Exam #3: Immunodeficiencies Flashcards
When should you be suspicious for an immunodeficiency?
- Unusually frequent, severe, resistant infections
- Refractory to treatment compared to patients of similar age & exposure risk
What is the difference between a primary & secondary immunodeficiency?
Primary= genetically determined
- Genetic defects in B or T lymphocytes
- Usually presents between 6 months & 2 years
Secondary= consequences of cancer, other infections, malnutrition, drugs
What are the clinical manifestations of primary immunodeficiencies?
- Recurrent infections
- Failure to thrive
What is the consequence of an ADA deficiency in lymphocyte development?
No pro-B or T cells
What is defect in lymphocyte development seen in X-Linked Agammaglobulinemia?
Pre-B cells are unable to mature
What is defect in lymphocyte development seen in Hyper IgM-Syndrome?
Lack of:
- CD40L
- Activation induced deaminase
*****Immature B-cells can mature into IgM but NOT other isotypes
What is defect in lymphocyte development seen in X-Linked SCID?
Cytokine gamma chain= pro T-cell cannot become immature T-cell
What is defect in lymphocyte development seen in Di George Syndrome?
Immature T-cell cannot mature
What is X-Linked Agammaglobuliemia of Burton?
- X-linked recessive disorder of males caused by mutation in Burton’s Tyrosine Kinase (BTK)gene
- Responsible for B-cell maturation via pro/pre-B cell signal transduction
*****B-cells don’t mature & can’t produce antibodies
What is agammaglobulinemia?
No antibody production i.e. absence of mature B-cells in the blood
When does Burton’s Agammaglobulinemia onset?
After maternal antibodies have been depleted, which is ~6months
What is the clinical presentation of Burton’s Agammablobulinema?
- Recurrent sinusitis
- Oropharyngeal
- Respiratory infections
*****All due to pyogenic bacteria that would normally be opsonized by circulating antibodies
What are the three major pyogenic bacteria that are opsonized by circulating antibodies?
1) Staphylococcus aureus
2) Streptococcus pneumoniae
3) H. Influenza
What are the viral & protozoal infections are patients with Burton’s Agammaglobulinemia are susceptible to?
Enteric viruses & giardia lamblia
What vaccination is especially dangerous for patients with Burton’s Agammaglobulinemia?
Polio from live vaccine–>leads to paralytic polio
When does Burton’s Agammaglobulinemia onset?
After maternal antibodies have been depleted
What is the treatment for Burton’s Agammagloulinemia?
Parenteral immuoglobulin replacement
What is Common Variable Immunodeficiency?
Variable group of disorders that occur later in life
What are the mechanisms of Common Variable Immunodeficiency?
The mechanisms of CVID are variable and include:
1) Intrinsic B-cell defects
2) Abnormal T-cell signaling to B-cells
*****Both lead to an inability of B-cells to become plasma cells
What are the lab findings associated with Common Variable Immunodeficiency?
Hypogammaglobulinemia, usually all antibody classes but occasionally isolated IgG
What are the clinical features of Common Variable Immunodeficiency?
- Recurrent bacterial infections of the sinuses & respiratory tract
- Increased enteroviral infections & chronic diarrhea due to Giardia Lamblia infection
- Paradoxical increase in autoimmune disorders
What are patients with Common Variable Immunodeficiency at increased risk for?
- Autoimmune disorders
- B-cell Lymphoma
- Gastric Cancer
What are the lab findings associated with Common Variable Immunodeficiency?
Hypogammaglobulinemia, usually all Ab but occasionally isolated IgG
What is selective IgA deficiency?
Isolated IgA deficiency in which infected individuals have low levels of serum & secretory IgA
What is the most common immunodeficiency?
Selective IgA deficiency (European)
What is acquired IgA deficiency associated with?
- Measles
- Toxoplasmosis
- Other viral infections
Describe the clinical features of Selective IgA Deficiency.
IgA is the major Ig in secretions; thus, infections are common in the:
1) Respiratory
2) GI
3) GU tracts
What do you need to remember about patients with Selective IgA Deficiency?
Blood transfusion with blood containing normal levels of IgA can induce anaphylaxis
