Primary Immunodeficiencies Flashcards
Niesseria Meningitis
Bacteria that causes breakdown in the complement system
Immunophenotypes
1) T-,B-,NK+
- Rag 1/ Rag 2 deficiency
- Artemis deficiency
2) T-,B-, NK-
- Adenosine deaminase deficiency
HSCT
- Hemopeoitic stem cell transplant
- common treatment for many of these issues
Fetus with SCID outcome
-At risk of abortion since baby can’t reject mother’s t-cells that cross placental barrier
Adenosine Deaminase Deficiency
Immunophenotype, IG levels, Biochemical/Clinical impacts, other
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
Purine Nucleotide Phosphorylase (PNP) Deficiency
Immunophenotype, Biochemical/Clinical impacts, Treatments
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!!!
SCIDs
- Bad T and B cell functional deficiencies
- Severe Lymphopenia
- Characterized by (FOD):
1) Opportunistic infections
2) Diarrhea
3) FTT
Artemis deficiency (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)
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
RAG1/RAG2 Deficiency
Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments
1) T-,B-,NK+
2) All Igs are low
3) Impaired VDJ recombination
4) Diarrhea, fungus, pneumonia
5) Avoid live viral vaccines
Jak3 Deficiency (Immunophenotype, IG levels, Biochemical/Clinical impacts)
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
Agammaglobulinemia (BTK deficiency)
Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments
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
Isolated Ig Subclass Deficiencies (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)
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
IgA Deficiency (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)
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
DiGeorge Syndrome (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)
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!
Hyper IgM Syndrome (HIGM)
Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments
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
CD40L Deficiency
X-linked HIGM syndrome (men only)
- Problem with LIGAND of CD40
- Autosomal is receptor defect - no class switching or somatic hypermutation
- Bacterial infection susceptibility
Transient Hypogammaglobinuria (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)
1) B+, T+, NK+
2) Low IgG/IgA, others normal
3) DELAY IN BAY IgG Production!!!
4) Sinopulmonary infections
Common Variable Immune Deficiency (CVID)
Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments
(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
T-cell Immunodeficiency (briefly description)
Problems with T-cell growth and maturation that can also affect NK cells and B cells in certain situations
Common Gamma (IL-2Ry) Chain Deficiency (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)
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
IL-R7 Alpha Chain Deficiency
Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments
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
Bare Lymphocyte II (BLSII)
Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments
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
MHC-I Deficiency
Deficiency, Biochemical/Clinical impacts, treatments
1) Defect in TAP1
2) Therefore, CD8 cells can’t do anything soooo viral infection —- CD4 cells and Abs normal
CD3 Complexes (Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments)
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
IL-12/IFN-y Pathway Defect
- 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
Th-17 Deficiency
- Mutations in IL-17, STAT1, AIRE genes
- Susceptibility to chronic fungus (Candida) since IL-17 is important in fighting fungus
IPEX
- 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
ALPS
- Defects in Fas, FasL, Caspase-8, Caspase-10 genes
- T-cell hesitance to apoptosis!!
NO CELL DEATH!!!
Wiscott-Aldrich Syndrome (WAS)
Immunophenotype, IG levels, Biochemical/Clinical impacts, treatments
X-linked
1) T-, B+, NK-
2) Low IgM, Norm Ig, High IgA & IgE
3) WAS Protein defect
4) Eczema, immunodeficiency, thrombocytopenia (low platelets)
NK Cell Deficiency (NKD)
- mutations in multiple genes
- severe viral infections results
