Primary Immune Disorders Flashcards
What is the difference between Primary and Secondary Immunodeficiency?
Primary:
Genetic
Secondary:
Infectious agents
Malnutrition
Neoplasia
Iatrogenic
Toxins
What part of the patients immune system can be predicted as deficient if they experience history of repeated viral infection?
Innate Immune defenses:
Type 1 IFN
NK cells
Adaptive Immune defenses:
CD8+ (CTL)
CD4+
What part of the patients immune system can be predicted as deficient if they experience history of repeated intracellular bacteria/fungi/protozoa infection?
Innate Immune defenses:
Phagocytes
NK cells
Adaptive Immune defenses:
CD4+ (Th1)
CD8+
What part of the patients immune system can be predicted as deficient if they experience history of repeated extracellular bacteria/fungi/protozoa infection?
Innate Immune defenses:
Complement
Phagocytes
Adaptive Immune defenses:
B cells / Ig
CD4+
What is characteristic of Bcell immunodeficiencies?
- Usually caused by specific abnormality in B cell development
- Increased susceptibility to infection by extracellular pathogens
- Increased susceptibility to enteric infections (lack IgA)
- Treatedd with antibody replacement therapy (IVIG)
What are examples of B cell immunodeficiencies? (primary)
X-Linked Agammaglobulinemia
X-linked Hyper-IgM Syndrome
Severe Combined Immunodefiicency
(defect in humoral and cell mediated immunity - can be T-B- or T-B+)
What is X-Linked Agammaglobulinemia (XLA)?
- Primary immunodeficiency caused by a mutation in Bruton’s Tyrosine Kinase (BTK)
- Required for B cell development in bone marrow:
Affected males have B-cell development arrested in bone marrow and are a B- phenotype - Carrier females may have some B cell developmental arrest due to X-inactivation, but many are functional and allowed into the peripheral blood
What is the XLA phenotype?
Disease develops at 5-6 months of age (loss of maternal Ig)
- Experience reduced levels of all Ig Isotypes
- T+B- lymphocyte phenotype
What is X-linked Hyper-IgM Syndrome?
- Primary immunodeficiency due to a mutation in CD40L
(long arm of X chromosome) - Defective class-switching to IgG, IgA, and IgE isotypes
- -> compensatory increase in IgM
What is the phenotype of X-linked Hyper IgM Syndrome?
- Increased levels of IgM
- -> Decreased levels of IgA, IgG, and IgE
- No germinal centers present in lymph nodes
- T+B+ lymphocyte phenotype
But B cells are unable to be activated due to lack of CD40L on Th2 cells
What do patients with X-linked Hyper IgM Syndrome have increased susceptibility to?
- Extracellular bacterial infections (No Ig)
- enteric infections (No IgA)
- Intracellular microbes (CD4+ Th1 cells cannot activate macrophages to kill phagocytosed microbes due to lack of CD40L)
What is Severe Combined Immunodeficiency (SCID)?
- Primary immunodeficiency with defects in humoral and cell-mediated immunity
- Either T-B+ or T-B-
- Patients present early in life with history of recurrent infections
- Display susceptibility to broad range of pathogens (viruses, intracellular and extracellular bacteria, fungi, parasites)
- Fatal unless treated with bone marrow translant
What is the most common cause of SCID?
Recessive mutation in the common y chain
(long arm of X chromosome)
IL-7 and IL-15 receptors are most critical for growth and development of T and NK cells, respectively
- Heterozygous females = normal
- Hemizygous males = clinically affected
Which Interleukin receptors have been identified as using the common y chain?
IL-2
IL-4
IL-7
IL-9
IL-15
What is DiGeorge syndrome?
Deletion at chromosome 22q11.2
- T cells reduced or absent
- Hypocalcemia (tetany, seizures)
- Facial deformities
Micrognathia
small, mis-shaped mouth
Low set abnormally folded ears
Bulbous nose
Palatal clefting
