Immunodeficiency Flashcards
(45 cards)
1
Q
What are the 4 elements in the process of immunity?
A
- Recognition
- Interaction
- Elimination
- Control and regulation
2
Q
What are the contributors to out immune defences?
A
- Barriers
- Innate immunity
- Adaptive immunity
3
Q
What cells are involved in innate immunity?
A
- Macrophages
- Monocytes
- Neutrophils
- Mast cells
- NK cells
- APCs
4
Q
What receptors are involved in innate immunity?
A
- Fc
- Complement -Mannose
- Toll-like
- C-type lectins
- Cytokine
5
Q
What molecules are involved in innate immunity?
A
- Complement
- Acute phase proteins
- Chemokines
- Cytokines
6
Q
What cells are involved in adaptive immunity?
A
- B cells
- T cells
7
Q
What receptors are involved in adaptive immunity?
A
- Ig
- TCR
- HLA
- Cytokine
- Complement
- Toll-like
8
Q
What molecules are involved in adaptive immunity?
A
- Immunoglobulins
- Cytokines
9
Q
What are the 4 main components of immune defence mechanisms?
A
- B-cells and antibodies (humoral, specific immunity)
- T-cells (cellular, specific immunity)
- Phagocytes (innate immunity)
- Complement system (innate immunity)
10
Q
What are primary immunodeficiencies?
A
- A group of >300 rare chronic diorders in which part of the body’s immune system is missing or functions improperly
- Caused by a single gene defect
- May affect a single part of the immune system or more components
11
Q
What is the most common subtype of PID in Europe?
A
Antibody disorders
12
Q
What are secondary immunodeficiencies?
A
- Components of the immune system are all present and functional but acquired disease affects the immune system and/or treatments negatively influence the immune system
- Much more common than PID
13
Q
What causes SID?
A
- Caused by environmental/iatrogenic insults.
- Most well-known examples are HIV infection and patients treated for malignancies.
14
Q
Give examples of causes of SID.
A
Environmental
- Malnutrition
- Trauma
- Burns
Disease
- Infection
- Diabetes
- Renal failure
- Asplenia
- Malignancy (leukaemia/lymphoma)
Iatrogenic
- Surgery
- Splenectomy
- Drugs (immunosuppressant’s, antiepileptic’s and antirhematics)
15
Q
What are antibody deficiencies due to?
A
- Deficiency of 1 or more (sub)classes of antibodies (e.g. IgG, IgM, IgA, IgG2) due to defective B cell function
- Absence of mature B cells
16
Q
What are cellular immunodefiencies due to?
A
Impaired T cell function or the absence of normal T cells
17
Q
What are innate immune disorders due to?
A
- Defects in phagocyte function
- Complement deficiencies
- Absence of polymorphisms in pathogen recognition receptors
18
Q
What infections are common in antibody deficiencies?
A
- Recurrent bacterial infections of the upper and/or lower respiratory tract
- S. pneumoniae, H. influenzae
19
Q
What infections are common in cellular immunodeficiencies?
A
- Unusual or opportunistic infections often combined with failure to thrive
- Pneumocystic jirovecii, CMV (pneumonia)
20
Q
What infections are common in defects of phagocyte function?
A
- S. aureus (sepsis, skin lesions, abscesses internal organs
- Aspergillus infections (lung, bones, brain)
21
Q
What infection is common in complement deficiencies?
A
N. menigitidis
22
Q
How can PID be recognised?
A
- Severe: requires hospitalisation or IV antibiotics
- Persistent: won’t completely clear up or clears very slowly
- Unusual: caused by an uncommon organism
- Recurrent: keeps coming back
- Runs in the family: others in your family have had similar susceptibility to infection
23
Q
What are the warning signs for PID in children and adults?
A
2 or more= see GP
- 4 or more (children) or 2 or more (adults) new ear infections in 1 year
- 2 or more serious sinus infections within 1 year
- 2 or more bouts of pneumonia in 1 year (children) or recurrent (adults)
- Chronic diarrhoea with weight loss, and failure to grow normally or weight gain in children
- Recurrent viral infections
- Persistent thrush or fungal infection
- Recurrent deep skin or organ abscesses
- Need for IV antibiotics to clear infections
- 2 or more deep-seated infections
- Family history
24
Q
What is the key role of innate immunity?
A
Phagocytosis
25
What neutrophil defects may occur?
- Absence of neutrophils > congenital neutropenia
- Adhesion > leucocyte adhesion defect
- Recognition and Phagocytosis > deficiencies of PRR
- Intracellular Killing > chronic granulomatous disease
26
What integrin complex is required for neutrophil adhesion?
CD11/CD18
27
What is necessary for neutrophil intracellular killing to take place?
NADPH-oxidase complex
28
What are the key components of the complement cascade?
- Chemotaxis of phagocytes to sites of inflammation (C3a, C5a)
- Opsonisation (C3b, C4b)
- Lysis of micro-organisms without cell wall (C5b-C9 complex)
29
What is hereditary angioedema caused by?
Autosomal dominant C1-inhibitor deficiency
30
What is hereditary angioedema characterised by?
- Recurrent episodes of painless, non-pitting, non-pruritic, nonerythematous swellings
- Can affect the subcutaneous tissues, intestines, oropharynx
31
How is hereditary angioedema treated?
- Acute emergency management of pharyngeal/laryngeal obstruction and acute abdominal pain
- C1-inhibitor infusion OR FFP
32
Give examples of disorders in B-cells.
- 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
- Absence of functional antibodies (upon immunisations)
33
Give examples of disorders of T cells
- Isolated T-cell subset deficiencies (CD3, CD4, CD8)
- Combined deficiencies (severe combined immunodeficiency)
- Syndromal immunodeficiencies
34
What is the genetics of 22q11 deletion syndrome
- Hemizygous 22q11.2 deletion
- Most common microdeletion syndrome
- De novo mutations (10% deletion identified in a parent)
- Highly variable expression
35
What is the epidemiology of 22q11 deletion syndrome?
- 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)
36
What is the clinical presentation of 22q11 deletion syndrome?
Congenital cardiac anomalies
- Palatal defects (affecting feeding and speech)
- Characteristic facial features
- Immunodeficiency –Thymus a-/hypo-plasia
- Hypocalcaemia
- Developmental disabilities
- Learning disabilities
- Behavioral problems
- Psychiatric illness
- Structural abnormalities (renal, eye, dental, skeletal, brain, GI-tract)
- Haematological & AI disorders
37
What are facial characteristics of 22q11 deletion syndrome?
- Short forehead
- Hooded eyelids with upslanting palpebral fissures
- Malar flatness
- Bulbous nasal tip with hypoplastic alea nasi
- Protuberant ear
38
What immune system disorders are associate with 22q11 deletion syndrome?
Recurrent RTI’s during infancy
- Low T-cell numbers (+ qualitative defects)
- Low IgA and IgM
- Reduced antibody responses
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Autoimmune phenomena (30%)
-Anaemia/thrombocytopenia
-Juvenile chronic arthritis (JIA; low IgA)
Raynaud’s
-Thyroid disease
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39
What are the subtypes of 22q11 deletion syndrome?
Complete DiGeorge anomaly
- = DiGeorge + thymus aplasia
- Fatal < age of 2 years
Atypical complete DiGeorge anomaly
- Oligoclonal T-cells, rash, lymphadenopathy
- T-cells can reject transplant
Typical complete DiGeorge anomaly
- Very low T-cell numbers, no rash
- May develop into ‘atypical’ phenotype
40
What immunodeficiency is pneumocystis spp. associated with?
Adaptive CD4 deficiency
41
What immunodeficiency is aspergillus spp. associated with?
Innate neutrophil disorders
42
What immunodeficiency is candida spp. associated with?
- Systemic: innate phagocytic disorders
| - Mucosal: adaptive IL-17 response
43
What immunodeficiency is Cryptococcus spp. associated with?
Adaptive CD4 deficiency
44
Who are invasive fungal infections seen in?
- Presenting symptom of PID
- 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 broadspectrum antibiotics and/or abdominal surgery
45
How is PID managed?
Symptomatic treatment= prevention of infections
Causative
- Immunoglobulin substitution
- Gene therapy (ADA-SCID)
- Stem cell transplant (CGD)
- Thymus transplant (diGeorge)
Genetic counselling and prenatal diagnosis
