Primary immunodeficiency Flashcards
(28 cards)
What are primary immunodeficeincies?
- 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
What are secondary immunodeficiencies?
- 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.
Secondary immunodeficiencies are split up into which three categories?
- Environmental
- Malnutrition
- Burns
- Trauma
- Disease
- Infection
- DM
- Renal failure
- Malignancies (leukaemia - lymphoma)
- Iatrogenic
- Surgery
- Splenectomy
- Drugs
What are the subtypes of primary immunodeficiencies?
-
Antibody deficiencies
- Characterized by a deficiency of one of more (sub)classes of antibodies (e.g. IgG, IgA, IgM, IgG2) due to defective B-cell function
- Mature B cell deficiency
-
Cellular Immunodeficiencies
- Impaired T cell function of absence of normal t cells
-
Innate immune disorders
- Defects in phagocyte function
- Complement deficiencies
- Absent of morphisms in PRR (pattern recognition receptors)
Which pathogens can attack:
Antibody deficiency?
Cellular immunodeficiencies?
Innate immune disorders?
-
Antibody
- Recurrent bacterial infections of the upper and/or lower respiratory tract
- S. pneumoniae, H. influenzae
-
Cellular
- Unusual/opportunistic pathogens
- Pneumocystic jirovecii
-
Innate
- Defects in phagocyte function
- staph aureus
- Aspergillus
- Complement deficiencies
- N. meningitidis
- Defects in phagocyte function
Is it just an infection…..?
When should we be suspicious that an infection may be a primary immunodeficiency?
Infection that is:
SPURR
- Severe
- Persistant
- Unusual
- Recurrent
- or
- Runos in the family
What is the key role in innate immunity?
- Phagocytosis
What are some of the neutrophil defects in primary immunodeficiency?
- Absence of neutrophils > congenital neutropenia
- Adhesion > leucocyte adhesion defect
- Recognition and Phagocytosis > deficiencies of PRR
- Intracellular Killing > chronic granulomatous disease
What is Hereditary Angioedema? How does it present?
- C1-inhibitor deficiency (autosomal dominant)
- Recurrent episodes of painless, non-pitting, non-pruritic, non- erythematous swellings
- Subcutaneous tissues, intestines, oropharynx
What is the Mx for hereditary angioedema?
- Acute emergency management of:
- Pharyngeal/laryngeal obstruction
- Acute abdominal pain
- C1-inhibitor infusion OR fresh frozen plasma
- (steroids, antihistamines ineffective)
What are the subclasses of disorders of the adaptive immune system?
- T cell and B cell disorders
Adaptive system
What are features of B cell disorders?
- 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)
Adaptive system
What are features of T cell disorders?
- Isolated T-cell subset deficiencies (CD3, CD4, CD8)
- Combined deficiencies (severe combined immunodeficiency)
- Syndromal immunodeficiencies
What is 22q11 deletion syndrome?
- DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by the deletion of a small segment of chromosome 22.
- While the symptoms can be variable, they often include congenital heart problems, specific facial features, frequent infections, developmental delay, learning problems and cleft palate
- Causes a depletion of helper T cells!!
What are the genetic features of 22q11 deletion syndrome?
- Hemizygous 22q11.2 deletion
- Most common microdeletion syndrome
- de novo mutations (10% deletion identified in a parent)
- Highly variable expression
- 1:4000 (Down syndrome 1:1200)
- UK/Ireland: 10,000-15,000 affected
- 2nd most common cause of developmental delay and
- major congenital heart disease (after DS)
How does 22q11 clinically present?
- Congenital cardiac abnormalities
- Palatal defects
- Immunodeficiency
- Learning disabilities
- other’s on the slides but not common
How do patients who have 22q11 look?
- Short forehead
- hooded eyelids
- Malar flatness
- Bulbous nasal tip with hypoplastic alea nasi
- Protuberant ears
What immune system disorders can arrive from 22q11?
-
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
What is complete DiGeorge anomaly?
- 22q11
- = DiGeorge + thymus aplasia
- Fatal < age of 2 years
What is atypical complete DiGeorge anomaly?
- 22q11
- Oligoclonal T cells, rash, lymphadenopathy
- T cells can reject transplant
What is typical complete DiGeorge anomaly?
- Very low T-cell numbers, no rash
- May develop into ‘atypical’ phenotype
How do invasive fungal infections present?
- Presenting symptom of primary immunodeficiency
Who is likely to get an invasive fingal infection?
- Children with neutropenia due to leukaemia and/or chemo
- Invasive candidiasis in premature neonates due to immature (but physiological) immune system
- In children admitted to PICU and treated with broadspectrum antibiotics and/or abdominal surgery
What is the management of PID (primary immunodeficiency)?
- Symptomatic treatment = prevention of infections
- Causative
- Immunoglobulin substitution
- Gene therapy (ADA-SCID)
- Stem cell transplant (CGD)
- Thymus transplant (diGeorge)
- Genetic counselling & prenatal diagnosis
