L16 Immunodeficiency disease

Question 1

What is an immunodeficiency?

Answer 1

Inability to form an immune response

Diagnosis is largely descriptive

Question 2

When are infections more likely to be significant?

Answer 2

Infections are verified rather than simply reported
Organisms can be identified
End-organ damage has occurred

Question 3

What is secondary immunodeficiency?

Answer 3

Immune defect is secondary to another disease process
Very common
Extremes of age

Question 4

What is primary immunodeficiency syndrome?

Answer 4

Immune defect intrinsic to immune system itself
Rare
Often genetic but not always

Question 5

What are the predominant infections in antibody-deficiency?

Answer 5

Bacterial infections of the respiratory tract

Question 6

What are the predominant infections in cellular immunodeficiency?

Answer 6

Viral, fungal and mycobacterial infections

Question 7

Why do CD4 T-cell defects affect B-cells?

Answer 7

T cell help is needed for B-cell maturation

Question 8

What are combined immunodeficiencies?

Answer 8

Immunodeficiency syndrome affecting both antibody production and T-cells

Question 9

Describe the levels of antibodies in predominantly antibody deficiency

Answer 9

Low IgG
Other isotopes may be affected
A low IgA / IgM with a normal IgG is rarely significant

Question 10

How does predominantly antibody deficiency manifest?

Answer 10

Recurrent pyogenic infections of upper and lower respiratory tract
Can get gut infections

Question 11

What are some physiological causes of antibody deficiency?

Answer 11

Transient hypogammaglobulinaemia of infancy

Question 12

What are some secondary causes of antibody deficiency?

Answer 12

IgG loss - renal nephrotic syndrome or skin in extensive burns
Impaired production - immunosuppressive drugs

Question 13

What are some primary causes of antibody deficiency?

Answer 13

X-linked agammaglobulinaemia

X-linked hyper-IgM syndrome

Question 14

What is transient hypogammaglobulinaemia of infancy?

Answer 14

Healthy physiological state of relative antibody deficiency around 6 months that can be correlated with increased infections

Question 15

What antibodies are infants protected with before 6 months?

Answer 15

Maternal IgG antibody

Question 16

What is X-linked agammaglobulinaema (XLA)?

Answer 16

Prototype antibody deficiency syndrome
Signally via Bruton’s tyrosine kinase required for signal transduction at pro-B stage
Maturation arrest occurs if absent so there is no heavy chain rearrangement, no B-cells leave marrow and no immunoglobulin production

Question 17

What is XLA also known as

Answer 17

Bruton’s disease
Btk deficiency
Bruton’s XLA

Question 18

What is X-linked hyper IgM syndrome?

Answer 18

CD40L deficiency
Failure of B-cell maturation 
Recurrent bacterial infections
Presents at 3-6 months
Immunological lesion resides on T-cell

Question 19

Describe the immunoglobulins in X-linked hyper IgM syndrome

Answer 19

Low IgG
Low IgA
Raised or normal IgM

Question 20

Describe treatment for antibody deficiency

Answer 20

Aim for early recognition before lung damage occurs
Aggressive treatment of intercurrent infections
Replace immunoglobulin using passive immunisation
Long-term suppression with antimicrobials

Question 21

What is cellular immunodeficiency?

Answer 21

CD4 T-cell deficiency

Question 22

How does cellular immunodeficiency manifest?

Answer 22

Opportunistic infection
Viral infection
Fungal infection
Mycobacterial infection

Question 23

What is SCID?

Answer 23

Rare, life-threatening primary immunodeficiency
Absent T-cells
B cells may be present but are non-functional

Question 24

How does SCID present?

Answer 24

Usually soon after birth
Rash
Failure to thrive
Chronic diarrhoea
Infections, especially opportunistic

Question 25

Describe some infections in SCID

Answer 25

Bacterial
Mycobacterial - BCG
Viral - CMV, EBV
Fungal - PCP, oral thrush

Question 26

What are the molecular causes of SCID?

Answer 26

Common gamma chain deficiency
JAK 3 deficiency
RAG 1 /2 deficiency

Question 27

What is common gamma chain deficiency?

Answer 27

X-linked SCID
Common gamma chain forms part of membrane receptor for several cytokines, some are required for T-cell maturation
Absent T-cells
B cells are present but non functional

Question 28

What is JAK-3 deficiency?

Answer 28

Autosomal recessive SCID
JAK-3 is downstream of common gamma chain
Absent T-cells
B cells present but non functional

Question 29

What is RAG 1 and 2 deficiency?

Answer 29

Autosomal recessive form of SCID
RAG 1 and 2 required for somatic recombination evens
Deficiency means no T and B cell receptors

Question 30

Describe the steps of stem cell transplant for SCID therapy

Answer 30

1) Stem cells harvested from HLA-matched donor
2) Given to recipient by infusion
3) Engraft in bone marrow
4) Reconstitution of T and B cells

Question 31

What is DiGeorge syndrome?

Answer 31

Failure of migration of 3rd / 4th branchial arches

Most patients have micro deletions on chromosome 22

Question 32

What is the full phenotype of DiGeorge syndrome?

Answer 32

Absent parathyroids - low calcium, tetany
Cleft palate
Congenital heart defects
Thymic aplasia - low T-cell numbers

Question 33

What is terminal complement deficiency?

Answer 33

Deficiency of terminal complement components C5-C9 leads to specific susceptibility to Neisseria species.
Diagnose by functional complement assays