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Pathology by week > W10 - Primary immunodeficiency part 2 > Flashcards

W10 - Primary immunodeficiency part 2 Flashcards

1
Q

A) What is the most severe form of SCID?

B) Describe which cells are lacking?

C) Treatment?

A

A) Reticular dysgenesis

B) failure to produce lymphocytes, neutrophils, monocyte/macrophages, platelets

C) fatal in very early life unless HSCT

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2
Q

How many different types of SCID are there?

A

>20, with many diff pathways affected

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3
Q

X-linked SCID

  • % of all SCID?
  • Mutation?
A

45% of all SCID

mutation of common gamma chain (chr Xq13.1)

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4
Q

What is the phenotype of X-linked SCID (T, NK, B cells)

A

very low/absent T cells

very low/absent NK cells

normal/increased B cells BUT LOW Igs

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5
Q

ADA-deficiency:

  • % of all SCID
  • enzyme affected
A

16.5% of all SCID

Adenosine deaminase deficiency

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6
Q

Phenotype of ADA deficiency SCID (T, NK, B cells)

A

Very low/absent T cells

Very low/absent B cells

very low/absent NK cells

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7
Q

What protects the SCID neonate in the first 3 months of life?

A
  1. Active transport of maternal IgG across placenta
  2. IgG in colostrum

=> depletes as baby reaches 3 months of age, and that is when neonatal IgG production should take over

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8
Q

Clinical presentation (6) of baby with SCID?

A
  1. Unwell by 3 months of age
  2. Infections of all types
  3. Failure to thrive
  4. Persistent diarrhoea
  5. Unusual skin disease:
    - Colonisation of infant’s empty BM by maternal lymphocyte => graft vs host disease
  6. Family history of early infant death
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9
Q

Another name for DiGeorge syndrome?

A

22q11.2 deletion syndrome

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10
Q

Describe clinical phenotype (7) of DiGeorge syndrome

A
  1. High forehead
  2. Low set, abnormally folded ears
  3. Cleft palate, small mouth + jaw
  4. Hypocalcaemia
  5. Osophageal atresia
  6. Underdeveloped thymus!
  7. Congenital heart disease

*there’s developmental defects of the pharyngeal pouch

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11
Q

Describe levels of B cells and T cells in someone with DiGeorge Syndrome? What is their immune function like?

A

B cells normal

T cells reduced

Immune function usually only mildly impaired and improves with age

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12
Q

What is the pathophysiology of Bare lymphcoyte syndrome (BLS) type 2

A

Defect in regulatory protein involved in Class II gene expression => absent expression of MHC class II => deficiency of CD4 T cells

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13
Q

Describe typical immune [] for BLS type 2

A

Deficiency of CD4+ T cells

Low IgG or IgA = due to lack of CD4+ T cell help

Normal number of CD8+ T cells

Normal number of B cells

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14
Q

What is the clinical phenotype (4) of BLS type 2

A
  1. Unwell by 3 months of age
  2. Infections of all types
  3. Failure to thrive
  4. Family history of early infant death
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15
Q

Name 4 disorders due to failure of T cell signalling, cytokine production, and effector functions

A

IFN gamma deficiency

IFN gamma receptor deficiency

IL12 deficiency

IL12 receptor deficiency

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16
Q
  • Viral infections (CMV)
  • Fungal infections (PCP, cryptosporidium)
  • Some bacterial infections - esp intracellular organisms such as TB, salmonella
  • Early malignancy

What do these suggest?

A

T cell deficiency

17
Q

Name 5 tests to order to investigate T cell deficiency

A
  1. Total WCC and differentials
  2. Lymphocyte subsets (CD4, CD8. B, NK)
  3. Immunoglobulins (if CD4 T cell deficient)
  4. Functional tests of T cell activation + proliferation

* useful if singalling or activation defects are suspected

  1. HIV test
18
Q
A
20
Q

Management (5) for T cell immunodeficiency

A
  1. prophylactic abx/prompt infection treatment
  2. HSCT => SCID, BLS
  3. Enzyme replacement => PEG-ADA for ADA-SCID
  4. Gene therapy
  5. Thymic transplantation
21
Q

Match them

A
  1. X-linked SCID
  2. IFN-gamma receptor deficiency
  3. 22q 11.2 deletion syndrome (DiGeorge Syndrome)
  4. BLS type 2
22
Q

severe recurrent infections from 3 months. T cell absent, B cells present, Igs low.

Norma facial features and cardiac echo

  • 22q112 deletion syndrome
  • bare lymphocyte syndrome type II
  • X-linked SCID
  • IFN gamma receptor deficiency
A

X-linked SCID

24
Q

Bruton’s X-linked agammaglobulinaemia:

A) What is the molecular problem?

B) What is the deficiency? When does it present?

A

A) Abnormal B cell tyrosine kinase in Pre-B cells = cannot develop any further

B) Absence of mature B cells = no circulating Ig after 3 months

25
Q

Bruton’s X-linked agammaglobulinaemia - what are the clinical features (4)?

A
  1. Boys present in 1st few years of life
  2. Recurrent bacterial infections: otitis media, sinusiits, pneumonia, osteomyelitis, septic arthritis, gastroenteritis
  3. Viral, fungal, parasitic infections = enterovirus, pneumocystis
  4. Failure to thrive
26
Q

Hyper IgM syndrome:

  • what is the mode of inheritance?
  • What is the molecular defect?
A

X-linked recessive

  • mutation in CD40L gene = T cell cannot communicate with B cell
27
Q

Hyper IgM syndrome:

  • # of circulating B cells
  • # of T cells
  • GCs within LNs and spleen
  • Isotype switching
  • Serum IgM, IgA, IgE, IgG levels
A
  • Normal # of circulating B cells
  • Normal number of T cells (but lack CD40L)
  • No GC in LNs + spleen
  • Failure of isotype switching:
  • High serum IgM
  • No IgA, IgE, IgG
28
Q

What is the clinical phenotype (4) of hyper IgM syndrome?

A
  1. Boys present in first few years of life
  2. Recurrent infections - bacterial
  3. Subtle abnormality in T cell function predisposes to pneumocystic jiorevi, autoimmune disease, malignany
  4. Failure to thrive
29
Q

Common variable immune deficiency - when does it present?

A

Adulthood or childhood

30
Q

What is the underlying pathophysiology in CVID?

What are the blood parameters like in terms of Igs?

A

heterogenous group of disorders - failure of full differentiation/function of B cells

Marked reduction in IgG, sometimes low IgA or IgM

31
Q

What are the clinical features of CVID (6):

A
  • Poor response to immunisations
  • Recurrent bacterial infections (pneumonia, sinusitis, gastroenteritis)
  • Pulmonary disease (instersitial lung disease, granulomatous interstitial lung disease, obstructive airway disease)
  • GI disease (Inflammatory bowel like disease, sprue-like illness, bacterial overgrowth)
  • Autoimmune disease (autoimmune haemolytic anaemia, thrombocytopaenia, RA, pernicious anaemia, thyroiditis, vitiligo)
  • Malignancy (NHL)
32
Q

What does this protein electrophoresis signify?

A

No band in gamma region = B cell deficiency

33
Q

Complete the table

A
34
Q

Selective IgA deficiency:

  • Prevalence?
  • Symptoms?
A

1/600

2/3 asymptomatic

1/3 = recurrent RTI

35
Q

Match them

A
  1. CVID
  2. X-linked Hyper IgM syndrome
  3. Bruton’s X-linked hypogammaglobulinaemia
  4. IgA deficiency
36
Q

What investigations (4) should we order to test for B cell deficiencies?

A
  1. Total WCC + differentials
  2. Lymphocyte subsets - CD4, CD8, B, NK cells
  3. Serum Igs and protein electrophoresis
  4. Functional tests of B cell function:

A) measure IgG antibodies to immunisations

B) If low, immunise with killed vaccine => repeat measurement

39
Q

Management (3) of B cell immunodeficiency

A
  1. Prophylactic abx/treatment of infection
  2. Ig replacement if required (lifelong)
  3. Immunisation (for IgA deficiency, not in diseases where IgG deicient as it won’t be effective)

Pathology by week (70 decks)

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