
dehidrogenaseDefisiensi mieloperoksidase
Sindrom Chediak-Higashi
Sindrom Job
Defisiensi tuftsin
Sindrom leukosit malas
Peninggian IgE, defek kemotaksis dan infeksi
 2. DEFISIENSI KOMBINASI
IMUNITAS SELULER DAN HUMORAL

Kombinasi defisiensi
Imun yang berat
(SCID) defisiensi
limfosit, thymus tidak
berkembang

Roitt et all.1998 Immunology

http://student.biology.arizona.edu/honors2000/group08/images/babybubble.jpg
3. DEFISIENSI KOMPLEMEN
HERIDITER

ANGIONEURETIC EDEMA
HERIDITAIR (HAE)
DEFISIENSI C1

Roitt. 1998. Immunology

 DEFISIENSI IMUNITAS
SEKUNDER

MALNUTRISI
KEGANASAN
INFEKSI
RADIASI
KORTIKOSTEROID
SITOSTATIKA
SINDROM NEFROTIK
PROTEIN LOOSING ENTEROPATHY
Roitt et al. 1998.Immunology
 10 TANDA MENGENALI
DEFISIENSI IMUN
1. 8 / LEBIH INFEKSI PADA TELINGA /
TAHUN

2. 2 / LEBIH INFEKSI SINUS / TAHUN

3. ANTIBIOTIKA 2 BULAN TANPA EFEK

4. 2 / LEBIH PNEUMONIA / TAHUN

5. ABSES KULIT / ORGAN YANG BERULANG

 10 TANDA MENGENALI
DEFISIENSI IMUN..lanj.
6. DUA / LEBIH INFEKSI YG DALAM :
OSTEO- MYELITIS, CELLULITIS DAN SEPSIS
7. PEMBEDAHAN PADA INFEKSI KHRONIK:
LOBEKTOMI
8. STOMATITIS PERSISTEN SETELAH UMUR
1 TAHUN
9. BERAT BADAN TIDAK NAIK

10. TURUNAN KELUARGA DENGAN

DEFISIENSI IMUN
Strategi Pendekatan
Diagnosis Suatu Sindroma
Imunodefisiensi Spesifik :
DIAGNOSTIK
1. GEJALA KLINIS
2. HERIDITER
3. PENEMUAN FISIK
4. SKREENING LABORATORIUM
5. TES DEFISIENSI SEL B
6. TES DEFISIENSI SEL T
7. TES DEFISIENSI SEL FAGOSIT
8. TES DEFISIENSI KOMPLEMEN
TERIMAKASIH