Congenital Immunodeficiency Flashcards
Primary immunodeficiency disorders most commonly effect which part of the immune system?
Humoral Immunity: B cells(50% of PIDs) Combined: B and T cells (20%) Phagocytic (18%) Cellular: T cells (10%) Complement (2%)
If a newborn has an immunodeficiency, recurrent infections are seen at 6 months of age and later….Why don’t infections occur in the first 6 months of life?
Infants have a delayed production of antibodies due to retention of Maternal IgG after birth. However Maternal IgG gradually declines over the first 6 months of life and infant starts to make their own IgG (also with low but increasing levels of IgA and IgM). Around 6 months Maternal IgG is almost gone so if infant has humoral PID it will not be noticed until 6-12 months of age-once maternal IgG is no longer present.
What are the four different red flags that would lead you to suspect a PID in a patient and how would you check?
- Recurrent sinopulmonary BACTERIAL infections –> screen humoral immunity (B Cells)
- Recurrent viral and/or fungal infections –> screen cellular immunity (T Cells)
- Recurrent skin abscesses and/or fungal infections –> Screen for phagocyte defect
- Bacteremia or meningitis with encapsulated bacteria –> Screen for complement deficiency
What 6 tests could you order to test for a PID?
- Differential count of blood cells (CBC)
- DTH skin test (delayed-type hypersensitivity skin test)
- Serum IgG, IgM, IgA
- Ab testing to specific Ag used for Immunization
- Total hemolytic complement assay
- Nitroblue tetrazolium test
What does a Differential Count of Blood Cells test and what would you be looking for to indicate a PID?
Differential Count of Blood Cells (CBC) could screen for T-cell, B-cell, T/B cell defects. To indicate a PID we would look for decreased numbers of T cells, B cells, or platelets
What does a DHT skin test and what would you be looking for to indicate a PID?
DHT (delay-type hypersensitivity skin test) could be used for T cell defects and a negative response would be indicative of possible impaired T cell response PID
What does a serum IgG, IgM, and IgA test and what would you be looking for to indicate a PID?
Serum IgG, IgM, and IgA would test for humoral immunodeficiency (B cells).
Decrease in any of all immunoglobulins would suggest a PID
What does Ab testing to specific Ag used for immunization test and what would you be looking for to indicate a PID?
Ab testing to a specific Ag used for immunization tests for humoral immunodeficiency.
Decreased or absent Ab response to vaccination would be suggestive of PID
What does a Total Hemolytic complement assay test and what would you be looking for to indicate a PID?
A total hemolytic complement assay tests for a complement deficiency.
Decrease or absence of components in classical pathway would be suggestive of a PID
What does Nitroblue tetrazolium test and what would you be looking for to indicate a PID?
Nitroblue tetrazolium tests for a phagocytic disorder.
Abnormal/Negative result would indicate that phagocytes are not working/PID
What are 3 examples of Severe Combined Immunodeficiency (SCID)?
ADA (adenosine deaminase) deficiency
RAG 1/RAG 2 deficiency
Artemis deficiency
What is ADA deficiency and what is the result?
ADA = Adenosine Deaminase (enzyme in purine catabolism pathway) - essential for metabolic function of various cells, especially T cells
Immune Phenotype: T-, B-, NK-
Ab Panel: IgM- IgG- IgA-
Inherited, autosomal recessive disorder
Infections: Severe opportunistic infections
No live vaccines
Treatment: Human stem cell treatment
ADA defect leads to accumulation of by-product: DEOXYADENOSINE - Toxic to lymphocytes (stem cells killed in bone marrow)
ADA deficiency is second most common cause of SCID
What is RAG 1/RAG 2 deficiency and what is the result?
RAG 1/ RAG 2 deficiency is inherited autosomal recessive disorder of SCID
RAG 1/RAG 2- enzymes essential for VJD recombination during development of TCR and BCR thus defect leads to defective expression of pre-TCR and pre-BCR –> apoptosis
Immune Phenotype: T- B- NK+
Ab Panel: IgM- IgG- IgA- but HIGH IgE
Severe opportunistic infections
No live vaccines
Treatment with Human Stem Cell Treatment
Presentation: in infacy; recurrent infections with bacteria, viruses, fungi; diarrhea, infections with opportunistic fungus (pnuemocystis jiroveci)
What is Omenn Syndrome?
Result of Leaky RAG 1/RAG 2 defects - allows partial function of RAG1/2 and can give rise to atypical form of SCID
characterized by severe erythroderma, splenomegaly, eosinophilia, and high IgE
Treatment with Human Stem Cells
What is Artemis and what is the result?
Artemis is a rare form of Autosomal Recessive radiosensitive SCID
Immune Phenotype: T- B- NK+
Ab Panel: IgM- IgG- IgA-
Severe Opportunistic Infections
No live vaccine
Treatment with Human Stem Cell Treatment
Presentation: in infancy; recurrent infections with bacteria, viruses and fungi; diarrhea, and infections with opportunistic fungus (pneumocystis jiroveci)
*B and T cells absent but NK cells normal (like RAG1/2 defect)
increased risk for lymphomas
**RADIOSENSITIVITY
