ACAAI Board Review Notes Flashcards
Name examples of conjugated vaccines.
13-valent pneumococcal vaccine (Prevnar 13)
Hib vaccine
Meningococcal vaccines (MCV4-Menactra and Menveo)
Which MHC molecule has beta2-microglobulin?
MHC Class I - has alpha1, alpha2, alpha3 and beta2-microglobulin
Regarding MHC Class I antigen presentation:
- Which virus can block TAP transportation of antigen peptides?
- Which virus can remove MHC class I molecules from the endoplasmic reticulum?
- HSV
2. CMV
What removes the class II associated invariant chain peptide (CLIP) from the MHC-binding cleft, thereby allowing antigenic peptides to be loaded?
HLA-DM
What cells express CD4, CD25 (IL-2Ralpha), and FoxP3? What cytokines are needed for survival of these cells?
T regulatory cells (Tregs)
IL-2 and TGF-beta are needed by Tregs.
Tregs secrete IL-10 (targets DCs and macrophages) and TGF-beta (inhibits lymphocytes and macrophages)
What are the CD numbers for Fas and Fas ligand (FasL)? How do Fas:FasL interactions signal?
Fas = CD95; and FasL = CD95L = CD178
Fas:FasL signals through the caspase system
Where does Papain cleave Ig?
Where does Pepsin cleave Ig?
Papain - above the hinge resulting in 2 Fab + 1 Fc fragments
Pepsin cleaves below the hinge resulting in 1 molecule of F(ab)2 (2 antigen binding sites)
Which IgG subclass has the shortest half-life?
IgG3
Which immunoglobulin fixes complement most efficiently?
IgM
What does the antibody called “Rheumatoid Factor” target?
Fc portion of IgG. RF is most commonly IgM.
- Which Ig class has the highest total body concentration/daily production?
- Which Ig class has the highest plasma concentration?
- IgA
2. IgG
What molecule transports IgA from basolateral surface to the luminal surface?
poly-Ig receptor (PIGR)
What protects IgG from degradation and accounts for the long half-life of IgG?
FcRn
What are the general functions of the 4 different histamine receptors?
H1 - pruritus, pain, vasodilation, hypotension, flushing, tachycardia, bronchoconstriction. Increased chemotaxis of EOS, PMNs, increased adhesion molecule expression
H2 - increased gastric acid secretion, vascular permeability, mucus production. DECREASE eos/pmn chemotaxis, increases IL-10, suppressed Th2 cells.
H3 - pruritus, nasal congestion, prevents excessive bronchoconstriction. Involved in neurogenic inflammation through neuron-MC feedback loop.
H4 - pruritus, nasal congestion, differentiation of myeloblasts. Increased chemotaxis of eos and IL-16 production.
What are
- concha bullosa
- Agger nasi cells
- Onodi cells
- Haller cells
- concha bullosa: pneumatization of the concha (air cell in the middle turbinate), no association to sinus disease, but can be assoc with septal deviation.
- Agger nasi cells: anterior ethmoid air cells above the middle turbinate
- Sphenoethmoid air cell, found in close proximity to the internal carotid artery and optic nerve, higher risk of damage to these during sinus surgery.
- Ethmoid air cells found on medial floor of the orbit, can increase risk of acute rhinosinusitis by blocking ostiomeatal complex
What sinuses are present at birth?
maxillary (earliest in fetus) and ethmoid are present at birth.
sphenoid develop around 2-3 yo
frontal develop around 5-6 yo
Where do the following sinuses drain?
- Frontal sinus
- Maxillary sinus
- Anterior ethmoids
- Posterior ethmoids
- Sphenoid sinus
Frontal, Maxillary, and Anterior ethmoids all drain into middle meatus (ostiomeatal complex).
Posterior ethmoids and Sphenoid drain into sphenoethmoidal recess above superior turbinate.
To determine whether BMI is associated with childhood asthma, a survey is mailed to all parents of middle school children in Chicago. Parents are asked to report their child’s current height, weight, and whether they currently have an asthma diagnosis.
What is this type of study called?
What type of bias is this study prone to?
Cross-Sectional study - an observational study where subjects from a population are sampled at one point in time.
Prone to Recall Bias (parents of children with asthma may be able to recall height and weight more accurately because of higher frequency of visits to the doctor)
To examine whether smoke exposure is associated with childhood asthma within the same population, smoke exposure among children who have asthma is compared with smoke exposure among children who do not have asthma.
What is this type of study called?
What are the strengths/weaknesses of this type of study?
Case-Control - an observational study that compares subjects who have the condition (“cases”) with patients who do not have the condition but are otherwise similar (“controls”) and examines how frequently the risk factor is present in each group.
Strengths: cheap and quick; useful for studying infrequent events or when populations would need to be tracked over long periods of time for the disease to develop (like cancer); can provide odds ratio (OR)
Weaknesses: retrospective, subject to recall bias, prone to confounders and therefore difficult to prove cause-effect relationships
Healthy infants are enrolled into a study after birth, and followed through 5 years of age for an outcome of asthma. The number of respiratory infections are recorded over this time period to see if frequency of respiratory infections are a risk factor for development of asthma.
What is this type of study called?
What are the strengths/weaknesses of this type of study?
Cohort study - an observational study that is longitudinal, comparing a defined group of people who share a common characteristic or experience within a defined period; groups are identified before any have developed the outcome of interest.
Strengths: prospective, reduced recall bias, gold standard in observational epidemiology, generates relative risk (RR)
Weaknesses: expensive, time consuming, and requires large numbers of subjects; sensitive to attrition
In statistics, what is a Type I (Alpha) error vs a Type II (Beta) error?
Type I error - null hypothesis was rejected falsely (observed a statistical difference exists when truly it does not)
Type II error - null hypothesis was not rejected when it should have been rejected (true difference exists but is not observed with the data)
25 year old female who recently moved to Ohio from Haiti complains of nasal crusting, nasal congestion, and pain upon inspiration from what she states is “dry nose.” On exam there is a foul smell (fetor) from the nasal vault. A nasal swab culture shows colonization with Klebsiella ozaenae. What is the diagnosis?
Atrophic Rhinitis.
Treatment involves nasal saline irrigation and topical antibiotics.
30 year old male complains of clear rhinorrhea persistently from the left nostril only. He did have a recent concussion suffered 3 weeks ago after playing soccer. He has no history of allergies or sick contacts. What test should you order to make the diagnosis?
β2-transferrin of nasal secretions.
Likely diagnosis: CSF rhinorrhea
What are the 5 criteria (Bent and Kuhn criteria) for diagnosis of Allergic Fungal Rhinosinusitis (AFRS)?
- Type I hypersensitivity to fungi confirmed on skin test or sIgE (Aspergillus, Alternaria, Penicillium, Bipolaris, Fusarium, Curvularia)
- Nasal polyposis
- Characteristic CT findings (heterogenous opacification with inspissated secretions in sinuses, nasal expansion, bony demineralization, polypoid tissue)
- Noninvasive fungal hyphae in mucin OR positive fungal culture of mucin
- Eosinophilic mucin without invasion into sinus tissue
What is special about FceRI on Langerhans cells?
lack the classic beta chain
What cytokine induces mucous gland hypertrophy in asthma?
IL-9
Which receptor is exploited by rhinovirus for entry into respiratory epithelium, and causing more severe asthma exacerbations?
ICAM-1 (CD54)
Match the food with the protein: Foods: Cow milk Egg Shrimp Fish Peanut Soy Tree Nut Apple
Proteins: Gly m5 Bos d4-8 Ara h1-11 Gad d5 Mal d1,2 Gal d1-5 Lit v1 Pen a1 Cor a1,8,9,14
Milk: Bos d4-8 Egg: Gal d1-5 Shrimp: Lit v1, Pen a1 Fish: Gad d5 Peanut: Ara h1-11 Soy: Gly m5 Tree Nut (hazelnut): Cor a1,8,9,14 Apple: Mal d1,2
What cytokines correlate with hypotension during anaphylaxis?
- IL-6
- TNF receptor I
- tryptase (mast cell)
- histamine
- C3a
Healthcare workers are most frequently sensitized to which latex protein allergens?
Hev b5, 6, and 7.
Hev b1 and 3 are less water-soluble and more commonly identified as allergens in patients with spina bifida.
What three treatments have been shown to prolong the life in patients with COPD?
- smoking cessation
- supplemental oxygen used 24hrs a day
- lung volume reduction surgery
For each, label as photoallergic (requires prior sensitization) or phototoxic (no prior sensitization):
- para-aminobenzoic acid (PABA)
- tetracyclines
- amiodarone
- psoralens
- furocoumarins
- tar
- chlorhexidine
- quinine
- PABA - photoallergic
- tetracyclines - phototoxic (especially doxycycline)
- amiodarone - phototoxic
- psoralens - phototoxic
- furocoumarins - phototoxic
- tar - phototoxic
- chlorhexidine - photoallergic
- quinine - photoallergic
- What group of chemicals are found in several plant families that cause allergic contact dermatitis in florists and bulb growers?
- What is the most frequent cause of hand eczema in flower workers?
- Sesquiterpene lactones (chrysanthemums, daisies, giant and dwarf ragweed) and tuliposides (tulips, hyacinth, asparagus, garlic)
- Peruvian lily (Alstroemeria) - classic dermatitis with intensely pruritic eruption affecting first three fingers and exposed areas of dorsal hands, forearms, V-region of neck, and face.
- What is the preservative that most frequently causes allergic contact dermatitis (ACD) in the US?
- What is the most common cause of ACD in hair dressers?
- What is the most common cause of ACD in nail stylists?
- Quaternium-15
- paraphenylenediamine (PPD-used in hair dyes and also used in Henna tattoos) (also think of glycerol thioglycolate for permanent wave solutions)
- acrylates (also think of formaldehyde-based nail resins)
What are the 4 major chemical classes of sensitizing topical corticosteroids?
Group A: hydrocortisone type
Group B: triamcinolone type
Group C: betamethasone type
Group D: hydrocortisone-17-butyrate type
If patch testing is positive for ethylenediamine dihydrochloride, what should be avoided?
Avoid nystatin, aminophylline, and piperazine-based antihistamines (e.g. meclizine and cyclizine)
If patch testing is positive for neomycin, what should be avoided?
bacitracin and aminoglycosides (gentamicin, tobramycin, streptomycin, kanamycin)
Conjunctivitis with otitis media in a child is more likely causes by what microorganism? What type of antibiotic should be used to treat?
nontypable H. influenzae.
Use broader-spectrum like amox-clavulnic acid
What is a destructive, expanding accumulation of keratinized squamous epithelium in the middle ear or mastoid, which can occur as a result of recurrent infection?
cholesteatoma
Diagnosing acute rhinosinusitis (ARS) requires 2 major or 1 major + 2 minor criteria. What are the major and minor criteria?
Major:
- purulent rhinorrhea
- nasal congestion/obstruction
- facial congestion/fullness
- facial pain/pressure
- fever
- hyposmia/anosmia
Minor:
- headache
- ear pain/pressure/fullness
- bad breath
- dental pain
- fatigue
- cough
A kidney biopsy shows a “full house” of immunofluorescence with IgG, IgA, IgM, C3, and C1q. what is the most likely diagnosis?
Lupus nephritis
What type of autoantibodies are seen in 95% of patients with drug-induced lupus?
antihistone antibodies
What are the 5 findings in limited cutaneous scleroderma (CREST syndrome)?
Calcinosis Raynaud's syndrome Esophageal dysmotility Sclerodactyly Telangiectasias
What is the name of the disease involving erythrodermic cutaneous T-cell lymphoma with leukemic involvement of malignant peripheral T-cell clones that show loss of CD26 and loss of CD27?
Sezary Syndrome.
Sezary Cells can be found in other malignant disease or in blood of healthy people in small numbers.
In a normal serum protein electrophoresis, there are the following protein peaks going from the positive electrode towards the negative electrode:
- albumin band
- alpha-1 fraction
- alpha-2 fraction
- beta fraction
- gamma fraction
What are the major proteins located in each of these fractions?
- albumin band contains albumin and is largest protein component
- alpha1 fraction: alpha-1 antitrypsin, TBG, transcortin
- alpha2 fraction: haptoglobin, ceruloplasmin
- beta fraction: transferrin, beta-lipoprotein, som IgG/A/M, complement
- gamma fraction: immunoglobulins
* between beta and gamma fractions: CRP, fibrinogen
What values on SPEP and bone marrow biopsy help diagnose multiple myeloma? What are the characteristic symptoms of multiple myeloma?
> 3 g/dL monoclonal paraprotein spike on SPEP
10% of clonal plasma cells on BM Bx
Symptoms of MM mnemonic is "CRAB": Calcium (increased) Renal failure Anemia Bone lesions
Which immunoglobulin is abnormally elevated in Waldenstrom’s macroglobulinemia?
IgM
*the light chain of the monoclonal IgM protein is usually the kappa light chain.
A patient with peripheral neuropathy, hepatosplenomegaly, endocrinopathy (hypogonadism), and hyperpigmentation with hemangiomas, is found to have osteosclerotic bone lesions on radiographs, a monoclonal paraprotein spike on SPEP, immunohistochemical staining of biopsy specimens showing lambda chain predominance, and chronic overproduction of proinflammatory cytokines: IL-1, IL-6, TNF-alpha, VEGF. What syndrome does the patient have?
POEMS = Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin abnormalities syndrome.
A patient presents with lymphadenopathy and has a lymph node biopsied showing the presence of a clonal population of cells staining positively for a heavy chain but negative for both kappa and lambda light chains. SPEP shows a broad band between alpha2 and beta fractions. What is the diagnosis?
Heavy-Chain disease - a rare B-lymphocyte proliferative disorder characterized by secretion of incomplete Ig heavy chains in which the deletion of an amino acid sequence results in the inability of Ig heavy chains to form disulfide bonds with light chains, and also prevents heat-shock proteins from normally binding to incomplete Ig heavy chains to target them for degradation by proteasomes. The 3 subtypes of Heavy-Chain disease in order of prevalence: Alpha, Gamma, and Mu.
What are the 3 different categories of cryoglobulin? What diseases are they associated with?
Type I: monoclonal IgM or IgG (sometimes IgA). Develops in the setting of monoclonal gammopathies (MGUS, MM, Waldenstroms, CLL). Precipitates within 24hrs.
Type 2: monoclonal IgM with rhematoid factor (RF) activity + polyclonal Ig. Associated with persistent viral infections, especially Hep C.
Type 3: polyclonal IgM (RF) + polyclonal IgG. Associated with autoimmune disorders moreso than infections. Precipitates 5-7d.
Clinically, palpable purpura/vasculitis, arthralgia, and weakness are seen in Type 2 and Type 3, whereas Type I presents with hyperviscosity and thrombosis
Name the type of autoantibody involved in the following hemolytic anemias:
- Warm-Reactive AIHA
- Cold-Reactive AIHA
- Paroxysmal Cold Hemoglobinuria
- polyclonal IgG against RBCs. RBCs attach to Fc receptors on macrophages in the spleen and are removed by phagocytosis. Can be idiopathic or secondary to SLE or CLL.
- IgM binds to I antigen (polysaccharide on all RBCs) at temperatures <37degC, leading to complement activation. Can be secondary to mycoplasma or EBV infection
- IgG against P antigen on RBC
A woman in her 1st pregnancy is found to be Rh(D) negative. What is recommended to prevent Rh(D) alloimmunization (development of anti-D antibodies in the mother)?
- anti-D immune globulin administered at 28 weeks gestation
2. anti-D immune globulin administered within 72hrs after delivery
What is Evans’ syndrome?
Simultaneous or sequential development of ITP and AIHA with a positive DAT in the absence of known underlying etiology. Can also have autoimmune neutropenia. Typically chronic and relapsing despite treatment with steroids, IVIG, and/or other immunosuppressive agents. Associated with CVID or ALPS.
What causes heparin-induced thrombocytopenia (HIT)?
IgG antibodies to platelet factor 4 (PF4) complexed to heparin, referred to as “HIT antibodies” or “PF4/heparin antibodies” cause thrombosis along with thrombocytopenia. The risk of thrombosis, including life-threatening limb gangrene, persists until both heparin is eliminated and a non-heparin anticoagulant is initiated.
What causes thrombotic thrombocytopenic purpura (TTP)?
Autoantibody against von Willebrand factor-cleaving protease (ADAMTS13). Clinical features "FAT RN": Fever Anemia Thrombocytopenia Renal failure Neurologic changes
What is lupus anticoagulant?
antiphospholipid antibody, which is an IgG or IgM antibody that binds to anionic phospholipids that have formed complexes with proteins, leading to prolongation of aPTT and increasing risk for thrombosis and recurrent, spontaneous abortions. Can be primary (antiphospholipid syndrome) or secondary to autoimmune diseases.
What genetic associations are seen in Graves and Hashimoto’s thyroid diseases?
HLA-DR3
CTLA-4 alleles
Type IA diabetes mellitus is associated with what autoantibody?
What about Type IB?
What about Type II?
Type IA: anti-GAD65 (antibody against glutamic acid dehydrogenase). LOW INSULIN and normal weight. 90% of pts have following haplotypes: DR3, DQ2 and DR4, DQ8
Type IB: anti-insulin receptor antibodies block insulin from binding, so HIGH INSULIN.
Type II: anti-islet cell antibody. majority of adult-onset diabetes.
Antibodies directed against the α3 chain of type IV collagen cause what disease?
antiglomerular basement membrane (Anti-GBM) disease.
Presents as limited to kidneys (RPGN) or pulmonary-renal vasculitic syndrome (Goodpasture’s syndrome).
Antibodies against type VII collagen cause what disease?
epidermolysis bullosa acquisita
How can you differentiate episcleritis from scleritis?
One drop of 10% phenylephrine will blanch episcleral redness, but true scleritis will persist.
Episcleritis: benign inflammation, minimal pain, not an emergency
Scleritis: 40% associated with RA, severe pain, decreased vision, EMERGENCY
Autoantibodies to parietal cell and intrinsic factor cause what disease?
pernicious anemia (autoimmune gastritis) - most common cause of vitamin B12 deficiency.
major molecular target of antibodies are the H+ and K+ ATPase.
Treat with lifelong B12 replacement.
A patient with IgA deficiency is being tested for Celiac’s disease, and the IgA autoantibodies against endomysium and tTG both come back negative as expected. What test can you send instead?
IgG antibodies against deamidated gliadin peptides (IgG-anti-dGli)–have been shown to be sensitive for the diagnosis of celiac disease in IgA-deficient patients.
What autoantibodies are associated with autoimmune hepatitis? How about primary biliary cirrhosis? Primary sclerosing cholangitis?
Type I AIH: ANA+ anti-smooth muscle anti-actin antibodies against soluble liver or pancreas Ag
Type 2 AIH:
ANA neg
anti liver-kidney-microsomes-1 (ALKM-1)
liver-cytosol antigen (ALC-1 or LC1)
PBC:
antimitochondrial antibody
PSC:
anti-smooth-muscle antibody
What mutations are associated in Crohn’s Disease?
- NOD gene (NOD2/CARD15) present in 20-50% of Crohn’s
- ATG16L1 - gene associated with autophagy
- IL-10 mutations
Stiff-person syndrome involves excessive firing of motor neurons causing lumbar+thoracic muscle spasms, progressive axial stiffness and rigidity. What autoantibodies cause this?
Anti-GAD (100-500X greater than in type I DM)
Anti-amphiphysin
What is the autoantibody in myasthenia gravis? What endocrine disease is MG associated with?
Anti-acetylcholine receptor (Anti-AChR).
Associated with thymoma/thymic hyperplasia.
HLA-B8/DR3 association
What are some markers for granulomas?
ACE 1,25-dihydroxyvitamin D3 osteopontin IFN-gamma TNF-alpha
What is the name of the syndrome that is an acute form of sarcoidosis presenting with bilateral hilar adenopathy, erythema nodosum, arthritis/arthralgia? Typically self-limited (lasts approximately 3 months) and treated with NSAIDs alone.
Lofgren’s syndrome
Class I region of chromosome 6 has classical (A,B,C) and nonclassical (E, G, F) HLA genes. What do HLA-G and F do?
HLA-G and F are expressed on the extra villous trophoblast. Their role is to protect the fetus from maternal immune rejection.
Fill in the blank: after birth, levels of maternally derived IgG in the baby rapidly decline and reach a nadir of ~400mg/dL at _____ months.
3 to 6
represents physiologic hypogammaglobulinemia
Which mitogen stimulates both B and T cell proliferation?
- Phyothemagglutinin
- Pokeweed mitogen
- concanavalin A
Pokeweed Mitogen
What does RAC2 deficiency do?
Ras-related C3 botulinum toxin substrate 2 (RAC2) deficiency: RAC facilitates actin cytoskeleton regulation; therefore, deficiency causes impaired adhesion and chemotaxis; clinically resembles LAD 1; transmission is autosomal dominant
When matching HLA alleles, which of the following is usually considered “permissable” to be mismatched and still have good outcomes?
a. HLA-A
b. HLA-B
c. HLA-C
d. HLA-DRB1
e. HLA-DQB1
e. HLA-DQB1
Therefore, HCST outcome from an 8/8 matched donor at HLA-A, -B, -C, and -DRB1 is associated with equally good outcomes as 10/10 matched.
The lipocalin family of proteins includes which animal/insect allergens?
Dog (Can f1, f2, f4 with f1 being the major allergen)
rat (Rat n1)
mouse (Mus m1)
horse (Equ c2)
cow milk (Bos d2 and d5; Bos d5 is beta-lactoglobulin)
rabbit (Ory c1)
cockroach (Bla g4)
