Immunodeficiencies

Question 1

What are primary immunodeficiencies?

Answer 1

→condition resulting from a genetic or developmental defect
→defect is present from birth and is mostly inherited

→May not be clinically observed until later in life

Question 2

What are secondary immunodeficiencies?

Answer 2

→a result of malnutrition, cancer, drug treatment or infection

Question 3

What are the clinical features of PIDs?

Answer 3

→Recurrent infections
→Severe infections,
→unusual pathogens
→unusual sites

Question 4

What are defects in innate immunity caused by?

Answer 4

→defect in phagocytic or complement function

Question 5

What are PIDs mostly caused by?

Answer 5

→antibody disorders

Question 6

Give examples of causes of PID in haematopoiesis?

Answer 6

→reticular dysgenesis
→congenital agranulocytosis
→SCID
→leucocyte-adhesion deficiency
→X-linked agammaglobulinemia 
→Di-George
→Wiskott-Aldrich
→X-linked hyper-IgM syndrome

Question 7

What do Tcell defects result inn?

Answer 7

→impair antibody production

Question 8

Give examples of major B cell disorders

Answer 8

→X-linked agammaglobulinaemia (Bruton’s disease)

→Common variable immunodeficiency (CVID)

→Selective IgA deficiency

→ IgG2 subclass deficiency

→ Specific Ig deficiency with normal Igs

Question 9

What gene defect causes XLA?

Answer 9

→BTK gene on X chromosome

Question 10

What does BTK gene encode?

Answer 10

→Bruton’s tyrosine kinase

Question 11

What are the results of XLA?

Answer 11

→Block in early B-cell development (stop at pre-B cells)
→Recurrent severe bacterial infections
→Autoimmune diseases

Question 12

Why is Bruton’s tyrosine kinase important in B-cell development?

Answer 12

→needed for pre-B cell receptor signalling

Question 13

How is XLA diagnosed?

Answer 13

→B cells absent / low; plasma cells absent
→All immunoglobulins absent / very low
→T cells and T cell-mediated responses normal
→using immunoelectrophoresis

Question 14

How is XLA treated?

Answer 14

→IVIg
→subcutaneous Ig weekly
→prompt antibiotic therapy (URI /LRI)
→Do not give live-attenuated vaccines

Question 15

What is selective IgA deficiency?

Answer 15

→Low levels serum & secretory IgA

→Sometimes: increased incidence allergic disease

Question 16

Which lymphocytes does ataxia telangiectasia affect?

Answer 16

→T and B cells

Question 17

Give examples of predominant T-cell disorders

Answer 17

→DiGeorge syndrome

→Wiskott-Aldrich syndrome

→Ataxia-telagiectasia

Question 18

Give examples of causes of SCID

Answer 18

→Common cytokine receptor γ-chain defect
→RAG-1/RAG-2 defect => no T and B cells
→ADA (adenosine deaminase deficiency)

Question 19

Why is gamma-chain important for cytokines?

Answer 19

→signal transducing component of receptors for IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21

Question 20

What is the function of IL-7?

Answer 20

→for survival T cell precursors

Question 21

What are RAG proteins?

Answer 21

→required for T and B cell receptor rearrangement

Question 22

What are the patterns of SCID?

Answer 22

→T cell function reduced proliferation

→reduced cytokine production

Question 23

How is SCID treated?

Answer 23

→Isolation to prevent further infections

→Blood products from CMV-negative donors

→IV Ig replacement

→Infection prophylaxis

→Bone marrow/haematopoietic stem cell transplant

→Gene therapy (for ADA and γ-chain genes)

Question 24

What are the physical symptoms of DiGeroge syndrome?

Answer 24

→Dysmorphic face:
→cleft palate,
→low-set ears,
→fish-shaped mouth

Question 25

What are the types of DiGeorge synrome?

Answer 25

→Complete DiGeorge- absent thymus | →Incomplete DiGeorge - reduced thymus

Question 26

What is thymic hypoplasia in DiGeroge syndrome due to?

Answer 26

→22q11 deletion | →Results in failure development 3+4th pharyngeal pouches

Question 27

How can DiGeorge be treated?

Answer 27

→thymus transplantation | →thymus from donor and transplanted

Question 28

What mode of inheritance is Wiskott-Aldrich syndrome?

Answer 28

→ X-linked

Question 29

What is the cause of W-A syndrome?

Answer 29

→Defect in WASP | →protein involved in actin polymerization

Question 30

What are the symptoms of W-A syndrome?

Answer 30

→Thrombocytopenia, eczema, infections →Progressive immunodeficiency (T cell loss) →Progressive reduction of T cells; reduction of T cell proliferation → Antibody production (reduced IgM, IgG; high IgE, IgA)

Question 31

What type of defect is chronic granulomatous disease?

Answer 31

→phagocyte defect →Defective oxidative killing of phagocytosed microbes →mutation in phagocyte oxidase (NADPH) components

Question 32

How is chronic granulomatous disease diagnosed?

Answer 32

→Nitro blue tetrazolium reduction test →Dihydrorhodamine assay How is chronic granulomatous disease diagnosed?flow cytometry →Becomes fluorescent in presence of NADPH activity

Question 33

What defct causes Chediak-Higashi syndrome?

Answer 33

→Defect in LYST gene (regulates lysosome traffic)

Question 34

What are the effects of C-H syndrome?

Answer 34

→Neutrophils have defective phagocytosis →Repetitive, severe infections

Question 35

How is C-H syndrome diagnosed?

Answer 35

→Decreased number neutrophils | →Neutrophils have giant granules with phagosome

Question 36

What is leucocyte adhesion deficiency(LAD)?

Answer 36

→Defect in β2-chain integrins →Defect in sialyl-Lewis X (selectin ligand) →Delayed umbilical cord separation => diagnosis defect in β2-chain integrins

Question 37

What are the presentations of LAD?

Answer 37

→Skin, GIT infections and perianal ulcers

Question 38

How is LAD diagnosed?

Answer 38

→Low Neutrophil chemotaxis →Low Integrins expression on phagocytes (flow cytometry)

Question 39

Describe PID gene editing

Answer 39

``` →Bone marrow cells removed →Separation of immune cell progenitors →Immune cell progenitors infected with virus to introduce a correct copy of mutated gene →Cells take up normal gene →Cells return to patient →Immune reconstitution ```

Question 40

What are the treatments for HIV/AIDS?

Answer 40

→HAART | →PrEP

Question 41

Which is more common- PID or secondary?

Answer 41

→secondary