primary immunodeficiencies

Question 1

many primary immunodeficiencies are associated with the ___________
implications?

Answer 1

x chromosome

males more likely symptomatic; females are freq carriers

Question 2

humoral immunity refers to?

cell mediated refers to?

Answer 2

B cells are humoral immunity

t-cells are cell mediated

Question 3

B cell immunodeficiencies have increased susceptibility to

Answer 3

extracellular pathogens and severe enteric infections (d/t lack of IgA)

Question 4

treatment for B cell immunodeficiencies is

Answer 4

IVIG = antibody replacement therapy

Question 5

XLA (x-linked agammaglobulinemia)

Answer 5

mutation in gene for Bruton’s tyrosine kinase (btk) ~ Xq21, which is required for B cell development in bone marrow
—-reduces levels of all Ig isotypes
o Affected male is btk - and B cell development arrested
o A carrier female is affected if the normal x gets inactivated –> B cell dev. Arrested

Disease develops at 5-6 months, since maternal IgG begins to decline = time of transiently low IgG

Question 6

mutation in btk (brutons tyrosine kinase) (xq21) is what disease?

Answer 6

X linked agammaglobulinemia

Question 7

x-linked hyper-IgM syndrome

Answer 7

IgG, IgA, and IgE all absent, with compensatory increase in IgM

o	Defective class switching due to mutation in CD40L (cd40 ligand) gene at Xq26
	CD40 usually activates B cell proliferation and differentiation

LNs show no germinal centers
Increased susceptibility to extracellular bacterial infections and enteric infections (e.g. Cryptosporidium) – No IgA
and Some increased susceptibility to intracellular microbes (Toxoplasma)
o Patients also have defects in cell-mediated immunity

Question 8

mutation in CD40L (Xq26)

Answer 8

x-linked hyper IgM syndrome

Question 9

CD40 usually does what

Answer 9

activates B cell proliferation and differentiation

Question 10

SCID

Answer 10

severe combined immunodeficiency

Defects in humoral and cell-mediated immunity; Either T cells or both B&T cells affected

Presents early in life with history of recurrent infections
o susceptibility to broad range of all pathogens
o Fatal unless treated with bone marrow transplant

Types = X-linked SCID or DiGeorge syndrome

Question 11

x linked SCID

Answer 11

type of SCID
Recessive mutation in the common g chain gene on x ch. (Xq13)
o Heterozygous females – normal
o Hemizygous males – clinically affected

Affects the IL-2,4,7,9, and 15 receptor gamma chain
 IL15 converts lymphoid progenitors to NK cells
 IL7 converts progenitors to T cells
 Without those ILs, greatly reduced Tcell and NK cell numbers!
o Normal B cell numbers
o B+/T-/NK- lymphocyte phenotype
o Impaired humoral immunity because lack of T cell help for antibody production

Question 12

digeorge syndrome

Answer 12

type of SCID
22q11.2 deletion, autosomal dominant, de novo
o T cells reduced or absent
o CATCH22 –> cardiac abnormalities like tetralogy of fallot (cyanosis), abnormal facies, thymic aplasia, cleft palate, hypocalcemia/hypoparathyroidism
 Facies = Micrognathia, Small, mis-shaped mouth, Low-set, abnormally folded ears, Bulbous nose, and Palatal clefting

Treatment:
 Peripheral mononuclear cell transfusion from HLA-matched donor
 Postnatal thymic tissue transplantation

Question 13

22q11.2 deletion

Answer 13

digeorge syndrome

Question 14

xq13 mutation

Answer 14

x-linked SCID

Question 15

what is reduced in digeorge? what is reduced in x-linked SCID?

Answer 15

DG –> T cells

XLS –> T cells and NK cells

Question 16

CATCH 22

Answer 16

digeorge syndrome
cardiac abnormalities like tetralogy of fallot (cyanosis), abnormal facies, thymic aplasia, cleft palate, hypocalcemia/hypoparathyroidism

Question 17

B-T-NK+ phenotype

Answer 17

due to autosomal recessive mutations in DNA recombination and repair enzymes (RAG1, RAG2, artemis)

Question 18

LAD-1

Answer 18

leukocyte adhesion deficiency type 1 = defect in innate immunity

Granulocytes affected - recurrent bacterial and fungal infections

Absent/deficient expression of b2 integrins - mutation in CD18
o	Autosomal (21q) Recessive

Question 19

CD18 mutation

Answer 19

affected b2 integrins

causes leukocyte adhesion deficiency type 1

Question 20

chronic granulomatous disease

Answer 20

Xlinked recessive Mutations in components of the phagocyte oxidase, esp. cytochrome b558/p91-phox (Xp21)

Defective production of superoxide anion = Failure to kill phagocytosed bacteria, fungi etc causes chronic activation of T cells and macrophages

recurrent bacterial and fungal unfections

o Nitroblue tetrazolium dye reduction test (NBT staining)

Question 21

treatment of chronic granulomatous disease

Answer 21

IFN-g therapy to enhance oxidase transcription

Restores superoxide production to ~10% of normal

Question 22

Xlinked recessive Mutations in phagocyte oxidase, esp. cytochrome b558/p91-phox (Xp21)

Answer 22

chronic granulomatous disease

Defective production of superoxide anion = Failure to kill phagocytosed