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Flashcards in primary immunodeficiencies Deck (22)
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1
Q

many primary immunodeficiencies are associated with the ___________
implications?

A

x chromosome

males more likely symptomatic; females are freq carriers

2
Q

humoral immunity refers to?

cell mediated refers to?

A

B cells are humoral immunity

t-cells are cell mediated

3
Q

B cell immunodeficiencies have increased susceptibility to

A

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

4
Q

treatment for B cell immunodeficiencies is

A

IVIG = antibody replacement therapy

5
Q

XLA (x-linked agammaglobulinemia)

A

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

6
Q

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

A

X linked agammaglobulinemia

7
Q

x-linked hyper-IgM syndrome

A

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

8
Q

mutation in CD40L (Xq26)

A

x-linked hyper IgM syndrome

9
Q

CD40 usually does what

A

activates B cell proliferation and differentiation

10
Q

SCID

A

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

11
Q

x linked SCID

A

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

12
Q

digeorge syndrome

A

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

13
Q

22q11.2 deletion

A

digeorge syndrome

14
Q

xq13 mutation

A

x-linked SCID

15
Q

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

A

DG –> T cells

XLS –> T cells and NK cells

16
Q

CATCH 22

A

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

17
Q

B-T-NK+ phenotype

A

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

18
Q

LAD-1

A

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
19
Q

CD18 mutation

A

affected b2 integrins

causes leukocyte adhesion deficiency type 1

20
Q

chronic granulomatous disease

A

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)

21
Q

treatment of chronic granulomatous disease

A

IFN-g therapy to enhance oxidase transcription

Restores superoxide production to ~10% of normal

22
Q

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

A

chronic granulomatous disease

Defective production of superoxide anion = Failure to kill phagocytosed