Immune System A video screencast covering this information can be accessed at: https://youtu.be/KqnV9niRdcw

Immune System Immune Response--the way in which your body recognizes and defends itself against bacteria, viruses, and other substances that are foreign and harmful. The nonspecific or innate immune response is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response. In the specific/acquired/adaptive immune response once an antigen has been recognized, the adaptive immune system creates an army of immune cells specifically designed to attack that antigen. Adaptive immunity also includes a "memory" that makes future responses against a specific antigen more efficient and usually prevents symptoms upon further infection.

Nonspecific Immune Response Components of the nonspecific immune response Skin—acts a barrier; secretes chemicals such as urea and sweat which kill pathogens. Stomach Acid—the low pH (around 2) of the stomach kills most pathogens which enter the body through the mouth. Interferons—group of signaling proteins released by white blood cells which help the body fight infections caused by viruses, bacteria, and other pathogens. Natural Killer Cells—immune cells which help the body fight viral infections and tumor formation. They have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction.  Complement--a complex system of more than 30 proteins that act in concert to help eliminate infectious microorganisms. Specifically, the complement system causes the lysis (bursting) of foreign and infected cells, the phagocytosis (ingestion) of foreign particles and cell debris, and the inflammation of surrounding tissue. Nat

Nonspecific Immune Response Inflammation—movement of plasma and leukocytes to an area of damaged tissue. Often stimulated by the release of histamines by mast cells. Normal flora—bacteria which live in the body and inhibit the growth of other pathogens. Macrophages—white blood cells which engulf foreign invaders and dead or damaged body cells. Saliva and Tears—contain an enzyme called lysozyme which breaks down bacterial cell walls.

Specific/Acquired/Adaptive Immune Response Important terms Antigen—a foreign substance (usually a protein) which can stimulate the immune response to initiate a specific immune response. Antibodies—Proteins made by the plasma cells in response to a specific antigen. The antibodies bind to and help the body neutralize foreign invaders.

Specific Immune Response Two Divisions Antibody-Mediated or Humoral Immune Response--immunity conferred to an individual through the activity of B cells and their progeny, which produce circulating antibodies in response to the presence of a foreign substance and recognize the substance upon renewed exposure. The process is also known as humoral immunity because it in only effective in the body fluids. Cell-Mediated Immune Response—immune response in which active Cytotoxic T cells destroy the body’s own cells which are infected with intracellular pathogens.

Antibody Mediated or Humoral Immunity Use this video as a teaching aid: https://www.youtube.com/watch?v=AucZlvEv29Y Activation/Function 1. A macrophage or other phagocyte engulfs and intracellularly digests (with the help of lysosomes) a pathogen and displays the pathogen’s antigens on its cell membrane using a protein called the MHC-2 complex. (antigen presentation) 2. Macrophages interact with T-helper cells, with binding sites for the specific antigen, and activate them. The macrophages release a cell signal known as interleukin-1 which activates the Helper-T cells. 3. The activated T-helper cells stimulate a specific type of B cell by releasing another signal known as interleukin-2. Only B cells with receptors for the specific antigen will be activated. These cells can make antibodies against the antigen causing the trouble. 4. Once the proper B cell type is found and activated, the cells divide into many exact copies or clones (monoclonal selection).

Macrophage Pathogen MHC--II Helper-T cell CD-4 Receptor

Antibody-Mediated or Humoral Immunity Continued 5. Most of the cloned B cells then undergo a maturing process and become Plasma cells. The plasma cells are specialized cells well equipped to produce lots of protein. 6. The plasma cells produce lots and lots of antibodies. Each antibody is a protein formed in a very specific shape to bind to the specific antigen involved in this infection. These antibodies are secreted in large amounts into the bloodstream where they attach to a specific antigen and mark it for destruction. 7. Once the infection has been dealt with, most of the plasma cells undergo programmed cell death (apoptosis). Some hang around for quite awhile producing more antibodies but eventually they fade away. 8. Some the activated B cells don’t become plasma cells but instead remain behind as memory cells so that if the antigen is encountered again, the whole process will be faster and stronger. These activated cells may remain in the body for years.

Variable and Constant Regions of an Antibody.

Antibody Mediated Immunity These proteins bind to the pathogens and mark them for death. They may cause: Agglutination--The clumping of cells such as bacteria or red blood cells in the presence of an antibody or complement. The antibody or other molecule binds multiple particles and joins them, creating a large complex. This increases the efficacy of microbial elimination by phagocytosis as large clumps of bacteria can be eliminated in one pass, versus the elimination of single microbial antigens. Opsonization-- the process by which a pathogen is marked for ingestion and eliminated by a phagocyte.

Antibody Diversity The human body has a limited number of genes which code for antibodies. Even so, the body can produce at least 1012 different antibody types. How? Alternative DNA splicing (done during RNA processing)--is a regulated process during gene expression that results in a single gene coding for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene

Cell-Mediated Immunity Used to destroy the body’s own cells with are infected with viral or intracelluar bacterial infections Steps involved: 1. A macrophage or other phagocyte engulfs and intracellularly digests (with the help of lysosomes) a pathogen and displays the pathogen’s antigens on its cell membrane. (antigen presentation) 2. Macrophages interact with T-helper cells, with binding sites for the specific antigen, and activate them. The macrophages release a cell signal known as interleukin-1 which activates the Helper-T cells. 3. The Helper-T cells release interleukin-2 which stimulates Cytotoxic T-Cells specific to the antigen.

Cell-Mediated Immunity Continued 4. The Cytotoxic T-cells, once stimulated by a T-helper cell, will search out and destroy any cells in the body that are displaying the specific antigen involved in this infection. Somatic (body) cells display antigens from intracellular infections on a protein call the MHC-1 complex. This alerts the Cytotoxic T-Cell to the infection. The MHC-1 complex can interact with a receptor (CD-8) on a Cytotoxic-T cell. 5. Once attached to the infected cell, the Cytotoxic-T cell releases proteins called perforins which kill the infected cell. 6. Once the infected cells are destroyed most of the activated T cells, both helper and cytotoxic, will undergo programmed cell death (apoptosis). 7. However, a number of activated T-cells remain as Memory cells. These cells will respond to the same antigen in a much faster manner than occurred during the original infection.

Somatic Cell MHC-1 CD-8 Receptor Cytotoxic T-Cell

Primary vs. Secondary Immune Response Primary Immune Response—This occurs the first time an individual is exposed to a particular antigen. The response is slow and the number of antibodies made is fairly low. This process creates memory cells. Secondary Immune Response—This occurs upon the 2nd, 3rd, 4th, etc… exposure to a specific antigen. Because of the memory cells created during the primary immune response, this process occurs much more quickly and the antibody concentration produced is much larger. Typically, this response is so large and so fast that individuals don’t experience any symptoms of the infection.