Question

1.Antibodies are not inherently toxic or destructive to microbes, so how do they protect us?

2. Describe the Germinal Center reaction?

3. Linked recognition – What is it? Why is it an important safeguard during the process of B cell activation by TFH cells? (What could happen if linked recognition was not required for a TFH cell to activate a B cell?)

Answer 1

Ans 1.

The variable region of antibodies bind antigens. Antibodies cause removal and/ or death of pathogen through interaction between constant region of heavy chain and other proteins, cells, and tissues.

The four major effector functions performed by antibodies are –

1. Opsonization – It is the promotion of phagocytosis of antigens by macrophages and neutrophils. Fc receptors (FcR) are present on the surfaces of macrophages and neutrophils which can bind the constant region of Ig molecules. The binding of phagocyte Fc receptors with several antibody molecules complexed with the same target e.g. bacterial cell, produces an interaction that results in the binding of the pathogen to the phagocyte membrane. This crosslinking initiates a signal-transduction pathway which results in the phagocytosis of the antigen-antibody complex. Inside the phagocyte, the pathogen becomes the target of various destructive processes such as enzymatic digestion, oxidative damage, and the membrane-disrupting effects of antibacterial peptides.
2. Complement activation - Complement system includes a collection of serum glycoproteins that can perforate cell membranes. It can be activated by most IgG subclasses. A protein fragment called C3b binds nonspecifically to cell- and antigen-antibody complexes near the site at which complement was activated. Many cell types such as RBCs and macrophages have receptors for C3b and so bind cells or complexes to which C3b has adhered. Binding of adherent C3b by macrophages leads to phagocytosis of the cells or molecular complexes attached to C3b. This collaboration between antibody and the complement system is required for the inactivation and removal of antigens and the killing of pathogens.
3. Antibody-dependent cell-mediated cytotoxicity (ADCC) - The linking of antibody bound to target cells (virus infected cells of the host) with the Fc receptors of natural killer (NK) cells can direct the cytotoxic activities of the effector cell against the target cell. In this process, the antibody acts as a newly acquired receptor enabling the attacking cell to recognize and kill the target cell.4.
4. Ability to undergo transcytosis – Antibodies can move across epithelial layers by a process known as transcytosis. In humans and mice, IgA is the major antibody species that undergoes such transcytosis. Humans and mice, also transfer significant amounts of most subclasses of IgG from mother to fetus. This transfer takes place during the third trimester of gestation. As a result, the developing fetus receives a sample of the mother’s repertoire of antibody as a protective endowment against pathogens.

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Ans 2.

Germinal centers are structures that form in secondary lymphoid organs within a week or so of immunization with an antigen that activates a T-cell-dependent B-cell response. It is the site of affinity maturation. The sequential events that occur within germinal center are –

• Migration of antigen-stimulated B-cells into germinal centers followed by reduction of surface Ig and rapid proliferation to form “centroblasts”.
• Somatic mutation of rearranged immunoglobulin V region genes within the dark zone.
• Migraton of centroblasts to the light zone and increase in their expression of surface Ig. The centroblasts are now called as “centrocytes”.
• Low affinity centroblasts undergo apoptosis.
• Selection of high-affinity centrocytes occur by their interaction with follicular dendritic cells and T helper cells.
• B cells that pass antigen selection and receive a second survival signal from TH cells differentiate into either memory B cells or antibody-secreting plasma cells.
• The encounter with TH cells also induces class switching.

A major outcome of the germinal center is to generate higher affinity B cells (Ka2) from B cells of lower affinity ( Ka1).

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