Immuno 3 Flashcards
X-linked agammaglobulinemia
defect in B cell maturation: premature B cells can’t mature to B cells –> males don’t have circ B cells –> no igA/D/M/E and little igG –> pyogenic infxn –> tx w/ IV ab
selective igA immunodefic
no igA but other ab nml –> mucosal infxn (sinus, lungs, intestines); MOST COMMON PRIMARY IMMUNODEF; most common clinical condition = anaphylactic transfusion rxn b/c have anti-igA ab
CVID
group of d/o; dec in igG/A/sometimes M –> plasma cells can’t mature –> recurrent bacterial infxn b/c ab can’t make immune responses; affects both sexes equally
x-linked vs auto rec SCID
mutation in common gamma chain of IL7 receptor –> pro-B/T cells can’t differentiate –> no B/T cells –> no IL15 –> no NK or CD8 –> no humoral/CMI vs any mutation not on X chrm
ADA
buildup of A & G –> toxic to lymphocyte stem cells –> stem cells die before they can differentiate into B/T cells –> lymphopenia, opportunistic infxns, inc autoimmunity (LOA)
Omenn Syndrome
Hypomorphic mutation in RAG1/2 –> T cells present but not fxnal, no B cells –> abnl T cells bind to thymus self ag –> GVHD or autoimmunity
MHC II defic
B/T cells present but not fxnal; MHC II not expressed on macs or B cells –> can’t present to CD4 –> can’t activate B/T cells (MHC I can still present to CD8 but need CD4 to expand immune response) –> GI infxns
hyper igM vs igE
x-linked; mutation in CD40L on X chrm –> T cells can’t express fxnal CD40L –> can’t costim to help macs or B cells –> B cell can’t isotype switch –> stays as igM –> defects in humoral and phag responses –> susceptible to P. jirovecii vs mutation in STAT3 –> no IL17 prod –> inc igE and eos –> FATE
Wiskott-Aldrich syndrome
B/T cells present but not fxnal; Defect in WAS protein –> ineffective B cell response to T-independent polysaccharide Ags –> susceptibility to encapsulated bacteria; Defect in WAS protein –> defective formation of immune synapse –> ineffective activation of T cell by APC; classic triad = thrombocytopenia, immunodefic, eczema
Bare Lymphocyte Syndrome II
Mutations in TRANSCPXN FACTORS that regulate MHC Class II gene expression –> little/no MHC-II expressed BUT MHC-I is expressed at normal or slightly reduced levels –> can’t present in thymus –> can’t activate T cells –> can’t activate B cells –> recurrent GI infxns, no DTH
TREC
excised DNA that help make TCRs; high TREC –> many TCR, low TREC –> few TCR; used to screen newborns for thymic activity
DiGeorge
microdeletion of 22q11.2 –> thymic aplasia –> no T cells –> viral, fungal, mycobacterial infxn; CATCH22
IL12 defic
Mutation in p35/40 –> fxnal IL12 heterodimer
Mutation in IL12 receptor –> IL12 can’t bind –> dec CD4 Th1 and CD8 –> dec IFNγ –> tx w/ exogenous IFNγ
MHC I defic
mutation in TAP –> can’t load peptide onto MHC I/bare surface –> no CD8 –> recurrent viral infxn; inc NK and gamma/delta T cells to compensate
malnutrition causing immunodef
lower CD4 –> low CD4:CD8 ratio –> impaired inflamm and wound healing, reduced phag
age causing immunodef
immunosenescence –> inc neoplasia to ca, susceptibility to dz, dec inflamm response b/c low IL1/6; dec stem cell prolif, thymic involution, dec innate and adaptive immunity
Iatrogenic (Drug-Induced) Immunodeficiency: targeted therapies
corticosteroids and immunotherapy (inhibits effector fxn), cytotoxic drugs (blocks B/T cell prolif and diff), chemotherapy (dmgs hematopoietic cells by altering DNA structure –> anemia, lymphopenia, neutropenia)
Iatrogenic (Drug-Induced) Immunodeficiency: non-specific therapies
Cyclosporine, gold, penicillamine, anti-epileptics –> induce transient igA defic b/c adverse drug rxn
alc causing immunodef
alc –> reduced intestinal absorption of proteins and micronutrient –> altered microbiome
releases endotoxin in GI –> Kupffer cells release ROS and cytokines –> destroy hepatocytes
stimulates hypothalamic-pituitary-adrenal axis –> release immunosuppressive corticosteroids –> reduced phagocyte chemotaxis and phagocytic/killing; diff in both sexes: males release testosterone –> immunosuppressive, females have dec estrogen –> immunosuppressive, and they have dec metab for alc –> liver cirrhosis
Infection-Induced Immunodeficiency
produces a transient suppression except retroviruses
another name for artificial passive immunity. who’s at risk?
passive immunization, immunoprophylaxis. ppl not exposed to ag before, at risk for severe/life threatening dz, immuno incompetent
salk vs sabin
IPV –> igGAM but not mucosal igA vs OPV –> igGAM and mucosal igA
bacterial vs viral vs parasitic vaccines
toxins/attachment/motility factors –> T dep B cell ag; polysaccharide capsules for T indep B cell ag; goal = conjugate capsule to T dep B cell ag vs need to induce CMI vs none yet b/c too many life stages but we have cheap antiparasitic drugs
vaccine routes: parenteral vs mucosal
IM, intradermal –> igG and CMI, little igA vs intranasal, a little more igA
passive vs active immunity
short lived, preformed ab, immediate protection, good for immunodef ppl, bad w/ rpted doses, no mem vs long lasting, need time to make response, lag, bad for immunodef ppl, rpt doses = good, mem
early vs late phase of T1HS
igE binds to allergen –> P ITAM –> mast cell degran/phag –> histamine, PG/LT, enzymes vs cytokines recruit Th2, mac, eos –> release toxic proteins/enzymes, ROS, pro-inflamm cytokines, eiconasoids –> chronic inflamm –> fibrosis
which type of DCs found in food allergies?
immunogenic DC > tolerogenic DC/nml
what does SCIT do?
dec igE, inc igG & Treg
key sxs and dx for acute hemolytic anemia
anemia, BLISTERING OF SKIN/MUCOUS MEMBRANES, jaundice. dx by COOMBS TEST or immunocytochem
key sx for pernicious anemia
tingly/numb hands/feet
key sx for pemphigus vulgaris vs goodpasture’s
BLISTERING OF SKIN/MUCOUS MEMBRANES vs dysuria/hematuria, hemoptysis/cough/dyspnea
key sx for graves dz
goiter, tachy, exophthalmos, itchy, sweat, tremors
acute vs chronic serum sickness
1 large ag dose –> ab prod –> phag vs chronic exposure to ag –> antigenemia
sensitization of T1HS vs T4HS
allergen to PRR –> Th2 cells –> IL4/5/13 –> isotype switch to igE –> igE bind to mast vs allergen to PRR –> Th1/2/17 –> memory cells
TRALI
donor plasma ab react to recip ag –> C’, cytokines –> fever/chills, hypoTN, frothy sputum, HYPOXIA –> tx by give O2 or mechanical ventilation
erythroblastosis fetalis vs hydrops fetalis
mom’s anti-Rh ab attack baby’s Rh on RBC –> RBC lysis –> high bilirubin –> anemia and jaundice in fetus vs DAMPs bind to PRR –> cytokines –> edema in fetus
most common GVHD?
bone marrow transplant
diff b/w serology prescreen vs serum based assay for tissue type vs cross match screen
is donor infected w/ anything? vs will recip serum ab attack donor MHC? vs will recip serum ab attack donor cells?
hyperacute vs acute vs chronic stages of allorecognition
min to hrs; more for xenotransplants; ab –> C’ –> clot –> inflam, endothelial dmg –> tx by removal vs days to wks, highest risk = 3mo; ab, CD4 (IL2; IFNa/B for DC, MHC I/II; IFNy for mac/NK, MHC II; TNFa/B for MHC I), CD8 (cytolysis) –> tx by immunosuppressant vs mo to yrs; slow progressive tissue destruction by inflamm –> ab, mac, CD4/8 –> fibroblasts –> fibrosis; highest susceptibility in sm arteries and airways
how to est maternal fetal tolerance?
amniotic fluid: AFP
placenta: HLAG, IL10/TGFB/IDO, hCG
ex of immunosuppressants
corticosteroids, cyclosporine, ab/biologics (block cytok binding), mTOR inhibitor/cytotoxic drugs (block prolif)
Arthus rxn vs serum sickness
IC in vessel/tissue –> inflamm, PLT, ischemia, necrosis vs IC in kid, vessel, joint –> glomerulonephritis, vasculitis, arthritis
central tolerance vs peripheral tolerance vs suppression
delete alloreactive T cells vs induce anergy of alloreactive T cells vs inc Treg
transfusion rxn vs allergic transfusion rxn
T2HS d/t mismatched blood type by human error –> transfused foreign RBC = destroyed by C’ mediated lysis/phag/ADCC –> fever/chills, tachy, change in bp, intravascular clots, lower back pain b/c blood entering kidneys –> stop transfusion and replace donor blood w/ nml saline vs recip = presensitized to donor RBC –> igE = activated upon next exposure –> stop transfusion
ARF
ab bind to S. pyogenes M protein –> circ –> bind to myosin in heart, joints, vessels –> C’ –> tissue dmg –> heart palpitations, swollen red joints/uncontrolled movements, stomach pain
key pathogenesis of autoimmune thrombocytopenic purpura?
bind to PLT –> activate splenic/hepatic mac –> clearance of spleen and liver –> low PLT
contact dermatitis
ag to DC –> Th1 –> mem –> activated mem –> IFNy –> tissue dmg
rheumatoid arthritis
broken tolerance –> synovial ag to Th1 –> IFNy and TNF –> mast, osteoclast, chondrocytes –> dmg synovium, bone, cartilage
TIDM
broken tolerance –> CD4/8 attack pancreatic B cells –> IL2/IFNy, cytolysis/perforin/granzyme/apop
DC based vs T cell based of cell based immunotherapy
active; Apheresis and remove myeloid cells –> make “right” DC –> make “right” Th1 and CD8 cells in vivo –> make “right” cytokines in vivo –> inhibit cytokines that favor tolerogenic DCs –> admin to pt vs passive; Remove T cells –> remove “natural” TCR –> replace w/ tumor-specific recombinant TCR –> make “right” cytokines in vivo; Chimeric TCR = Fab of tumor specific ab + CD3 tail
what does receptor blockade do?
prevents immune system from turning off
advantages of immunotherapy?
specifically targets –> no lost anti-ca activity –> mem
complication of immunotherapy tx: latent infxn
when immune mediators of infectious agent = removed –> reinfxn; ex: TNF targeted immunotherapies remove TNF –> dissoc of TB granuloma –> TB wreaks havoc
immune checkpoints and their inhibitors
CTLA-4 bind to CD80/86, or PD1 binds to PDL1 –> turns off T cell; inhibitors (antiCTLA4/PD1/PDL1) keep T cell on. ICI can break tolerance –> autoimmune dz –> re/appearance of autoreactive T cells
BiTE
Bispecific T cell Engager: take Fab of tumor specific ab and antiCD3, link em together –> forces T cell and tumor cell binding; ex: CD3 T cell w/ CD19 tumor cell (blincyto)
stages of tumor progression
dysplasia (growth factors, apop inhibition), invasion, angiogenesis, metastasis (altered expression of cell adhesion molec, chemokines/receptors)
3 stages of immunity fighting tumors
1) elim: by CD8, NK, mac/DC, IL12, IFNy
2) equil: by CD8, ab, CD4 Th1, IL12, IFNy; immunoedit and ca edit
3) escape: by tolerogenic DC, monocyte-derived suppressor cells, Treg; immunoevasion (B/T exhaustion) and immunosuppression (turn off immune response w/ FasL, CTLA4, PD1)
graft and tumor rejection = mostly done by which cells?
CD8
blood A/B ag specificity depends on?
single terminal sugar residue
