Immunology - Antibody Structure & Function Flashcards Preview

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Flashcards in Immunology - Antibody Structure & Function Deck (26):
1

What is the Fab region of an antibody?

The Fab region is the same as the variable region. It comprises the terminal ends of both light & heavy chains, binds to whole antigen usually on the surface of the pathogen in extracellular fluid. The antigen-binding sites bind to the antigens that induced their formation by B cells.

2

Do the VDJ segments of the Fab region on an antibody change after the B-cell changes from naive to mature B cell? 

No. 

Although the Fab region is also called the "variable region," this variation only occurs with gene recombination of the B-cell in the bone marrow. Once the B cell exits the bone marrow as a naive B-cell via the sinusoids to enter the circulation, its Fab region's VDJ segments don't change.

Their genetic code does not change throughout the development of the B-cell, from naive to activated & mature to memory and apoptosis.

3

What is the order of VDJ recombination for B-cell receptors, starting earliest to latest?

D-J recombination

V-to-DJ recombination

Transcription, Splicing, Polyadenylation

Translation

Assembly

 

4

What is the Fc region on an antibody, aka soluble B-cell receptor? What does it do? 

The constant region, aka Fc region, comprising the two heavy chains, serve as “anchors” on the B-cell surface as surface receptors when not circulating freely in the circulation blood, and do not bind antigen.

The Fc region can bind to the Fc receptors of other leukocytes that express them, such as neutrophils, macrophages, eosinophils & mast cells, enhancing their mechanisms of pathogen-eradication, such as neutralisation, opsonisation and complement activation.

The Fc region determines the biological function of the antibody -- eg., whether it will become IgM, which activates the complement pathway against bacteria, or IgG, which opsonises target pathogens by coating them (binding to their surface antigens) and then binding to the Fc regions of macrophages and neutrophils for phagocytosis, etc.

5

How is the Fc, or constant region, formed? 

The heavy chains of the Fc region are formed initially in the bone marrow, when “placeholder” or default heavy-chain genes delta and mu are both used to generate the monomeric IgM receptor and IgD receptor, prior to B-cell activation by antigen in secondary lymphoid tissue.

Once a B cell encounters antigen in secondary lymphoid tissue (ie., lymph nodes), it alters its heavy-chain genes in the Fc region, swapping mu or delta for epsilon, alpha or gamma. The variable-region heavy-chain genes stay the same.

6

What is the structure & role of IgG in the immune process?

Dimeric

Most abundant Ig in blood (80% of serum Ig) & tissue fluid. Neutralizes toxins & combats microorganisms by activating the complement system & facilitating binding of phagocytic cells (neutrophils & macrophages) via opsonisation. Only class of antibody to cross human placenta.

7

What is the structure of IgA and what is its role in the immune response?

Monomeric in serum, Dimeric in secretions, linked by “secretory component” & J chain

Major Ab in seromucous secretions such as saliva, tears, broncial secretions, nasal mucosa & SI secretions, where it serves to defend the external body surfaces via neutralisation.

8

What is the structure of IgM and what is its role in the immune response?

Monomeric on surface of naive B cells, Pentameric as soluble receptor, binding 10 antigens at once

It is an intravascular (in blood) Ab & is produced very early in the immune response. Extremely effective as a bacterial agglutinator and is the best mediator of complement-dependent cytolysis, making it a powerful first-line defense against bacterial pathogens.

9

What is the structure of IgD and what is its role in the immune response?

Dimeric

It is present on the lymphocyte and functions together with monomeric IgM as the antigen receptor on naïve B-cells.

10

What is the structure of IgE and what is its role in the immune response?

Sensitizes tissue mast cells’ to specific antigen by binding to their Fc receptors via IgE’s Fc region (forming an antigen-seeking coat of armour on mast cell).

Triggers degranulation of mast cell & release of inflammatory mediators upon contact with antigen. Important for parasitic infections & responsible for symptoms of atopic allergies like eczema and asthma.

11

Explain the role of antibodies in enhancing the innate immune mechanisms of phagocytosis.

Phagocytosis is a  mechanism of pathogen-destruction by neutrophils & macrophages of innate immune system.

B-cells use OPSONISATION by coating the surface of pathogens with antibody, specifically IgG. Neutrophils and macrophages more easily “recognise” antibody-coated pathogens, and their own Fc receptors bind to the Fc regions of the bound antibodies, facilitating phagocytosis. IgM also opsonises to a lesser extent.

12

Explain the role of antibodies in the innate immune mechanisms of complement activation.

Antibody, particularly IgM and to a lesser extent IgG, bind to antigen on the surface of bacteria and activate complement cascade leading, leading to formation of Membrane Attack Complex.

13

Explain the role of antibodies in the innate immune mechanisms of sensitization of mast cells.

Mast cells & eosinophils are active against parasites.

B-cells sensitize mast cells by sending antibody, mainly IgE, to bind to the Fc receptors on their surface. This IgE “coat” causes self-destruction of the mast cell when it binds a parasite antigen.

14

Antibodies bind to:

a) Antigen peptide fragments digested by macrophages

b) Epitopes on antigen proteins in extracellular fluid only

c) Antigen peptides presented by MHC I molecule

d) Antigen peptides presented by MHC II molecule

b.

Antibodies bind to whole antigen proteins in extracellular fluid only; they bind specifically to epitopes on the proteins.

 

15

In a blood sample, where would you find antibodies?

a. clotted blood

b. buffy coat

c. serum 

d. uncoagulated blood

b & c

Serum = buffy coat

16

Antibodies can bind to two types of antigenic epitope. What are they? 

Conformational & Linear

17

What is the molecule that links the innate immune system (involving antibody) to the adapative immune system (involving complement lysing/MAC)?

C1q

The intermediate molecule C1q allows antibody (adaptive) to link into complement (innate) pathway.

Antibody activates complement, leading to formation of Membrane-Attack Complex on the surface of the organism - ie., lysing of bacteria.

18

What are the two types of light chains that can be "chosen" for antibody receptors during development in the bone marrow?

Either Lambda or Kappa light chains. 

19

During the life of an infection, which part of the antibody can be change? 

The heavy chains of the constant region, not the Fab region (variable region). 

20

Which of the antibodies we've studied isn't soluble, ie., isn't secreted by the B-cell and thus isn't found in serum? 

IgD - it is bound to the plasma membrane of the B-cell and binds antigen on the surface.

21

What is the first antibody secreted in an immune response? 

IgM. 

It is expressed as a monomeric receptor on the surface of B cells but is secreted as a pentameric antibody in serum, where it can bind up to 10 antigens at once. 

It is a potent activator of the complement cascade that ends in the Membrane Attack Complex, which lyses bacteria. 

It's also an agglutinin.

22

What is the most common antibody found in serum? 

IgG. It makes up 80% of serum antibodies.

23

What are the major differences between T-cell-independent antibody response & T-cell-dependent antibody response? 

This refers to how B cells respond to antigen and how they end up proliferating and producing antibodies.

In the TI response (independent of T-cells), the B-cell receptor just responds to a NON-PROTEIN bacterial component, some epitope that isn't a protein but is recognised as foreign. The B-cell might encounter these antigenic components in the paracortex of the lymph nodes, & they bind to the IgM surface receptors. This binding & cross-linking triggers proliferation of the B-cell (cloning) & IgM production, but no memory cells or class-switching of antibodies.

In the TD response (T-cell dependent), the B-cell receptors bind not only to whole protein antigen in paracortex, but its receptors are able to endocytose some of the protein & present it via MHC II molecules (remember, B-cells act as APCs in this pathway). This attracts binding with Th-2 helper T-cells, as well as co-stimulatory binding of CD40L on Th-2 cells with CD40 on B-cells. Th-2 helpers also secrete IL-4, which promotes B-cell proliferation in the paracortex. 

24

After B-cells proliferate in the paracortex of the lymph nodes following activation by Th-2 helper T cells and IL-4, what happens to them? 

Proliferating B cells enter the LN’s follicle, the “home” for B cells, where they proliferate more and come into contact with the follicular dendritic cells (FDCs).

Here, the proliferation leads to the formation of a germinal centre within the follicle, now called a secondary follicle, where the B cells will mature into plasma cells and migrate to the medullary cords, where they will secrete antibody to be carried into the circulation via the efferent lymph. Later in the infection, as the animal begins to recover, the proliferating B- cells will differentiate into Memory Cells, to mount a longer and more effective secondary immune response.

25

Discuss how class-switching occurs & how T cells influence the isotype of antibody produced.

When the B-cells make cell-to-cell contact with Th2-cells via the MHC II-peptide complex, CD40L/CD40 co-stimulatory proteins and the cytokine IL4, the T cells cause the B cell to “switch” from producing IgM to IgG, effectively by “switching off” the delta gene that needs to be “on” with the mu gene in the primary transcript for the translation of IgM.

With delta “off”, and only “mu” on, then only the transcription and translation of IgG occurs.

This class-switching from IgM to IgG is a function of the ADAPTIVE IMMUNE RESPONSE.

Cytokines from INNATE IMMUNE RESPONSE can lead to further class-switching to IgA (triggered by mucosal infection) or IgE (triggered by parasite infection). Delta & mu genes are deleted in both cases, and gamma is turned on.
 

26

Is the secondary response greater, smaller or the same in terms of antibody-production after an initial infection by a bacteria that triggered a T-cell INDEPENDENT primary response?

It would be the same, not greater or lesser, as a TI primary response doesn't generate any Memory cells or class-switching of antibodies. Only IgM is made, in general, but is made quickly.

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