 In this video, I will describe the process of antibody-mediated immunity, also known as humoral immunity, describe the role of helper T cells in humoral immunity, describe the process of clonal selection of B cells, describe the role of plasma cells and memory B cells, and describe the structure and function of antibodies. Here we see the antibodies, also known as immunoglobulins, have a structure made from two heavy chain polypeptides and two light chain polypeptides. The FC region of the antibody is the constant region, whereas the light chain as well as a portion of each heavy chain forms the variable region of the antibody. And this variable region forms the antigen binding site. The variable region is different for all of the antibodies produced during the initial process of B lymphocyte maturation to make an enormous variety of different B lymphocytes that all have a distinct antigen binding site on their antibodies. However, during clonal selection, when a B lymphocyte is activated to divide and make more B lymphocytes, all of the B lymphocytes produced during clonal selection will make the antibodies that have the same antigen binding site and can therefore defend against the same specific pathogen. Here we see the example of clonal selection for B lymphocytes or B cells, where we have three hypothetical examples of naive B lymphocytes using different colors to distinguish the different shapes of the antigen binding site of the antibodies on these naive B lymphocytes. The blue, red, and purple antibodies bind to different antigens, so the specific antigen shown in the illustration can only bind to the red antibody and not to the blue antibody or the purple antibody. So there's trillions of distinct lymphocytes with different shaped variable regions of their antibodies enabling the body to potentially respond to an enormous variety of different antigens from any pathogen we might be exposed to. But when we're exposed to a pathogen, the antigen from that pathogen can bind to the antibody on the surface of a specific lymphocyte leading to activation of that lymphocyte. That lymphocyte will proliferate, it will divide to make more B lymphocytes that all produce the same antibody. So here we see the formation of clones where the activated B cell divides making more B cells that have the red antibody. Some of those cells will be the memory B cells that are long-lived B cells providing immunological memory in case we encounter the same pathogen again in the future. But many of the B cells that are formed will be the effector B cells known as the plasma cells or plasma sites. These effector B cells secrete antibodies. The plasma cells are secreting antibodies and the antibodies then are responsible for antibody mediated immunity when antibodies bind to antigen on the surface of a pathogen. They can help label that pathogen to direct the innate immunity to help defend against that specific pathogen. So the innate immunity can be recruited by the adaptive immunity. The antibodies can also just work to neutralize the pathogen or help to stimulate defense proteins that will help to destroy that pathogen preventing the infection from spreading or helping to eliminate the infection. And so during the primary response both memory B cells and effector cells are produced and then after the infection is cleared most of the effector cells will die but there will still be the memory B cells circulating in the body and found in the secondary lymphoid organs and those memory B cells can then become activated if we're exposed to the same pathogen again and this will lead to a much more rapid response to produce the effector cells and secrete antibodies to defend against that infection the second time we're exposed. So there's a T cell independent mechanism for activation of antibody mediated immunity and this requires a repetitive antigen. The epitope refers to the specific binding site of an antigen where the antibody can bind to and if there are multiple binding sites for antibodies that are repetitive on the surface of a bacterial cell this can lead to the activation of a B cell independent from a helper T cell. So the crosslinking of antibodies that are on the surface of the B cell the crosslinking of B cell receptors by repetitive antigen will lead to activation of that B cell clonal selection of the B cell producing both memory B cells and plasma cells and then those plasma cells will secrete antibodies. You can see here the form antibody secreted by this plasma cell is labeled pentameric IgM and so IgM is one specific subclass of antibodies. IgM forms the B cell receptors on the surface of a B cell but IgM is also form a secreted pentamer meaning five antibody proteins are linked together and these pentamers then are very efficient at binding to extracellular pathogens and causing them to clump together which is known as aglutination and that clumping will help to enable the immune system to clear the infection from the body. T cell dependent activation of antibody mediated immunity occurs when an antigen that is not repetitive binds to the B cell receptor. The B cell will perform phagocytosis to engulf the pathogen bringing that antigen within and then package that antigen into an MHC2 protein so the B cell will then become a professional antigen presenting cell using the MHC2 protein to display antigen to a helper T cell that has a CD4 T cell receptor complex. The activated helper T cell then releases cytokines that complete the activation of the B cell so now that the B cell is completely activated it will divide go through clonal selection making the effector plasma cells as well as memory B cells during an initial exposure to a pathogen there are no memory B lymphocytes there are are only the naive B lymphocytes and when a naive B lymphocyte becomes activated by exposure to a pathogen it will produce memory B lymphocytes as well as the effector plasma cells that secrete antibody so we can see that it over the time course of the initial infection the antibody concentration of the blood gradually rises and then when the infection is cleared the antibody concentration of the blood will fall but not all the way back to zero there will still be some memory B cells that are long lived and then on a secondary exposure those memory B cells will become activated more quickly and produce a stronger secondary immune response where lots of plasma B cells will be produced to secrete antibodies there are five major classes of antibodies antibodies are also known as amino globulins and so the major classes of antibodies are IgM or amino globulin M IgG IgA IgE and IgD the IgD monomer functions as a B cell receptor embedded in the plasma membrane of B lymphocytes there's also a monomer form of the IgM antibody that functions as a B cell receptor however the IgM antibody also forms pentamers as is shown in the illustration here where five IgM antibodies are linked together and the pentamer form of IgM is the primary form of IgM that is secreted by plasma cells the pentamer has 10 antigen binding sites enabling the IgM pentamer to be very good at creating clumps of antigen in a mechanism known as agglutination IgM pentamers are also very good at activating the complement system the amino globulin G or IgG monomer is the primary form of antibodies that are secreted by plasma cells and so plasma cells secrete IgM during the early phase of the antibody mediated immunity and then class switching occurs where plasma cells start to secrete more IgG monomers you can see the majority of the antibodies in blood plasma are the IgG monomers approximately 80% of antibodies in blood serum are IgG IgG is particularly efficient at activating phagocytosis in a mechanism of opsonization where the phagocytic cells have FC receptors that bind to the constant region of the IgG antibody IgA is the primary form of antibodies that are secreted by exocrine glands and secreted onto mucus membranes IgA is a dimer where two IgA antibodies are linked together creating a structure with four antigen binding sites IgE is an antibody that is particularly effective at stimulating the inflammatory response IgE activates mast cells and basophils that release pro-inflammatory mediators like histamine to stimulate inflammation IgE antibodies contribute to allergies by promoting inflammation when they stimulate mast cells and basophils IgE antibodies are also efficient at stimulating antiparasitic activity when IgE antibodies bind to antigens on the surface of multicellular parasites they can stimulate the activity of mast cells basophils and eosinophils that are effective at eliminating these multicellular parasites here we can see the time course of the antibody mediated immune response to a primary and secondary exposure to a specific pathogen before you've been exposed to the pathogen there's essentially no antibodies in the blood that could defend against that specific pathogen but after the primary exposure it takes around two weeks for the concentration of IgM to rise in the blood and it's around three weeks before the concentration of IgG reaches its maximum and so the primary immune response is relatively slow in contrast to the secondary response when you're exposed to the same pathogen a second time after having already formed an adaptive immune response to that pathogen it will take less than a week to start producing the IgM antibodies and by 10 to 15 days the concentration of IgG in the blood is much higher than was seen during the primary response by three weeks this illustration shows us the mechanism of IgA antibody secretion by mucosa associated lymphoid tissues the pyrus patches are mucosa associated lymphoid tissues found in the small intestines when antigens are encountered by lymphocytes in the mucosa associated lymphoid tissues this can lead to activation of the antibody mediated immunity where plasma cells will start secreting antibodies and some of the antibodies secreted will be the immunoglobulin A IgA secretory antibodies that will be secreted along with mucous through the exocrine gland at the mucous membrane these IgA antibodies can then bind to antigens on the surface of pathogens that are trying to enter the body or an infection that is at the surface of a mucous membrane IgE activates mass cells and basophils to promote inflammation and this mechanism can contribute to excessive inflammation producing the symptoms associated with allergies so and the allergy is an immune response to an antigen from something like a dust particle or pollen or some other antigen that's not actually associated with a pathogen but instead is being associated with something that would not cause an infection and be harmful but is just part of the environment that the immune system has recognized as foreign and has started to mount an adaptive immune response to try and attack in the illustration here we can see that an allergy could start with a phagocytic cell recognizing the allergen and performing phagocytosis engulfing antigens from that allergen and then using the class 2 MHC protein to display antigens to a helper T cell the helper T cell then will release cytokines that stimulate the immune response including helping to complete activation of a B lymphocyte this B lymphocyte has its B cell receptor activated first by antigen on the surface of the allergen and then the cytokines from the activated helper T cell complete activation of the B lymphocyte then the activated B lymphocyte will go through clonal selection proliferating to make more B lymphocytes and some of these will be the plasma cells that secrete antibodies some of the B lymphocytes will secrete the IgE antibodies and the IgE antibodies then can bind to the antigens on the surface of the allergen with the antigen binding site of the IgE but the constant region of the IgE antibody will bind to the FC receptors on the surface of mass on the surface of mass cells and basophils so mass cells that are resident inside tissues will then become activated by the allergen and start to release their inflammatory signals such as histamine which will contribute to the symptoms of the allergy neutralization is one of the mechanisms through which antibodies can help defend against infection here in the illustration we three see three different examples of neutralization where an antibody binds to a pathogen or a toxin from a pathogen and helps to block the harmful effects of that pathogen so on the left we see a virus being neutralized by antibodies when the antibodies bind to antigens on the surface of the virus this blocks the virus's ability to enter our cells neutralizing the virus preventing it from being able to spread infection in the middle we see the example of antibodies binding to a diphtheria toxin a toxin secreted by bacterial cells the diphtheria toxin needs to bind to receptors on our cells in order to have a toxic effect when the antibodies bind to the toxin this prevents the toxin from binding to receptors on the surface of ourselves neutralizing the toxin and preventing its toxic effects and then on the on the right here we see an example of antibodies binding to the flagellum of a bacterium and so by binding to that flagellum the antibodies are preventing the bacteria from being able to move efficiently through the body slowing the spread of the infection a glutenation refers to the clumping of antigens by antibodies here we see the IgM antibody has multiple antigen binding sites making it especially efficient at a glutenation so most antibodies have just two antigen binding sites but IgM pentamer has 10 antigen binding sites making it very efficient at a glutenation clumping together the antigens in this case we see bacterial cells are clumping together in the mechanism of a glutenation and this clumping will help prevent the spread of infection as well as making it easier for other mechanisms of the immune system to come and target this bacterium and remove it from the body opsonization is when a defense protein marks a pathogen for phagocytosis and so while the complement proteins are capable of functioning in opsonization antibodies also serve as labels for opsonization the FC region of the antibody the constant region serves as a tag that is recognized by FC receptors on the surface of phagocytic cells like this macrophage so when the FC receptors on the macrophage bind to antibodies on the surface of the pathogen this will stimulate the mechanism of phagocytosis antibodies can also stimulate complement fixation in the classical pathway for activation of the complement cascade antibodies mark antigens on the surface of the pathogen leading to the activation of the C1 complement protein and C1 will then stimulate C2 and C4 to activate C3 and from that point on C3 will then join together with C5, 6, 7, 8, and 9 forming the membrane attack complex a portion of C3 will also function as a chemokine attracting phagocytic cells to come and engulf the particles that remain after the pathogen has been killed by the membrane attack complex antibody dependent cell mediated cytotoxicity is when antibodies label antigen on the surface of an extracellular pathogen or a cell infected with an intracellular pathogen and then this stimulates either natural killer cells or cytotoxic T cells to release cytotoxic granules activating apoptotic cell death in the extracellular pathogen or cell that's been infected by an intracellular pathogen so this illustration shows us the example of antibody dependent cell mediated cytotoxicity where an antibody on the surface is labeling either a pathogenic cell or a cell infected with an intracellular pathogen and those antibodies are helping to stimulate activation of a cytotoxic T cell that can then release cytotoxic granules containing perforins and granzymes that activate the apoptotic cell death mechanism in the target cell whether it's a extracellular pathogen or a cell of our own body that's infected with an intracellular pathogen