WEEK 4: PRIMARY IMMUNODEFICIENCIES Flashcards by Amber Walker

What is a primary immunodeficiency?

people born with an immune system that does not work correctly, intrinsic, sometimes inherited defects of the immune system

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What is a secondary immunodeficiency?

an immune system that doesn’t work but is acquired through life, eg lifestyle

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How many unique PIDs have been identified?

over 250

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Why are PIDs predominantly found in males?

More immune related genes on the x chromosome, males have 2 x. Females Y chromosome could mask it.

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How many respiratory tract infections are a sign of PID?

> 8 in a child and >4 in an adult in one year.

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What are some signs of a PID?

recurrent respiratory tract infections
> 1 infection requiring hospital admission
IV antibiotic treatment
opportunistic microbial infections that are uncommon
infections at unusual sites
chronic infection that is unresponsive to usual treatmen
family history

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are PID genes homogenous or heterogenous?

heterogenous

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How are PIDs diagnosed? give 3 examples

Genetic testing & sequencing (WGS vs exome), family history
Patient history: exposure to HIV, drugs, ionising radiation
Assess immunoglobulin production
Assess complement production
Assess neutrophil/phagocyte function
Assess cell-mediated immune function

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What does SCID stand for?

severe combined immuno deficiency

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Are PIDS genetic, inherited, or caused by infection?

All are genetic, some are inherited. None caused by infection.

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What is the most common SCID?

(X-SCID) - x linked which means there’s a defect in the gamma chain

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What is SCID?

immunodeficiency affecting lymphocyte production.

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What gender does X-SCID occur in?

exclusively in males

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How common is X-SCID?

Affects 1 in 100,000 new-borns.

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What cells are affected by SCID?

T cells and B cells.

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When is SCID usually diagnosed?

Symptoms usually obvious before 3 months

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What is SCID caused by?

mutation occurring in the x chromosome - 13.1 locus

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What does an xq13.1 mutation in the locus cause?

the interleukin 2 receptor gene is mutated. It is essential in T cell development.

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What does the IL2RG (interleukin 2 receptor gene) encode for?

a protein called the common gamma (Y) chain

What is the common gamma chain essential for?

the maturation and functioning of all lymphocytes. Without it the lymphocytes do not mature.

What other IL receptors is the gamma chain protein a critical signalling component for?

IL2R, IL4R, IL7R & IL21R

What is the treatment for SCID?

HSCT (haematopoietic stem cell transplantation)

What is required for an unmatched HSCT donor to work?

mature T cell depletion. T cells can attack the recipient.

How successful is HSCT?

> 80%. Even higher for SCID patients that had HSCT < 3 months old

What is gene therapy?

a technique that modifies a person's genes to treat or cure disease

How does gene therapy work?

take patient stem cells and transect them with a vector that will put the correct version of the gene in their genetic code. Retroviral vectors are used.

what syndrome is caused by failure of expression of HLA molecules?

Bare lymphocyte syndrome

What is CD40 ligand deficiency?

It is a severe primary immunodeficiency caused by mutations in the CD40L gene

What is CD40 ligand deficiency caused by?

Mutations in the CD40 ligand gene. T cell disorder is a mutation in the ligand whereas a B cell disorder is a mutation in the receptor

What does CD40 ligand do?

this ligand is found on T cells and binds to the CD40 receptor on B cells.

Why is CD40L important for B and T cells?

- both B and T cells activate by the engagement of the ligand with the receptor - it is critical in B cell proliferation and immunoglobin isotype switching -

What is CD40L deficiency also known as?

Hyper IgM syndrome

How is CD40L deficiency detected?

increased level of serum IgM and significantly decreased level of IgA, IgG and IgE

How is Hyper IgM syndrome treated?

immunoglobin replacement therapy, HSCT, antibiotics

What is meant by leaky SCID?

Genetic mutation leads to partial enzymatic activity, partial development of the immune system. Limited amount of T and B cells.

What is a sign of primary antibody deficiency?

Recurrent bacterial infections of the respiratory and GI tract

What is the most common antibody deficiency?

Selective IgA deficiency. Most people have no symptoms

What deficiency is caused by low levels of IgG?

common variable immune deficiency (CVID)

What does WAS stand for?

Wiskott-Aldrich Syndrome

What gene defect causes WAS?

the WASP protein

Why is WASP important?

the WASP protein is important in actin cytoskeleton in T cell function

What does an absence or defect of the WASP protein cause? Name 3

- T cells ability to control its own cytoskeleton is lost, lack of movement - No signalling due to lack of actin - NO phagocytosis - NK cells are unable to put perforin in target cell

What are some features of WAS? name 3

1. Increased tendency to bleed - reduced and small platelets 2. Recurrent infections 3. Eczema 4. Leukymia

What are some features of WAS? name 3

1. Increased tendency to bleed - reduced amount and small platelets 2. Recurrent infections 3. Eczema 4. Leukaemia

Can a patient of WAS receive a live vaccine?

What are the 3 pathways that the complement is activated?

alternative pathway, classical pathway, lectin pathway