Primary Immunodeficiencies

Question 1

Niesseria Meningitis

Answer 1

Bacteria that causes breakdown in the complement system

Question 2

Immunophenotypes

Answer 2

1) T-,B-,NK+
- Rag 1/ Rag 2 deficiency
- Artemis deficiency

2) T-,B-, NK-
- Adenosine deaminase deficiency

Question 3

HSCT

Answer 3

• Hemopeoitic stem cell transplant

- common treatment for many of these issues

Question 4

Fetus with SCID outcome

Answer 4

-At risk of abortion since baby can’t reject mother’s t-cells that cross placental barrier

Question 5

Adenosine Deaminase Deficiency

Immunophenotype, IG levels, Biochemical/Clinical impacts, other

Answer 5

1) T-, B-, NK-
2) Low Igs (all)
3) Accumulation of Deoxyadenosine, which is toxic!!!
4) Bad for T-cell metabolism
5) 2nd most common SCID

Question 6

Purine Nucleotide Phosphorylase (PNP) Deficiency

Immunophenotype, Biochemical/Clinical impacts, Treatments

Answer 6

1) T-,B+,NK+/-
2) Accumulation of dGTP (toxic)
3) T-cell numbers in peripheral cells DECREASE
4) Autoimmune disorders common: (Think HALT)
- Hemolytic anemia
- Arthritis
- Lupus
- Thyroid disease

5) HSCT best treatment

Mneumonic — it’s a purine, so remember dGTP!!!

Question 7

SCIDs

Answer 7

• Bad T and B cell functional deficiencies
• Severe Lymphopenia
• Characterized by (FOD):
  1) Opportunistic infections
  2) Diarrhea
  3) FTT

Question 8

Artemis deficiency 
(Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)

Answer 8

1) T-,B-,NK+
2) All Igs are low
3) Mutations in Artemis gene, which is enzyme in VDJ and repairs double-strand breaks
4) Diarrhea, fungus, pneumonia; risk of lymphoma
5) Avoid live viral vaccines

Question 9

RAG1/RAG2 Deficiency

Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments

Answer 9

1) T-,B-,NK+
2) All Igs are low
3) Impaired VDJ recombination
4) Diarrhea, fungus, pneumonia
5) Avoid live viral vaccines

Question 10

Jak3 Deficiency 
(Immunophenotype, IG levels, Biochemical/Clinical impacts)

Answer 10

Janus Kinase 3
(<10% of SCIDS)

1) T-,B+,NK+
2) All Igs very low
3) Defect in IL-2 signaling
4) Boys/Girls affected equally

Jack&Jill – boys and girls affected equally

Question 11

Agammaglobulinemia (BTK deficiency)

Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments

Answer 11

x-linked primarily

1) B-, T+, NK+
2) No Igs
3) Ig heavy chain rearrangement deficiency
4) B-cells arrested in development at pre-B stage

Think B-cell - Btk

Question 12

Isolated Ig Subclass Deficiencies 
(Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)

Answer 12

1) B-,T+,NK+
2) LOW IgG, Normal others
3) Defects in several genes
4) Asymptomatic or recurring infections

-MANY PEOPLE HAVE AND DON’T KNOW

Question 13

IgA Deficiency 
(Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)

Answer 13

1) B+, T+, NK+
2) No IgA, normal others
3) Autoimmune disease, recurrent infection, allergy

4) NO IVIG treatment – can result in anaphylaxis

IgA = A for anaphylaxis

Question 14

DiGeorge Syndrome 
(Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)

Answer 14

1) T-, B+, NK+
2) Normal Igs
3) Deletion of 22q11.2 region
4) T-cell deficiency; CLASSIC TRIAD:
- Cardiac anomalies
- Hypocalcemia
- Hypoplastic thymus

5) Live viral vaccines GOOD!

Question 15

Hyper IgM Syndrome (HIGM)

Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments

Answer 15

1) B+, T+, NK+
2) High IgM, low others
3) Can’t class switch – makes sense since IgM is high and everything else is low
4) Low Memory B-cells, bacterial infection susceptibility

Question 16

CD40L Deficiency

Answer 16

X-linked HIGM syndrome (men only)

• Problem with LIGAND of CD40
  - Autosomal is receptor defect
• no class switching or somatic hypermutation
• Bacterial infection susceptibility

Question 17

Transient Hypogammaglobinuria (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)

Answer 17

1) B+, T+, NK+
2) Low IgG/IgA, others normal
3) DELAY IN BAY IgG Production!!!
4) Sinopulmonary infections

Question 18

Common Variable Immune Deficiency (CVID)

Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments

Answer 18

(hypogammaglobulinemia)

1) B-/+, T+, NK+
2) All low, sometimes low IgM
3) Defect in Ab production (Bcell receptors and co stimulators); B-cells DO NOT become plasma
4) Infection, autoimmune disease, malignancies

Key: diagnosed at age 20-30

Question 19

T-cell Immunodeficiency (briefly description)

Answer 19

Problems with T-cell growth and maturation that can also affect NK cells and B cells in certain situations

Question 20

Common Gamma (IL-2Ry) Chain Deficiency 
(Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)

Answer 20

MOST COMMON SCID
X-LINKED

1) T-,B+,NK-
2) V. low Igs
3) Deficiency in IL-2Receptor gamma = No functional B-cells since T-cells can’t mediate

4) FTT, diarrhea, opportunistic infections, thrush (mouth fungus)
5) NO VIRAL VACCINES

Question 21

IL-R7 Alpha Chain Deficiency

Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments

Answer 21

1) T-,B+,NK+
2) V. low Igs (no co stimulatory signaling between b and t)
3) IL-7 deficiency = poor T-cell development (duuhhh)
4) Classic phenotype:
- Fungus
- Diarrhea
- Pneumonia
- Viral infection

Mneumonic -
Veit’s Fuck Da Police

Question 22

Bare Lymphocyte II (BLSII)

Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments

Answer 22

1) CD4 T-, CD8 T+, B+, NK-
2) Low IgA and IgG2
3) No MHC-II on APCs – genes are intact, expression is not
4) Recurrent infections, DEATH in childhood

Question 23

MHC-I Deficiency

Deficiency, Biochemical/Clinical impacts, treatments

Answer 23

1) Defect in TAP1

2) Therefore, CD8 cells can’t do anything soooo viral infection —- CD4 cells and Abs normal

Question 24

CD3 Complexes (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)

Answer 24

1) T-,B+,NK+
2) All Igs low
3) CD3 subunit deficiency
4) low Ab response, decreased T cells, classical symptoms: FOD (FTT, oportunistic infections, diarrhea)
5) HSCT good for severe case

Question 25

IL-12/IFN-y Pathway Defect

Answer 25

• IL-12 needed for T cell differentiation to Th1
  - NO Th1 cells produced and therefore, NO IFN-y, which is needed for intracellular bacterial response

Clinical: Infections from intracellular pathogens, mycobacteria, fungus

Question 26

Th-17 Deficiency

Answer 26

• Mutations in IL-17, STAT1, AIRE genes

- Susceptibility to chronic fungus (Candida) since IL-17 is important in fighting fungus

Question 27

IPEX

Answer 27

• x linked
• Happens after T-cell maturation
• Laxck of self-reactive Cell regulation because FoxP3, the novel transcription factor, is defective and thus no T-Reg—- loss of inhibition

Question 28

ALPS

Answer 28

• Defects in Fas, FasL, Caspase-8, Caspase-10 genes
• T-cell hesitance to apoptosis!!

NO CELL DEATH!!!

Question 29

Wiscott-Aldrich Syndrome (WAS)

Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments

Answer 29

X-linked

1) T-, B+, NK-
2) Low IgM, Norm Ig, High IgA & IgE
3) WAS Protein defect
4) Eczema, immunodeficiency, thrombocytopenia (low platelets)

Question 30

NK Cell Deficiency (NKD)

Answer 30

• mutations in multiple genes

- severe viral infections results