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Immunology Y5 > Primary immunodeficiencies 2 - adaptive immune system > Flashcards

Primary immunodeficiencies 2 - adaptive immune system Flashcards

1
Q

What are the different types of SCID?

Which is the most common?

A
  1. Reticular dysgenesis
  2. X- linked SCID
  3. ADA deficiency

Most common = x linked scid!!

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2
Q

Why is it called SCID?

A

Combined: affects B and T cells

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3
Q

Reticular dysgenesis:

a) molecular mechanism
b) blood cell abormalities
c) management

A

a) molecular mechanism

  • autosomal recessive severe SCID (most severe form)
  • mutation in mitochondrial energy metabolism enzyme AK2
  • affects haemoatpoietic stem cells–> failure of production of myeloid and lymphoid cells

b) cells affected (low):

  • lymphocytes - B and T
  • neutrophils
  • monocytes/macrophages
  • platelets

Treatment:

Stem cell transplant - fatal in early life otherwise

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4
Q

X-linked SCID

a) molecular mechanism
b) blood cell abormalities
c) clinical phenotype

A

a) molecular mechanism

  • mutation in Xq13.2
  • mutation in cytokine receptor - failure to respond to cytokines and produce cells

​b) blood cell abnormalities

  • low T cells - CD4 and CD8
  • low NK cells
  • Normal B cell counts - but LOW IMMUNOGLOBULIN (failure of production of MATURE b cells)

c) clinical phenotype

  • presents in early childhood with severe sepsis
  • eczema like rash
  • systemic candida infections
  • failure to thrive
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5
Q

ADA deficiency

a) molecular mechanism
b) blood cell abnormlaities
c) tx

A

a) molecular mechanism

  • deficiency of adenosine deaminase enzyme
  • enzyme required by lymphocytes for cell metabolism
  • failure of maturation along any of the cell lineages

b) blood cell abnormalities

  • low/absent T cells
  • low/absent B cells
  • low/absent NK cells
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6
Q

What age does SCID present? Typical clinical features?

A
  • presents at 3-6 months of age
    • before this they are protected by maternal IgG (through placenta)
  • typical clinical features
    • Infections of all types
    • Failure to thrive
    • Persistent diarrhoea
    • Unusual skin disease:
      • Colonisation of infant’s empty bone marrow by maternal lymphocytes
      • This is sort of like graft-versus-host disease because the maternal lymphocytes are in the baby’s bone marrow
    • Family history of early death
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7
Q

Classes of T cell disorders

A
  1. disorders of t cell maturation
  2. disorders of selection of CD4 and CD8 positive T lymphocytes
  3. disorders of t cell effector function
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8
Q

What disorder causes defect in T cell maturation

A

Di george syndrome

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9
Q

Di George syndrome

a) clinical features
b) cell counts

A

Autosomal dominant deletion of 22q11.2 (but can also be sporadic- in most cases)

CATCH 22

  • Cardiac defects: truncus arteriosus, TOF
  • Abnormal facies and atresia
    • Facies
      • High forehead
      • Low set, abnormally folded ears
      • Cleft palate
      • Small mouth and jaw
    • Oesophageal atresia
  • thymic hypoplasia: absence of thymic shadow on x ray
  • Cleft palate
  • Hypocalcaemia - due to underdevelopment of parathyroid gland
  • 22: 22q11.2 deletion

b) cell counts

  • low T cells
  • Normal B cells
  • Low IgA/IgG/IgE (AGE) - as defect in T cells leads to lack of maturation of B cells
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10
Q

What happens to T cell counts in Di George syndrome over time?

A

Homeostatic proliferation

so immune function increases with age

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11
Q

Which disorder leads to defect in selection of CD4 and CD8 lymphocytes?

A

Bare lymphocyte syndrome

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12
Q

Two types of Bare lymphocyte syndrome

Pathophysiology/cell counts

A

1. Bare lymphocyte syndrome type II

  • defect in protein involved in expression of MHC II
  • MHC II is not expressed at all –> so CD4 T cells are not selected
  • Cell counts
    • Low/absent CD4+ T cells
    • CD8+ T cells usually normal
    • Antibodies
      • IgM: normal (as this does not require T cells)
      • IgA and IgG: lOW - as these require T cells to develop

2. Bare lymphocyte syndrome type I

  • MHC I is absent
  • CD8+ T cells fail to develop
  • Cell counts
    • Low/absent CD8+ T cells
    • Normal CD4+ T cells
    • Normal immuoglobulins
      • as CD4 T cells are intact
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13
Q

Clinical features of BLS

A

Unwell by 3 months of age

Infections of all types

Failure to thrive

Family history of early infant death

Sclerosing cholangitis

hepatomegaly

jaundice

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14
Q

Outline some disorders of T cell effector function

A

Could affect:

  • Cytokine production (e.g. IFN-gamma)
  • Cytokine receptors (e.g. IL2 receptor)
  • Cytotoxicity
  • T-B cell communication
  • involving CD40 ligand and CD40
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15
Q

Overall clinical features of T cell deficiencies

A
  • viral infections
  • some fungal infections: eg cryptosporidium, PCP
  • some bacterial ifnections: especially intracellular bacteria such as salmonella and myobacterium TB
  • early malignancy
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16
Q

What technique is used to do a lymphocyte differential?

A

FACS - fluorescence activated cell sorting

17
Q

Differentiating between SCID, Di George and BLS (type II) via cell counts

A
18
Q

what are the 4 defects that can occur in B cell maturation?

A
  1. bruton’s x linked hypogammaglobulinaemia
  2. hyper IgM syndrome
  3. common variable immunodeficiency
  4. selective IgA deficiency
19
Q

Bruton’s X-linked Hypogammaglobulinaemia

A
  • x linked recessive
  • mutation in BTK gene
  • affects B cell maturation - at the point where pre- b cells enter the circulation from the bone marrow
  • so you don’t get any mature B cells
    • so no antibody production
  • all immunoglobulins affected: IgM, IgA and IgG
  • T cells - CD4 and CD8 ae present
  • B cells are absent
  • affects children after 6 months - before this they have maternal antibodies

Clinical phenotype (typical presentation)

  • 1 year old boy
  • Recurrent bacterial infections
  • CD4 and CD8 T cells present
  • B cells absent
  • IgG, IgA and IgM absent
20
Q

What vaccines must be avoided in Bruton’s X linked hypogammaglobulinamiea?

A

Live attenuated vaccines must be avoided

21
Q

Hyper IgM syndrome

A

Pathophysiology

  • X linked recessive
  • Mutation in CD40ligand on T cells
  • Technically a T cell problem
  • Results in failure of maturation of B cells

Cell counts

  • Excess IgM
  • low IgA and IgG
  • T cells and B cell count is normal

Typical presentation

  • recurrent bacterial infections as a child
  • episode of PCP
  • high IgM
  • absent IgA
  • and absent IgG
22
Q

Recurrent bacterial infections in a 1yo child wih episode of PCP

A

Hyper IgM syndrome

23
Q

1 year old boy

Recurrent bacterial infections

CD4 and CD8 T cells present

B cells absent

IgG, IgA and IgM absent

A

Bruton’s X linked hypogammaglobulinaemia

  • as T cells are unaffected
  • B cells are absent
  • all antibodies are absent
24
Q
A
25
Q

recurrent bacterial infections as a child

episode of PCP

high IgM

absent IgA

and absent IgG

A

Hyper IgM syndrome

*NB the PCP!!

26
Q

adult with bronchiectasis

recurrent sinusitis

and development of atypical SLE

A

Common variable immunodeficiency

27
Q

Common variable immunodeficiency

A
  • Generally adults (>4 years old)
  • Low IgG, with low IgA or IgE
  • normal igM
  • Poor/absent response to immunisation
  • Absence of other defined immunodeficiency

Clinical features: recurrent bacterial infections, pulmonary disease, GI disease, autoimmune disease, malignancy (NHL)

28
Q

Selective IgA deficiency

A
  • 2/3rd individuals asymptomatic
  • 1/3rd have recurrent respiratory tract infections
  • And gastrointestinal infections/ GI infections
  • At risk of anaphylaxis from blood transfusions due to donor IgA
29
Q

recurrent respiratory tract infections

absent IgA

normal IgM

and normal IgG

A

Selective IgA deficiency

30
Q

Lymphocyte count in children vs adults

A

Children have much higher lymphocyte counts

31
Q

What is a surrogate marker for CD4 T helper cell function?

A

IgG

32
Q

Differentiate between SCID, Bruton’s, Hyper IgM, Selective IgA and CVID

A
33
Q

Why is immunisation not a good treatment for B cell defects?

A

Because they can’t produce IgG so can’t mount an immune response

Immunology Y5 (11 decks)

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