Primary Immunodeficiency Flashcards
What are the features of immunity?
Recognition
interaction
Elimination
Control and regulation
Types of immune defences
Innate
Adaptive
Barriers
Cells that make up the innate immune system
Macrophages Monocytes Neutrophils Mast cells NK cells APCs
What can all cells in the innate immune system do?
Phagocytose microbes
Receptors that make up the innate immune system
Fc Complement Mannose Toll like C type letines Cytokines
Molecules that make up the innate immune system
Complement
Acute phase proteins
Chemokines
Cytokines
Cells that make up the adaptive immune system
B cells
T cells
Receptors that make up the adaptive immune system
Ig TCR HLA Cytokine Complement Toll-like
Molecules that make up the adaptive immune system
Immunoglobulins
Cytokines
Examples of barriers used in the immune system
Saliva
Breast milk
Cilia airways
4 main components of immune defence mechanisms
B cells and antibodies - humoral - specific immunity T cells - cellular - specific immunity Phagocytes - innate immunity Complement system - innate immunity
What kind of diseases are primary immunodeficiencies?
Chronic
What is wrong is primary immunodeficiencies?
Part of the immune system is missing or functions improperly
What are primary immunodeficiencies caused by?
Single gene defects
Classification of primary immunodeficiencies
Predominately antibody disorders Predominately T cell disorders Phagocyte disorders Other well defined PIDs Complement deficiencies Autoimmune and immune dysregulation syndromes Auto-inflammatory syndromes Unclassified PIDs
What is an antibody deficiency?
Deficiency of one or more subclasses of antibodies (e.g. IgG, IgA, IgM) due to defective B cell production
What is there an absence of in antibody deficiency?
Mature B cells
What is common presentations of antibody deficiencies?
Recurrent bacterial infections of the upper and / or lower resp tract - S, pneumonia, H. influenza
What are cellular immunodeficiency caused / characterised by?
Impaired T cell function OR
The absence of normal T cells
What are common presentations of cellular immunodeficiencies?
Unusual or opportunistic infections often combined with failure to thrive - pneumocystic hirovecci, CMV (pneumonia)
What are innate immune disorders characterised / caused by and their presentations?
Defects in phagocyte function
- S aureus (skin lesions, sepsis, abscesses of internal organs)
- Aspergillus infections (lung, bone, brain)
Complement deficiencies
- N. meningitis
Absence or polymorphism in pathogen recognition receptors
Be suspicious if you have an infection that is…..
Severe - requires hospitalisation or IV antibiotics
Persistent - wont clear up or clears very slowly
Unusual - caused by an uncommon organism
Recurrent - keeps coming back
Runs in the family - others in the family who have similar susceptibility to infection
- X linked M > F
10 warning signs of PID in children and adults
4 + more ear infection within 1 year for children and > 2 for adult
2 + more serious sinus infections in one year
2 + bouts on pneumonia in 1 year for children and recurrent pneumonia in adults
Chronic diarrhoea with weight loss and failure to grow normally or gain weight in children
Recurrent viral infections
Persistent thrush or fungal infection on the skin or elsewhere
Need for IV antibiotics to clear infection
2 + more deep seated infections
FH of PID
What steps of phagocytosis can be defective in disorders of innate immunity?
All 3 can be defective
- recognition defect
- cannot engulf pathogen
- cannot release products or kill the pathogen intracellularly
What defects of the neutrophils can be defective in the disorders of the innate immunity?
Absence of neutrophils -> Congenital neutropenia
- congenital cells in bone marrow cannot produce neutrophils
- treated and presented very early on
Adhesion -> leucocyte adhesion defect
- CD11/18 is missing on the neutrophil and so the neutrophil cannot migrate
Recognition and phagocytosis
- deficiencies of PRR
Intracellular killing - > chronic granulomatous disease
- can recognise but not kill the pathogen
What parts of complement involves the chemotaxis of phagocytes and sites of inflammation?
C3a, C5a
What parts of complement involve opsonisation?
C3b
C4b
What parts of complement involve lysis of micro organisms without cell walls?
C5b - C9 complex
Pathology of Hereditary angioedema
C1-inhibior deficiency (autosomal dominant)
Presentation of hereditary angioedema
Recurrent episodes of painless, non-pitting, non-pruritic, non erythematous swellings
What does hereditary angioedema affect?
Subcutaneous tissues
Intestines
Oropharynx
Treatment of hereditary angioedema
Acute emergency of
- pharyngeal / laryngeal obstruction
- acute abdominal pain
C1 inhibitor infusion OR fresh frozen plasma (FFP)
Possible disorders of B cells of the adaptive immunity
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)
Absence of functional antibodies (upon immunisations)
Possible disorders of T cells of the adaptive immunity
Isolated T cell subset deficiencies (CD3, CD4, CD8) Combined deficiencies (severe combined immunodeficiency - SCID) Syndromalimmunodeficiencies
Gene mutation that can result in PID
22q11 deletion syndrome
Genetics of 22q11 deletion syndrome
Hemizygous deletion
De novo mutation (10% deletion identified in parent)
What is the most common microdeletion syndrome?
22q11 deletion syndrome
Presentation of 22q11 deletion syndrome
Congenital cardiac anomalies Palatal defects (Affecting speech and feed) Characteristic facial features Immunodeficiency - thymus a-/hypo-plasia Hypocalcaemia Developmental disabilities Learning disabilities Behavioural problems Psychiatric illness Structural abnormalities Haematological and AL disorders Short forehead Hooded eyelid with unslanting palpebral fissures Malar flatness Protuberant ears Recurrent RTIs during infancy Autoimmune phenomena - anaemia / thrombocytopenia - JIA - Raynauds - thyroid disease
Anomaly of 22q11 deletion syndrome
DiGeorge Anomaly
Treatment of 22q11 deletion syndrome
Thymus transplantation
What results in fungal infection?
A problem in the adaptive and innate immunity
Pathology of the immune system that results in fungal infection
Adaptive CD4 Deficiency - pnuemocystitis Innate neutrophil disorders - aspergillus Systemic; innate (phagocytic disorders) or mucosal; adaptive (IL-17 response) invasive fungal infections
What is a presenting symptom of PID?
Invasive fungal infections
Management of PI
Symptomatic = prevention of infections Treatment of causes - Immunoglobulin substitution - Gene therapy (ADA-SCID) - Stem cell transplant (CGD) - thymus transplant (DiGeorge) Genetic counselling and prenatal diagnosis
What is a secondary immunodeficiencies?
Components of the immune system are all present and functional but acquired diseases affecting the immune system and / or treatments negatively influencing the immune system
What are secondary immunodeficiencies caused by?
Environmental - malnutrition - trauma - burns Disease - Infection - DM - renal failure - asplenia - leukaemia / lymphoma Surgery Splenectomy Drugs - immunosuppressive - Antirheumatic - Antiepileptic
Which type of the immunodeficiencies is more common?
Secondary much more common than primary
What is Wiskott-Aldrich syndrome?
Causes primary immunodeficiency due to a combined B and T cell dysfunction
Inheritance of wiskott Aldrich syndrome
X linked
What mutation causes of wiskott Aldrich syndrome?
WASP gene
Features of wiskott Aldrich syndrome
Recurrent infection (e.g. chest)
Eczema
Thrombocytopenia
Low IgM levels
