(L27) Primary Immunodeficiencies

Question 1

What are the types of primary immunodeficiencies?

L27 S4

Answer 1

Innate:

• phagocytosis
• complement

Adaptive:

• B cells (antibodies)
• T cells
• combined T and B cells (CD4+ related)

Question 2

What are possible indicators of immunodeficiency?

L27 S5

Answer 2

• 8+ ear infections/year
• 2+ sinus infections/year
• 2+ pneumonias/year
• 2+ deep-seated infections or infections in unusual areas
• recurrent abscesses
• need for IV antibiotic therapy
• opportunistic or unusual infections
• family history

Don’t memorize these, just understand why it might be an indicator

Question 3

What immunodeficiency is infection with bacterial meningitis possibly indicative of?

L27 S7

Answer 3

Complement deficiency

Question 4

What tests are used to test for T cell defects, humoral immunodeficiency, complement deficiency, and phagocytic disorders?

L27 S8

Answer 4

T cell:
-delayed-type hypersensitivity (DTH) skin test

Humoral immunodeficiency:

• serum IgG, IgM, and IgA
• specific Ab following immunization

Complement:
-hemolytic assay

Phagocytic:
-nitroblue tetrazolium (looks for oxidative activity)

Question 5

What is adenosine deaminase (ADA) deficiency?
What is its immunophenotype and what Abs are made?

L27 S14

Answer 5

T-, B-, NK-
Low Abs (all types)

Autosomal recessive

Enzyme clears deoxyadenosine from purine metabolism which is toxic to lymphocytes

Question 6

What is purine nucleotide phosphorylase (PNP) deficiency?
What is its immunophenotype and what Abs are made?

L27 S15

Answer 6

T-, B+, NK+/-
Normal Abs

Autosomal recessive

Enzyme clears deoxyguanosine which is toxic to T cells at high levels

Question 7

What is Artemis deficiency?
What is its immunophenotype and what Abs are made?

L27 S16

Answer 7

T-, B-, NK+
Low Abs (all types)

Autosomal recessive (radiosensitive)

Presents in infancy with diarrhea, candidiasis, and fungal pneumonia.

Artemis gene product involved in ligation of hairpin loops in V(D)J recombination

Question 8

What is RAG1/RAG2 deficiency?
What is its immunophenotype and what Abs are made?

L27 S17

Answer 8

T-, B-, NK+
Low Abs (all types)

RAG1/RAG2 crucial in V(D)J recombination for TCR and BCR

Question 9

What is Jak3 deficiency?
What is its immunophenotype and what Abs are made?

L27 S18

Answer 9

T-, B+, NK+
Low Abs (all types)

Causes defect in IL-2 signaling which is required for T cell survival and activity

Question 10

What is Omenn syndrome?

L27 S17

Answer 10

Due to partial function of RAG1/RAG2

Characterized by:

• severe erytrhoedema
• splenomegaly
• eosinophilia
• high IgE

Question 11

What is HSCT and how can it be used to treat certain immunodeficiencies?

L27

Answer 11

Hematopoietic stem cell transplant

Can be used in deficiencies where there are genetic defects in immune cells, or their precursors, that derived from bone marrow.

Question 12

What is primary agammaglobulinemia? What is its immunophenotype and what Abs are made?

L27 S20

Answer 12

T+, B-, NK+
Low Abs (all types)

Caused by arrest of B cell development at pre-B cell resulting in low or absent circulating B cells

X-linked and autosomal recessive variants

Question 13

What is X-linked Btk kinase deficiency?
What is its immunophenotype and what Abs are made?

L27 S21

Answer 13

T+, B-, NK+
No Abs (all types)

X-linked

Defect in rearrangement of Ig heavy chain in B cells

Question 14

What IgG subclass deficiencies are there and what are the associated symptoms?

L27 S22

Answer 14

IgG2:
-poor polysaccharide response

IgG4:
-minimal symptoms

Question 15

What is IgA deficiency?
What is its immunophenotype and what Abs are made?

L27 S24

Answer 15

T+, B+, NK+
No IgA, normal IgG and IgM

Various methods that either result in faulty maturation of IgA secreting plasma cells or formation of anti-IgA IgG

Question 16

What is DiGeorge syndrome?
What is its immunophenotype and what Abs are made?

L27 S26

Answer 16

T-, B+, NK+
Normal Abs (all types)

Mostly occurs due to microdeletion of 22q11.2 which results in hypoplasic thymus preventing T cell development

Question 17

What is hyper IgM (HIGM) syndrome?
What types are there?
What is its immunophenotype and what Abs are made?

L27 S28

Answer 17

T+, B+, NK+
-high IgM, low IgG and IgA

Inability to class switch due to lack of CD40L (X-linked)

Inability to class switch due to CD40 (autosomal recessive)

Question 18

What is transient hypogammaglobulinemia?
What is its immunophenotype and what Abs are made?

L27 S32

Answer 18

T+, B+, NK+
Normal IgM, low IgG and IgA

Delay of infant production of IgG/IgA for up to 36 months after birth

Question 19

What is common variable immune deficiency (CVID)?
What is its immunophenotype and what Abs are made?

L27 S34

Answer 19

T+, B+/-, NK+
Low IgG and IgA, sometime low IgM

Group of conditions that result in hypogammaglobulinemia

Symptoms at 4-5 diagnosed at 20-30

Question 20

What is common γ chain deficiency?

L38 S38

Answer 20

No T cells or NKs
B cells present but don’t produce Ig

X-linked

T cells lack γ chain of IL-2R and are unable to activate B cells

Question 21

What is IL-7R α chain deficiency?

L38 S39

Answer 21

No T cells or NK cells
B cells present but don’t produce Ig

Autosomal recessive

Failure of early T cell development due to unreactiveness to IL-7. B cells inactive due to lack of costimulation

Question 22

What is bare lymphocyte syndrome type 2?

L27 S40

Answer 22

No CD4+ T cell cells

Lack of MHC class II on APCs due to lack of transcription factors

Question 23

What is MHC class I deficiency?

L27 S41

Answer 23

No CD8+ cells

Lack of TAP1 gene preventing loading of MHC class I

Question 24

What is CD3 complex deficiency?

L27 S42

Answer 24

No T cells
B cells present but low Ig

T cells unable to generate signal from antigen binding TCR due to CD3 subunit deficiency

Question 25

What occurs in result of a defect in IL-12 and IFN-γ pathway? L27 S43-44

Answer 25

IL-12 produced by Mφ and DCs and induced Th1 differentiation and release of IFN-γ Susceptibility to intracellular infections

Question 26

What is Th17 deficiency? L27 S45

Answer 26

Failure in Th17 differentiation due to IL-17, IL-17R, STAT1, STAT3, or AIRE defects Recurrent fungal infections

Question 27

What is IPEX? L27 S46

Answer 27

Immunodysregulation, polyendocrinopathy, and enteropathy X-links syndrome Self reactive T cells are not deleted due to mutation of FOXP3 gene resulting in no generation of Treg cells

Question 28

What is ALPS? L27 S46

Answer 28

Autoimmune lymphoproliferative syndrome (ALPS) Defect in Fas, FasL, caspase-8 or caspase-10 resulting in resistance to T cell induced apoptosis

Question 29

What is WAS? L27 S47

Answer 29

No T cells or NK cells B cells present but low IgM with normal IgG and high IgE/IgA Mutation in WAS protein (WASP)

Question 30

What are NK cell deficiencies? L27 S48

Answer 30

Group of diseases that result in lack of NK cells or lack of NK cell function

Question 31

What is a chronic granulomatous disease? L27 S52

Answer 31

Caused by failure of phagocytes to kill phagocytized cells Deficiency in NADPH oxidase resulting in lack of ROS Results in collection of immune cells at infection site (granuloma) Susceptibility to catalase+ bacteria

Question 32

What is G6PD deficiency? L27 S53

Answer 32

Unable to regenerate NADPH Formation of granulomas due to inability to inability to produce ROS

Question 33

What is leukocyte adhesion deficiency? What symptom is indicative of this in new bornes? L27 S54-55

Answer 33

Inability of neutrophils to binds activated epithelium and enter sites of infection Lack of CD11 or CD18 DELAYED DETACHMENT OF UMBILICAL CORD

Question 34

What is Chediak-Higashi syndrome? L27 S56

Answer 34

Defect in neutrophil granule structure. Lack of cathepsin G and elastase from granules result in ineffective killing of bacteria no NK activity

Question 35

What is MyD88 deficiency? L27 S71

Answer 35

Inability to respond to all TLR signaling except TLR 3. Will not have a fever during infection or have elevated CRP and ESR