Allergy and Immunology Flashcards
Describe the innate immune system and its 3 main components of the innate immune system?
rapid-acting, non-specific no memory with complement, macrophages, and NK cells.
what are the two parts of the adaptive immune system?
- Humoral: B-cells, plasma cells, and immunoglobulins
- Cell-Mediated: T-cells, activated macrophages and NK cells.
what are the components of myeloid cells?
- Granulocytes (neutrophils, basophils, eosinophils)
- Antigen-Presnting cells (monocytes/macrophages/dendritic cells)
- Others: mast cells, erythrocytes, platelets
where are MHC cells located?
chromosome 6
what are class I HLA antigens?
- these are types of MHC to differentiate self vs. nonself
- Class I includes HLA-A/B/C on most nucleated cells
- Present non-self material to CD8 T cells and play role in transplant rejection, neoplasms, and viral infections
what are class 2 HLA antigens?
- HLA-DP/DQ/DR
- On antigen-presenting cells
- mediate reaction between macropahges, T and B-cells
- CD4 cells recognize material presented only on Class 2 HLA antigens
what are class 3 HLA antigens?
consist of a few cytokines like TNF and lymphotoxin, some complement structures
what are the CD markers for T-cells/
CD2, CD4, CD4 and CD8
What are the types of CD4 cells?
- TH1 - Activates CD8 cells and leads to cell-mediated immunity
- TH2 - activates B cells to produce antibody and leads to humoral immunity
- Th17- plays in role in immunity against fungi, bacteria, and in auto-immune disorders
what is the role of CD8 T-cells?
cytotoxic T cells, important against viruses and neoplastic cells.
what are natural killer T-cells?
they have the CD16 and CD56 like natural killer lymphoid cells but has a MHC molecule of CD1 which recognizes primarily lipids and glycolipids
describe the B-cell lineage and diseases associated in the blood and bone marrow?
describe the B-cell lineage and diseases associated in the periphery?
describe the B-cell lineage and diseases associated in the bone marrow?
what are eosinophils involved with?
allergic reactions and immunologic defense of parasites
what are the 3 antigen-presenting cells?
- b-cells (most specific)
- monocytes/macrophages - eat opsonized cells, stimulate interleukin 1, which stimulates T-cells
- Dendritic cells - ingest pathogen, change conformation, travel to lymph node and activate lymphocytes
key things about IgG?
- contains kappa and lambda light chains
- crosses placenta
- activates complement
- Main antibody in serum
Key things about IgA?
- main igG in secretions
- Has 2 immunoglobulins (dimer) with J chain and secretory component
- Main igG secreted in breast milk
- Does not activate complement
Key things about IgM?
- 1st immunoglobulin produced in infection
- pentamer
- Useful in dx of recent illness
- Activates complement
what are the 3 complement pathways and leads to?
- classical pathway
- Lectin (mannose-binding) pathway
- Alternative pathway
- These all lead to the common terminal pathway (membrane attack complex)
what function do the 3 complement pathways all perform?
- opsonizing target cells with C3b
- inducing more inflammation with anaphylatoxins C3a, C4a, and C5a
- forming the “membrane attack complex”
describe the classical complement pathway?
- immunoglobulin (IgG/IgM) activate the classical pathway.
- C1 complex (q,r,s subunits) initiates response when a C1q subunit attaches to the antibody in an antigen-antibody complex
- C1q binds to Fc portion at least 2 igGs for 1 IgM.
- Binding activate C1q
- Activated C1q cleaves C2 and C4 forming C4b2A (c3 convertase)
- Activates C3
Describe the common terminal pathway?
- C3 when combined with either factor C4b2a or factor b activates C5
- Cause formation of C5-C9 MAC
- Mac pokes hole in bacterial cell membranes and cause the bacteria to lyse
What condition is associated with C1 inhibitor? clinical presentation?
- Hereditary angioedema is an autosomal dominant disorder caused by a decrease in C1 inhibitor activity?
- recurrent non-pitting edema with each episode lasting 1-3 days
- NO ITCHING or urticaria
- Attacks may include laryngeal obstruction and affect GI tract (abdominal pain)
- minor trauma from dental procedures can precipitate attacks
how would you diagnose hereditary angioedema?
- First, check C4 levels, which would be low
- Check C1-INH functional assay
- If C4 and C1-INH low, type I HAE
- If C4 low, and C1-INH normal, it is due to non-functional C1-INH, then it’s type 2.
what is the treatment of hereditary angioedema?
- Epinephrine is not effective
- Androgens (danazol) increase C1-INH levels and decrease swelling episodes (preventative med)
- Can use kallikrein inhibitor and bradykin receptor antagonist for acute attacks
what does C1, C2, or C4 deficiencies cause?
- decreased activation of complement via the classical pathway.
- Can have recurrent sinopulmonary disease with encapsulated bacteria
- increased incidence of rheumatoid diseases (SLE)
what do C3 deficiency presentation?
C3 is complete absence, results in severe pyogenic (bacterial) infections
how do you diagnose C5-C9 MAC deficiency? what is the presentation?
- called terminal complement deficiency
- Results in increased Neisseria meningococcal/gonococcal infections (especially meningitis/septicemia)
- Screen for terminal complement deficiency with CH50
what does CH50 assay measure?
- measures total complement hemolytic activity of the classical pathway
- CH50 assay levels can still be normal even if C3 or C4 levels are lower
- Good screen for complement deficiencies
what are the 3 conditions that result in immune complexes that are INCREASED in the seurm?
- Hepatic vein thrombosis (Budd-Chiari)- decreased clearance
- PNH - - results in decreased binding
- SLE - results in a decreased amount of CRI on RBCs
what are the four types of hypersensitivities?
- Type I: IgE mediated - immediate (anaphylactic, atopic)
- Type II: IgG or IgM mediated - cytotoxic
- Type III: immune complex (antibody-antigen) mediated
- Type IV: Cell-mediated - delayed-type
Describe the classic response of type I hypersensitivity acute response? mechanism?
- acute phase of immediate IgE hypersensitivity reactions within 1 hour after exposure
- allergen reacts to FAB portion of IgE causing mast cell stimulation, releasing histamine
- Measure tryptase to confirm anaphylactic reactions
Describe the histamine receptors?
- H1: receptor activation causes the wheal and flare, bronchoconstriction and puritis
- H2: receptor activation causes increased gastic acid
- H3: activation causes decreased histamine synthesis and release (negative feedback)
- H4: immunomodulatory effect and affects eosinophil and mast cell recruitment
Describe the late-phase response of type I hypersensitivity? mechanism?
- late phase response occurs 3-12 hours after acute response, lasting hours to days.
- Caused by an immediate IgE reaction stimulating synthesis of cytokines, recruitment of eosinophils and basophils
how do you diagnose anaphylaxis?
1 of 3 criteria of either:
- Sudden onset of skin/mucosal tissue with either sudden respiratory symptoms or hypotension
- 2 or more following exposure of skin/mucosal involvement, respiratory involvement, GI symptoms, hypotension
- Hypotension after exposure to a known allergen.
what is the tx for anaphylaxis?
- Epinephrine 1:1000 IM
- H1 and H2 antiganoists (diphenhydramine/cimetidine)
- steroids may help prevent delayed late-phase reactions
- If significant hypotension, Epi 1:10K IV
what do you need to watch out for in treating anaphylaxis?
- Epinephrine affects alpha and beta-adrenergic systems.
- If the patient is on beta-blockers, these are relatively contraindicated in patients at risk for anaphylaxis
- Can give glucagon or vasopressin injections after epinephrine is given
what are type 2 hypersensitivity reactions?
- Type 2 reactions occur when an IgG or IgM antibody binds to a fixed tissue antigen or cell receptor creating autoantibodies.
- Binding of antibody results in target cell destruction via complement
what are examples of type 2 reactions involving fixed tissue antigens?
- Goodpasture - target antigen is basement membrane of lung and kidney
- Myasthenia gravis - AcH receptors on muscle cells
what type hypersensitivity reactions are vasculitis?
type 3
what are type 3 hypersensitivity reactions?
- antibody (usually IgG) reacts with target antigen to form immune complexes that precipitate and activate complement with subsequent small vessel inflammation and necrosis.
- start to see more antigen than antibody then IC form and quickly cleared
- IC interlace and become bigger/less soluble, precipitates in small vessels
- Complement is activated, cytokines, see leukocytoclastic vasculitis (hemorrhagic indurated lesions)
what are the 2 models for what happens clinically in type 3 HSN?
- Serum sickness with systemic activation, within 1-2 weeks, necrotic vasculitis
- Arthrus reaction - IC at injection site, within 4-12 hours, painful indurated lesions appears and may progress to sterile abscess
what is the difference between type i and type IV HSN?
- Type 1 is food and occurs earlier
- Type 2 - contact dermatitis, tuberculin sensitivity, peaks 24-72 hours
what is the difference between type 2 and type 5 HSN?
- type V has autoimmune IgG has a stimulatory effect on receptor while type 2 has a destructive effect.
- Graves is type 5
what causes cholinergic urticaria?
- precipitated by heart
- presents as punctate lesions that are pruritic.
what is chronic urticaria?
hives last >6 weeks, resolves to minute to hours or migrates to other areas. check for thyroid antibodies.
what is urticarial vasculitis?
urticaria that lasts >24 hours in a fixed location, dx ith skin biopsy.
what is vasomotor rhinitis?
sneezing attacks followed by nasal congestion on exposure to a stimuli
what is rhinitis medicamentosa?
rebound congestion caused by prolonged use of vasoconstricting nasal drops (phenylephrine or oxymetazoline). Treat by stopping drug.
what is atrophic rhinitis?
atrophy of nasal mucosa, crusting, fetor, loss of smell.
patients are typically younger and from warmer climates
some are colonized by klebsiella ozanae
treat with nasal saline lavage
what is the tx of rhinitis?
antihistamines is first line
intranasal steroids are the most effective for allergic rhinitis
what are the first generation H1 blockers? Side effects?
- diphenhydramine, chlorpheniramine, and hydroxyzine
- cross BBB, interacts with acetylcholine receptors causing blurry vision, dry mouth, and urinary retention
- Avoid in elderly
which rhinitis medications can you use in pregnancy?
- H1: chlorpheniramine, diphenhydramine, tripelenamine
- H2: lortaradine and cetirizine
- monteleukast, cromolyn, and budenosine (preferred)
why should you avoid oral decongestants in pregnancy?
- can cause congenital malformations like gastroschisis and small intestine atresia.
- Gastroschisis is where baby’s small intestines grow outside the abdomen through hole near belly button.
what are the 2 major components of assessing asthma control?
impairment (symptoms) and risk (exacerbations)
step up therapy for asthma for which of the following (simple)?
- symptoms during the day>2x/week
- night time awakenings >2x/month
- ED visits/admissions >2x/year