The Lymphatic System Innate Immunity 1
Types of Immunity Innate (non-specific) immunity Adaptive (specific) immunity The human body has several different ways that it defends itself against infection by pathogens. One way of looking at it is that we have three lines of defense against infection. The first line of defense includes physical barriers that try to keep pathogens out of the body in the first place. The second line of defense are fastacting responses in the body that target all invaders, regardless of whether their antigens are recognized. The third line of defense is the immune system and is activated when an antigen is encountered that our body has seen before and knows is bad. The immune system is very effective, but is slow to activate. 2
Innate Immunity Non-specific No memory cells Not me. When talking about immunity, we distinguish between innate (also called nonspecific) immune responses and adaptive (also called specific) immune responses. Innate immunity includes all of the body s general methods of defense. Basically, any substance in the body that is not recognized as part of the body is attacked and removed whether or not memory cells have been formed against it. Innate immunite begins very rapidly once a pathogen is detected, but the response is usually not as strong as adaptive immune responses. Adaptive immune responses take time and involve mounting an attack against a specific type of pathogen that the body has been infected with before. 3
Responses: Innate Immunity Surface barriers Internal (cells/chemical) responses Phagocytes Natural killer (NK) cells Inflammation Anti-pathogen proteins Fever There are several ways that nonspecific immunity works. 4
Surface Barriers Skin and mucous membranes. Physical barrier Secretions (mucous, sweat, tears, saliva, stomach secretions) Lysozyme Surface barriers (the skin and mucous membranes) are the body s first line of defense against infection. Even without their secretions, they are a very effective mechanical barrier very few pathogens can travel through the skin to infect us. In addition to physically blocking pathogens, though, the skin and mucous membranes secrete a number of substances that aid in the protection. Just a few examples: Mucous in the respiratory tract serves to trap and remove pathogens before they get into the warm, moist lungs. Sweat, saliva and (especially) stomach secretions are acidic and inhospitable to most bacteria. The stomach secretions also contain digestive enzymes which digest bacteria as well as the foods we eat. Lysozyme is an enzyme found in saliva and tears that breaks down the cell walls of bacteria. This helps us combat eye infections as well as bacteria in foods as we chew our food, saliva mixes with it. 5
Phagocytes Internal Responses Macrophages, microglia, neutrophils May be aided by chemical mediators. Phagocytosis is the destruction of a pathogen by engulfing it through endocytosis and digesting it with lysosomes. Some common phagocytes include macrophages, microglia and neutrophils. Macrophages start out in the blood as monocytes, but when they leave the blood and enter tissues, they grow into very large macrophages. Macrophages move around through their tissues, patrolling for pathogens. Microglia are found only in the central nervous system. They aren t mobile they stay in one place and wait for pathogens to come to them. Neutrophils are fast-acting WBCs that circulate in the blood and are usually the first to respond to infection. Phagocytes can be attracted and stimulated by chemicals that promote inflammation. 6
Internal Responses Natural Killer (NK) cells Pitbulls of the defense system Cause apoptosis Enhance inflammatory response NK cells are specialized lymphocytes that are especially good at targeting tumor cells. Since they are tuned to specific antigens, we can think of them as the pitbulls of the defense system. While they cause the death of their target cells, they work very differently from phagocytes. Instead of engulfing and digesting their targets, they cause the targets to undergo apoptosis (programmed cell death). In addition, they enhance the inflammatory response by attracting macrophages and neutrophils. 7
Inflammation Internal Responses Benefits Cardinal signs Stimulus: Toll-like like receptors Mast cells & histamine Chemical mediators Inflammation is one of the most well-known non-specific responses to infection. Three major benefits of inflammation include the isolation and destruction of pathogens (first by neutrophils, then within several hours by macrophages), the breakdown of damaged tissue, and setting the stage for tissue repair. Inflammation is always started by a chemical help! signal of some kind. This signal can come from white blood cells that have recognized an invader (via toll-like receptors, mast cells, etc.) or from damaged tissues itself (such as prostaglandins released when tissue is damaged). The five cardinal signs of inflammation include redness, heat, swelling, pain and loss of function. 8
Inflammation Effects: Internal Responses Vasodilation Increased permeability Chemotaxis The cardinal signs of inflammation are basically side-effects of three important events. Inflammation causes vasodilation an increase in size of the blood vessels. This vasodilation brings more blood to the site of infection, and therefore more WBCs and plasma proteins. As side effects, the increased amount of blood causes redness and heat in the affected area. Capillaries near the infection site show increased permeability. This means that more fluid as well as more WBCs can cross the capillary wall and enter the tissues. Why more fluid? The extra fluid helps to dilute any exotoxins (poisons) that have been secreted by bacteria or parasites in the tissues. Chemotaxis means moving towards a chemical. In this context, inflammation results in WBCs moving towards chemicals that identify the site of infection (protaglandins, kinins, histamines, complement, etc.) 9
This flow chart shows how the effects of inflammation cause the cardinal signs, and why they are beneficial. 10
Internal Responses Antimicrobial proteins Complement Enhances inflammation Stimulates NK cells MAC attack Interferons: SOS signals from virus- infected cells Complement is a collection of about 20 plasma proteins that normally exists as inactivated enzymes in the blood. During infection (as part of both specific and nonspecific immunity), though, the complement becomes active. It promotes inflammation by stimulated NK cells and attracting WBCs to the site of injury. It also creates MAC (membrane attack complex) protein complexes, which literally punch holes in the cell walls of bacteria, causing them to lyse. Interferons are chemical signal molecules secreted by virus-infected cells to warn nearby cells that they have been infected. This causes nearby cells begin producing antiviral proteins (added protection) and start secreting interferons of their own. Nothing can be done for the already-infected cells, but this slows or stops the spread of a viral infection. 11
Fever Internal Responses Pyrogens (from macrophages & lymphocytes) Effects: Reduces iron & zinc Speeds up repair When macrophages and lymphocytes become activated, they secrete (among other things) pyrogens. The pyrogens circulate to the hypothalamus where they adjust the body s temperature set up upwards. This causes the body to increase it s temperature (by keeping blood away from the surface, increasing metabolism, causing shivering, etc.), resulting in a weak, achy, icky feeling associated with being sick. Why would the body do this? One reason is that when body temperature rises, the liver and spleen sequester iron and zinc, both minerals that bacteria need in order to reproduce. In addition, the increase in temperature causes a rise in metabolism, which helps speed up repair and helps WBCs work more efficiently. 12