The Immune System PDF

Chapter 24 -- The Immune System =============================== Overview -------- The Immune System will be covered in two parts: ***The Nonspecific Immune System*** will cover the first lines of defense -- your skin, your killer cells, and your bodily processes. ***The Specific Immune System***...

Chapter 24 -- The Immune System =============================== Overview -------- The Immune System will be covered in two parts: ***The Nonspecific Immune System*** will cover the first lines of defense -- your skin, your killer cells, and your bodily processes. ***The Specific Immune System*** will cover your coordinated immune response -- your Killer T and B cells, your chemical responses, and your Memory T and B cells. Introduction ------------ For a pathogen to proliferate within your body, it must: - Overcome external barriers and reach the interior of the body - Overcome resistance by the host The immune system is our defense system for preventing those things from happening. It is composed of widely distributed cells, tissues, and organs, which recognize foreign substances and act to neutralize or destroy them. Our acquired ***immunity*** is our ability to resist diseases or infections. *Again, think back to PSYC 1115's section on Later Adulthood -- older adults tend to have a lesser rate of weekly sicknesses.* ### The Two Branches of The Immune System #### The Nonspecific Immune Response This is your nonspecific resistance. It acts as a first line of defense against anything in your body that's not supposed to be there -- bacteria, pathogens, infections... It's a fast-response system poised to always attack. It's the reason why we don't get sick too often from microbes or foreign materials that enter us daily. Since it purges anything and everything that doesn't belong within the body, it has no need for a long-term immune memory, and therefore lacks one. It includes mechanical, chemical, and cellular defenses. Barriers like our skin and gastrointestinal tract, cells like our neutrophils, macrophages, and natural killer cells, and processes like inflammation all comprise the Nonspecific Immune System. #### The Specific Immune Response The Specific Immune Response steps up where the Nonspecific one fails. It builds our resistance to specific foreign agents. It's slower on the uptake than our Nonspecific Immune Response but makes up for it in its memory capacity. Every interaction it has with a pathogen makes it better at fighting it, up until it no longer makes you sick anymore. Our Killer T and B cells, Antibodies and Cytokines, and our Memory T and B cells compose the Specific Immune Response. A good understanding of this foundation will go a long way to understand the rest of this unit. The Nonspecific (Innate) Immune Response ---------------------------------------- Innate immunity includes nonspecific defenses, such as physical and chemical barriers and phagocytic cells, that are present from birth and are always active. ### Barriers #### The Skin The skin is an inhospitable environment for microbes. The pH is acidic and it's salty, it goes through bouts of drying and is overall just a not fun time for microbes. #### The Gastrointestinal Tract It's an acidic environment overall. The digestive enzymes in the small intestine will cut through anything that they get on, including invading microbes. #### Lungs The mucociliary escalator sweeps trapped microbes away from the lungs. ### The White Blood Cells of the Immune System #### Macrophages and Neutrophils Macrophages and Neutrophils destroy foreign material that has managed to get inside the body. They find these materials via chemotaxis and ingest them, digesting them and destroying them. #### Natural Killer Cells Natural killer cells are the body's first line of defense for derelict cells (e.g., cancer, virally infected cells). They destroy these infected cells by releasing granzymes and a protein called perforin that cause the cell to rupture. ### Interferons and Complement Proteins #### Interferons Interferons are proteins released by virally infected cells that help other cells resist viruses. When a cell gets infected, it's doomed. Before that, it releases a "Hail Mary" in the form of Interferon that notifies other cells that it has been virally infected. The other cells, in response, increase production of antiviral proteins that destroy viruses before they infect cells. ### Inflammation Any damage to tissue sets off inflammation. Inflammation unites all the components of immunity and healing. It can be caused by any pathogen or physical trauma. The suffix "-itis" indicates any inflammatory process, e.g., appendicitis, cellulitis, myocarditis, meningitis... etc. Look at this diagram. Suppose you get a splinter, and now bacteria have been introduced into your system. Histamines and other chemical mediators are now released by mast cells to introduce water into the cell battlefield and summon phagocytic cells to clean up this mess. You notice this as a mild redness and swelling. Histamines are also responsible for triggering runny noses, watery eyes, coughs, and sneezes to expel bacterial invaders. Histamine is a very potent vasodilator that makes your capillaries very leaky and permits white blood cells to move into the tissues. There are five cardinal signs of inflammation: - Redness, caused by blood flow to the site and warmth. - Swelling, as fluid and response cells move into the local interstitium to fight off infection. - Pain, because of the vasodilation allowing capillaries to press on the nerves - Altered function #### Why Inflammation is Good Inflammation is good because it dilutes, destroys, and neutralizes any agents that have permeated the tissues. It also repairs any damage done to the tissues, preferably through regeneration, in which parenchymal cells replace other damaged ones. If regeneration is not possible, then they'll repair via fibrosis (scar tissues). You'll often find a combination of the two. #### Why Inflammation Can Be Bad Inflammation can be bad, however, if it does something that it was never supposed to do or is triggered by something it was never supposed to be triggered by. Anaphylactic Shock is a potentially fatal result of an allergic reaction, where an inflammatory response happens all over the body. Inflammatory conditions can also lead to irreparable damage, such as Pericarditis, where the Pericardial Sac can be scarred and inhibit proper cardiac function. The Specific Immune Response ---------------------------- ### The Four Characteristics of Specific Immunity The Specific Immune System has four distinct characteristics: - Discrimination between self and nonself - The SIR can respond selectively to nonself, producing specific responses against a stimulus - Diversity - The SIR can generate enormous diversity of molecules. - Specificity - The SIR can direct itself against one specific pathogen or foreign substance among trillions. - Memory - The response to a second exposure to a pathogen is fast enough and precise enough that you won't even get sick upon a second exposure. ### Cells of the Adaptive Immune System The adaptive immune system consists of B lymphocytes and T lymphocytes. Either requires exposure to a target antigen before coming online. Each lymphocyte is specific to one antigen... but you have billions. #### B Lymphocytes B Lymphocytes respond to pathogens by producing antibodies. These proteins neutralize foreign objects like bacteria and viruses. B lymphocytes are responsible for the humoral(antibody) mediated response, where humoral means the outside-of-cell environment. #### T Lymphocytes There are 2 types of T Lymphocytes: - Helper T lymphocytes are the directors of the immune system. In other words, they're very important. They help trigger B lymphocytes. - Cytotoxic T cells produce toxic molecules that contain powerful enzymes that induce the death of derelict cells (virally infected and cancer cells). Collectively, they're a part of the cell-mediated response, where cell-mediated means pathogens currently inside of cells. #### Where do B and T Lymphocytes Come From? B and T lymphocytes develop from stem cells in the bone marrow. B lymphocytes mature in the bone marrow, while T lymphocytes migrate to the thymus gland to mature. Once they finish maturing, they'll move to the lymphatic system (spleen and lymph nodes) to await a specific foreign invader. #### Humoral and Cell-Mediated Immunity So, to recap: - Humoral immunity produces antibodies in response to extracellular pathogens and toxins. - Cell-mediated immunity responds to intracellular pathogens, transplanted tissues, and cancer cells. It depends on the direct action of Cytotoxic T cells instead of antibodies. Humoral immunity is the type of adaptive immunity that fights infections in the circulation and lymph fluid. Look at this graph. Basically, when a pathogen's response activates the B cells in the lymph nodes, a single B lymphocyte with the help of a Helper T lymphocyte will divide rapidly and the resulting cells will secrete antibodies into the bloodstream that bind to the backs of the invaders and render them inert and unable to infect so they can be eaten by phagocytes. Long-living Memory B Cells will also be made as a result of this that prime your immune system to respond to the antigen if it ever enters the body again. #### T Cells T cells mount the cell-mediated response in which deal with viruses within cells. The humoral immune response doesn't work on virally infected cells, so the Cell-Mediated response must step up to the plate. Cytotoxic T cells recognize a specific antigen on the surface of an infected cells that triggers the T cell to create an army of lethal cells. The resulting cells release granzyme and perforin that cause similar infected cells to the original cell to kill themselves. Some leftover lethal cells become Memory T cells that trigger a rapid response to the same infection next time it comes around, so that it doesn't make you sick next time. ### Antibodies Antibodies, also known as immunoglobulins, act as the weapons of humoral immunity. Think of the B cells like a HIMARS System and the antibodies like HIMARS missiles. Antibody molecules have antigen binding sites specific to the antigenic determinants that elicited its secretion. Antibodies can neutralize viruses so they can't move, agglutinize them so they're all stuck together waiting for phagocytes can eat them and precipitate them out of solution and render them inert. Antibodies can also trigger inactive proteins in the blood (complement proteins) produced by the liver that puncture holes in bacteria that lead to ***cell lysis***, where the innards of a bacterium begin spewing out. This is an example of the Adaptive Immune System triggering the Innate Immune System. ### Immunological Memory Generation of memory lymphocytes is the key to long-term immunity, and the key to vaccination success. Very simply put, they trick your adaptive immune system into thinking there's a virus or bacterial infection to stimulate the creation of memory cells. Two exposures to an antigen trigger two phases of immunity. The primary immune response is the first response of an antigen to the lymphocyte and clonal selection occurs, where a single activated lymphocyte divides several times. This response doesn't happen right away and may take several days. The highest antibody concentration occurs after 2 weeks. ### Types of Specific Immunity #### Naturally Acquired Active Immunity This is the type of immunity a host develops after exposure to a foreign substance. Ergo, you got sick, you got over it, and now you have the Memory T and B cells so that that strain will never harm you again. #### Naturally Acquired Passive Immunity Naturally Acquired Passive Immunity is a transfer to antibodies (e.g., mother to fetus across the placenta, mother-to-infant transfer across breastmilk) #### Artificially Acquired Active Immunity Vaccination. An intentional exposure to a foreign material. #### Artificially Acquired Passive Immunity Preformed antibodies or lymphocytes produced by one host are introduced to another host, for example, antivenoms or antibody injections. ### Vaccination Edward Jenner discovered in the 1800s that milkmaids were naturally immune to smallpox, because they became infected with cowpox, a similar disease to smallpox that was not deadly. He decided to try inoculating people with the goo from cowpox pustules to see if that would prevent their infection with smallpox. The *unethical* part is where he exposed a child to cowpox first, and then smallpox. No one knows if they were his child or someone else's. Vaccination is the administration of antigenic material to stimulate adaptive immunity to a disease. They attempt to induce antibodies and activated T lymphocytes to protect a host from future infection. The administered material can either be a: - Killed or inactivated form of the pathogen - Live, but weakened forms of the pathogen - Purified material such as proteins or inactivated bacterio-toxins from the pathogen - Viral mRNA #### Vaccine Success Poliomyelitis is a viral infection that targets motor neurons and enterocytes in your digestive tract, leading to paralysis. It was one of the most dreaded childhood diseases in the 20^th^ century. The iron lung was a machine that was used on children with polio so that they could continue to breathe. One of the last Children of the Iron Lung died in 2024. Jonas Salk developed the first polio vaccine. ### Immune Malfunction Autoimmune diseases happen when the immune system turns against the body's own molecules. For example, Type I diabetes happens when the insulin creation cells are falsely targeted by the Immune System Allergic reactions happen when a non-harmful substance (e.g., peanuts) is targeted by the immune system. Immune Deficiency disorders happen when the immune system components are lacking and can no longer fight off an infection. #### Bubble-Boy Disease Severe Combined Immunodeficiency or SCID is a primary immune deficiency that results in a defect in both T and B lymphocyte systems. This usually results in the onset of one or more serious infections within the first few months of life. People with SCID typically don't live long, even in total pathogenic isolation. The cancer typically does them in because the immune system isn't present to deal with those cells. #### AIDS The HIV virus attacks helper T cells and cripples both cell-mediated and humoral immunity. AIDS is not the one that does you in, but rather, any opportunistic infection that your immune system cannot mount a response against. AIDS is, at the time of writing, completely incurable, but HIV can be staved off to the point where it doesn't morph into AIDS anymore. This brings us to the end of ***The Immune System***. We are nearing the end of BIOL 1111. Are we good to go? Good.