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IMMUNODEFICIENCY
By: Oki Suwarsa, dr, MKes, SpKK(K)
IMMUNODEFICIENCY
 Risk of opportunist infection & tumors
Divided in two types:
Primary immunodeficiency :
Relatively rare
Genetic basis
Secondary immunodeficiency:
More common
Caused by lesion outside the immune system
Repeated/unusual infection  immunodeficiency
Type of infection  cause & degree of
immunodeficiency
Repeated bacterial infection  defective antibody
Respiratory infection caused by Pneumococcus or
Haemophilus spp.  bronchiectasis
Gram - & fungi  abnormal phagocytes
Meningococcal meningitis  defective complement
Defective T cells or macrophages  infection of
intracelullar organisms : protozoa, virus, intracellular
bacteria (mycobacteria & salmonella)
Reactivation of herpes virus infection  T cell
immunodeficiency
Herpes virus induce tumors, kaposi’s sarcoma, nonHodkin’s lymphoma  T cell dysfunction
the degree of T cell immunodeficiency  pattern of
mycrobial infection
Mild  Mycobacterium tuberculosis (virulent)
spreads outside the lungs
Severe  infection of mycobacterium of low
virulence, found in environment (Mycobacterium
avium) or vaccine
Features of immunodeficiencies
affecting T & B lymphocytes
Immunodeficiency caused by
defect in B & T cells maturation
Immunodeficiency caused by defects in B & T cell
activation
Defect of lymphocyte maturation
Defect in lymphocyte activation
PRIMARY IMMUNODEFICIENCY
Infection
Tumors
Primary immunodeficiency
Gene therapy
Mutation
Polymorphisms
Polygenic
Immunoglobulins
Causes of primary immunodeficiency
Mutation :
Rare, affect any part of immune system
Severe disease
Polymorphisms :
Common traits, affect any part of the immune
system
Moderate increased risk of infection
Polygenic disorders :
Relatively common, affect mainly antibody
Severe disease
Repeated or unusual infection suggests
immunodeficiency
Defects in innate immune system are characterized
by extracellular pathogen infections
Mutations and immunodeficiency
12 important mutations  immunodeficiency
> Mutation  severe combined immunodeficiency
(SCID)
Affecting both B & T cells
Autosomally inherited  RAG deficiency
X linked  γ-chain deficiency & hyper-IgM
syndrome
The Di George syndrome  translocated of
chromosome 22, not inherited
T cell defects
Polymorphisms & immunodeficiency
Polymorphisms : alleles of the same gene occurring
at a single locus in 1% population
HLA alleles  polymorphic  affect the outcome of
infection (hepatitis B, hepatitis C & HIV)
Polymorphisms promoter of TNF genes   risk
cerebral malaria & septic shock
Polymorphisms chemokines & their receptors   risk
HIV
Polymorphisms in MBL & complement   risk
infections
Polygenic disorder
Caused by interaction of several genes with
environmental factors
Common variable immunodeficiency (CVID) &
deficiency of IgA & IgG  common polygenic disorder,
affecting Ab
IgA deficiency  1:600 people
Celiac disease  more common in IgA deficiency
CVID  commonest immunodeficiency  treatment
CVID  recurrent infection of respiratory tract, start in
early adult
Autoimmunity is common in CVID & frequently includes
pernicious anemia & thyroid disease, arthritis & immune
thrombocytopenia
Diagnosis SCID should be considered if:
Unusual or recurrent infection
Failure to thrive & diarrhea
Unusual rashes
A family history of neonatal death or of
consanguinity
A very low total lymphocyte count (below 1 x 109/L)
Avoid serious infection:
Avoid live vaccine : BCG, measles, mumps,
rubella & polio
Use prophylaxis against opportunist infections :
Pneumocystis carinii pneumonia
Suspect SCID  exclude HIV  refer to spesialist to
confirm diagnosis  definitive treatment (often
bone marrow transplant)
Diagnosis
Chronic or recurrent bacterial respiratory infection 
Indication for testing  measure of IgG, IgA & IgM
If total Ig normal  measure IgG subclasses & spesific
Ab against Haemophilus & Pneumococcus spp.
If all test normal  check complement or neutrophil
function
Patient with atypical viral, protozoal or mycobacterial
infection  rule out T cell immunodeficiency
Patient with suspected cellular immunodeficiency 
measure lymphocyte numbers
Genetic testing  PCR
Sepuluh tanda imunodefisiensi
Dua atau lebih gejala dalam satu
tahun
Jeffrey Modell
Empat atau lebih
infeksi telinga
dalam setahun
Dua atau lebih
infeksi sinus
berat dalam
setahun
Pada bayi terjadi
kegagalan
peningkatan
berat badan dan
gagal tumbuh
Dua bulan atau
lebih pemakaian
antibiotik dengan
sedikit efek
Dua episode
atau lebih
pneumonia
Kandidiasis
persisten di
mulut atau di
mana saja usia
>1 tahun
Abses
berulang pada
kulit dan
organ dalam
Kebutuhan
penggunaan
antibiotik
intravena untuk
mengatasi infeksi
Riwayat
keluarga
dengan
imunodefisiensi
primer
Dua atau lebih
infeksi dalam
termasuk
septikemia
Treatment
Aim of treatment  prevent infection
Mild cases  prophylactic antibiotics
More severe Ab deficiency  immunoglobulin
replacement therapy (intravenous or subcutaneus)
T cell deficiency  bone marrow transplant (BMT)
If BMT isn’t option  gene therapy
Congenital disorders of innate immunity
SECONDARY IMMUNODEFICIENCY
Infection
Tumors
Secondary immunodeficiency
vaccines
Immunomodulation
vaccines
HIV
Stress
Nutrition
Extremes of age
Drugs
Immunomodulation
Secondary immunodeficiency
Can be severe :
HIV infection
Myeloma
Some drug treatments
Acquired immunodeficiencies
HIV Infection
Most important caused of secondary
immunodefiency  affecting over 30 million people
Monitoring infection :
Immunological monitoring  CD4 cell counts 
form part of assessment schemes for progression
of HIV infection (CDC)
CD4 < 200 /l  high risk PCP  prophylaxis
CD4 < 100 /l  consider CMV & atypical
mycobacteria
Virological monitoring  viral load
HIV infection and viral mutations
Structure of HIV-1
HIV-1 genome
HIV life cycle
Mechanism of HIV entry into a cell
Progression of
HIV infection
Clinical course of HIV disease
Clinical features of HIV infection
Cellular reservoirs of HIV
Candidate HIV vaccines
Other secondary immunodeficiency
Nutrition
Deficiency of zinc & magnesium  impairs cell
mediated immunity, particularly TH1-cytokine
secretion
Loss of fat  low levels of leptin  mild
immunodeficiency
Physiological stress
The immune system in the first year of life
Spesific immune system remain immature
Neonates have high number of T cells  all naive 
not respond to Ag
Transient hypergammaglobulinemia of infancy 
delay in maturation of Ig, especially IgG2 (maternal
Ab ↓)
Other secondary immunodeficiency
The aging immune system
Elderly  thymic function ↓  more infection
Miscelaneous factors
B cell malignancy
Myeloma & chronic lymphocytic leukemia  ↓ Ab
 common caused of immunodeficiency in
elderly
Thymoma  rare tumor  cause
immunodeficiency
Other secondary immunodeficiency
Drugs  Common caused
Eliminating offending drug  improve immune
response
Immunosupression  side effect steroids, cytotoxic
drugs & immunosupressive regimens
Kidney disease
Nephrotic syndrome
Renal protein loss
↓ blood level of IgG & IgA, normal IgM
Severe diarrhea  lost igG via the gut
Renal failure & diabetes  secondary phagocyte
defect
Infection
Malaria & congenital rubella  Ab deficiency
Measles  defects in cell mediated imunity 
could reactivate tuberculosis
Combined immunodeficiency
• Syndrome:
Wiskott-Aldrich syndrome
• Trias: eksim, trombositopenia, imunodefisiensi
Ataksia-teleangiektasia
• Ataksia serebelar, teleangiektasia okulokutaneus
Sindrom DiGeorge
• Delesi kromosom 22q11
• Malformasi jantung, hipotiroid, hipokalsemi, wajah
dismorfik, gangguan perkembangan timus
Thank You