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Questions and Answers
What is the primary purpose of using immunoassays?
What is the primary purpose of using immunoassays?
Which immunoassay method is typically used for the rapid detection of substances and is similar to a pregnancy test?
Which immunoassay method is typically used for the rapid detection of substances and is similar to a pregnancy test?
Which of the following is NOT a method of immunoassay?
Which of the following is NOT a method of immunoassay?
What role does the Fc receptor for IgA primarily play in the immune system?
What role does the Fc receptor for IgA primarily play in the immune system?
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Which of the following is a common method used in immunophenotyping?
Which of the following is a common method used in immunophenotyping?
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What is the primary function of neutralizing antibodies?
What is the primary function of neutralizing antibodies?
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Which type of antibody is primarily responsible for irreversibly binding to toxins in the blood and tissues?
Which type of antibody is primarily responsible for irreversibly binding to toxins in the blood and tissues?
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Which of the following antibodies helps prevent the attachment of microbes at mucosal surfaces?
Which of the following antibodies helps prevent the attachment of microbes at mucosal surfaces?
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Why are high affinity binding sites important for neutralizing antibodies?
Why are high affinity binding sites important for neutralizing antibodies?
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What characteristic of IgM antibodies makes them considered weakly neutralizing?
What characteristic of IgM antibodies makes them considered weakly neutralizing?
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What is a specific example of a neutralizing antibody and its function?
What is a specific example of a neutralizing antibody and its function?
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How do neutralizing antibodies interact with microbial toxins?
How do neutralizing antibodies interact with microbial toxins?
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Which type of antibody is less effective in neutralization due to weak affinity?
Which type of antibody is less effective in neutralization due to weak affinity?
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What role do erythrocytes (RBCs) play in the removal of immune complexes?
What role do erythrocytes (RBCs) play in the removal of immune complexes?
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Which cells are involved in the elimination of circulating immune complexes in the kidney?
Which cells are involved in the elimination of circulating immune complexes in the kidney?
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What activates eosinophils in the context of anti-parasite defense mechanisms?
What activates eosinophils in the context of anti-parasite defense mechanisms?
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How do circulating immune complexes potentially damage blood vessels?
How do circulating immune complexes potentially damage blood vessels?
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Which mechanism is primarily involved in allergies and asthma?
Which mechanism is primarily involved in allergies and asthma?
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What is the consequence of not removing circulating immune complexes from blood?
What is the consequence of not removing circulating immune complexes from blood?
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What triggers degranulation in mast cells during an allergic reaction?
What triggers degranulation in mast cells during an allergic reaction?
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Which factor primarily facilitates the clearance of immune complexes from the bloodstream?
Which factor primarily facilitates the clearance of immune complexes from the bloodstream?
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What is the role of anti-F protein antibodies in relation to Streptococcus pyogenes?
What is the role of anti-F protein antibodies in relation to Streptococcus pyogenes?
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Which class of antibodies is required to activate the classical pathway of complement via antigen-antibody complexes?
Which class of antibodies is required to activate the classical pathway of complement via antigen-antibody complexes?
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Which IgG subclasses are known for exposing the C1q binding site even without antigen binding?
Which IgG subclasses are known for exposing the C1q binding site even without antigen binding?
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What happens when C1q attaches to pentameric IgM?
What happens when C1q attaches to pentameric IgM?
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Which option best describes the role of C3a and C5a in the immune response?
Which option best describes the role of C3a and C5a in the immune response?
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What defines the difference between C4A and C4B in their roles?
What defines the difference between C4A and C4B in their roles?
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What is the minimum requirement for IgG to activate C1q?
What is the minimum requirement for IgG to activate C1q?
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Which statement about haplotypes is true?
Which statement about haplotypes is true?
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What is a key function of the membrane attack complex (MAC) in the immune response?
What is a key function of the membrane attack complex (MAC) in the immune response?
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What is a characteristic of monoclonal antibodies?
What is a characteristic of monoclonal antibodies?
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Which of the following types of antibodies is formed from various epitopes?
Which of the following types of antibodies is formed from various epitopes?
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What is the purpose of using fluorescent-labelled antibodies in flow cytometry?
What is the purpose of using fluorescent-labelled antibodies in flow cytometry?
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Which advancement represents the evolution of monoclonal antibodies?
Which advancement represents the evolution of monoclonal antibodies?
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Which of the following is NOT a characteristic of monoclonal antibodies?
Which of the following is NOT a characteristic of monoclonal antibodies?
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What are chimeric antibodies primarily composed of?
What are chimeric antibodies primarily composed of?
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Which drug is an example of a therapeutic monoclonal antibody?
Which drug is an example of a therapeutic monoclonal antibody?
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What does immunophenotyping accomplish in the context of flow cytometry?
What does immunophenotyping accomplish in the context of flow cytometry?
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Among the following, which is the most advanced type of monoclonal antibody?
Among the following, which is the most advanced type of monoclonal antibody?
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Which characteristic defines polyclonal antibodies compared to monoclonal antibodies?
Which characteristic defines polyclonal antibodies compared to monoclonal antibodies?
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Which immune cells primarily respond to inflammatory signals?
Which immune cells primarily respond to inflammatory signals?
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What effect does FcɣRIIB1 have on mast cells and B cells?
What effect does FcɣRIIB1 have on mast cells and B cells?
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What is the role of FcɣRIIA variants in the context of IgG2?
What is the role of FcɣRIIA variants in the context of IgG2?
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How does the binding of C-reactive protein (CRP) influence the immune response?
How does the binding of C-reactive protein (CRP) influence the immune response?
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What type of receptor is FcɣRIII and its main function?
What type of receptor is FcɣRIII and its main function?
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Which cells use FcɣRIII to exert their function?
Which cells use FcɣRIII to exert their function?
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What is the affinity level of FcαRI for monomeric IgA?
What is the affinity level of FcαRI for monomeric IgA?
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What characteristic is shared between FcɣRI and FcɣRII?
What characteristic is shared between FcɣRI and FcɣRII?
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What function do ITAM domains serve in the context of Fc receptors?
What function do ITAM domains serve in the context of Fc receptors?
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What is a primary consequence of the strong activation of complement by IgG2?
What is a primary consequence of the strong activation of complement by IgG2?
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Study Notes
Adaptive Immunity: B-Cell Mediated Immunity III
- Antibodies are soluble proteins produced by plasma cells.
- They are found in blood, lymph, and mucosal surfaces.
- Antibodies bind to extracellular pathogens/antigens.
- Antibodies directly disable pathogens/antigens and mark them for destruction by complement and/or phagocytes.
- Each antibody is specific, binding to one antigen or a small number of very similar antigens.
Typical Antibody Structure
- Antibodies have four polypeptide chains: two heavy and two light chains.
- Disulfide bonds link the chains.
- Light chains are either κ or λ.
- The N-terminus is at the top of the structure.
- The C-terminus is on the bottom.
- Antigen-binding sites are formed by the variable regions (VL + VH) of the light and heavy chains, respectively.
- The variable region's amino acid sequence determines antibody diversity and specificity.
- The hinge region is flexible, allowing for diverse antigen-binding abilities.
- Proteolytic cleavage can separate the antibody into Fab (two antigen-binding fragments) and Fc (crystallizable) fragments.
- Fc fragments are crucial for cell-receptor (FcR) binding and complement activation.
Immunoglobulin Domains
- Immunoglobulin domains are compact, stable, folded structures.
- They consist of approximately 100-110 amino acids.
- Two β-sheets connect via loops.
- Disulfide bonds and hydrophobic interactions stabilize the folding.
Variable Domains
- Variable domains have hypervariable regions (HVs) that contribute to antigen-binding specificity.
- Three HVs (complementarity-determining regions, CDRs) per light chain variable (VL) and heavy chain variable (VH) domain.
- These form the antibody's antigen-binding site.
- Framework regions (FRs) are structurally stable regions in the V domains.
Epitope (Antigenic Determinant)
- Epitopes are parts of an antigen that an antibody binds to.
- Antigens can be multivalent, having multiple epitopes, or multiple copies of the same epitope.
- Epitopes can be linear (contiguous amino acids) or discontinuous (noncontiguous amino acids).
Antigen-Binding Site Shapes
- Antibody binding sites can be pockets (for small, compact epitopes), grooves (for short, linear epitopes), or extended surfaces (for curved, globular epitopes).
Heavy Chain Constant Domains
- Heavy chains have constant (C) domains (either γ, μ, δ, α, or ε).
- These domains differ in location of disulfide bonds, carbohydrates, presence/absence of hinge regions and other structural characteristics.
- Antibodies can be IgG, IgM, IgD, IgA, or IgE, depending on the constant heavy chain region.
Antibody Affinity
- Affinity is the binding strength between an antibody and an antigen.
- Antibody affinity increases during the adaptive immune response because of somatic hypermutation.
- Antibody affinity maturation leads to stronger binding during the immune response.
- Affinity is determined by non-covalent attractions such as van der Waals forces, hydrophobic interactions, charge interactions, and hydrogen bonds, combined for a total binding affinity.
From BCR to Secreted Antibodies
- Secreted antibodies are produced from the same heavy-chain genes, with differences in RNA processing.
- This alternative processing allows for either membrane-bound or secreted antibodies.
IgM
- IgM is the first antibody class produced and secreted.
- IgM is found in blood and lymph.
- IgM has low affinity but high avidity (overall strength of binding to multiple epitopes on an antigen).
Secreted IgM
- Secreted IgM is a pentamer, containing 10 antigen-binding sites.
- Large size prevents easy entry to tissues but it has efficient complement activation properties.
IgG
- IgG is the most abundant blood-borne antibody.
- IgG has 2 high-affinity antigen-binding sites.
- IgG easily enters infected tissues.
Antibody Classes & Subclasses
- Each antibody class has different functions and properties based on the heavy chain constant regions.
- The tables provided in the notes (from pages 2-5) provide further details.
Dimeric IgA
- Produced by plasma cells in mucosal-associated lymphoid tissue (MALT).
- Found in gut, milk, tears, and saliva.
- Plays a crucial role in maintaining commensal populations, and prevents pathogen entry at mucous membrane locations.
Pentameric IgM & Dimeric IgA (Passive Immunity)
- Protect against microbes or toxins at mucosal surfaces and in the bloodstream.
- Maternal IgG crosses the placenta to provide passive immunity to the fetus.
- Breast milk provides dimeric IgA to newborns via the intestines.
Neutralizing Antibodies
- Prevent pathogen attachment to body cells.
- High-affinity binding sites are essential for neutralizing antibodies.
C'-Activating Antibodies
- Classical complement activation pathway is initiated by antigen-antibody complexes.
- IgM is a potent activator due to its pentameric structure.
- Some IgG subclasses (IgG3 and IgG1) can also efficiently activate complement.
Immune Complexes (ICs)
- Formed when antibodies bind to soluble multivalent antigens.
- Immune complexes can activate the complement system, leading to their removal by phagocytes.
- Removal is important to avoid them lodging in the basement membrane of small blood vessels, especially in the kidneys.
Circulating Immune Complexes in Kidney
- Immune complexes can damage kidney tissue (and other areas) through complement activation and deposition in glomeruli.
Anti-Parasite Defense Mechanisms
- Eosinophils and basophils play a role directly targeted at parasite destruction and elimination via IgE or IgG coating of the parasite.
Allergies & Asthma
- Allergens trigger a massive mast cell degranulation response that can lead to allergies and asthma.
Antibody Receptors (Fc Receptors)
- Fc receptors bind to the Fc region of antibodies.
- This binding can either activate effector cells or inhibit them in specialized immune situations.
- Some receptors are involved in antibody transcytosis or transport of antibodies across cells and tissues.
Polymeric Immunoglobulin Receptor (pIgR)
- Transports IgA and IgM across mucosal epithelial cells.
- This process is mediated by binding the J-chain on these molecules.
- The secretory piece of pIgR prevents antibody loss and allows them to function in the mucosal secretions.
FcyRI, FcyRII, and FcyRIII
- Activating Fc receptors for IgG are associated with cell activation, pathogen uptake & destruction by phagocytes; and antibody-dependent cell-mediated cytotoxicity (ADCC).
- Inhibiting Fc receptors of the IgG family moderate inflammatory response from effector cells.
Flow Cytometry
- Differentiates cells based on surface molecules and cytoplasmic structures that are labeled with fluorescent antibodies.
- Antibodies are used to tag particular cell surface molecules, which are identified and quantified by fluorescence labeling.
Evolution of Monoclonal Antibodies
- Monoclonal antibodies are produced through hybridoma technology.
- There are advancements in the development of chimeric, humanized and fully human forms.
Immunoassays
- Used for detection and quantitation of specific antigens.
- Immunoassays are based on antibody-antigen reactions.
- Examples include ELISA, lateral flow assays, and Western blotting.
Polyclonal Antisera vs. Monoclonal Antibodies
- Polyclonal antisera are mixtures of antibodies, each recognizing different epitopes on an antigen.
- Monoclonal antibodies are identical, specific for a single epitope.
Monoclonal Antibody Production
- A process used to produce a single type of antibody for a specific epitope.
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Description
This quiz covers adaptive immunity, specifically focusing on B-cell mediated immunity, including the structure and function of antibodies. Learn how antibodies operate against pathogens and explore their diverse binding capabilities. Test your knowledge about antibody specificity and the unique features of their structure.