Mar27 M2-The immune work up Flashcards
types of diseases of errors of immunity
- immunodeficiencies (primary and secondary. primary = single gene disorders. secondary = acquired)
- immune dysregulation syndromes
- auto-inflammatory syndromes
different arms of the immune system + how related to disease
- humoral (B cells)
- cellular (T cells)
- combined (B and T)
- phagocytic arm (neutrophils, macrophages)
- complement system
- each disease = one or many arms defective
examples of diseases where an arm of the immune system is compromised
- defect in IFN gamma prod (interferonopathies)
- inflammasome related problems
- immunity related to non-hematopoietic tissues (spleen, osteoclasts, epidermis, fibroblasts, neurons)
causes of secondary immunodeficiencies
HIV, neoplasia, transplant, splenectomy, chemo, radiation, diabetes
how many genes involved in immunity
2150 (approx 10% of our 20 000 protein coding genes)
how many PIs
350 (344 genes). hypo or hypermorphic mutations. symptoms differ from patient to patient, even within same gene mutated
at what age do PIs appear
any age!! even age 50. so don’t assume it’s a secondary one
incidence of PIs
1 in 2500 persons
important PI to know about and why
SCID (1 in 50 000 affected)
- 95% survival if detected
- 100% death before age 1 if not detected
10 reasons to investigate for IEI (inborn error of immunity)
- 8+ ear infections in 1 yr
- 2+ sinus infections in 1 yr
- 2+ months on Abx with no effect
- 2+ pneumonias in 1 yr
- failure to gain weight or grow normally
- recurrent deep skin or organ abscesses
- persistent oral candidal infection mouth (thrush) or skin after age 1
- Need IV Abx to clear infections
- 2+ deep-seated infections
- FHx of PI
specific things that should make us think of inverstigating PI
- unusual infections (opportunistic)
- very mild inflammatory signs in pretty bad infections
- sick after vaccine
- recurrent autoimmune phenemona
IEI: most to least common defective arms
- humoral (B) (most common)
- combined (B and T)
- cellular (T)
- phagocytic
- complement (very rare)
important think that can hint us towards what arm is defective in an IEI
- finding the bugs that cause the recurrent infections (send to culture)
- each defective arm = get specific infections
bugs found in culture depending on defective immune arm
- B deficit AND complement deficits = EC organisms, enterovirus, giardia lamblia.
- T deficit: viruses, IC organisms, opportunistic organisms like candida
- phagocytic deficit: atypical bacteria, mycobacteria, fungi, protozoa
- complement deficit = often Neisseria
when to suspect B cell deficit
- many bacterial infections
- resp infections (strep, haemophilis)
- seen after 6 months of age (when lose mom Ab)
example of phagocytic deficits
- LAD (leukocyte adhesion deficiency)
- chronic granulomatous disease (CGD): neutrophils can’t produce oxygen radicals to kill pathogens after engulf them
phagocytic deficits when to suspect
- skin, liver, GI infections
- no detachment of umb cord
- abscesses
- gingivitis, periodontitis
2 types of complement deficits and what you see
C1-C4 deficiency = rheumatic disorders, pyogenic (means produce pus) infections
C5-C9 deficiency = susceptibility to encapsulated organisms (pneumococcus, meningococcus, H. flu), recurrent sinopulmonary infections
1st lab done when suspect IEI
CBC (want nbr and fct of the immune cells)
how to check B cell fct (things you can do)
- qt of all the Igs in the blood
- serology before and after vaccination
- DNA sequencing for known defects
good vaccine serology (good resp after vaccine shows what)
functional B AND T cells
how to check T cell fct
- vaccine serology
- T cell stimulation or proliferation assay
- PPD (type IV delayed HS test). response = T cells working
- DNA sequencing for known defects
T cell prolif assay how it works
put in mitogenic milieu (specific substances known to make T cells replicate) with radioactive thymidine. measure if T cells proliferate (functional) or not (non functional) with how much radioactivity from cells
how to check phagocytic fct
- CBC, ANC
- for LAD, measure adhesion molecules at neutrophils surface with flow cytometry
- DHR (dihydrorhodamine) test for CGD. if cells CAN make ROS, will reduce DHR to strongly fluorescent rhodamine
- DNA seq for known defects
3 complement pathways
- classical pathway (Ag-Ab complexes). CRP for ex
- lectin pathway (microbial surfaces like mannose and others (like IgA)
- alternative pathway (spontaneous and foreign substances like LPS)
end effect of complement pathway
MAC (membrane attack complexes) formed
complement molecules easily measured
C3 and C4
how to check complement system fct
- measure C3 and C4
- ELISA (enzyme immunoassay) to stimulate the 3 complement pathways and measure how much MAC proteins are formed (C5b to C9)
- CH50 (classical pathway testing)
- AH50 (MBL, mannose-binding lectin, and alternative pathways testing)
