Term
Recall that B cells are capable of isoptype switching in response to Th cytokines.
What are the different IgH (i.e. heavy chain) isotypes corresponding to different C regions in these BCRs and what are their basic functions? |
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Definition
1) Mu (IgM)
(Classical complement pathway)
2) Delta (IgD)
(rare, but involved in enhancing immune surveillance and basophil activation with inflammatory antimicrobial agents)
3) Gamma 1-4 (IgG)
(Neutralize microbes and toxins, Opsoniztion, antibody-dependent cellular toxicity (ADCT), Neonatal immunity, Feedback inhibition of B cell activation
4) Alpha 1 and 2 (IgA)
(Mucosal immunity: IgA secretion in GI and Respiratory tracts to neutralize microbes and toxins)
5) IgE
(Antibody-dependent cellular cytotoxicity (ADCC) by eosinophils, Mast cell degranulation [immediate hypersensitivity reactions]) |
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Term
| Why is IgM referred to as the "antigen sponge" Igh, and what is its primary effector function? |
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Definition
Recall, IgM is the FIRST chain to be produced by immature B-cells following antigenic stimulation (exists as pentamer that held held together by "J-chain" protein).
IgM has multiple antigenic binding sites, leading to high AVIDITY ("sponge-like")
Clustering of Fc's in IgM allow excellent COMPLEMENT DEPOSITION (associates with J-chain in secreted form). |
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Term
| Which Igh isotype has the longest half-life and what is its primary effector functions? |
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Definition
The 4 different IgG gene products have the longest half-lives (arose b/c of gene duplication). Recall, IgG release in seen in T-cell-dependent B2 cells, primarily during SECONDARY immune responses.
1) ONLY Ig isotype to cross from mother to fetus, mediated by Bramble (Fc) receptor, which concentrates maternal IgG and transports it to fetus.
2) Classical complement pathway Activation
3) Opsonization for phagocytosis by macrophages and neutrophils
4) ADCC by NK cells
5) Feedback inhibition of B-cells
6) Neutralization of microbes and toxins
2) |
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Term
| Why might mutations in the "Bramble" receptor be of clinical concern in a subset of women? |
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Definition
| In PREGNANT women, this Fc receptor is critical for IgG concentration and transmission of immunity to the fetus. |
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Term
How is IgE kept at low levels in the serum under normal conditions, but activated in an allergic response?
How does this relate to genetic predispositions to allergies? |
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Definition
1) Kept low in the serum by Mast Cells through Fc-epsilon-R1 (high affinity version)
2) Cross-linking IgE with antigens results in Mast Cell degranulation, immediate hypersensitivity and inflammation.
3) Genetic predispositions usually map to MHC (presentation efficacy) or T-cell repertoire (recognition efficacy) |
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Term
| Why might a defect in Mast Cell Granulation/Degranulation lead to abundant allergic response? |
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Definition
| Mast Cell Degranulation prevents the cell from keeping IgE levels low and preventing cross-linking through interactions with the Fc-epsilon-R1. |
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Term
| Why might you be concerned if a fetus cannot receive milk from the mother? |
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Definition
This is how IgA is usually transmitted (it is made by plasma cells in the mammary glands and matures there).
Remember, early vaccination depends upon the ability of a newborn to respond with IgG vs. IgA. You don't want to vaccinate until the child has started making their own antibodies (around 3 months after birth) |
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Term
| Where is IgA produced and how does it pass through epithelial cells into mucosa to transition into its secretory form? |
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Definition
1) GALT and Mammary glands (Switch recombination of B-cells is induced by TGF-b)
Recall, IgA is low in the serum, but abundant in mucosal secretions and milk.
2) poly-Ig receptor!
Associates in plasma cell (PC) with J-chain forms dimers that can pass through epithelial cells into mucosa by binding to poly-Ig receptor, which is cleaved to form the secretory component (SC).
A complex of cleaved poly-Ig/IgA is released to neutralize microbes and toxins |
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Term
Define
1) B-cell isotype
2) Allotypic Determinant
3) Idiotypic Determinant |
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Definition
1) C region differences among L and H Ig chains. Kappa versus lamba light chains, mu vs. gamma heavy chains.
2) Natural population differences among Igh (heavy) chain genes (Ig genes show allelic exclusion)
3) AA differences that result in antigenic specificity differences between two antibody's' combining sites with antigen (molecule-specific!). |
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Term
| What are the 2 major Fc Receptor roles? |
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Definition
Delivery and Attachment of Ig molecules!
1) Deliver Ig to correct site (Brambel for IgG and poly-Ig for IgA)
2) Attach to cells of innate immune response (phagocytes for IgG, Mast cells for IgE, NK cells for IgG). |
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Term
| What happens to IgD after mature B-cells reach the germinal centers of lymph nodes? |
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Definition
Recall, IgD and IgM are expressed on the surface of mature B-cells.
At germinal centers, B-cells encounter antigens and undergo T-cell-dependent rearrangements in the CDRs.
IgD is lost and IgM begins to be secreted. |
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Term
| What portion of Antibodies allow them to bind to cells of the adaptive and innate immune systems? |
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Definition
The Fc region!
This region is also what determines Ab isotype. |
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Term
| What innate immune cells utilize antibody-dependent cellular cytotoxicity (ADCC), linking to the adaptive immune system. |
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Definition
NK cells!
Remember, they express Fc, which can recognize IgG antibodies. They then inject perforin into infected cells. |
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Term
| Which Antibody isotopes are involves in complement deposition |
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Definition
| Primarily pentameric IgM, but IgG also if many of them are cross-linked at the membrane. |
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Term
| What is "Type 1 Hypersensitivity"? |
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Definition
| Antigens cross-link IgE antibodies, leading to Mast cell degranulation and inflammation (usually mapped to MHC or to T-cell repertoire). |
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