Immunoglobulin Structures & Functions

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary function of the variable region in an antibody?

To engage effector mechanisms

To determine the antibody class

To recognize antigens (correct)

To stabilize heavy and light chains

Which of the following statements is true regarding the constant region of antibodies?

It determines the primary structure of the antibody

It elicits uniform effector mechanisms across the same class (correct)

It is unique to each antibody

It varies greatly among different antibodies of the same class

What is the molecular weight of an antibody approximately?

600 kDa

150 kDa (correct)

75 kDa

300 kDa

Which chain types do the light chains of antibodies consist of in humans?

Kappa and lambda Signup and view all the answers

How many sequences do heavy chains consist of?

4 sequences Signup and view all the answers

What happens to an antibody when papain cleaves it?

It releases 2 Fab fragments and 1 Fc fragment Signup and view all the answers

What is the ratio of kappa to lambda light chains in humans?

2:1 Signup and view all the answers

Which domain represents a part of the variable region of antibodies?

VL Signup and view all the answers

What type of bonds hold the heavy and light chains of antibodies together?

Disulfide bonds Signup and view all the answers

How many amino acid sequence repeats are present in each heavy chain of antibodies?

110 Signup and view all the answers

What is a distinguishing feature of the IgG subclasses?

They differ in the number of disulphide bonds. Signup and view all the answers

What is the primary function of IgA in external secretions?

Neutralizing antibodies. Signup and view all the answers

Which subclass of IgG is the least abundant in serum?

IgG4 Signup and view all the answers

What is the structural form of IgM found in serum?

Pentamer. Signup and view all the answers

What type of immunoglobulin is primarily involved in mediating hypersensitivity reactions?

IgE Signup and view all the answers

How many types of subclasses does IgA have?

Two Signup and view all the answers

Which of the following immunoglobulins is the first antibody class released during an immune response?

IgM Signup and view all the answers

What is the serum concentration of IgG1?

9 mg/mL Signup and view all the answers

What percentage of total serum immunoglobulin does IgM account for?

5 - 10% Signup and view all the answers

What serves as the binding component for IgG to cross the placenta?

FcRn. Signup and view all the answers

What is the main purpose of the hinge region in the immunoglobulin structure?

To allow flexibility between Fab regions Signup and view all the answers

How are the hypervariable regions of the immunoglobulin's V domain characterized?

By their variation designated as HV1, HV2, and HV3 Signup and view all the answers

Which structural feature is primarily responsible for the stabilization of the immunoglobulin fold?

S=S bonds Signup and view all the answers

What do the complementarity-determining regions (CDRs) in antibodies correspond to?

The hypervariable regions of the V domains Signup and view all the answers

Which of the following describes the nature of epitopes in relation to antibodies?

Epitopes are structures recognized by B cell receptors Signup and view all the answers

Combinatorial diversity in antibodies is primarily due to which factor?

The combination of different heavy and light chains Signup and view all the answers

What kind of interactions stabilize antigen-antibody binding?

Non-covalent bonds such as hydrogen bonds and Van der Waals forces Signup and view all the answers

The variable region of the immunoglobulin is characterized by which of the following?

Presence of both hypervariable and framework regions Signup and view all the answers

Which description best fits the framework regions (FR) of an immunoglobulin's V domain?

They form stable b-strands contributing to the overall structure Signup and view all the answers

How is the structural stability of the immunoglobulin maintained?

By the arrangement of b-pleated sheets in the domains Signup and view all the answers

Study Notes

Immunoglobulin Structures & Antibody Functions

Immunoglobulins, or antibodies, have a structure and function intimately linked.
Antibodies have two key functions: recognizing antigens and activating effector mechanisms to eliminate antigens.
Antibody recognition sites differ between antibodies, making up the variable region (V region).
Antibodies of the same class (isotype) trigger identical effector mechanisms through their constant region (C region).

Ig Structure

Antibody molecules are Y-shaped, composed of two heavy (H) and two light (L) polypeptide chains connected by disulfide bonds.
The molecular weight (MW) of antibodies is roughly 150 kDa. The heavy chains are about 50 kDa and the light chains are about 25kDa.
Light chains can be either kappa (κ) or lambda (λ) in type.
In humans, the ratio of κ to λ light chains is roughly 2:1. In mice, it’s approximately 20:1.
The constant region (C region) of heavy chains determines the antibody class.
Heavy chains (μ, δ, γ, α, ε) specify class – IgM, IgD, IgG, IgA, IgE.

Ig Structure - Domains

Each antibody chain consists of repeating units of approximately 110 amino acids. The antibodies are made of structural domains, both within the heavy and light chains, that are defined by specific sequences of amino acids. Further substructure has been identified in the chains.
The N-terminal domains are highly variable in sequence and are labeled V₁ (heavy chain variable) and V₂ (light chain variable).
C-terminal domains (CL, CH1, CH2, CH3), are constant for each isotype, forming the C region of the antibody molecule.
V and C domains create similar structures with beta-sheets arranged like a beta-sandwich. These beta-sandwiches are stabilized by disulfide bonds.
V regions have specific, hypervariable regions (HV1-3) within the antigen binding sites (Fab) which mediate antigen recognition. The framework regions (FR) are less variable. The amino acid sequences within the HV1-3 regions vary significantly, and account for much of the variability between unique antibodies. The antibody binding site is formed by associating the light and heavy chain variable domains in specific configurations.
The immunoglobulin fold, found in many proteins like immunoglobulins and T cell receptors, utilizes these 4-strand and 5-strand structures. This fold is critical for maintaining the antigen-binding site's function.

Antigen Binding Sites

The antigen-binding site is composed of the V regions of the heavy and light chains.
The hypervariable regions (HV1-3) of the V domains are key to the high variability in specificity and affinity between antibodies, making up the complementary determining regions (CDRs) or antigen contact regions.
The framework regions (FR1-4) form the beta-strand structure.
The hypervariable regions (HV1, HV2, HV3) are collectively termed complementarity-determining regions (CDRs) as they form a surface for antigen interactions.
The combination of different heavy (H) and light (L) chains leads to the vast diversity of antigen-binding sites, called combinatorial diversity. An antibody that binds to an antigen often has unique CDR regions for that antigen contact.
The interactions between antibodies and antigens are driven by different topological and chemical factors.

Antigen-Antibody Interactions

The part of an antigen that an antibody attaches to is the epitope.
Epitopes can be continuous or discontinuous amino acid sequences on the antigen surface.
Covalent or non-covalent interactions, such as ionic, hydrogen, hydrophobic, and Van der Waals forces, stabilize antigen-antibody interactions.
B cells bind to various molecules like proteins, carbohydrates, and small molecules.

Antibody Function – Classes

There are five antibody classes (isotypes): IgM, IgD, IgG, IgA, and IgE, each with different functions and properties within the immunology system.
Class differences relate to constant region sequences, number of constant regions, location and number of disulfide bonds, and presence of different glycans.
IgG is the most abundant in serum and extracellular fluid (∼80%). Specific subclasses of IgG (IgG1, IgG2, IgG3, IgG4) vary in structure in terms of hinge regions and the number/location of disulfide bonds within the molecule structure. Individual subclasses have their own unique functions regarding pathogen clearance and interactions with the immune system. Different antibodies have varying degrees of functionality in terms of activating complements and opsonizing pathogens.
IgM is the primary class of antibodies in the primary adaptive immune response and is the largest immunoglobulin. It circulates as a pentamer (five linked Y-shaped structures).
IgA is predominant in external secretions (mucosy membrane functions).
IgE antibodies attach to mast cells and basophils, playing a role in allergic reactions.
IgD is involved in B-cell activation.

Antibody Responses

There are three types of antibody responses:
- T-cell-independent (TI) response: a rapid, innate-like response to repetitive antigens, predominantly producing IgM antibodies.
- Early T-cell-dependent (TD) response: produces a higher affinity antibody response involving marginal zone and follicular B cells.
- Germinal center reaction: a secondary antibody response that involves a germinal center within B-cell follicles, resulting in long-lived plasma cells secreting highly specific antibodies.

Humoral Response

The primary response involves naive B cells, producing IgM.
The secondary response is more rapid and produces higher IgM and IgG responses with higher affinity.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz explores the critical structure and functions of immunoglobulins, or antibodies. It covers their Y-shaped composition, the functions of different regions, and the differences in light chains among species. Test your knowledge on how antibodies recognize antigens and activate immune responses.