The Immune System Grant Black Ryker Potokar

The Immune System The immune system is a way for animals to eliminate or avoid pathogens, or something that causes a disease. There are two types of immunity:  Adaptive immunity, which all vertebrates have, is “learned” from prior exposure to a foreign substance like a toxin or bacteria.  Innate immunity, which all animals have, is active from the time of birth and doesn’t require any exposure to pathogens to function The immune system recognizes cells by structures on the cell wall.

Innate Immunity Barriers:  Skin, mucous membranes  The skin has a low pH, which prevents growth of many types of bacteria  Mucus traps bacteria and other pathogens Internal defenses: Different types of cells, such as phagocytic cells and natural killer cells Inflammatory response  Innate immunity is a rapid response system, and is a nonspecific response system.  All animals and plants have innate immunity  Foundation of adaptive immunity

Natural killer cells  Circulate through body and detect abnormal cells  Said abnormal cells are then killed by the release of chemicals  Natural killer cells help prevent cancerous cells from spreading, along with cells that have been infected with viruses/virii/a virus

Different types of phagocytic cells  Neutrophils are drawn by infected tissues, circulate in blood  Macrophages are found all throughout the body, not just in blood  Dendritic cells help boost adaptive immunity in cells that come into contact with the outer environment, such as skin cells  Eosinophils release enzymes beneath mucosal surfaces, killing pathogens there

Innate in invertebrates  Exoskeleton is first line of defense, keeping bacteria from entering the body  The enzyme lysozyme breaks down cell walls  Hemocytes are found in hemolymph, which break down bacteria by phagocytosis.  After phagocytosis, bacteria are stored in vacuoles until lysosomes destroy them.

Adaptive immunity  Antibodies defend against threats  Very specific response, you have to “learn” to defend against each specific pathogen. Adaptive immunity also has a much slower response time than innate immunity.

How are pathogens recognized?  Phagocytic cells have special receptors called Toll-like receptors  These bind to certain molecules that particular sets of pathogens have

 When a pathogen is recognized, peptides and proteins are released that either directly attack pathogens or impede their reproduction  Interferons, part of innate immunity, interfere with viruses and help alert macrophages

Inflammatory response  Includes reactions like pain and swelling  Can be local or systemic  Histamine is released, which dilates blood vessels and makes them more permeable  Signaling molecules, called cytokines, promote blood flow to infected area  This increased blood flow assists in delivery of antimicrobial peptides  In turn, this results in accumulation of pus, which is rich in white blood cells, dead pathogen, and cell debris  Septic shock - a life-threatening condition, caused by an overwhelming inflammatory response

Two types of white blood cells, or lymphocytes, are relied upon for the adaptive response: T cells and B cells  WBC that mature in thymus are T cells  WBC that mature in bone marrow are B cells  These react to antigens, which are basically just things that can get a response from one of these cells.

 B and T cells recognize antigens by binding to them via antigen receptor  Every antigen receptor on a particular cell is identical to every other receptor  The part of the antigen that is bound to the antigen receptor is called the epitope

Cell Wars V: The Pathogen Fights Back  Some pathogens have adaptations that allow them to evade annihilation by phagocytic cells  For instance, Tuberculosis resists being dissolved by lysosomes after being engulfed  Some pathogens have evolved to change the epitope expressed to avoid detection, called antigenic variation. This is seen in pathogens such as the influenza virus.  Others avoid a response by entering an inactive state after infecting a cell, until reactivated by some stimuli

B Cell Antigen Receptors  Each is shaped like a “Y” and has two identical pairs of heavy and light chains  Each chain has constant (C) and variable (V) regions, where the constant regions change little between B cells and the variable regions differ greatly.  The V regions of both heavy and light chains bind to the antigen  After binding to the V region, an antibody, or immunoglobulin, is released.  It is these that fight the pathogen, not the actual B cell

T Cell Antigen Receptors  Two different polypeptide chains, called ɑ and β  The tips are V regions, the rest are C regions  Once again, the V region is where the binding happens  Only bind to antigen fragments displayed or presented on host cell  MHC, or Major Histocompatibility Complex, molecules are proteins that display fragments on cell surface.

4 Major traits of Adaptive Immune Sys. 1. Diversity of lymphocytes and receptors 2. Self-tolerance 3. Immunological memory 4. Proliferation (deployment) of B and T cells after activation

B and T cell Diversity  The immune system can combine multiple elements to create a huge variety of antigen receptors  Many different chains can be created from one gene by rearranging DNA  This rearranged DNA is transcribed and translated, creating the antigen receptor  Example: A gene for a light chain has one C segment, 50 different V segments, and 6 different joining segments, creating a total of 300 possible combinations

Self-tolerance  Since the rearrangement is random, cells sometimes have receptors for the body’s own molecules  In such a case, apoptosis occurs to some, while the remainder are rendered non- functional

Proliferation of B and T cells  In lymph nodes, an antigen is constantly exposed to lymphocyte after lymphocyte until a match is made  After this occurs, the matching lymphocyte undergoes multiple divisions to create clones, called clonal sections  There are two types of clones: effector cells and memory cells  Effector cells act immediately against the antigen  The memory cells live much longer and can produce effector cells if the same antigen is encountered again

Immunological memory  Long-term disease prevention  Primary immune response occurs after first exposure to an antigen  Secondary immune response involves memory cells helping to defend the body faster, stronger, and longer  This memory can last many decades

 Antibodies do not kill pathogens, but rather mark them for destruction  They may neutralize the pathogen by binding to its surface, preventing it from entering another cell  They may also do this to toxins in bodily fluids  When they bind together, they may also bind to a complement protein that triggers a series of events  This series of events eventually results in lysis of the foreign cell

 B cells have five possible forms, each of which have similar antigen binding specificity, but different C regions  One type is membrane bound, but the rest are soluble  Those that are soluble include those found in blood, tears, saliva, and breast milk

Active and passive immunization  Active automatically occurs when infected  Passive provides immediate, short-term protection  Both can be artificially induced

Artificial inducement of immunity  Vaccination, or immunization, induces active immunity by introducing antigens into the body that have been weakened or killed  Passive immunity can be artificially conferred by injecting antibodies into a nonimmune person

Immune rejection  Cells transferred from one person to another are vulnerable to attack from the recipient’s immune system  This is a problem when transferring blood and organs  To minimize the risk of rejection, tissues are chosen that closely resemble the recipient’s  Immunosuppressants are also administered, but this increases the risk of infection

Allergies  Allergies are exaggerated responses by the immune system to certain antigens  In localized allergies like hay fever, antibodies are secreted onto the pollen grains which triggers release of histamines  If you recall, histamines are part of the inflammatory response  Antihistamine can be used to block receptors for histamine and help alleviate symptoms

 A severe allergic reaction can lead to anaphylactic shock, which is life threatening  For this reason, epinephrine is often carried to counteract this reaction

Autoimmune Diseases  In individuals who have an autoimmune disease, the immune system targets certain molecules of the body  Examples include multiple sclerosis (MS) and rheumatoid arthritis