Primary Immune Deficiencies + Random Shit Flashcards
CD31
PECAM1, on leukocytes & endothelial cells to help transmigration in inflammation
PECAM1
CD31, on leukocytes & endothelial cells to help transmigration in inflammation
vasodilation
histamine nitric oxide prostaglandins
fever
IL-1 TNF
pain
prostaglandins bradykinin
increased vascular permeability
histamine, serotonin C3a, C5a, bradykinin leukotrienes C4, D4, E4 platelet activating factor substance P
chemotaxis, leukocyte recruitment and activation
IL-1, TNF chemokines C3a, C5a leukotriene B4 bacterial products
tissue damage
lysosomal enzymes of leukocytes reactive oxygen species nitric oxide
What happens with early complement defects? (C2, C4)
- sinopulmonary infections
- increased susceptibility to S. pneumoniae, H. influenzae
- autoimmune disease (SLE, glomerulonephritis)
What happens with late (C5-C9) defects?
- increased susceptibility to Neisserial infections
What happens with C3 defects?
- severe pyogenic infections
What lab tests should you do for complement disorders?
- initial: CH50 (do this for ALL complement)
- secondary:
- individual component testing if CH50 is low
- If more than 1 complement protein is low/absent –> suspect complement consumption
- AH50 useful for rare alternative pathway defects
Describe the initial lab work for B-cell/antibody defects?
initial:
- quantitative immunoglobulins (IgG/A/M/E)
- vaccine titers (Diphtheria, tetanus, pneumococcus) – measures ability to make specific Abs
What else should you consider in B-cell/antibody defects?
- CH50
- sweat chloride (check for cystic fibrosis)
- CT sinuses/chest
Describe C1 inhibitor deficiency
- hereditary angioedma characterized by edema of skin and mucosal surfaces (especially periorbital)
- (overactive C1 will overactivate complement –> vasodilation, increased vascular permeability, formation of edema)
Describe the secondary lab work for B-cell/antibody defects.
secondary:
* flow cytometry for lymphocytes subsets/B cell subsets
What is the initial lab workup for T cell defects?
- FISH (old test), RT-PCRTBX1, DNA
chromosome microarray (preferred) - Lymphocyte subset enumeration (flow cytometry)
-
Numbers of T-/B-/NK-cells, memory and naïve T cells
- normal infants should have almost all naive T cells, but SCID infants will show almost all memory T cells
- CANNOT diagnose T-cell deficiency by an ALC alone
- Immunoglobulins (quantitative, functional)
- T-cell proliferation (Mitogens/Ag stimulation, DTH)
Functions of IL-2R
- control of peripheral self-tolerance
- development of T-reg cells
- differentiation of helper and cytotoxic T lymphocytes
- in vitro expansion and differentiation of antigen-specific NK cells and T cells
Functions of IL-4R
- Regulate B-cell function in concert with IL-21
- Immunoglobulin class switching
- T-helper cell differentiation to Th2
- Co-stimulant for growth in T, B, and mast cells
- Inhibition of Th1 maturation and macrophage activation
Functions of IL-7R
- thymic development and survival of T cells
- homeostasis of peripheral lymphocytes
- grwoth and survival of B-cell progenitors
Functions of IL-9R
- goblet cell hyperplasia
- mucus production
Functions of IL-15R
- Development, differentiation, survival, and activations of NK cells
- expansion of CD8+ memory cells
- homeostasis of peripheral T cells
Functions of IL-21R
- regulation of immunoglobulin production
- proliferation and activation of NK cells
- proliferation of B and T cells
Clinical presentation of DiGeorge Syndrome (DS)?
CATCH22
- Cardiac abnormalities
- Abnormal facies
- Thymic hypoplasia
- Cleft palate
- Hypocalcemia
- Chromosome 22
How do you diagnose DiGeorge Syndrome?
DNA microarray (copy number variation)
FISH
To screen: Realtime PCR of TBX1 (a homeobox protein/gene important in devo of pharyngeal pouches)
How do you diagnose SCID?
Diagnostic Studies:
- Screening Test: CBC; lymphopenia (< 1.5 k in majority of cases)
- Confirmatory Test: Lymphocyte enumeration (T cells-naïve/memory, B cells, NK cells)
- Newborn screening for SCID in several states (WI started in 2008)
How do you diagnose CVID?
- Decrease in IgG (>2 SD below mean) and a low IgA and/or IgM
- IgA is low in 90%
- if you see a low G and a low A, think CVID
Other details:
– Onset > 2yo
– Absent isohemagglutinins and poor response to vaccines
– Exclude primary Ab deficiency (XLA)
– Exclude secondary Ab deficiency
– Drugs (corticosteroids, rituximab)
– Protein losing enteropathy
– B cell lymphomas
