Term
| Molecular genetic control of IgE Synthesis |
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Definition
1. Initially, all B cells produce IgM
2. B cells switch isotype and retain their original antigenic specificity
3. IgE prodcution is triggered by soluble factors and cell surface interactions
4. DNA is spliced and rejoined (deletional switch recombination/class switching) |
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Term
| What are the 2 signals that are required to stimulate IgM-bearing B cells to undergo heavy-chain switching to produce IgE? |
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Definition
1. First signal: IL4 or IL13 (induce B cell transcription of germ-line mRNA for IgE)
2. Second signal: physical association of CD40 (on B cells) with CD40L(on T cells). CD40L aka CD154. This causes deletional class switch recombination. |
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Term
1. IgE levels in childhood
2. What is the T1/2 of plasma IgE?
3. What is the T1/2 of mast cell-bound IgE? |
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Definition
1. IgE levels increase from birth to age 10; preschool levels do not correlate well with levels at older ages
2. 1-5 days
3. 2 weeks |
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Term
1. IgE deficiency in humans is assoc with what type of infxns and diseases?
2. Effects of omalizumab tx on anaphylaxis and risk for infection |
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Definition
1. Familial IgE deficiency: Recurrent sinopulm infections and autoimmune diseases
2. They develop anaphylaxis and slight increased risk of geohelminth infxns (Brazilian study) |
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Term
| Name 7 conditions assoc with increased IgE levels |
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Definition
1. infections with orgs having superantigens
2. Parastitic infxns
3. non-parastic infxns (HIV, TB, candida)
4. Tobacco smoking
5. Cutaneous diseases (bullous pemphigoid)
6. GVHD
7. Neoplasms (Hodgkin's) |
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Term
| Name 4 immundeficiency diseases assoc with increased IgE |
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Definition
1. Hyper-IgE syndrome
2. Netherton's disease (cutaneous ichthyosis)
3. Wiskott-Aldrich Syndrome
4. IPEX |
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Term
| Which allergic/resp conditions are assoc with increased IgE? |
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Definition
1. Atopic dermatitis
2. ABPA
3. Asthma: atopic & non-atopic
4. Persistent wheezing in children
5. Airway hyperresponsivenes
Note: evidence confirms a relationship btwn IgE and pathogenesis and symptoms of resp disease |
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Term
| Local IgE Production: Where does it occur? |
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Definition
1. Nasal mucosa (in AR and NAR)
2. Broncial mucosa: mostly in asthmatics, regardless of stopic status
3. Adenoids
4. Nasal polyps |
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Term
| What is the effect of allergen season on nasal IgE synthesis? |
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Definition
| Cells expressing RNA for IgE increase during the allergen season |
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Term
2. Is there evidence that NAR is actually allergic?
2. What was found with regard to nasal challenge? |
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Definition
1. Yes
2. 22% of NAR pts had sIgE to dust mite; 54% had reacted on nasal challenge with dust mite |
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Term
| What is the evidence for local IgE production and asthma? |
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Definition
1. Local IgE production might be more important than circulating IgE in severe asthma.
2. Lung tissue from pts with fatal asthma found increased FCeRI cells in lamina propria (most of them were mast cells---none were eosinophils) |
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Term
True or False:
1. Crosslinking of FceRI leads to mast cell/basophil degranulation.
2. IgE increases survival of mast cells.
3. Monomeric IgE does not trigger mediator release.
4. There is a log-linear relationship btwn IgE levels and FceRI expression. |
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Definition
1. True
2. True (via IL6)
3. False (it can)
4. True |
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Term
CD23 (FceRII, aka low affinity receptor:
What is its function? |
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Definition
1. Regulation of IgE synthesis
2. Antigen capture for presentation
3. Growth and differentiation of B cells |
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Term
| FceRI (high affinity) IgE receptor expression in asthma |
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Definition
1. FceRI is increased in asthmatics vs controls.
2. FceRI expression is higher in atopic asthmatics and non-atopic asthmatics as compared to non-atopic controls. |
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Term
| What are the biologic effects of omalizumab? |
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Definition
| 1. Decreased basophil FceRI expression (occurs as early as Day 7!) |
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