Primary Immune Deficiencies

Question 1

Selective IgA Deficiency - what type of infections? epidemiology?

Answer 1

Most Common defiency Recurrent gastro and resp infections affects 1/600 Caucasians but 70% are asymptomatic

Question 2

Complement Deficiencies - Treatment?

Answer 2

Vaccination, prophylactic Abx, high levels of suspicion, screen family members

Question 3

Leukocyte Adhesion Deficiency- what is it? deficiency in?

Answer 3

Failure to express leukocyte adhesion markers. Deficiency of the beta-2 integrin subunit (CD18) of the Leukocyte adhesion molecule in LAD1 LAD2 is much rarer and has severe growth restriction and mental retardation

Question 4

B cell deficiencies - Consequences

Answer 4

Increased susceptibility to bacterial and some viral infections and toxins (tetanus, diphtheria)

Question 5

Cyclic Neutropenia - what causes it?

Answer 5

caused by mutations in the ELA1 gene

Question 6

Kostmann Syndrome - Treatment?

Answer 6

Treatment includes G-CSF, prophylactic antibiotics and BMT if G-CSF is ineffective

Question 7

IgM immunity?

Answer 7

on surface of B cells

Question 8

Chronic Granulomatous Disease - associated diseases?

Answer 8

PLACESS Pseudomonas Listeria Aspergillus Candida E. coli Staph aureus Serratia patients can resist catalase-negative bacteria

Question 9

Severe Combined Immune Deficiency (SCID) - defect in? blood results?

Answer 9

defect in lymphoid precursors (IL2-R), leading to low or normal B cells, reduced T cells and low antibodies

Question 10

DiGeorge’s Syndrome - what is it?

Answer 10

Impaired development of the 3rd and 4th pharyngeal pouches (oesophagus, thymus, heart)

Question 11

Hyper-IgM Syndrome - chromosome? defect in? how does it cause symptoms?

Answer 11

X-Linked Condition - Xq26 CD40L, CD40, AlCDA or CD154 defect Activated T cells can’t interact with B-cells to class switch therefore B cells can’t make IgA and IgG but instead IgM levels increases

Question 12

T cell deficiencies - Consequences

Answer 12

Increased susceptibility to viral, fungal and bacterial infections and early malignancy

Question 13

Common Variable Immune Deficiency - signs/symptoms/diagnosis

Answer 13

Frequent infections during early life, increased incidence of autoimmune or inflammatory manifestations, granulomata and increased susceptibility to cancer. Both males and females can get the deficiency, most likely to be diagnosed in 3rd/4th decade of life although 20% are found to be immunodeficient in childhood

Question 14

Cyclic Neutropenia - Treatment

Answer 14

Treat with G-CSF

Question 15

Brutons Agammaglobinemia - symptoms and age of onset?

Answer 15

recurrent and severe bacterial infections from 3-6 months old when maternal IgG denature. Most common infections are • Ear infections • Sinusitis • Pneumonia • Diarrhea due to a parasite called Giardia

Question 16

Ig half life?

Answer 16

18 days

Question 17

2 syndromes of T cell deficiencies?

Answer 17

Bare Lymphocyte Syndrome DiGeorge’s Syndrome

Question 18

Common Variable Immune Deficiency - Ig levels? cause?

Answer 18

Low IgG, IgE and IgA many genetic causes

Question 19

Complement Deficiencies - Lectin Pathway Deficiency

Answer 19

Very common, 10% are MBL deficient. Not so clinically important

Question 20

IgG immunity?

Answer 20

can cross from placenta to foetus

Question 21

IgA immunity?

Answer 21

Mucosal areas, saliva, tears, breast milk

Question 22

Reticular Dysgenesis - is a form of what deficiency? causes a deficiency in what? treatment?

Answer 22

most severe form of SCID (Severe Combined Immune Deficiency) (AK2) Causes an absolute deficiency in Neutrophils, Lymphocytes, Monocytes/ Macrophages, Platelets Fatal in v. early life unless treated by BMT

Question 23

Kostmann Syndrome - what is it? dominant or recessive? prevalence?

Answer 23

A severe congenital neutropenia (increased risk of infection) Mainly Autosomal Recessive (HAX-1) 1-2cases per million

Question 24

Chronic Granulomatous Disease - treatment?

Answer 24

Treatment involves prophylactic Trimethoprim and Itraconazole and Interferon. Sometimes use stem cell transplant

Question 25

DiGeorge's Syndrome - what chromosome?

Answer 25

deletion of 22q11.2

Question 26

Chronic Granulomatous Disease - what test is used to diagnose?

Answer 26

Negative Nitro-Blue Tetrazolium (NBT) test. NBT is a dye that changes colour from yellow to blue following interaction with hydrogen peroxide. Also use Dihydrorhodamine (DHR) flow cytometry test. DHR is oxidised to rhodamine, which is strongly fluorescent, following interaction with hydrogen peroxide

Question 27

B cell deficiencies - Treatment

Answer 27

Ig replacement BMT in some situations vaccination (not effective except in IgA deficiency)

Question 28

Leukocyte Adhesion Deficiency - features of disease

Answer 28

High neutrophil count and delayed umbilical cord separation

Question 29

Which cytokines/receptors can we be deficient in? What are these molecules all involved in?

Answer 29

Deficiencies in IFN-gamma, IFN-gamma receptor, IL-12 and IL\_12 receptor. all involved in signalling between T-cells and macrophages to stimulate TNF and activate NADPH oxidase

Question 30

4 Phagocyte deficiencies?

Answer 30

Kostmann Syndrome Leukocyte Adhesion Deficiency Chronic Granulomatous Disease Cyclic Neutropenia

Question 31

Kostmann Syndrome - when? diagnosis?

Answer 31

infections start shortly after birth Diagnosis based on chronically low neutrophil count and bone marrow test showing an arrest of neutrophil precursor maturation

Question 32

Bare Lymphocyte Syndrome (BLS) is a defect in what?

Answer 32

Regulatory Factor X or Class 2 transactivator

Question 33

Hyper-IgM Syndrome - presentation

Answer 33

Boys present first years of life with recurrent bacterial infections especially Pneumocystis carinii and failure to thrive. Increased risk of autoimmunity and malignancy

Question 34

Complement Deficiencies - Classical Pathway Deficiency. Associated with? What test is abnormal?

Answer 34

Involves lack of C1q/r/s, C2 is the commonest and C4 Associated with SLE as classical pathway involved in removing immune complexes CH50 test is abnormal

Question 35

Phagocyte deficiencies - Consequences?

Answer 35

Increased susceptibility to bacterial and fungal infections, often with deep abscesses

Question 36

Severe Combined Immune Deficiency (SCID) - symptoms?

Answer 36

recurrent infections - Failure to thrive and persistent diarrhoea and early infant death

Question 37

Complement Deficiencies - Consequences?

Answer 37

Increased susceptibility to encapsulated bacterial infections

Question 38

Cytokine Deficiencies - associated infections..

Answer 38

predisposed to infections caused by Salmonella, atypical Mycobacteria, TB and BCG. Patients are unable to form granulomata

Question 39

Cyclic Neutropenia - what is it?

Answer 39

Episodic neutropenia occurring every 3 weeks and lasting several days

Question 40

IgE immunity?

Answer 40

Allergy - Histamine released from Mast cells

Question 41

What disease is BLS associated with?

Answer 41

Sclerosing Cholangitis (uncommon chronic liver disease in which the bile ducts inside and outside the liver progressively decrease in size due to inflammation and scarring (fibrosis)

Question 42

Bare Lymphocyte Syndrome (BLS) 7 main symptoms and age of onset?

Answer 42

Persistent diarrhea Malabsorption Mucocutaneous candidiasis Upper respiratory tract bacterial infection Lower respiratory tract bacterial infection Failure to thrive Fatigue unwell by 3months of age

Question 43

Leukocyte Adhesion Deficiency - Treatment

Answer 43

BMT is treatment of choice

Question 44

Mixed B and T cell deficiency?

Answer 44

SCID

Question 45

DiGeorge's Syndrome - physical features, blood test results

Answer 45

Low set ears, cleft lip and palate Low Calcium, Low number of mature T cells Sesceptible to viral infections

Question 46

Severe Combined Immune Deficiency (SCID) - X linked?

Answer 46

45% are X-linked

Question 47

Bare Lymphocyte Syndrome (BLS) is the absent expression of...?

Answer 47

HLA molecules within the thymus causing lymphocytes to fail to develop

Question 48

T cell deficiencies - Treatment

Answer 48

Infection prophylaxis Ig replacement if necessary specific other treatments

Question 49

Complement Deficiencies - Common and Terminal Pathway Deficiency Associated with? whats abnormal?

Answer 49

Involves lack of C3, 5-9 Susceptibility to bacterial infections (Meningitis/Pneumoniae) May be associated with membranoproligerative glomerulonephritis. Cannot form MAC to kill bacteria, Both CH50 and AP50 abnormal

Question 50

What are the different types of Bare Lymphocyte Syndrome? Which cells are depleted in each type?

Answer 50

Type 1 - MHC I absent - decreased CD8 cells Type 2 - MHC II absent - decreased CD4 cells (more common) B-cell class switch needs CD4 therefore less IgA and IgG made

Question 51

Chronic Granulomatous Disease - what is it? defect in?

Answer 51

Failure of oxidative killing - defect of NADPH oxidase leading to reduced reactive oxygen species Due to many mutations, mostly X-linked

Question 52

Severe Combined Immune Deficiency (SCID) - treatment

Answer 52

BTM only established treatment

Question 53

DiGeorge's Syndrome - Treatment?

Answer 53

Thymus Transplant

Question 54

Bruton's Agammaglobinemia - defect and mutation in? leading to a failure to produce..?

Answer 54

X- linked Tyrosine Kinase Defect Mutation in BTK gene Fail to produce mature B-cells and no antibodies

Question 55

Complement Deficiencies - Alternative Pathway Deficiency what infections do they get? what test is abnormal?

Answer 55

Involves Factors B/I/P infections with Encapsulated bacteria such as -Streptococcus pneumoniae (Pneumococcus) -Group B streptococcus Haemophilus influenza -Neisseria meningitides (Meningococcus) alternative pathway only involved in killing bacteria AP50 test is abnormal