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Allergy and immunology
Terms in this set (33)
Characteristics of adaptive immune system
Specificity: Epitopes on molecules are recognized by lymphocytes.
Diversity: Diverse lymphosite reservoir
Memory: Subsequent exposure results in more rapid and pronounced response.
Self-regulation: Returns to basal homeostasis after attach.
Nonreactivity to self/tolerance.
Thymus and bone marrow
Thymus = site of T cell maturation. Highly vascularized with efferent lymphatics to mediastinal LNs. Only mature T-cells exit the thymus and enter peripheral circulation.
Bone marrow = site of B-cell maturation. Proliferation and maturation of cells is stimulated and controlled by cytokines. Contains plasma cells which are responsible for secretion of antibodies.
Lymph node anatomy and function
Site of adaptive immune response of antigens delivered to lymphatic system.
Cortex contains lymphoid follicles rich in B-cells.
Paracortex has mostly T-cells and antigen presenting cells.
Medulla has T cells, B cells, and plasma cells
Humoral vs cell-mediated immunity
Humoral = Mediated by B cells and their secreted antibodies.
Cell-mediated = mediated by T cells and their secreted cytokines
T-cell CD markers
CD2 and CD3 are on all T-cells.
CD4 found on T helper cells
CD8 on cytotoxic/suppressor T cells
TH1, TH2, and TH17
Derived from naive CD4 T helper cells.
TH1 = Participate in microbial immunity. Produce IL-2 and IFN gamma and inhibit B cells.
TH2 = Participate in allergic responses. Produce IL-4, 5, 6, and 10 to stimulate B cells. Involved in recruitment and activation of eosinophils.
TH17 = Respond to infections with specific bacteria and fungal species. Involved in recruitment of neutrophils and create a profound local inflammation. Appear to be involved in autoimmune conditions such as MS
CD markers of B cells
CD 19 and CD21
Natural killer cells
large, granular lymphocytes that are neither T or B cells.
Function in innate immunity. Can lyse and eliminate virus-infected cells and tumor cells.
Major histocompatibility complex proteins
Specialized proteins responsible for displaying antigens for recognition of antigens by and presentation of peptides to T cells.
Principle function is to bind fragments of foreign protein thereby forming complexes that are recognized by T-cells.
MHC class 1 are on nearly all nucleated cells. Interact with CD8+ cells
MHC class 2 are on B-cells, macrophages, dendritic cells, or endothelial cells. Interact with CD4+ cells
IL-2, IL-3, IL-4
IL-2: Responsible for T-cell clonal expansion. Derived from T-cells. Promotes proliferation and differentiation of other immune cells.
IL-3: Promotes development and expansion of immature bone marrow elements. Promotes mast cell proliferation, eosinophil activation. Derived from CD4+ T-cells.
IL-4: Stimulates B-cell isotype switching to IgE and stimulates development of TH2 cells from naive CD4+ cells.
IL-5, IL-10, IL-13
IL-5: Activates eosinophils and links t-cell activation and eosinophilic inflammation. Stimulates growth and differentiation of eosinophils and stimulates eosinophil chemotaxis. Derived from CD4+ T-cells.
IL-10: Inhibits activated macrophages and inhibits cytokine synthesis. Maintains homeostatic control. Derived from activated macrophages and CD4+ T cells
IL-13: Functions similarly to IL-4. induces adhesion molecules at sites of allergic inflammation contributing to increased populations of eosinophils and lymphocytes.
Anatomy of antibody
Composed of 4 polypeptide chains connected with disulfide bonds.
Two identical light polypeptide chains - kappa or lambda.
Two identical heavy chains that bind to host tissues and determine Ig class.
C (constant) region or Fc fragment and Variable region at N terminal end (Fab fragment)
Active against viruses, bacteria, parasites, and some fungi.
Only Ig that crosses placenta and provides 3-6 months of immunity after birth.
Fixes complement through classical pathway.
Involved in early immune response.
Fixes complement through classical pathway
Predominant Ig in seromucinous secretions.
Dimer with a secretory component that prevents proteolysis by digestive enzymes.
Type 1 hypersensitivity
Due to crosslinking of IgE molecules on mast cells which causes degranulation of mast cells and release of histamine.
Type 2 hypersensitivity
Hemolytic anemia, transfusion reactions, Goodpasture, Myasthenia gravis.
IgG or IgM mediated.
Antibodies react with antigens on cell surface leading to complement activation.
Type 3 hypersensitivity
Immune complex-mediated hypersensitivity
Onset of symptoms can be delayed by days.
Serum sickness, PSGN, Angioedema.
Immune complexes form, usually with IgG. Complexes deposit in tissues causing activation of complement and acute inflammation reaction
Type 4 hypersensitivity
Acute and chronic contact dermatitis.
TB, sarcoid, candida
Sequence of events in immediate hypersensitivity reactions
Exposure to antigen in atopic individuals stimulates naive T-cells to differentiate into Th2 effector cells.
Activated T-cells secrete IL-4 promoting B cells to produce IgE-producing cells.
IgE binds to Fc sites on circulating basophils and mast cells.
Reexposure causes cross-linking of IgE and release of preformed mediators in mast cells and basophils. Also stimulates production of new inflammatory mediators through arachadonic acid metabolism (Leukotrienes, prostaglandins, platelet-activating factor)
Phases of allergic response
Early phase is primarily histamine mediated and occurs within 5-10 minutes of exposure.
Late phase is delayed and is mediated by newly generated mediators of inflammation (leukotrienes and eosinophils). Begins 4-8 hours after exposure and can last 24+ hours.
Spring = tree pollen (Feb - May)
Summer = grass pollen (April - August)
Fall = ragweed, weed pollen (July - first frost)
Prick/puncture allergy testing
Most widely used allergy testing method worldwide.
Drop of antigen is placed on the skin and a small needle penetrates into the epidermis through the drop.
Measure the reaction after 20 minutes.
Quick, easy, and safe with good consistency. However, only qualitative and can have false negatives if low degrees of sensitization
Intradermal skin testing - Single dilutional
Using a small guage needle, antigen is injected intradermally. Allow 20-30min and measure reaction.
Highly sensitive, but can be poorly specific with higher likelihood of false positives.
Danger of anaphylaxis**
Intradermal dilutional testing (IDT) AKA skin endpoint titration
Fivefold dilutions are created and injected beginning with very dilute. Start with 1cc of concentrated solution and add 4cc of saline (this is #1). Then use #1 to further dilute until you reach #6. Start with #6 when testing.
When injecting, create a 4mm wheal. Expect it to expand to 5mm naturally. Any wheal greater than 7mm is considered positive.
If no significant result after 10 minutes, use next stronger dilution until you get a result. The endpoint is the dilution that initiates progressive positive whealing. To be progressively positive, must be 2mm greater than the previous.
Use of H1, H2 blockers, TCAs, Montelukast, oral and nasal steroids, beta blockers on allergy testing
H1: Suppress wheal and flare - Dont take for 48-72 hours.
H2: Wheal suppression for 7 days.
TCAs: Have antihistamine properties. Avoid for 7 days.
Montelukast: Controversial, likely no effect, but can also hold for 7d.
Steroids (oral or topical): No effect.
Beta blocker: Cause resistance to epinephrine and shouldn't be used. Can cause unopposed alpha antagonism and hypertensive crisis.
RAST/in vitro allergy testing
Measures antigen-specific IgE levels.
Eliminates subjectivity, eliminates drug effects on the skin.
Permits safe testing on patients on beta blockers.
Provides quantitative assessment to determine antigen sensitivity.
First generation H1 blockers
Highly lipophilic and cross BBB -> sedation
Highly anticholinergic and may have tachyphylaxis (Decreased efficacy with use).
2nd generation H2 blockers
Loratadine, fexofenadine, citirizine.
Lipophobic, so don't cross BBB as readily with less sedation.
Little or no anticholinergic effects and no tachyphylaxis.
Stabilizes mast cell membranes and inhibits degranulation and release of histamine.
No systemic absorption, lipophobic.
Available in topical form for both eyes and nose. Must be given 3-4x/day
Needs to be used prophylactically.
Immunotherapy for allergies
Either subcutaneous or sublingual delivery.
Likely induces Treg production. Increased IL-10 and IL-12 and decreased IL-4 and IL-5.
Initially, see a rise in IgE, but over time, see decreased specific IgE levels with increased specific IgG4 levels agains the allergen.
Generally requires 3-5 years of treatment to have persistent improvement after stopping treatment.
Subcutaneous immunotherapy (SCIT)
Injection of sequentially greater concentration of allergens to induce hyposensitization and immune tolerance. Inject highest dose possible that doesn't cause systemic effects (maintenance dose).
After starting, increase dose up to twice a week to get to this maintenance dose.
Can often stop therapy after 3-5 years of receiving maintenance dosing.
Expect a local reaction of 3-4 cm after injection.
Sublingual immunotherapy (SLIT)
Administer antigens orally or as drops under the tongue. Dose may be fixed or escalating
Often not covered by insurance
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