Primary Immunodeficiencies Flashcards

1
Q

name the 4 main components of the immune system and their immune mechanism

A

B cells and antibodies (humoral, specific immunity)
T cells (cellular, specific immunity)
Phagocytes (innate immunity)
complement system (innate immunity)

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2
Q

what are primary immunodeficiencies?

A
  • Group of > 300 rare, chronic disorders in which part of the body’s immune system is missing or functions improperly
  • Caused by single genetic defects
  • May affect a single part of the immune system or more components of the immune system
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3
Q

main causes of primary immunodeficiencies in europe

A
predominately antibody disorders
predominantely T cell disorders
phagocyte disorders
other well defined PIDs
complement deficiencies
auto-immune and immune dysregulation syndromes
auto-inflammatory syndromes
unclassified
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4
Q

what are secondary immunodeficiences

A
  • Components of the immune system itself are all present and functional.
  • Acquired diseases affecting the immune system and/or treatments negatively influencing the immune system.
  • Caused by environmental/iatrogenic insults.
  • Most well-known examples are HIV infection and patients treated for malignancies.
  • Much more common than primary immunodeficiencies.
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5
Q

causes of secondary immunodeficiencies: environmental

A

malnutrition
trauma
burns

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6
Q

causes of secondary immunodeficiencies: disease

A
infection
diabetes
renal failure
asplenia
malignancies (leukaemia, lymphoma)
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7
Q

causes of secondary immunodeficiencies: iatrogenic

A

surgery
splenectomy
drugs (immunosuppressive, antirheumatic, antiepileptic)

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8
Q

3 categories of primary immunodeficiencies

A

antibodies deficiencies
cellular immunodeficiencies
innate immune disorders

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9
Q

primary immunodeficiencies: antibody deficiency

A

characterised by a deficiency of one or more (sub)classes of antibodies e.g. IgG, IgA, IgM, IgG2 due to defective B cells
or
absence of mature B cells

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10
Q

primary immunodeficiencies: cellular immunodeficinces

A

characterised by impaired T cell funciton or the absence of normal t cells

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11
Q

primary immunodeficiencies: innate immune disorders

A

defects in phagocyte function
complement deficiencies
absence or polymorphisms in pathogen recognition receptors

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12
Q

infections in primary immunodeficiencies: antibody deficiencies

A

recurrent bacterial infections of the upper and/or lower RT

s. pneumoniae, H. influenzae

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13
Q

infections in primary immunodeficiencies: cellular immunodeficiencies

A

unisal or opportunistic infections often combined with failure to thrive
pneumocystic jirovecii, CMV pneumonia

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14
Q

infections in primary immunodeficiencies: innate immune disorders

A
defects in phagocyte function:
s. aureus  (sepsis, skin lesions, abscesses internal organs)
aspergillus infections (lung, bones, brain)

complement deficiencies
n. miningitidis

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15
Q

consequences of neutrophil defects

A
  • Absence of neutrophils > congenital neutropenia
  • Adhesion > leucocyte adhesion defect
  • Recognition and Phagocytosis > deficiencies of PRR
  • Intracellular Killing > chronic granulomatous disease
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16
Q

describe hereditary angioedema

A

• C1-inhibitor deficiency (autosomal dominant)
• Recurrent episodes of painless, non-pitting, non-pruritic, non erythematous swellings
• Subcutaneous tissues, intestines, oropharynx

Acute emergency management of:

Pharyngeal/laryngeal obstruction

Acute abdominal pain

C1-inhibitor infusion OR fresh frozen plasma

(steroids, antihistamines ineffective)

17
Q

disorders of adaptive immunity: B cells

A
  • Absence of mature B-cells due to maturation stop in the bone marrow (BTK mutation)
  • Absence of immunoglobulin production
  • Absence of specific immunoglobulins and/or subclasses
  • IgG, IgA, IgM, IgG1, IgG2, IgG3, IgG4
  • Absence of functional antibodies (upon immunisations
18
Q

disorders of adaptive immunity: T cells

A
  • Isolated T-cell subset deficiencies (CD3, CD4, CD8)
  • Combined deficiencies (severe combined immunodeficiency)
  • Syndromal immunodeficiencies
19
Q

describe with a diagram b cell maturation and defects

A

see notes

20
Q

what is 22q11 deletion syndrome aka

A

diGeorge

21
Q

what is 22q11 deletion syndrome

A
•
Hemizygous 22q11.2 deletion
•
Most common microdeletion syndrome
•
de novomutations (10% deletion identified in a parent)
•
Highly variable expression
•
1:4000 (Down syndrome 1:1200)
•
UK/Ireland: 10,000-15,000 affected
•
2ndmost common cause of developmental delay and major congenital heart disease (after DS)
22
Q

clinical presentation of 22q11 deletion syndrome

A
•
Congenital cardiac anomalies
•
Palatal defects (affecting feeding and speech)
•
Characteristic facial features
•
Immunodeficiency –Thymus a-/hypo-plasia
•
Hypocalcaemia
•
Developmental disabilities
•
Learning disabilities
•
Behavioralproblems
•
Psychiatric illness
•
Structural abnormalities (renal, eye, dental, skeletal, brain, GI-tract)
•
Haematological & AI disorders
23
Q

physical appearance in 22q11 deletion syndrome

A
  • Short forehead
  • Hooded eyelids with upslanting palpebral fissures
  • Malar flatness
  • Bulbous nasal tip with hypoplastic alea nasi
  • Protuberant ears
24
Q

immune deficiency in 22q11 deletion syndrome

A
•
Recurrent RTI’s during infancy
•
low T-cell numbers (+ qualitative defects)
•
low IgA and IgM
•
reduced antibody responses
•
Autoimmune phenomena (30%)
•
anaemia/thrombocytopenia
•
juvenile chronic arthritis (JIA; low IgA)
•
Raynaud’s
•
thyroid disease
25
Q

complete diGeorge anomaly

A

diGeorge + thymus aplasia

fatal < 2

26
Q

atypical complete diGeorge anomaly

A

oligoclonal t cells, rash, lymphadenopathy

t cells can reject transplant

27
Q

typical complete diGeorge anomaly

A

very low t cell numbers, no rash

may develop into atypical phenotype

28
Q

infections in: adaptive CD4 def

A

pneumocystitis spp

ophthalmic pneumocystosis
pneumocystitis pneumonia
hepatosplenic infiltrates
renal pneumocystosis
bone marrow infiltrates
29
Q

infections in: innate neutrophil disorders

A

aspergillus spp

cerebral aspergillosis
kerattis
sinusitis
allergic and invasive pulmonary aspergillosis 
aspergilloma
invasive aspergillosis
osteomyelitis
cutaneous aspergillosis
30
Q

infections in: systemic innate (phagocytic disorders)/mucosal addaptice (IL-17 response)

A

candida spp

cerebral abscess
endopthalmitis
thrush
oesphagitis
endocarditis
candidemia
hepatic abscess
urinary candidiasis
vilvovaginal candidiasis
osteomyelitis
cutaneous candidiasis
onychomycosis
31
Q

infections in: adaptive CD4 def cryptococcus spp

A
meningitis
cerebral abscess
endophthalmitis
pulmonary infiltrates
endocardititis
crpytococcemia
renal abscess
subcut abscess
32
Q

invasive fungal infections in PID

A
  • Presenting symptom of primary immunodeficiency
  • In children with neutropenia due to leukaemia and/or chemotherapy
  • Invasive candidiasis in premature neonates due to immature (but physiological) immune system
  • In children admitted to PICU and treated with broad spectrum antibiotics and/or abdominal surgery
33
Q

management of PID

A
•
Symptomatic treatment = prevention of infections
•
Causative
•
Immunoglobulin substitution
•
Gene therapy (ADA-SCID)
•
Stem cell transplant (CGD)
•
Thymus transplant (diGeorge)
•
Genetic counselling &amp; prenatal diagnosis