Immunodeficiencies - Kane Flashcards
Indicators of B-cell immunodeficiency
Absence of follicles and germinal centers and reduced serum Ig levels.
Consequences of B-cell immunodeficiency
Pyogenic and enteric bacterial and viral infections.
Indicators of T-cell immunodeficiency
Reduced T-cell zones, reduced T-cell proliferation in response to antigen
Consequences of T-cell immunodeficiency
Bacterial and viral intracellular infections and pathogen-associated cancers.
Phase I of Neutrophil response
Intracellular killing by ROS and NETs
Phase II of Neutrophil response
Clearance of dying cells (efferocytosis) and suppression of inflammasomes
Enzyme responsible for generating ROS in phagolysosomes
Phagocyte oxidase
Chronic Granulomatous Disease
Characterized by impairment of neutrophil respiratory burst. Usually an X-linked mutation in CYBB gene which results in non-functional gp91phox.
Common infections in CGD patients
Catalase positive bacteria (ex. staph aureus)
Diagnosis of CGD
Reduction of ROS measured by flow cytometry.
Severe Combined Immunodeficiency (SCID)
Loss of B or T-cell development or function by a multitude of impaired pathways.
Common Gamma Chain Deficiency (X-linked SCID).
Major deficiency in common gamma chain (linked to many cytokine receptors). Most important is IL-7 which is involved in T-cell survival and maintenance as well as thymic development.
Why would mutations that directly affect T-cell function also impair B-cell function?
Fully functional B-cell responses require CD4+ T-cell involvement to develop into plasma cells.
Why would some these conditions not manifest until after the first several months of life?
- Fc-mediated passive transfer of IgG via syncytiotrophoblasts prevent infection during first few weeks after birth.
- After birth, PIgR-mediated IgA is transferred via breast milk.
Clinical manifestations of X-linked SCID
Highly susceptible to all infections, sensitive to live attenuated vaccines, and susceptible to opportunistic pathogens (ex. CMV, HSV, and EBV).
Treatments for SCID
Hematopoietic stem cell transplant, enzyme transplant, gene therapy
Bruton’s X-linked Agammaglobulinemia
Absence of all immunoglobulins and few lymph nodes. No circulating B-cells due to defective BTK pro-B-cell heavy chain signaling.
Clinical manifestations of Bruton’s X-linked disease
Highly susceptible to encapsulated bacteria, respiratory viruses and fungal infections are well tolerated.
Common Variable Immunodeficiency (CVID) caused by what genes
Many mutations can lead to CVID but primarily: PI3K and LRBA
Hyper-IgE Syndrome (Job Syndrome)
Deficiency in Th17 cell development via multiple pathways affecting IL-23, IL-17, and IL-23 signaling.
What type of defect is caused by mutation in STAT3 gene
Dominant negative – Even one good copy = defective
Acquired Immunodeficiency Syndrome
Caused by HIV infection of CD4+ T-cells. T-cells are depleted leading to increased susceptibility to opportunistic infections
X4 (T-tropic) HIV infects which cells.
CD4+ T-cells expressing co-receptor CXCR4
R5 (M-tropic) HIV infects which cells.
Macrophages expressing co-receptor CCR
