Immunodeficiency

Question 1

Secondary immunodeficiency

• Description
• Causes

Answer 1

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

Question 2

Primary immunodeficiency syndrome

Answer 2

Immune defect intrinsic to immune system.

Often caused by genetics

Includes:

• SCID
• Common gamma chain deficiency
• JAK-3 deficiency

Question 3

Anti-body deficiency/ Humoral immunodeficiency

Answer 3

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

Question 4

Transient hypogammaglobulinaemia

Answer 4

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

Question 5

X-linked agammaglobuinaemia

Answer 5

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.

Question 6

X-linked hyper IgM syndrome

Answer 6

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

Question 7

Treatment for Ab deficiency

Answer 7

Aggressive treatment of intercurrent infections

Replacement of immunoglobulin

Long term suppressive anti-microbial

Question 8

Cellular immunodeficiency

Answer 8

CD4 T cell deficiency

Presents

• Opportunistic infections
• If congenital, Ab production affected
• Viral infections
• Fungal infections
• Mycobacterial infection

Cause
- HIV

Question 9

Infections common to cellular immunodeficiency

Answer 9

Candida

Cytomegalovirus retinitis

Pneumocystis pneumonia

Toxoplasmosis

Kaposi sarcoma

Question 10

SCID

• Description
• Molecular causes [3]
• Presentation [4]

Answer 10

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

Question 11

Common gamma chain deficiency

Answer 11

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

Question 12

Common gamma chain

Answer 12

Forms part of the membrane receptor for cytokines
- Cytokines are required for T cell maturation

The receptor uses JAK-3 intracellular signalling

Question 13

JAK-3 deficiency

Answer 13

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

Question 14

RAG 1/2 deficiency

Answer 14

Autosomal recessive SCID
- Unable to undergo V(D)J recombination due to lack of RAG1/2 enzymes

Presents

• No T cells
• No B cells

Question 15

SCID therapy

Answer 15

Stem cell transplant (infusion–> engrafts into bone marrow)

- HLA match from donor

Question 16

DiGeorge syndrome

Answer 16

Congential disorder, can present as:

• Congenital heart disease
• Cleft palate
• Absent Parathyroid

Cause of SCID
- Failure of 3rd and 4th branchial arches to migrate

Can present with no thymus

• T cells cannot mature= no T cells, non-functional B cells
• if 22q11 microdeletions, presentation is variable.
• Can also present with autoimmunity

Question 17

Terminal complement deficiency

Answer 17

Deficiency of C5-9 [innate immunosuppression]
- Cannot form membrane attack complex

Presents
- Neisseria infections

Diagnosed
- Functional complement assays