BLOCK 3: IMM: (3.2) ANTIBODIES PT. 1

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Questions and Answers

What is the primary function of the Fab fragment of an antibody?

To provide structural support to the antibody

To bind to antigens (correct)

To activate the complement system

To stabilize the Fc fragment

Which of the following statements is true about hypervariable regions in antibodies?

They determine the specificity for different antigens (correct)

They are located in the Fc region

They do not play a role in antigen binding

They are constant across all antibody classes

How do discontinuous epitopes differ from linear epitopes?

Linear epitopes are created when proteins are denatured

Discontinuous epitopes are formed from contiguous amino acids

Both types consist only of amino acids from the same protein segment

Discontinuous epitopes consist of amino acids that are far apart in the polypeptide chain (correct)

What consequence might occur upon proteolytic cleavage of an antibody?

The antibody can no longer recognize its antigen Signup and view all the answers

What distinguishes IgG from other antibody isotypes?

IgG is the only isotype that can cross the placenta Signup and view all the answers

What are the components of an IgG molecule?

Two identical heavy chains and two identical light chains Signup and view all the answers

What is the role of the hinge region in IgG?

To allow flexibility between the arms and stem Signup and view all the answers

How is the IgG molecule dissected into fragments?

By cleaving the hinge with a protease and breaking disulfide bonds Signup and view all the answers

What distinguishes the Fab fragment from the Fc fragment?

Fab contains both heavy and light chains; Fc contains only heavy chains Signup and view all the answers

What is the characteristic feature of the variable regions in an IgG molecule?

They vary among different IgG molecules Signup and view all the answers

Why is the Fc fragment named as such?

It was the fragment crystallized first in early studies Signup and view all the answers

What is a characteristic feature of the amino-terminal regions of the heavy and light chains in IgG?

They are known as hypervariable regions Signup and view all the answers

In terms of structure, how do IgG molecules differ from other antibody isotypes?

IgG possesses a unique hinge region Signup and view all the answers

What is the significance of the flexible hinge in the IgG molecule?

It allows IgG to bind to multiple antigens simultaneously. Signup and view all the answers

Which statement correctly characterizes the Fab and Fc fragments of antibodies?

The Fc fragment is the region that determines the antibody isotype. Signup and view all the answers

What are hypervariable regions (HVR) in the context of antibodies?

Loops at one end of the V domains that determine antigen specificity. Signup and view all the answers

Which of the following correctly identifies a difference among the immunoglobulin classes?

IgG possesses a hinge region while IgM does not. Signup and view all the answers

How do antibody isotypes primarily differ from one another?

They have unique amino acid sequences and structural configurations. Signup and view all the answers

What happens to the structure of an antibody during proteolytic cleavage?

The Fab and Fc fragments are separated, affecting antigen binding. Signup and view all the answers

What is one structural characteristic of IgG that contributes to its functionality?

It is formed from 12 immunoglobulin domains that offer stability. Signup and view all the answers

Which feature of the antibody structure plays a critical role in binding diversity?

The hypervariable regions contribute variations in antigen binding specificity. Signup and view all the answers

What is a key function of macrophages in the immune response?

Engulfing and digesting pathogens Signup and view all the answers

Which immunoglobulin molecule was noted as not fully understood in its function?

IgD Signup and view all the answers

What aspect of B cell development is primarily discussed in relation to antibody-mediated immunity?

Effector functions Signup and view all the answers

Which statement accurately describes the role of antibodies in the immune system?

They facilitate pathogen recognition and neutralization. Signup and view all the answers

What is an important factor to consider when developing a vaccine?

The presence of nucleic acids and proteins Signup and view all the answers

What is the role of plasma cells in the immune system?

They secrete antibodies specific to the same antigen as their B cell receptor. Signup and view all the answers

Which immunoglobulin molecule is primarily known for being the first produced during an immune response?

IgM Signup and view all the answers

Why is clonal expansion of B cells important in response to specific antigens?

It ensures that more B cells can produce antibodies for the specific antigen. Signup and view all the answers

What is the significance of the structure of IgM in the immune response?

Its pentameric form increases its overall binding capacity to multiple antigens. Signup and view all the answers

In the context of antibody-mediated immunity, what distinguishes a resting B cell from an activated B cell?

Activated B cells undergo a transformation into antibody-secreting plasma cells. Signup and view all the answers

What is the primary function of the medullary cavity in bones?

To house and support bone marrow Signup and view all the answers

Which statement best describes the role of reticular cells?

They are structural cells that support the movement of immune cells. Signup and view all the answers

What defines the term 'niche' in the context of bone marrow?

It includes stem cells, stromal cells, and extracellular matrix. Signup and view all the answers

What is the significance of the vascular niche in the bone marrow?

It provides a pathway for oxygen and nutrients to reach developing cells. Signup and view all the answers

How do immune cells move through the bone marrow?

They weave along the reticular fibers like a rope course. Signup and view all the answers

What is the primary function of stromal cells in the bone marrow niche?

To provide structural support for hematopoiesis. Signup and view all the answers

What role do blood vessels play in the bone marrow environment?

They deliver oxygen and cytokines required for cell signaling. Signup and view all the answers

Which statement accurately characterizes hematopoiesis?

It involves the development of different types of blood cells, including immune cells. Signup and view all the answers

Study Notes

IgG Molecule

An IgG molecule is composed of two identical heavy chains and two identical light chains.
Carbohydrate is attached to the heavy chains.
The amino-terminal regions of the heavy and light chains are variable in sequence.
The remaining regions of the heavy and light chains are constant in sequence.
A flexible hinge region is located between the two arms and stem of the IgG molecule.

Fragmentation of IgG by Protease

A protease can cleave the hinge of each heavy chain resulting in two Fab fragments and an Fc fragment.
The Fab fragment contains the light chain and the amino-terminal half of the heavy chain.
The Fc fragment contains the carboxy-terminal halves of the two heavy chains.
The Fc fragment was named because it was readily crystallized in early studies of IgG antibody structure.

Epitopes

A linear epitope is formed from contiguous amino acids.
A discontinuous epitope is formed from amino acids from different parts of the polypeptide chain.

Shiv Pillai, MD, PhD

Director of the Harvard Immunology PhD program.
His lab studies B lymphocytes.
Pillai's lab has discovered novel treatments for B-cell leukemias and autoimmune diseases.
They study how immune cells can "go rogue" in autoimmune diseases.

IgG Hinge Flexibility

The flexible hinge of the IgG molecule allows it to bind to many different arrangements of antigens on the surfaces of pathogens.

Human Immunoglobulin Isotypes

The different immunoglobulin classes (IgG, IgA, IgM, IgD, & IgE) differ in the length of their heavy-chain C regions, the locations of disulfide bonds, and the presence of a hinge region.
The isotypes differ in the distribution of N-linked carbohydrate groups.
Each antibody isotype is designated by a Greek letter (where we get their names).
All immunoglobulins are monomers in their membrane-bound form.
In their soluble, secreted form, IgD, IgE, & IgG are monomers.
IgA forms monomers and dimers.
IgM forms pentamers.

Immunoglobulin Domains

Immunoglobulin chains fold into compact and stable protein domains.
Each Fab and Fc fragment is composed of four immunoglobulin domains that produce a similarly shaped globular structure.

Antibody Diversity

The antigen-binding site of an antibody is formed from the hypervariable regions (HV or HVR) of the heavy and light-chain V domains.
CDR = HVR
Variability is the ratio of the number of different amino acids found at a position to the frequency of the most common amino acid at that position.
The maximum value possible for variability is 400 (square of 20 - the number of different amino acids found in antibodies).

Bone Marrow Structure and Function

Medullary cavity: Hollow part of the bone that contains bone marrow.
Reticular cells: Structural cells that provide support and framework for bone marrow.
Reticular fibers: Synthesized by reticular cells, creating a network that allows immune cells to move around.
Hematopoiesis: Process of blood cell formation, regulated by reticular cells.
Endosteal niche: Complex structure within bone marrow containing stem cells, progenitor cells, stromal cells (including reticular cells), growth factors, and extracellular matrix.
Vascular niche: Network of blood vessels within the endosteal niche, supplying oxygen and nutrients to the bone marrow.
Cytokines: Signaling molecules that travel through the blood vessels to communicate with bone marrow cells.

B Cell Development

B cell development: Takes place in bone marrow, unlike thymus, where T cell development occurs.
IgD: Immunoglobulin molecule that's function is not fully understood but may play a role with mast cells and basophils.
Plasma cells: Specialized B cells that secrete antibodies with the same antigen specificity as the B cell receptor of the cell they differentiated from.
Clonal expansion: The process of increasing the number of B cells and plasma cells specific to an antigen, ensuring effective immune response.

Immunoglobulin Molecule

IgM: Pentameric immunoglobulin molecule with a star-shaped form, one of the first molecules produced in the immune system.
Resting B cell: A B cell that is not currently actively involved in an immune response.

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Description

Explore the structure of IgG molecules and their fragmentation by proteases in this quiz. Learn about the significance of Fab and Fc fragments, as well as the concepts of linear and discontinuous epitopes. Test your knowledge of antibody structure and its functional implications in immunology.