Immunology and Immunodeficiency, ASPHO Flashcards
WBC of innate immune system?
neutrophils, macrophages, dendritic cells, NK cells
WBCs of adaptive immune system?
CD3/CD4 T, CD3/8 T, B cell cells
NK cells express?
CD16, 56
diff between CD4 and CD8 cells?
CD4: help B cells class switch and help CD8 T cell kill…CD8 cells have cytolytic activity
killing viruses requires?
NK cells, CD4, CD8 cells
killing pneumocystis, fungi requires?
CD4, CD8
killing bacteria requires?
b cells
adaptive immune system has what two arms?
cellular (t cells), humoral ( b cells)
ALC of less than ___ -____ in an infant is highly abnormal
1000-2000
how to measure quantity of lymphocytes?
lymphocyte subset ennumeration
how to measure immune function for t and b cells?
NONSPECIFIC:
t: proliferation to mitogens
b: measure total immunoglobulins (GAM) and can also measure IgG subclasses
SPECIFIC:
t: -proliferation to antigen for tetanus, candida
- intradermal candida control skin test
b: antigen-specfiic antibodies:
- protein: tetanus, hep b surface antigen
- carbohydrate: anti-A adn Anti-B is someone who’s blood type O; response to 23-valent pneumovax vaccine
3 major types of circulating immunoglob?
IgM, IgG, IgA
structure of IgM, IgG, IgA?
IgM: pentameric
IgG: monomeric
IgA: mono-, dimeric
which immunoglob has highest affinity?
IgG
which immunoglob corsses the placenta?
IgG…it’s small! monomeric
causes of immunocomproimse?
- loss of physical barriers (mucosal impairment, CVCs)
- medication (corticosteroids, cyclosporine, rituximab, etc)
- acquired or cong defects in cell # (neutropenia, CD4 lymphopenia)
- acquired or congen defects in cell function
re-do protein vaccines when after SCT?
~9-12 months
re-do live vaccines and carbohydrate vaccines when after SCT?
24 mos
alemtuzumab, ATG, methylpred (high dose) all do what to t cells?
lysis
cyclosprine and tacro do what to t-cells?
inhibit TCR activation and early cytokine production
methotrexate, mycophenolate, sirolimus do what to t cells?
inhibit clonal expansion, prolilferation
in the pre-engraftment period, day 0-30: deal with waht defect? what infections happen then?
- neutropenia, catheter
- bacterial: gram pos, neg, anaerobes
- fungal: candida, aspergillus
- viruses: HSV, resp
in the post-engraftment early period (30-100): defects? infections?
- lymphopenia esp CD4
- t cell suppressive meds
- acute GVHD
- catheter
infectious: gram pos, neg, anaerobes…asperfillus…CMV, resp, EBV-Lymphoprolif disease….pneumocystitis, toxoplasma
if hte post-engraftment late period, >100 days: defects? infections?
- lymphopenia esp CD4, t cell supp meds, cGVHD, poor Ig production
- enapsuled organisms…aspgerillus…VZV, CMV, resp, EBV-LPD… pneumocystits, toxoplasma
organisms we target for F&N?
- gram neg rods (e. coli, pseudomonas, klebsiella), gram pos cocci (strep viridans, staph aureus, enterococcus)
- prevalent but mild: coag neg staph, anaerobes
driving risk in F&N
severe neutropenia, presence of catheter, mucosal barrier breaktown
F&N management
blood cultures
start antibx ASAP..dont’ wait for urine
anti-pseudomonal beta-lactams or 4th gen cepahlo or carbapenem
antibx ppx: give to who?
can consider levoflox in AML induction, relapsed ALL
if decide on double gram neg rod coverage, can stop that when?
after 48 hours of neg cultures
when can you stop antibx for F&N?
- no fever
- neg cultures
- strong evidence of marrow recovery
fungal ppx: target what?
yeast= candida mold= aspergillus, zygomycosis, fusarium
who gets fungal ppx?
- allo HSCT pts
- pts undergoing AML induction/MDS
- auto SCT recipients with neutropenia for >7 days
what agent should be used for fungal ppx? alternatives?
fluconazole
alt: echinocandin (caspo), posaconazole (at least 13 yrs), itraconazole for CGD pts
fungal orgs ataht we target for F&N?
candida, aspergillus, zygomycosis, fusarium
consider empirc fungal coverage for which F&N pts?
allo HSCT pts, pts undergoing AML indcution/MDS, pts with HR ALL or relapsed leukemia
start antifungals when for F&N?
high risk pts with at least 96 hours of F&N that’s not responsive to broad spectrum antibx
antifungal agent to use in F&N?
echinocandin (like caspo) or liposomal amphotericin b
pneumocystitis jirovecci: who’s at risk?
anyone with CD4 lymphopenia (high dose chemo, HSCT, solid organ transplant, primary immunodef with low CD4 count or function
ppx for pneumocystits jirovecii?
trimethoprim sulfamethoxazole 5 mg/kg/day divided BID three days per week
3 alternatives to septra for pcp ppx?
atovaquone dapsone inhaled pentamidine IV pentamidine etc
who gets HSV ppx?
allo transplant who is seropositive pt <30 days
viral ppx for HSV?
acyclovir(foscarnet if resistant)
who gets CMV ppx?
allo transplant who is seropos themselves or who’s donor is seropositivie, give for first 100 days
med for CMV ppx?
ganciclovir or valganciclovir or foscarnet or cidofovir
who gets VZV ppx?
allo SCT pt who has had wild type varicella infection…give up to 1 yr post
med for VZV ppx?
acyclovir IV or PO
or valacyclovir
VZIg give when?
give for exposure to varicella within 96 hours
absence of t-cells eg?
SCID
present t-cells but broken eg?
WAS
absence of b-cells eg?
XLA
present but broken b cells eg?
CVID
absence of neutrophils eg?
SCN
present but broken neurphils?
CGD
how does SCID get diagnosed now?
detected at birth via detection of ABSENT t cell receptor excision circles= ABSENT TRECs…
then check ALC, lymphocyte subsets (t cells very low or absent)
-lymphocyte proliferation studies (see absent/very low proliferation of t cells to mitogens
-total IgG, IgM, IgA
-specific Abs if vaccinated
…remember: if no t-cells, b-cells won’t work properly either!
explanation for normal ALC but still having scid?
maternal engraftment
main genes in SCID?
IL2RG (x-linked)= most common!!> JAK3, IL7R (both AR)
SCID management:
- protect from infection
- IgG replacement
- aggressive diagnosis and prompt response to infection
- ppx against pneumocystis
- irrad bood products!
- if ADA deficiency, give peg-ADA
- immediate referral to bone marrow transplant
XLA= x-linked agammaglobulinemia: problem? tx?
no peripheral b cells–> becomes sick at 6-9 months once no longer has mom’s IgG; replacement IgG
milder version of WAS?
x-linked thrombocytopenia: generally no eczema,normal immune function
immune issue in WAS?
normal to low T clelnumber, normal B cell number but poor Ab production (carbo responses…doesn’t rspond to pneumovax)
immune features of WAS?
eczema allergies high ige aiha itp vasculitis of the skin arthritis colitis
was dx how?
was protein levels on flow
gene sequencing
tx for was?
splenectomy
supportive
HSCt <5 yrs
x-linked lymphoprolif disease: gene? presentations? tx?
SAP
- fulminant/fatal EBV;lymphoprolif; recurretn infections with hypogamma or dysgamma
- transplant
CVID dx? issue?
decrease igg/iga/ or igm and/pr poor ab production…defects in t cell numbr or function–> autoimm, granulomatous disease, lymphoma
infections seen in CVID?
sinopulmonary infections, enteroviral meningoencephalitis
heme issues seen with CVID?
ITP, evans, AIHA, autoimmune neutropenia
tx for CVID?
IgG replacement, supportive care for infectious and autoimmune issues
ALPS: pathophys?
defect in pathways controling apoptosis of lymphocytes
major mutation in ALPS?
FAS
why are hematologists poised to see ALPS?
oftne prsent with autoimmune cytopenia
what are the 2 requied criteira for ALPS?
- chronic (>6 months) non malig, noninfect LAD, and/pr splenomegaly
- elevated CD3+, TCR alpha beta + CD4 neg CD8 neg DNT cells
accessory criteria for ALPS? (2)
- defective lymphocyte apoptosis
- somatic or germline pathogenic mut
secondary criteira for ALPS? (4)
- elevated plasma sFASL or IL-10 or vit B12 or IL18
- typical findings on histo
- autoimmune cytoepnias and hypergammaglob
- fam hx of nonmalig/noninfectious lymphoprolif with or without autoimmunity
tx ALPS how?
- manage cytopenias: steroids, MMF, 6MP, ritxu, sirolimus
- role for splenectomy is controversia
- watch for lymphoma
immunodef indications for transplant?
WAS CD40ligand def XLP CGD Leuk adhesion def
conditoning for immunodef SCT?(not SCID)
busulfan (Stem cell kill) + cyclophos or fludarabine (to prevent rejection)
why do you not need conditioning for MSD in SCID?
profound lack of functional t-cells…HSCs can easily engraft in the thymus adn generate t-cells
if you have a MSD for SCID transplant do you need conditioning? t cell depletion?
no
no (matched t cells unlikely to cause GVHD)
if you have a haplo parent for SCID transpalnt do you need conditioning? t cell depletion?
no
yes
if you have an unrealted donor for SCID, do you need conditioning? t-cell dep?
yes
either one
