Primary Immunodeficiency Disease

Question 1

Name pneumonic for remembering the hallmarks of immune deficiency and what it stands for?

Answer 1

Serious infections
Persistent infections
Unusual Infections
Recurrent infections

SPUR

Question 2

if unresponsive to oral antibiotics what type of infection is it?

Answer 2

serious

Question 3

chronic infections are what type of infection?

Answer 3

persistent

Question 4

name some other features of immune deficiency apart from spur

Answer 4

Weight loss or failure to thrive
Severe skin rash (eczema)
Chronic diarrhoea
Mouth ulceration
Unusual autoimmune disease
Lymphoproliferative disorders
Cancer
Family history

Question 5

when does an immune disorder become secondary?

Answer 5

when it involves more than one component of the immune system

Question 6

name the conditions associated with secondary immune deficiency- physiological immune deficiency

Answer 6

extremes of life

eg ageing, prematurity

Question 7

name the conditions associated with secondary immune deficiency- infections

Answer 7

HIV
Measles
compromised immune system cos its fighting something else

Question 8

why does ageing cause secondary immunodeficient disease?

Answer 8

thymus shrinks with age, cant produce T cells

Question 9

why does prematurity cause secondary immunodeficient disease?

Answer 9

doesn’t have all the maternal AB

Question 10

name the conditions associated with secondary immune deficiency- treatment interventions

Answer 10

immunosuppressive therapy
anti-cancer drugs
corticosteroids

Question 11

name the conditions associated with secondary immune deficiency

Answer 11

physiological deficiency
infection
treatment interventions
malignancy
biochemical and nutritional disorders

Question 12

describe the features of primary immunodeficiency disorders

Answer 12

Immune dysregulation,
Autoinflammatory disorders
Defects in innate and adaptive immunity

Question 13

what is the first warning sign of PID?

Answer 13

recurrent respiratory infections

Question 14

name 3 upper respiratory complications or PIDs

Answer 14

sinusitis
otitis media
laryngeal angioedema

Question 15

name 3 lower respiratory complications or PIDs

Answer 15

malignancies
interstitial lung diseases
pneumonia
bronchitis, bronchiectasis

Question 16

name 3 Examples of Primary immunodeficiency disorders with significant respiratory tract complications

Answer 16

PAD primary antibody deficiency eg. sinusitis and otitis
complement system disorders
pneumonia

Question 17

What are the microorganisms Involved in Infectious Pulmonary Complications of Primary Immunodeficiency?

Answer 17

Streptococcus pneumoniae, Haemophilus influenza

Question 18

what is PAD?

Answer 18

primary antibody deficiency (PAD):

Selective IgA deficiency

Question 19

d: angioedema

Answer 19

by localized swelling that is generally asymmetric owing to increased vascular permeability with leakage of plasma

Question 20

when may a PID be a complement system one?

Answer 20

considered in patients with laryngeal angioedema:
Hereditary angioedema (HAE)

Question 21

d: neutropenia

Answer 21

is an abnormally low concentration of neutrophils in the blood

Question 22

name the ways the neutrophil life cycle can go wrong

Answer 22

Defects in Neutrophil development
Defects in Neutrophil trans-endothelial migration
Defects in Neutrophil killing

Question 23

what syndrome is severe congenital neutropenia?

Answer 23

Kostmann syndrome

Question 24

what is Kostmann syndrome?

Answer 24

Failure to produce neutrophils

e.g. Specific failure of neutrophil maturation

Question 25

How can Kotsmann syndrome be treated?

Answer 25

with granulocyte colony-stimulating factor (G-CSF), which increases the neutrophil count and decreases the severity and frequency of infections

Question 26

What would you expect to happen if a patient’s phagocytes were unable to bind to endothelial adhesion molecules?

Answer 26

recurrent bacterial and fungal infections v. high neutrophil blood count deep tissues infected with no pus formation

Question 27

What is Leukocyte adhesion deficiency? LAD

Answer 27

autosomal recessive primary immunodeficiency | Results in failure of neutrophil adhesion and migration

Question 28

Clinical presentation of LAD?

Answer 28

leucocytosis localised bacterial infections infected umbilical stump

Question 29

What is Chronic granulomatous disease, CGD and what is there a problem with?

Answer 29

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

Question 30

clinical features of CGD?

Answer 30

``` Recurrent deep bacterial infections Especially Staphylococcus, Aspergillus, pseudomonas cepacia Mycobacteria, atypical mycobacteria Recurrent fungal infections Failure to thrive Lymphadenopathy and hepatosplenomegaly Granuloma formation ```

Question 31

name some treatments of phagocyte deficiencies

Answer 31

immunoglobulin replacement therapy (IVIg) aggressive management of infection ( antibiotics and anti-fungals) Definitive Therapy eg stem cell transplant

Question 32

Name 3 important PIDs associated with respiratory complications in children

Answer 32

transient hypogammaglobulinemia of infancy severe combined immunodeficiency X-linked agammaglobulinemia

Question 33

what is SCID?

Answer 33

severe combined immunodeficiency | failure to produce normal B+T cells

Question 34

symptoms of SCIDs?

Answer 34

``` 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 ```

Question 35

name some potential causes of SCIDs?

Answer 35

Deficiency of cytokine receptors Deficiency of signalling molecules Metabolic defects Defective receptor rearrangements

Question 36

what is the commonest form of severe combined immunodeficiency and what is it?

Answer 36

X-linked SCID | Mutation of a component of the IL-2 Receptor

Question 37

d: prophylactic

Answer 37

intended to prevent disease

Question 38

name some prophylactic treatments

Answer 38

Avoid infections Prophylactic antibiotics Prophylactic antifungals No live attenuated vaccines Aggressive treatment of existing infections Antibody replacement - Intravenous immunoglobulin

Question 39

name some definitive treatments

Answer 39

Stem cell transplant from HLA identical sibling if possible | Stem cell transplant from other sibling or parent, or from matched unrelated donor

Question 40

How does gene therapy work for SCID?

Answer 40

Lymphoid cells are dysfunctional Stem cells can be treated ex vivo to express the missing component These cells have a survival advantage in vivo

Question 41

what is Bruton's X-linked hypogammaglobulinaemia?

Answer 41

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)

Question 42

name the disorders of T cell effector function

Answer 42

cytokine production cytotoxicity T/B cell communication

Question 43

what is the function of the IL-12, INFgamma network?

Answer 43

defence against intracellular mycobacteria

Question 44

describe how the IL-12 INFgamma network works?

Answer 44

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

Question 45

what diseases is the IL-12 INFgamma network linked to?

Answer 45

TB Atypical mycobacteria BCG infection after vaccination Deep fungal infections eg aspergillus