Immunoglobulins

Immunoglobulins

Antibodies are little proteinsLarge molecules made of amino acids with various functions in the body. that are found in the plasmaThe liquid component of blood. part of whole blood. The official word for antibodies is immunoglobulins(Ig) Antibodies: Proteins produced by the immune system to target specific antigens.. This term indicates that these proteins are measured among the gamma globulin proteins. These proteins can be measured in plasma.  The heavy chain is a sequence of approximately 400 amino acids. The heavy chains are connected together by disulphide bonds which are similar to the bonds that connect nucleotidesThe building blocks of nucleic acids. in DNA. The heavy chains form the core of the Y shaped immunoglobulin. There are binding sites for complement proteins on the trunk of the Y shaped protein. The heavy chains come in five flavors: M   A   D   G   E. 

Constant region of the heavy chains does not change among immunoglobulins of the same class.  Therefore, all M immunoglobulins have the same heavy chain constant region.  The variable region of the heavy chain binds to specific antigensMolecules on the surface of cells that trigger an immune response. and has an antigen-binding site at the tip.  This allows an immunoglobulin to bind to the antigens inserted in the plasma membraneThe outer boundary of a cell that controls what enters and exits. of pathogens. 

Light chains are the smaller chains of about 200 amino acids on the outside of the heavy chains. There are two different light chains: Kappa and Lambda. Just as with the heavy chain, the constant region is conserved within a class of immunoglobulins. The variable region can bind with a specific antigen.

Heavy Chain Variants

A immunoglobulins are common in breast milk and in mucus. Conditions such as the flu and COVID would increase A immunoglobulins in your respiratory mucous membranes. All four mucous membranes of the body include reproductive, urinary, digestive, and respiratory systems. Each has a coating of mucus between the cellsThe basic structural and functional units of life. and the lumenThe inside space of a hollow organ or structure.. The coating of mucus is rich in A immunoglobulins.

G immunoglobulins are significant in that they cross the placentaThe organ that facilitates nutrient and waste exchange between the mother and fetus. and confer passive natural immunity to baby from mom. If you have a negative blood type, you produce G immunoglobulins. They tend to attach to the Rh antigens embedded in the cells of someone with a positive blood type.

Rhogam is a shot given to blood type negative women usually upon their second child. During the first birth, mom is exposed to the baby’s blood. Mom starts to create G immunoglobulins. These immunoglobulins attack the RH protein in blood type positive cells. Therefore during the second pregnancy mom will have immunoglobulins capable of attacking the cells of an RH positive baby.

E immunoglobulins are common in basophils and mast cells. Basophils circulate through your blood vessels while mast cells being take up residence in tissues. If you encounter an allergen to which you are allergic, you will begin to make E immunoglobulins. For example, I am allergic to the penicillium fungus that makes blue cheese. These immunoglobulins will be inserted into the cell membranes of basophils floating in your blood. They will also be inserted into mast cells residing in your tissues. Upon second contact with the allergen, the blue cheese antigens connected with the E immunoglobulins. This occurred the second time I ate blue cheese. The immunoglobulins were inserted into the cell membranes of the basophils and mast cells. This connection of antigen and antibody triggers these cells to release histamine.

The last two immunoglobulins are commonly inserted into B cells. These cells are responsible for initiating the process of making immunoglobulins. B cells that have immunoglobulins inserted are ready. They are primed to act quickly if the antigen is detected. For example, many vaccinations expose your body to attenuated viruses or viruses that have been chopped into little tiny pieces. These tiny virus pieces can produce M&D immunoglobulins. When you encounter the virus again, these immunoglobulins will connect with the antigen. This connection speeds up your immunological response.  This picture does not do the M Immunoglobulin justice.  It is a very large protein.

How Igs are Made

Antibody production begins with stem cells in the liverA large organ that produces bile, detoxifies blood, and stores nutrients. or bone marrow. Hematopoietic stem cells differentiate into myeloid and lymphoid stem cells.  The lymphoid stem cells can become different types of lymphocytes. These include B cells, T cells, or natural killer (NK) cells. Once a lymphoid stem cell becomes a B cell, it is pre-loaded with immunoglobulins determined by genetics.  You have a predetermined set of genes that make immunoglobulins.  So, these B cells are in your lymph nodes. They are just kinda hanging out. They wait for their antigen to show up. 

Over time, if the body encounters an antigen (e.g., a  peanut antigen), the antigen binds to the antibodies on the B cell and is displayed to T cells simultaneously.

When this happens, the B cell signals T cells for help and starts cloning itself. The clones create plasma cellsImmune cells that develop from B cells and produce antibodies. that produce immunoglobulins. Additionally, memoryThe ability to store and recall information. cells are formed, which store the antibodies for quicker responses during future encounters with the same antigen. The initial response to an antigen involves multiple steps. Memory cells expedite the process. This allows for a faster and more effective immune reaction upon re-exposure.

This antibody production process is relevant to concepts like the Rhogam shot. For instance, if a person with O-negative blood carries an Rh-positive baby, their body may not initially produce antibodies. These antibodies are against Rh antigens. However, during delivery, blood mixing can expose the mother’s immune system to Rh antigens, leading to antibody production. In subsequent pregnancies, these antibodies could attack the baby’s blood. Rhogam works by binding to these antibodies, preventing them from attacking the baby’s antigens.

How Igs work

Antibodies play several roles in pathogen elimination.

As we saw back in blood typing, immunoglobulins and antigens link up and cause agglutinationThe clumping of red blood cells when antibodies bind to their specific antigens. or clotting. These clumps are then phagocytozed.

Immunoglobulins can precipitate antigens from solutionA homogeneous mixture of two or more substances..  The linkage of antibody and antigen forms a lattice-type structure that basically becomes un-dissolved.  Just as in agglutination, these clumps are phagocytozed.

Immunoglobulins can also assist in cell lysis.  Antibodies smothering a pathogen can provide a place where complement proteins can fix themselves and do a MAC attack.  This was where the complement proteins assemble to make a hole that causes a cell to lyse or split.

Immunoglobulins can smother pathogens by binding to their surface. This is called opsonization. This term refers to antibodies or complement proteins covering an invader. For instance, a pathogen covered by antibodies can lead to agglutination or precipitation. Essentially, opsonization makes the pathogen more attractive to macrophages, which see it as “tasty.” The root word for opsonization actually means “condiments,” like ketchup. Just as ketchup makes fries more appealing, antibodies covering a pathogen make it more attractive to immune cells.

Okay, now all these types of marking antibodies marking antigens can lead to the destruction of the membrane-bound antigen. We can attract phagocytes, and they can engulf the antigen. We can use cytokines to get macrophages to the area. This attracts basophils. They release histamines and trigger an inflammatory response to the antigen.