Final: Primary Immunodeficiencies Flashcards
What is the pathology behind B cell deficiencies? What are you more susceptible too?
- Absent or reduced follicles and germinal centers in lymphoid organs
- Reduced serum Ig levels
Susceptible to bacterial and viral infections
What is the pathology behind T cell deficiencies? What are you more susceptible too?
- Reduced T cell zones in lymphoid organs
- Reduced DTH reactions
- Defective T cell proliferative responses
Susceptible to intracellular and viral infections + cancers
What is the pathology behind innate immunity deficiencies? What are you more susceptible too?
Really depends on what is defective
Susceptible to bacterial and viral infections
What are some key features of immunodeficiencies?
- Chronic, severe, recurrent
- Not responsive to antibiotic therapy
- Atypical microbes and opportunistic pathogens involved
What are Primary Immune Immunodeficiencies?
- Manifested in first years of life after maternal immunoglobulins disappear
- Can be defects in innate or adaptive immunity
Why would you screen for humoral immunity?
Recurrent sinopulmonary bacterial infections
Why would you screen for cell-mediated immunity?
Recurrent viral/fungal infections
Why would you screen for phagocyte deficiency?
Recurrent skin abscesses/fungal infections
Why would you screen for complement deficiency?
Bacteremia
Meningitis with encapsulated bacteria
What lab test would you order for adaptive immunity deficiency?
Differential count of blood cells (Complete CDC)
What lab test would you order for T-cell deficiency?
DTH skin test
What lab test would you order for humoral deficiency?
Serum Antibody Count
Ab testing to specific Ag
What lab test would you order for complement deficiency?
Total hemolytic complement assay
What lab test would you order for phagocytic deficiency?
Nitroblue Tetrazolium Test
What is SCID?
Reduced T Cell, B Cell, and NK Cells
- present with persistent infections, oral thrush, chronic diarrhea, and failure to thrive
- Severe lymhphopenia
- As a fetus, risk of abortion from maternal T cells
What are the different immunophenotypes for SCID?
T-B-NK-: Adenosine-deaminase Deficiency
T-B-NK+: Artemis or RAG 1/2 Deficiency
What is Adenosine Deaminase Deficiency?
T-B-NK-
- ADA important for adaptive immunity maintenance and development (especially T cells)
- Without ADA, build-up of deoxyadenosine, which is toxic
- Low Ig count
- Autosomal recessive disorder
What is Purine Nucleoside Phosphorylase Deficiency?
T- B+/- NK+/-
- Accumulation of dGTP, which is toxic
- Early onset of neurological abnormalities
- Autoimmune disorders are common: hemolytic anemia, thyroid disease, arthritis, lupus
What is Artemis Deficiency?
T- B- NK+
- Artemis is important for repairing double strand breaks and an enzyme in VDJ recombination
- Diarrhea, candidiasis, Pneumocystis jiroveci pneumonia
What is Rag 1 and Rag 2 Deficiency?
T- B- NK+ and Low Ig
- Impaired VDJ recombination
- Diarrhea, candidiasis, Pneumocystis jiroveci pneumonia
- Can lead to Omen Syndrome: severe erythroderma, splenomegaly, eosinophilia, high IgE
What is Jak3 Deficiency?
T- B+ NK+
- Mutation in Janus Kinase 3
- Defect in Il-2 signaling
- Autosomal Recessive
What is agammaglobulinemia?
B cell development is arrested at Pre-B stage
- very few circulating B cells
- mostly X-linked but can be autosomal recessive
What is X-linked Btk Kinase Deficiency?
Mutation in a tyrosine kinase that causes a defect in rearrangement of Ig Heavy Chains
No IgM, IgG, or IgA serum antibodies
What are Isolated IgG deficiencies?
Decreased concentrations of IgG subclasses
- Associated with recurrent viral/bacterial infections in respiratory tract
- Normally low levels of IgG2
What is IgA deficiency?
IgA secreting B cells have disorders or maturation or terminal differences
- Recurrent infections with encapsulated bacteria
- Often develop autoimmune diseases and allergies
- Can have anti IgA antibodies that can lead to anaphylaxis in response to IVIG transfusions
- Relatively high incidence
What is Digeorge Syndrome?
T Cell deficiency due to deletion in 22q11.2
- Important symptoms: Cardiac anomalies, hypocalcemia, and hypoplastic thymus
- Humoral immunity is present
- Can give live viral vaccine in some cases
What is Hyper IgM syndrome?
High IgM and low other Ig
- Mutations in CD40L (no triggering of class switching)
- Increased susceptibility to bacterial infections
- Low number of CD27 memory B cells
- can be X linked or autosomal
What is transient hypogammaglobulinemia?
For the first few years of life, IgG/IgA production is delayed
- IgM is normal
- Increased susceptibility to sinopulmonary infections
What is common variable immune deficiency?
Defect in Ab production and associated with hypogammaglobulinemia
- History of recurrent sinopulmonary infections
- reduced circulating B cells: low Ig (sometimes IgM normal)
- Onset starts around 4-5 but diagnosed at 20-30
- Autosomal disorder
What is γ Chain Deficiency? (aka IL-2Rγ)
- Deficiency in IL-2 Receptor
- No functional B cells
- Most common reason for SCID
- Patient presents with failure to thrive, severe thrush, opportunistic infections, and chronic diarrhea
- X linked
What is IL-7R α Chain deficiency?
- IL 7 plays early role in T cell development
- Low Ig levels but B cells are present
- Classic SCID symptoms
What is Bare Lymphocyte Syndrome Type II?
No MHC Class II expression on APC cells
- mutations in TF that regulate expression
- Deficiency in CD4
- Variable hypogammaglobulinemia
What is MHC Class I Deficiency?
Mutation in TAP 1
- CD8 Deficient
- Recurrent viral infections
- Normal Ab production
- Normal DTH
What are CD3 complex deficiencies?
CD3 deficiencies in subunits
- Lymphopenia and decreased T cell numbers
- specific antibody responses decreased
- Patients present with failure to thrive, opportunistic infections, and chronic diarrhea
What happens with defects in IFN γ and IL-12?
Cytokines released by T Cells and NK Cells
-susceptible to nontuberculous mycobacteria
What is Th17 Deficiency?
Mutations in IL-17, IL-17R, STAT 1, STAT3, or AIRE
-susceptible to chronic muocutaneous candidiasis
What is IPEX?
Mutation in FOXP3 resulting in loss of inhibition in Treg cells
- self reactive T cells are not inhibited
- X linked
What is ALPS?
Autoimmune Lymphoproliferative Syndrome
- defects in Fas/FasL, caspase 8, or caspase 10
- resists apoptosis
What is Wiskott-Aldrich Syndrome?
Mutations in protein that leads to:
- Decreased IgM
- Normal IgG
- Increased IgA and IgE
Recurrent encapsulated bacterial infections
Also pneumocystis and candida
What is NK Cell Deficiency?
Mutations in multiple genes
- Classical: GATA2 deficiency (no NK cells)
- Function NKD: NK cells present but are defective
Severe viral infections
What is C8 Complement Deficiency?
Increased susceptibility to Neisserial Infections
-Autosomal Recessive
What is Bradykinin-Induced Angioedema?
C1-INH Inhibition
-deals with vasodilation, capillary permeability, fluid extravasation, and edema
What is Hereditary Angioedema?
Mutation with C1 inhibitor
-painful, recurring attacks fo swelling
What is Paroxysmal Nocturnal Hemoglobinuria?
Failure to regulate formation of MAC
- deficiency of glycosylphosphatidylinositol
- lack GPI anchor proteins (DAF) and CD59
- intravascular hemolysis
What can cause deficiencies in TLR?
MyD88 deficiency
-severe infections from pyogenic bacteria
