PHARM 310: LEC 2 - Antibody Structure and Function

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Questions and Answers

What is the role of the Fc fragment of an antibody?

It determines the antibody isotype.

It binds directly to the antigen.

It contains the hypervariable regions.

It assists in opsonization. (correct)

Which of the following statements about the variable region of antibodies is true?

It is composed solely of constant regions.

It is the same across all antibody types.

It is exclusively found in the light chain.

It exhibits significant diversity due to gene recombination. (correct)

Which isotypes of antibodies are defined by having different heavy chain constant regions?

IgE and IgM

IgM and IgD

IgG and IgA

IgG, IgA, IgM, IgE, and IgD (correct)

Which enzyme cleaves antibodies into two Fab fragments and one Fc fragment?

Papain Signup and view all the answers

Which part of the antibody structure is referred to as the paratope?

The antigen-binding site Signup and view all the answers

What are the two isotypes of light chains in antibodies?

Kappa and Lambda Signup and view all the answers

Which statement correctly describes the C regions of antibodies?

They have little or no amino acid sequence diversity. Signup and view all the answers

What is the approximate molecular weight of one heavy chain of a typical antibody?

50 kDa Signup and view all the answers

What is the role of the RAG-1 and RAG-2 enzymes in immunoglobulin gene segment recombination?

They mediate the rearrangement of germline DNA. Signup and view all the answers

What describes the 'germline configuration' of immunoglobulin genes?

It is a fragmented organization that cannot be expressed in all cells. Signup and view all the answers

Which sequence is NOT part of the variables coded for by immunoglobulin genes?

P-persistent Signup and view all the answers

How do Recombination Signal Sequences (RSS) facilitate the process of immunoglobulin gene rearrangement?

They serve as positions for RAG cutting and joining. Signup and view all the answers

What is the significance of the 12/23 rule in immunoglobulin gene recombination?

It indicates the distance between two RSS types. Signup and view all the answers

Which domains increase diversity in immunoglobulin variable regions?

Hypervariable (HV) regions and junction regions. Signup and view all the answers

Which of the following statements about immunoglobulin constant and variable regions is true?

Constant regions do not require recombination for expression. Signup and view all the answers

What types of cells contain RAG-1 and RAG-2 enzymes?

Both B- and T-cells. Signup and view all the answers

What is a common characteristic of most antigens?

They often have multiple epitopes. Signup and view all the answers

Which type of bond is NOT typically involved in the interaction between organic macromolecules?

Covalent bonds Signup and view all the answers

In the context of DNA, what do exons represent?

The coding segments that code for proteins Signup and view all the answers

What role do introns play in eukaryotic cells?

They are non-coding sequences found within genes. Signup and view all the answers

Which statement best describes the 'Lock and Key' model in molecular binding?

It illustrates specific shape and compatibility between molecules. Signup and view all the answers

What is the significance of glycosylation in post-translational modification?

It involves the attachment of sugars to proteins. Signup and view all the answers

What is a characteristic of polypeptides that qualifies them as proteins?

They must be composed of more than 50 amino acids. Signup and view all the answers

Which of the following best describes the information carried by organic macromolecules?

It is expressed using weak noncovalent bonds. Signup and view all the answers

What is the role of differential mRNA splicing in B-cell development?

It results in the production of IgM and IgD from a single primary RNA transcript. Signup and view all the answers

Which statement is true regarding isotype switching in B-cells?

Isotype switching only involves the constant region without affecting V-region specificity. Signup and view all the answers

How does allelic exclusion impact B-cell development?

It prevents further V rearrangements after the first antibody is produced. Signup and view all the answers

What is the final form of IgM upon secretion from B-cells?

Pentamer Signup and view all the answers

What is the purpose of the hydrophobic MC region in immunoglobulins?

To anchor the Ig molecules into the cell membrane of B-cells. Signup and view all the answers

Which immunoglobulin is commonly responsible for immediate hypersensitivity reactions?

IgE Signup and view all the answers

What is the outcome of affinity maturation in antibodies?

The overall affinity of antibodies for the antigen increases. Signup and view all the answers

Study Notes

Antibody Structure

Antibodies are Y-shaped glycoproteins made of 4 polypeptide chains: 2 heavy (50 kDa each) and 2 light (25 kDa each) chains.
Chains are connected by disulfide bonds, consisting of a variable region (N-terminus) and constant regions.

Antibody Specificity and B-cell Activation

Each antibody (Aby) has a unique specificity; the human antibody repertoire contains approximately 10^16 variations.
B-cells express a single immunoglobulin (Ig) type on their surface and differentiate into plasma cells upon antigen (Ag) binding.

Antibody Functional Regions

Protease digestion reveals antibody functional regions:
- Papain cleaves antibodies into 2 Fab (Fragment antigen binding) and 1 Fc (Fragment crystallizable).
- Pepsin digests the Fc fragment, yielding F(ab')2.
The Fc region is crucial for opsonization.

Antibody Isotypes

Immunoglobulin isotypes (classes) differ in the constant regions of heavy and light chains; five major isotypes exist: IgG, IgA, IgM, IgE, IgD (GAMED).
Heavy chains are denoted by Greek letters: γ, α, μ, ε, δ; light chains have two types: Kappa (κ) and Lambda (λ).

Variable and Constant Domains

Immunoglobulin domains range from 100-110 amino acids.
The variable region (V-region) includes VH (heavy chain) and VL (light chain) domains, while the constant regions have limited sequence diversity.

Antigen-binding Site

Known as the paratope, consists of framework regions (FR) and hypervariable (HV) loops called complementarity determining regions (CDRs).
CDRs are responsible for the specificity of antigen binding.

Antigenic Determinants (Epitopes)

Antibodies bind antigens at specific sites known as epitopes, often composed of carbohydrates, proteins, or both.
Most antigens present multiple epitopes, making them multivalent.

Binding Mechanism

Antibody-antigen interactions exhibit molecular complementarity through non-covalent binding (ionic, hydrogen bonds, hydrophobic effects, van der Waals attractions).
The "Lock and Key" model indicates specific interactions based on shape and charge compatibility.

Gene Structure and Protein Coding

Antibodies are proteins coded by segments of DNA (genes); base pairs include A (Adenine), T (Thymine), C (Cytosine), G (Guanine).
Eukaryotic DNA contains coding (exons) and non-coding (introns) segments.

Transcription and Translation

Primary RNA transcripts from antibodies include introns, while the processed mRNA (messenger RNA) excludes them, coding for polypeptides.

Post-translational Modifications

Polypeptide glycosylation involves sugar attachment in the Endoplasmic Reticulum and Golgi, specifically N-glycosylation and O-glycosylation.
Glycosylation is critical for protein folding and localization.

Immunoglobulin Diversity

Antibody diversity is generated prior to antigen encounter via gene segmentation and recombination.
Ig genes are fragmented in all cells except B-cells, giving rise to a unique germline configuration.

Gene Segment Recombination

RAG-1 and RAG-2 enzymes mediate gene segment recombination in B and T-cells.
Ig constant regions are prepared for transcription, while variable regions require RAG-mediated rearrangements.

Germline Ig Genes and Diversity

Ig genes undergo rearrangement to produce multiple combinations of V, D, and J segments, significantly enhancing diversity.

Affinity Maturation and Isotype Switching

Somatic hypermutation in B-cells improves antibody specificity over time.
Isotype switching allows B-cells to produce different antibody isotypes (IgM, IgG, IgA, IgE) through DNA recombination, altering the immune response without changing the V-region specificity.

Isotype Switching Mechanism

IgM and IgD are initially expressed on B-cells via differential mRNA splicing.
Subsequent switch to IgG, IgA, or IgE allows diversification of immune function based on the need.

Summary of Antibody Attributes

Each antibody class features distinct functions facilitated by different constant regions, while the V-region specificity remains consistent across isotypes.

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Description

This quiz explores the structure and function of antibodies, including their varying isotypes and specificity. Understand how antibodies are structured from polypeptide chains and their roles in B-cell activation and immune response. Delve into the functional regions of antibodies and their significance in opsonization.