Immunodeficiency Flashcards
Secondary immunodeficiency
- Description
- Causes
Immune defect is secondary to another disease process.
- More common than primary ID
Causes:
- Prevalent in neonates/ toddlers and elderly.
- Metabolic disease: diabetes
- Drugs: chemo, steroids
- Infections: HIV
- Malignancies
Primary immunodeficiency syndrome
Immune defect intrinsic to immune system.
Often caused by genetics
Includes:
- SCID
- Common gamma chain deficiency
- JAK-3 deficiency
Anti-body deficiency/ Humoral immunodeficiency
Due to dysfunction of B cells
Presents
- Recurrent bacterial infections of the rest. tract
Causes:
- Transient hypogammaglobulinaemia of infancy
- IgG loss
- Impaired production
- X-lined agammaglobulinaemia/ Hyper IgM syndrome
Transient hypogammaglobulinaemia
Relative Ab deficiency that occurs in infants around 6 months
- This is the period when maternal IgG (transferred from placenta) has finished.
- Infant immune system is just starting to develop adaptive immune system and produce IgG
X-linked agammaglobuinaemia
Cause of primary immunodeficiency
Deficiency in Bruton’s tyrosine kinase (btk)–> maturation arrest
- Inhibits the maturation of B cells from pro-B cells (required for cell signalling)
Presents as:
- Low levels of antibodies
- Lack of circulating B cells
- Normal T cells.
X-linked hyper IgM syndrome
CD40L deficiency
- Primary immunodeficiency
B cell cannot mature from primary to secondary due to lack of co-stimulation by T cells (via CD40L)
- Cannot undergo affinity maturation
Presents
- Age 3-6months
- Low IgG, IgA
- Raised/ normal IgM
- Recurrent pyogenic infections
Treatment for Ab deficiency
Aggressive treatment of intercurrent infections
Replacement of immunoglobulin
Long term suppressive anti-microbial
Cellular immunodeficiency
CD4 T cell deficiency
Presents
- Opportunistic infections
- If congenital, Ab production affected
- Viral infections
- Fungal infections
- Mycobacterial infection
Cause
- HIV
Infections common to cellular immunodeficiency
Candida
Cytomegalovirus retinitis
Pneumocystis pneumonia
Toxoplasmosis
Kaposi sarcoma
SCID
- Description
- Molecular causes [3]
- Presentation [4]
Primary immunodeficiency caused by absent T cells
- B cells can be present but are non-functional
Molecular causes
- Common gamma chain deficiency
- JAK-3 deficiency
- RAG 1/2 deficiency
Presentation
- After birth
- Graft vs host rash due to maternal lymphocyte
- Failure to thrive
- Opportunistic infections: bacterial, BCG infection, CMV, EBV viral infection, PCP Candida infection
Common gamma chain deficiency
Cause of SCID
- X-linked
- Due to incomplete receptor for cytokines required for T cell maturation
Presentation
- Present, but non function B cells
- No T cells
Common gamma chain
Forms part of the membrane receptor for cytokines
- Cytokines are required for T cell maturation
The receptor uses JAK-3 intracellular signalling
JAK-3 deficiency
Autosomal recessive SCID
- Loss of intracellularly signalling via JAK-3 (in cytokine receptor), required for maturation of T cells
Presents:
- Absent T cells
- Non functional B cells
RAG 1/2 deficiency
Autosomal recessive SCID
- Unable to undergo V(D)J recombination due to lack of RAG1/2 enzymes
Presents
- No T cells
- No B cells
SCID therapy
Stem cell transplant (infusion–> engrafts into bone marrow)
- HLA match from donor
