Key facts Flashcards
xthrough what does the spleen receive lymphocytes and antigen?
splenic artery
*no afferent lymphatic supply
Which Tregs express FOXp3?
natural T regs
(NOT induced Treg1 or 3)
what is Bruton’s tyrosine kinases required for? what do its defects lead to?
pro to pre-B cell > B cell maturation
XLA
pre B cell receptor chains and main signal
u heavy chain with surrogate light-chain (gamma5 + VpreB)
signals B cells to stop heavy chain gene rearrangement
VDJ recombination results in __ diversity
Addition of nucleotides by TdT (terminal
deoxynucleotidyl transferase) and removal of endonuclease results in __ diversity (greatest variability for diversity)
combinatorial
junctional
most common form of T-B-NK+ SCID mutation in _, which affects _
RAG1 or 2
several proteins involved in VDJ recombination
what chemokines attract neutrophils to tissue
IL8 (CXCL8)
LTB4
defects in types of LAD
Type 1 LAD: defective CD18 integrin *Defective adhesion
Type 2 LAD: absent sialyl lewisX *defective rolling
Type 3 LAD: defective kindlin-3 which activates integrin *defective adhesion
Which cells secrete cytokines that activate neutrophils>
Th17
neutrophil granules in chediak-higashi syndrome vs specific granule deficiency
CHS - 1* granules enlarged
specific granule deficiency - 2* granules absent
what is FCepisolonRI expressed on?
mast cells
basophils
NOT EOS
what is KIT
receptor for cytokine stem cell factor
critical growth factor of mast cells and target of imatinib
encoded by photo-oncogene c-KIT
how does IgE bind to FCepisilonRI
main proteins in mast cell signaling
binds via alpha chain
proteins: lyn, fyn, syk
where does Xolair bind?
CH3/Fc (heavy chain) domain of free IgE, at FCepisilonRI binding site
Cepisilon3
do basophils produce tryptase, chimase, carboxypeptidase, heparin, PGD2, and LTB4?
NO
major basic protein
from EOS -> MC and basophils degranulate -> histamine release
can be used to detect recent presence of EOS in tissue
1 cause of marked eosinophilia in US vs worldwide
US: drug reactions
world: parasitic infection
CD14
highly expressed receptor on monocytes and macrophages
binds LPS and activates immune response
component of TLR4
mutation in what gene cause X linked lymphoproliferative syndrome
SH2D1A (encodes SAP protein)
*susceptible to HLH from EBV
langerhans cell histiocytosis
rare malignancy of langerhans cells
s/s: eczema, seborrhea, lytic bone lesions, mutlisystem involvement
dx: biopsy with positive staining for CD1a and CD207 (IDs langerhans cells)
do intestinal epithelial cells present Ag from gut lumen via MHCI or II
MHCII
IL4 and IL13 suppress __, contributing to pathogenesis of AD?
beta defensins
cathelicidin
stem cell factor (SCF)
aka kit ligand
signals through c-kit receptor (CD117)
what do platelets from patients with asthma release?
CCL5
IL33
intracellular TLR
NEST
9
8
7
3
which TLR signaling is MyD88 dependent pathway not involved in?
TLR3
which TLR can signal through both MyD88 dependent and MyD88 independent pathways
TLR4
which diseases are activating mutations in NLRP3 associated with
hereditary periodic fever syndromes
- familial cold auto inflammatory syndrome (FCAS)
- muckle-wells syndrome (MWS)
- chronic infantile neurologic cutaneous and articular syndrome (CINCA)
HOW CAN YOU DISTINGUISH plasmacytoid DCs from other types of DCs?
lack of CD11c expression (they express CD123)
most variable part of Ig molecule?
CDR3
what is the hapten carrier effect
allows for small molecules that cannot activate T cells to stimulate immune responses
basis for many drug allergies
where do superantigens bind?
Vbeta region of TCRs (outside of peptide binding groove on MHC molecule)
what is MHC restriction?
when T cells can recognize and respond to a peptide only if bound to a specific MHC molecule
NK T cells recognize lipids and glycolipids displayed by class I MCH-like molecule __
CD1
which region of the TCR imparts the most significant sequence variability?
alpha-beta CDR3 region
what process creates TCR vs BCR/Ig diversity?
TCR: VDJ recombination
BCR/Ig: class switching, somatic mutation
shared mechanism of cyclosporin and tacrolimus?
inhibit calcineurin
-> block translocation of NFAT into the nucleus
-> prevent transcription of IL2 and other cytokines
disease from AIRE mutations
autoimmune polyglandular syndrome (APS-1) aka APECED
- lymphocytes are not deleted or tolerized to endocrine self antigens during selection in thymus -> endocrine organ attacked by self reactive T cells and autoAb
order of BCR editing
kappa light chain rearranged
then if receptor editing needed, lambda light chain used
when does lymphocyte become anergic?
T lymph recognizes Ag repeatedly without costimulation
FOXP3 mutation disease
IPEX = watery diarrhea + eczema + endocrinopathy
Immune dysregulation
Polyendocrinopathy
Enteropathy
X-linked
ALPS mutations
in Fas or caspase 10
ALPS = autoimmune lymphoproliferative syndrome
lymphs accumulate in peripheral lymph organs
lack of tolerance causes autoimmune features, esp cytopenias
how do CTLs and helper T cells cause cytokine mediated damage to grafts?
direct and indirect alloantigen recognition
*only CTLs generated by direct allorecognition can kill graft cells
which transplanted tissues don’t require immunosuppression?
cornea
bone
joint tissue
what is a syngeneic transplant
genetically identical, from twin
what is a xenogeneic transplant
across species
what is considered a match for umbilical cord blood and for adult donors?
UCB: 6 out of 6 at A, B, and DRB1 alleles
adult donor: at least 6 out of 8 at A, B, C, and DRB1 alleles
how are leukemia cells killed in graft vs leukemia?
- graft T lymphs contribute to eradication of tumor
- recipient NK cells express HLA I that is different than donor HLA I -> results in donor NK mediated cellular killing of leukemic cells (killer inhibitory receptors KIRs aka inhibitory killer Ig-like receptor on donor NK cells are inhibited by cells that display HLA I markers that they recognize)
what is the major factor in long term survival in SCT?
chronic GVH reaction
where are HLA-G and F expressed and purpose
extra villous fetal trophoblast
protect fetus from maternal immune rejection
what explains the long half life of IgG?
FcRn protects from catabolism
IL-1-5 main actions
Hot T Bone stEAk
IL1: hot, fever
IL2: T lymph stim
IL3: Bone marrow stim
IL4: IgE stim
IL5: IgA stim
IL1beta maturation mediated by_
ass’n mutation
caspase-1, requires activation by multiple proteins including NALP (NLRP)
GOF mutations in NALP causes uncontrolled IL1 production and autoinflammatory syndromes
- can be treated with IL1 receptor antagonists (anakinra, canakinumab, rilonacept)
IL-12Rbeta1 mutation cause susceptibility to _?
infections with intracellular bacteria
*salmonella, atypical mycobacteria
what receptor is shared by IL-4 and IL-13
IL4Ralpha (dupixent target)
which receptors share a common beta chain (CD131)
IL3
IL5
GM-CSF
what is hyperproduced in castleman’s disease and what does it cause?
IL6
causes angiofollicular LN hyperplasia -> pts p/w fever, microcytic anemia, LAD, normal BM iron, hypoalbumin, and elevated CRP
which receptors all contain the common gamma chain (affected in SCID)?
IL2
IL4
IL7
IL9
IL15
IL21
IRAK-4 deficiency leads to susceptibility to __
pyogenic infections
*strep pneumo, staph aureus, pseudomonas aeruginosa
which chemokine expression is increased in skin of eczema patients
CCL27
what activates CCR3 receptor and what does it cause?
“Three-osinophil”
CCR3 receptor activation by eotaxin leads to eos recruitment to tissues
defect in LAD2
PMNs can’t express carbohydrate ligands (sialyl lewisX) for E and P selectin
what does fourth beta integrin family alpha4beta7 do?
mucosal addressin that binds to mucosal addressin cell adhesion molecule (MAdCAM), important for gut homing
what stabilizes Factor B in the alternative complement cascade?
Properdin
*only known positive regulator of complement
Binding affinity of C1q to IgG subtypes and IgM (classical complement cascade)
IgM > IgG3, IgG1, IgG2
IgG4 cannot bind C1
rate potency of anaphylotoxins
C5a >C3a>C4a
what complement receptors are markers for dendritic cells?
CR4, CD11c
What does CR2 (CD21) bind and do?
binds C3d
provides 2nd signal for B cell activation by antigen, helps trap Ab-Ag complexes in germinal center
what is DAF? (in complement system)
decay activating factor
dissociates C3 convertase
which complement receptors are used for cell entry or phagocytosis by microorganisms?
CR1 by HIV
CR2 by EBV
CR3 by mycobacterium tuberculosis
complement deficiencies in SLE
C1q»C1r/C1s, C4, C2
C1 inhibitor key points
- sole plasma inhibitor of factor XIIa and factor XIIf, a cleavage product derived from factor XIIa by digestion with kallikrein or plasmin
one - one of the major inhibitors of kallikrein, factor XIa, C1r, and C1s
- consumed by plasmin
what does a negative DTH test indicate?
lack of exposure to antigen
OR
anergy as a result of 1* or 2* cellular immunodeficiency
effect of histone acetylation/deacetylation
*COPD link?
histone acetylation –> opens chromatin/allows transcription
histone deacetylation –> repressed gene expression *reduced in COPD
in what type of study is OR most often used
case-control study
in what type of study is RR most often used
cohort
what 2 signals induce IgE production:
- Th2 lymph secreted IL4/IL13
- CD40-CD40L B and T cell interaction
___ is a sensitive markers of type 2 inflammation that is increased in AR and decreased in sinusitis
exhaled nitric oxide
what type of MOA do H1 antihistamines have?
inverse agonists
downregulate H1 receptor constitutive activity
what patients have more severe alcohol induced rhinitis
patients with AERD or CRSwNP (w/ or w/o asthma)
what type of sinusitis is a surgical emergency?
isolated sphenoid sinusitis
refer to ENT immediately
what type of patients does AFRS affect
young, immunocompetent
*it’s noninvasive
what are signs of moderate to severe AFRS
bony expansion or erosion leading to double vision, proptosis, periorbital edema, focal neuro signs, severe HA, meningeal signs
*urgent referral to ENT
what staining is required to identify fungal hyphae in mucin?
PAS or GMS staining
*they are usually sparse
giant papillary conjunctivitis is associated with ___ and has ___
ass’d with contact lens use
has tarsal papillary hypertrophy (typically smaller than VKC - <0.3mm - but can increase to 1-2mm with dz progression)
where do the various sinuses drain?
“Sinuses listen to radio channels - FM, AM, PS, SS”
Frontal and Maxillary and anterior ethmoid drain to middle meatus
posterior ethmoids and sphenoid drain into sphenoethmoidal recess above superior turbinate
useful PCD screening test
very low or absent nasal nitric oxide
PCD patients have MORE or LESS airway infections than CF patients
LESS
*suggest that altered mucus plays a larger role in dz progression than ciliary mvmt in chronic bacterial infections
what % of patients with PCD have situs inversus
50%
what % of adults does chronic cough affect?
peak onset age?
10-12% adults F>M
peak onset in 6th decade
most likely causes (4) of chronic cough in non-smoking immunocompetent adult with normal CXR and not taking ACEi
upper airway cough syndrome
asthma
non-asthmatic eos bronchitis
GERD
clinical markers of irritant contact derm
sharp borders
acute onset (w/in min to hr)
rapid peak and variable time course to resolution
what type of hypersensitivity rxn is allergic contact dermatitis
type VIa/c
typical onset 24-72 hours after exposure often with exposure to low molecular weight hapten molecule (after prior sens)
what bug is a common cofactor in seborrheic dermatitis
malassezia
what cytokine is most strongly associated with pruritus in AD
IL31
most frequently associated environmental allergen for triggering atopic dermatitis flares
DM
association of anterior vs posterior subcapsular cataracts
anterior = Atopkic keratoconjunctivitis
posterior = Prednisone
what contact dermatitis materials to think of with day 6 or 7 delayed peak reaction
corticosteroids
neomycin
nickel
gold
cholinergic urticaria can present similarly to __
exercise induced anaphylaxis
can even have hypotension
pts with EIA won’t react with passive heating
cold urticaria syndromes with negative ice cube test (6)
PLAID
delayed cold urticaria
cold induced cholinergic syndrome
systemic cold urticaria
familial cold autoinflam syndromes
cold dependent dermatographism
most common cause of acute angioedema presenting to the ED
ACEi
most common genetic abnormality resulting in HAE
SERPING1 on chromo 11
estrogens in HAE?
should be avoided or used with extreme caution
what acute HAE treatment is approved for all peds patients and pregnancy/breastfeeding
plasma derived C1 INH
icatibant MOA and ages
for acute HAE attacks
bradykinin B2 antagonist
approved for 18+ but can be used down to 2yo
oral HAE ppx options
berotralstat (kallikrein inhibition) *only 12+
androgens *adults
langerhans cell histiocytosis presentation
caused by clonal proliferation of langerhans cells
nonspecific inflame response and multifocal organ involvement *bone, skin, BM, LN, endocrine, lungs
what is filaggrin
what have mutations in filaggrin been linked to
matrix protein promoting aggregation and disulfide boning of keratin filaments
AD, asthma, FA, ichthyosis vulguris
where are connective tissue mast cells vs mucosal mast cells
CT MC: have tryptase + chymase (MCtc)
- in skin, conjunctiva, heart, intestinal submucosa
- have CD88 receptor for C5a anaphylatoxin
- responds to vanc, opioids
mucosal MC: have tryptase (MCt)
- in alveolar wall, resp epithelium, and small intestinal mucosa
biopsies for suspected immunobullous disease
2!
One for intact vesicle/bullae and one for perilesional skin (for immunofluorescence since immunoreactants may not be present in lesions tissue)
Ab to desmoglein and epidermal immunoflouorence =?
pemphigus disease
(pemphigus vulgaris, pemphigus follaceous, paraneoplastic pemphigus, IgA pemphigus)
accumulation of __ in the airway is a hallmark of fatal asthma
neutrophils
what are the biomarkers for Type 2 Th2 high asthma
elevated total IgE
+sIgE
elevated FeNO
what are mucus plugs composed of?
serum proteins
inflammatory cells
mucus
cellular debris
pathognomonic findings that should make you consider CF (4)
hypoNa, hypoCl, meta alka
rectal prolapse
nasal polyposis
digital clubbing
when to consider ABPA in CF pt
continues to clinically worsen despite 1-2 weeks of antibiotics
what is echogenic bowel on prenatal US suggestive of
CF
sputum cell count test can be used to diagnose? (2)
eosinophilic bronchitis or occupational asthma induced by high molecular weight agent
what percentage of adult onset asthma cases are occupationally related?
2-25%
occupational rhinitis typically precedes occupational asthma for __ molecular weight agents
HIGH
years for animal lab workers to sensitize for occupational asthma/sxs
2 years
*flour workers take much longer
plicate acid (anhydride) activates ___
complement
what industry is OA from isocyanates seen
roofers, insulators, painters including auto body
*can induce both immunologic and non-immunologic mechanisms
is ABPA due to fungal colonization or local invasion?
fungal colonization
does absence of IgE sensitization to aspergillum exclude ABPA?
yes
treatment goal of ABPA
prevent development or progression of bronchiectasis and worsening of pulm function
what lab can help predict ABPA recurrence?
rising IgE levels *esp doubling of baseline IgE level
what can cause intermittent symptoms in hypersensitivity pneumonitis
episodic exposure to inciting agent
how does cigarette smoking impact risk of HP
decreases risk
helpful clues to recognize HP (6)
- hx of recurrent atypical PNA
- sxs develop after moving to new job or home
- sxs improve when away from work/home
- unusual exposures or hobbies
- lab workers
- hay handling
how much more/less common is organic dust toxic syndrome than farmers lung HP?
ODTS is 50x more common than farmers lung
what is the most common extra-pulm feature of EGPA
mononeuritis multiplex = periph neuropathy due to vasculitis involving the vasa nervorum
basics of:
eos granulomatosis with polyangitis VS
granulomatosis with polyangitis (Wegners) VS
microscopic polyangitis
EGPA: sinus dz + asthma + eos >1500 + neuropathy +/- MPO or p ANCA
GPA: sinus + lung + kidney dz +/- PR3 or c ANCA
MPA: lun g+ kidney dz +/- MPO or p ANCA no sinus or granulomatous inflam
sarcoidosis vs HP BAL CD4:CD8 analysis
sarcoidosis (one word) = higher CD4 (lower number)
HP (2 words): higher CD8 (higher number)
leading cause of mortality in EGPA
cardiac involvement
alpha1 antitrypsin should be obtained for which patients?
all patients with sxs of COPD and persistent airflow obstruction on spirometry, esp if <45yo nonsmoker
CXR findings in COPD
lung hyperinflation and hyper lucency
rapid tapering of vascular markings
*doesn’t help dx but can exclude other dx
loss of lung function in smokers vs nonsmokers
smokers decline in FEV1 60ml/year
normal loss 30mL/year
which treatments prolong life in COPD (3)
smoking cessation
supplemental O2 used 24hr/day
lung volume reduction surgery
what airway epithelial cells are the major producers of lung surfactant
type II pneumocytes
are neutrophils and eos permanent residents of the lung
NO - recruited there during inflammation
definition of significant bronchodilator response in adults and children
adult: FEV1 or FVC increase >10% relative to predictive value
children: FEV1 increase >12% from baseline
can you exclude seasonal pollen induced asthma with methacholine challenge or histamine challenge in winter
no
selective vs nonselective bronchoprovocation testing
selective aka allergic agents - looks at specific triggers in susceptible asthmatics
nonselective - potential to induce bronchoconstriction in all asthmatics
direct vs indirect bronchoprovocation testing
direct: acts on smooth airway muscle receptors (muscarinic and histamine)
indirect: mediator release is needed for actions
sens/spec of methacholine and mannitol testing for asthma dx
methachOline - high sens, useful to rule Out asthma
mannItol - high spec, useful to rule in asthma *esp exercise induced
factors that increase (7) vs decrease (6) FeNO
increase:
1. asthma
2. atopy
3. URIs
4. >12yo
5. nitrogen rich foods
6. COPD exacerbation
7. non asthmatic eosinophilic bronchitis
decrease:
1. bronchiectasis
2. tobacco smoke
3. drugs - steroids, antileukotrienes, oxymetazoline, NOS inhibitors
4. exercise
5. moderate altitude
6. hypothermia
highest risk factor for developing IgE mediated food allergy
AD
*filaggrin LOF variant also confer risk independent of AD
what percentage of egg and milk allergic kids can tolerate baked egg and milk
60-70%
latex fruit allergy syndrome
~30-50% of latex allergic patients haver hypersensitivity to some plant derived foods, esp fresh fruits: Avocado, Banana, Chestnut, kiwi, white potato, bell pepper, tomato
linear vs conformational epitopes in food allergy
linear = more prolonger allergy, allergen is stable and persistent
conformational = mild and transient allergy
what % of drug reactions does drug allergy account for?
type A or B reaction?
10%
Type B reaction
risk factors for drug allergy
latex or radiocontrast reactions
*not atopy
what is the hapten hypothesis?
small drugs which are not by themselves immunogenic become immunogenic or allergenic after bindings to a carrier protein to form a hapten-carrier complex
what is the most common form of delayed drug reaction
maculopapular (morbilliform) drug eruption
what to screen for prior to starting abacavir
HLA B*57:01
decrease in PCN-specific IgE Ab over time
~10% per year
- 50% with immediate rxn negative at 5 years, 80% at 10yrs
*similar for cephalosporins
common drug that causes IgA bullous dermatitis
vAncomycin
during ASA desens for AERD, do reactions typically occur at lower or higher doses
lower (~40mg)
what is anaphylaxis to cetuximab due to
IgE against carbohydrate galactose alpha-1-3-galactose
levels of __ correlate with severity of anaphylaxis
PAF - platelet activating factor
PAF acetylhydrolase levels correlate inversely with PAF levels/anaphylaxis severity
receptor on mast cells that can be activated by small molecular weight drugs resulting in degranulation
MRGPRX2 receptor
most common cause of fatality in anaphylaxis
circulatory collapse or resp failure
definition of significant increase in tryptase
(baseline tryptase x1.2) + 2
what is over sulfated chondroitin sulfate
contaminant in heparin caused by activation of the contact system with elevated C5a –> hypotension, abd pain, variable angioedema
*typically without urticaria or pruritus
most common cofactors in exercise induced anaphylaxis
NSAIDS
wheat
most common food implicated in food dependent exercised induced anaphylaxis
wheat (omega 5 gliadin)
most commonly identified latex allergens
Hev b1 and 3 - patients with multiple surgeries, spina bifida
Hev b5, 6.01, 6.02 - healthcare workers
which Hymenoptera are most cross reactive
hornets and yellow jackets - both vespers
vespid
less so:
-honeybee and Yellowjacket due to cross reacting carbohydrate determinants
-bumblebee and honeybee variable
what causes sterile pustule from fire ant venom
venom is 95% piperidine alkaloids
when are whole body extracts routinely used for venoms
fire ant only
what % of asymptomatic healthy adults are sensitized to Hymenoptera skin tests
20% - only 5-15% of these individuals will have systemic reaction to subsequent sting
Hymenoptera intradermal testing [ ] and starting dose of VIT
intradermal testing [ ]: 1mcg/ml
starting dose of VIT: 1mcg
what insect is most common cause of systemic reaction from BITING insect
kissing bug (Triatoma)
nocturnal painless bites in Western and southern US/Mexico
what cytokine is required for mast cell survival
SCF
is ligand for KIT (CD117)
most common form of mastocytosis in children
cutaneous
*often spontaneously resolves by puberty, persistence after puberty is indication for BM biopsy
how many organ systems need to have objective findings for MCAS diagnosis
2 organ systems
principle methods of volumetric air sampling
impaction - slit, rotating arm, or sieve samplers
impingement - air drawn into liquid, particles suspended in fluid
filtration - particles sucked through filter
major northern vs southern grasses
northern: Timothy, rye, bluegrass, sweet vernal
southern: Bahia, bermuda, johnson
grass cross reactivity
bermuda - other members of subfamily chloridoideae
Bahia and Johnson have limited cross reactivity
Timothy + sweet vernal - subfamily poodieae
foods that cross react with birch
ABC PPPP
Apple, apricot
BIRCH
celery, cherry, carrot
pear, peach, plum, potato
which mold sensitization is a risk factor for fatal asthma
alternaria
major outdoor vs indoor molds
outdoor: ACE = alternaria, cladosporium, epicoccum
indoor: aspergillus, penicillium
what is pancake syndrome
storage mites cause oral mite anaphylaxis after consuming wheat flour contaminated with storage mites
homology between Der p1-Der f1 and Derp2-Der f2
> 80% homology
how long after cat removal are cat allergen levels significantly removed
4-6 months
what dog allergen is associated with tolerating female dogs or castrated male dogs without sxs
monosensitization to can f5
which genotypes have increased susceptibility to pro-oxidant effects of pollutants contributing to airway inflammation
null genotypes in antioxidant enzymes (GSTM1, GSTP1)
effect of global climate change on pollen seasons
earlier, prolonged, and increased pollen seasons
particulate matter may also enhance delivery of pollen to the airway
standardized allergen extracts
hymenoptera - mcg protein (hyaluronidase and phospholipase)
DM - AU
cat hair/pelt - BAU
grass - BAU
short ragweed - Amb a1, AU or wt/vol
allergen extracts you cannot mix
cockroach or mold with pollen
venom and aeroallergens
what type of hypersensitivity reaction is serum sickness
type III
Immune complexes
rapidly progressive glomerulonephritis
crescent glomerulonephritis and rapidly deteriorating renal function
seen in anti GBM dz, pauci immune glomerulonephritis, and immune complex mediated disease
drug induced lupus
occurs months after medication exposure
sxs similar to SLE
anti-histone Ab
meds: procainamide, hydralazine, penicillin, minocycline, diltiazem, isoniazid, anti-TNF
drug induced subacute cutaneous lupus
photo distributed rash
+anti-Ro/SSA
what can prodromal phase of bullous pemphigoid be
urticarial without bullae
eye drop that can help distinguish episcleritis from scleritis
1 drop of 10% phenylephrine will block episcleral redness within 20min, but scleritis will persist
what is proteinase 3
serine protease enzyme expressed mainly in neutrophil granulocytes
epitope of c ANCA Ab
ass’d with granulomatosis with polyangiitis (wegners)
causes of caseating vs noncaseating granulomas
caseating - generally infectious
noncaseating granulomas - generally noninfectious
what is castleman’s disease
aka angiofollicular LN hyperplasia
heterogeneous group of lymphoproliferative disorders that share common path
ass’d with nonHodgkin and Hodgkin lymphoma and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes)
elevated IL6 activity -> cytokine storm with hypogamm and amyloidosis
HSCT survival rate for SCID prior to 2mo
95%
declines rapidly after 6mo
what is the only complement deficiency with X-linked inheritance
properdin deficiency
what percentage of the population have MBL deficiency?
5%
what complement deficiency is associated with the greatest risk of SLE
C1q
what gene defects related to TLR signaling cause severe influenza infection
IRF7 and IRF9
defects in which pathway are associated with Mendelian susceptibility to mycobacterial disease
IL12/IFN gamma
what gene mutation confers resistance to HIV infection acquirement
double allelic CCR5 32 mutation (CCR5 is a coreceptor that allows HIV entry into cells)
single allelic mutation ass’d with slower progression
what is the hypergamm in HIV infection from
Ab response to HIV
polyclonal activation of B cells
how does ritonavir affect inhaled or intranasal steroids
strong CYP3A4 and CYP2DG inhibitor -> can increase inhaled or intranasal steroids to systemic levels leading to Cushings or diabetes
sxs of multiple myeloma
CRAB
Calcium high
Renal failure
Anemia
Bone abnormalities
griscelli vs chediak-higashi hair shafts
griscelli - larger irregular clumps of melanin granules mainly near medulla, hair shaft appears uniformly white under polarized light microscopy
chediak-higashi - small aggregates of clumped pigmentation that are evenly distributed, hair shaft appears bright and polychromatic under polarized light microscopy
most over expressed gene in EOE
eotaxin3 aka CCL26
receptor = CCR3
eos chemotactic
increased by IL13
most common food trigger in EOE
milk
when treating patients for hypereos syndrome with steroids, remember:
to treat strongyloides empirically with ivermectin for patients with possible exposure to avoid disseminated disease
major integrin on gut homing B and T cells
what it binds to and other related proteins
major integrin: alpha4-beta7
binds to MADCAM1 on postcapillary venular endothelial cells
homing also requires CCR9 receptor on B and T cells and CCL25 ligand on epithelial cells
retinoid acid induces expression of these gut homing molecules
MOA of vedolizumab
monoclonal Ab against Alpha chain of alpha4-beta7
used in IBD tx
antihistamines to sue in renal or hepatic failure
renal: Claritin or 1st gen
hepatic: alllllegra (lllliver) *avoid first gen due to inc adverse effects
what type of receptor does albuterol bind to
G protein coupled receptor –> increases cAMP
what type of inhalers are contraindicated for asthma treatment
mono LABAs
what is the duration of action of beta agonists dependent on
bulk and size of beta agonist structure
examples of ultra long acting beta agonists (3)
carmoterol
indaceterol
vilanterol
what monitoring is needed on zafirlukast and zileuton therapy
liver function
which part of allergic response to antigen challenge is preventing with LTRA and mast cell stabilizers?
both early and late response
effect of blocking M2 vs M3 muscarinic receptors
M2 (inh) -> inc acteylcholine -> bronchoconstriction
M3 (stim) -> dec acteylcholine release -> bronchodilation
which part of allergic response to antigen challenge is prevented with steroids?
late phase response only
ciclesonide is what type of drug
prodrug with little binding affinity
requires conversion by esterase’s in the airway to the active metabolite (desisobutyryl-ciclesonide) for efficacy, reducing potential systemic side effects
how many heavy chains are in the constant regions of IgG/A/M/E
4 heavy chains in IgE and IgM
3 heavy chains in IgA and IgG
what infection has been associated with mepolizumab
herpes zoster
through what pathway does Alum work as an adjuvant as
the NLRP3 pathway involving the inflammasome
at what dose is acetaminophen typically tolerated in AERD pts
<1000mg
ID skin testing to __ has risk of anaphylaxis
food
latex
venom ID skin tests are performed with up to what [ ]?
1mcg/mL
effect of Xolair on total and sIgE
increases IgE
what Ig don’t activate complement
IgG4
IgE
IgD
when/where are CD19 (what does it associate with) and CD20 seen
CD19: early B cell progenitors until Cell plasma blast stage
CD20: pre-B cells and B cell blasts but not in early B cells or plasma cells
CD19, CD21, CD81 is coreceptor complex that functions to amplify BCR generated signals
what does activating dominant mutation in CXCR4 cause
WHIM syndrome
warts
hypogamm
infection
myelokathexis
what defect is responsible for LAD type 1
defect in common beta chain in CD18
what is OKT3
Monoclonal antiCD3 Ab used in treatment of solid organ transplant rejection and acute T cell ALL
Leads to activation then apoptosis of T cells causing immunosuppression
high levels of what type of B cells occur in some CVID patients
CD21-low B cells
what receptor does IVIG exerts its action through
binding to FcyRIIb
most common genetic variant in CVID
TACI
what is the most potent complement receptors and what does it bind
CR3 = most potent
binds iC3b (opsonin like Ig)
hereditary C3 deficiency leads to:
defective phagocytosis of encapsulated bacteria
presents with autoimmune disease and recurrent infections
coreceptors for HIV entry into CD4+ T cells
CCR5
CXCR4
CGD - gene mutations affect __
susceptible to what infections
NADPH oxidase system
catalase + organisms
most common cause of low complement
poorly handled specimen
when does anaphylaxis to cetuximab occur
when there are preexisting IgE Ab to the oligosaccharide galactose alpha 1, 3, galactose (on the cetuximab Fab heavy chain)
effect of HIV-1 infection on TRECs
decreased TREC levels
successful treatment with HAART leads to increased levels
