Immunodeficiency
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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.

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Immunodeficiency

IMMUNODEFICIENCY

By: Oki Suwarsa, dr, MKes, SpKK(K)


Immunodeficiency1

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

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)


Immunodeficiency

  • Reactivation of herpes virus infection  T cell immunodeficiency

  • Herpes virus induce tumors, kaposi’s sarcoma, non-Hodkin’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

Features of immunodeficiencies affecting T & B lymphocytes


Immunodeficiency caused by defect in b t cells maturation

Immunodeficiency caused by defect in B & T cells maturation


Immunodeficiency caused by defects in b t cell activation

Immunodeficiency caused by defects in B & T cell activation


Defect of lymphocyte maturation

Defect of lymphocyte maturation


Defect in lymphocyte activation

Defect in lymphocyte activation


Primary immunodeficiency

Infection

Tumors

Primary immunodeficiency

Gene therapy

Mutation

Polymorphisms

Immunoglobulins

Polygenic

PRIMARY IMMUNODEFICIENCY


Causes of primary immunodeficiency

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

Repeated or unusual infection suggests immunodeficiency


Defects in innate immune system are characterized by extracellular pathogen infections

Defects in innate immune system are characterized by extracellular pathogen infections


Mutations and immunodeficiency

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

T cell defects


Polymorphisms immunodeficiency

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

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

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)


Immunodeficiency

  • 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

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

Sepuluh tanda imunodefisiensi

Duaataulebihgejaladalamsatutahun

Jeffrey Modell Foundation


Immunodeficiency

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


Immunodeficiency

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

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

Congenital disorders of innate immunity


Secondary immunodeficiency

vaccines

Infection

Tumors

Immunomodulation

Secondary immunodeficiency

vaccines

HIV

Immunomodulation

Stress

Nutrition

Extremes of age

Drugs

SECONDARY IMMUNODEFICIENCY


Secondary immunodeficiency1

Secondary immunodeficiency

  • Can be severe :

    • HIV infection

    • Myeloma

    • Some drug treatments


Acquired immunodeficiencies

Acquired immunodeficiencies


Hiv infection

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

HIV infection and viral mutations


Structure of hiv 1

Structure of HIV-1


Hiv 1 genome

HIV-1 genome


Hiv life cycle

HIV life cycle


Mechanism of hiv entry into a cell

Mechanism of HIV entry into a cell


Progression of hiv infection

Progression of HIV infection


Clinical course of hiv disease

Clinical course of HIV disease


Clinical features of hiv infection

Clinical features of HIV infection


Cellular reservoirs of hiv

Cellular reservoirs of HIV


Candidate hiv vaccines

Candidate HIV vaccines


Other secondary immunodeficiency

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 immunodeficiency1

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 immunodeficiency2

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


Immunodeficiency

  • Infection

    • Malaria & congenital rubella  Ab deficiency

    • Measles  defects in cell mediated imunity  could reactivate tuberculosis


Combined immunodeficiency

Combined immunodeficiency

  • Syndrome:


Thank you

Thank You


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