By: Oki Suwarsa, dr, MKes, SpKK(K)
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Transcript of By: Oki Suwarsa, dr, MKes, SpKK(K)
By: Oki Suwarsa, dr, MKes, SpKK(K)
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, kaposis sarcoma, non-Hodkins 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 Mutation Polymorphisms Polygenic Tumors Gene therapy
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 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 -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 Foundation
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 dalam setahun Kandidiasis persisten di mulut atau
di mana saja usia >1 tahun
Abses berulang pada kulit dan organ dalam Riwayat keluarga dengan
imunodefisiensi primer Kebutuhan penggunaan antibiotik intravena
untuk mengatasi infeksi 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 isnt option
gene therapy Congenital disorders of innate immunity SECONDARY
IMMUNODEFICIENCY
Infection HIV Stress Nutrition Tumors vaccines Immunomodulation
Extremes of age Drugs 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