Primary Immunodeficiency Disease Flashcards
Name pneumonic for remembering the hallmarks of immune deficiency and what it stands for?
Serious infections
Persistent infections
Unusual Infections
Recurrent infections
SPUR
if unresponsive to oral antibiotics what type of infection is it?
serious
chronic infections are what type of infection?
persistent
name some other features of immune deficiency apart from spur
Weight loss or failure to thrive Severe skin rash (eczema) Chronic diarrhoea Mouth ulceration Unusual autoimmune disease Lymphoproliferative disorders Cancer Family history
when does an immune disorder become secondary?
when it involves more than one component of the immune system
name the conditions associated with secondary immune deficiency- physiological immune deficiency
extremes of life
eg ageing, prematurity
name the conditions associated with secondary immune deficiency- infections
HIV
Measles
compromised immune system cos its fighting something else
why does ageing cause secondary immunodeficient disease?
thymus shrinks with age, cant produce T cells
why does prematurity cause secondary immunodeficient disease?
doesn’t have all the maternal AB
name the conditions associated with secondary immune deficiency- treatment interventions
immunosuppressive therapy
anti-cancer drugs
corticosteroids
name the conditions associated with secondary immune deficiency
physiological deficiency infection treatment interventions malignancy biochemical and nutritional disorders
describe the features of primary immunodeficiency disorders
Immune dysregulation,
Autoinflammatory disorders
Defects in innate and adaptive immunity
what is the first warning sign of PID?
recurrent respiratory infections
name 3 upper respiratory complications or PIDs
sinusitis
otitis media
laryngeal angioedema
name 3 lower respiratory complications or PIDs
malignancies
interstitial lung diseases
pneumonia
bronchitis, bronchiectasis
name 3 Examples of Primary immunodeficiency disorders with significant respiratory tract complications
PAD primary antibody deficiency eg. sinusitis and otitis
complement system disorders
pneumonia
What are the microorganisms Involved in Infectious Pulmonary Complications of Primary Immunodeficiency?
Streptococcus pneumoniae, Haemophilus influenza
what is PAD?
primary antibody deficiency (PAD):
Selective IgA deficiency
d: angioedema
by localized swelling that is generally asymmetric owing to increased vascular permeability with leakage of plasma
when may a PID be a complement system one?
considered in patients with laryngeal angioedema: Hereditary angioedema (HAE)
d: neutropenia
is an abnormally low concentration of neutrophils in the blood
name the ways the neutrophil life cycle can go wrong
Defects in Neutrophil development
Defects in Neutrophil trans-endothelial migration
Defects in Neutrophil killing
what syndrome is severe congenital neutropenia?
Kostmann syndrome
what is Kostmann syndrome?
Failure to produce neutrophils
e.g. Specific failure of neutrophil maturation
How can Kotsmann syndrome be treated?
with granulocyte colony-stimulating factor (G-CSF), which increases the neutrophil count and decreases the severity and frequency of infections
What would you expect to happen if a patient’s phagocytes were unable to bind to endothelial adhesion molecules?
recurrent bacterial and fungal infections
v. high neutrophil blood count
deep tissues infected with no pus formation
What is Leukocyte adhesion deficiency? LAD
autosomal recessive primary immunodeficiency
Results in failure of neutrophil adhesion and migration
Clinical presentation of LAD?
leucocytosis
localised bacterial infections
infected umbilical stump
What is Chronic granulomatous disease, CGD and what is there a problem with?
Deficiency of the intracellular killing mechanism of phagocytes - absent respiratory burst
Excessive inflammation
→ failure to degrade chemoattractants and antigens
→ persistent accumulation of neutrophils, activated macrophages and lymphocytes leads to granuloma formation
clinical features of CGD?
Recurrent deep bacterial infections Especially Staphylococcus, Aspergillus, pseudomonas cepacia Mycobacteria, atypical mycobacteria Recurrent fungal infections Failure to thrive Lymphadenopathy and hepatosplenomegaly Granuloma formation
name some treatments of phagocyte deficiencies
immunoglobulin replacement therapy (IVIg)
aggressive management of infection ( antibiotics and anti-fungals)
Definitive Therapy eg stem cell transplant
Name 3 important PIDs associated with respiratory complications in children
transient hypogammaglobulinemia of infancy
severe combined immunodeficiency
X-linked agammaglobulinemia
what is SCID?
severe combined immunodeficiency
failure to produce normal B+T cells
symptoms of SCIDs?
Unwell by 3 months of age Persistent diarrhoea Failure to thrive Infections of all types Common infections – more severe than usual Unusual & opportunistic infections Vaccine associated diseases Unusual skin disease Graft versus host disease Colonisation of infant’s “empty” bone marrow by maternal lymphocytes Family history of early infant death
name some potential causes of SCIDs?
Deficiency of cytokine receptors
Deficiency of signalling molecules
Metabolic defects
Defective receptor rearrangements
what is the commonest form of severe combined immunodeficiency and what is it?
X-linked SCID
Mutation of a component of the IL-2 Receptor
d: prophylactic
intended to prevent disease
name some prophylactic treatments
Avoid infections
Prophylactic antibiotics
Prophylactic antifungals
No live attenuated vaccines
Aggressive treatment of existing infections
Antibody replacement - Intravenous immunoglobulin
name some definitive treatments
Stem cell transplant from HLA identical sibling if possible
Stem cell transplant from other sibling or parent, or from matched unrelated donor
How does gene therapy work for SCID?
Lymphoid cells are dysfunctional
Stem cells can be treated ex vivo to express the missing component
These cells have a survival advantage in vivo
what is Bruton’s X-linked hypogammaglobulinaemia?
No circulating B cells
No plasma cells
No circulating antibody after first 6 months
BTK* gene is essential for B cell development
(* Bruton’s Tryosine Kinase)
name the disorders of T cell effector function
cytokine production
cytotoxicity
T/B cell communication
what is the function of the IL-12, INFgamma network?
defence against intracellular mycobacteria
describe how the IL-12 INFgamma network works?
infected macrophages produce IL-12
stimulates NK cells and Th1 cells to secrete IFN gamma
which feeds back to macrophages and neutrophils
stimulates the production of TNFalpha
activating NADPH oxidase complex
what diseases is the IL-12 INFgamma network linked to?
TB
Atypical mycobacteria
BCG infection after vaccination
Deep fungal infections eg aspergillus
