10.+Innate+Immunity.docx

**Immune System** - The immune System is composed of 2 divisions - Innate Immunity (aka nonspecific immunity) - Immune cells attack anything it views as foreign to the host - Adaptive immunity (aka specific immunity) - Immune cells ONLY target specific microorg...

**Immune System** - The immune System is composed of 2 divisions - Innate Immunity (aka nonspecific immunity) - Immune cells attack anything it views as foreign to the host - Adaptive immunity (aka specific immunity) - Immune cells ONLY target specific microorganisms **Innate Immunity** - The structures, chemicals, and cells that act against pathogens in the body can be broken down into 3 main lines of defense - The first two lines are part of innate immunity (aka nonspecific immunity) - Called innate because these are present from birth, prior to contact with any infectious agents - The 3rd line of defense involves methods of immunity for specific pathogens following exposure and is part of Adaptive Immunity (aka specific immunity) **[The Body\'s 1st Line of Defense]** - The body\'s natural barriers and secretions - Prevent pathogens from entering the body in the first place **Mechanical and Chemical Barriers** - **Skin** - The largest organ of the body - Composed of 2 main layers - Epidermis - Outer layer - Dermis - Deeper layer - Contains hair follicles, glands, nerve endings, etc\... - **Physical** **Barrier** Protection - Epidermis made up of many layers of cells that are so tightly packed together that pathogens cannot penetrate them unless it is injured (e.g. burn, cut, etc\...) - The lowest levels (basal layer) of epidermal cells constantly divide and push dead and dying cells to the top - These cells are continually sloughed off along with any pathogens that may be resting on them - This helps to remove microbes from the skin's surface. - Dermis contains tough fibers called collagen - Gives strength and elasticity to skin - Allows it to withstand damage and puncture - **Chemical Barrier** Protection - Dendritic cells - Located in the epidermis - Perform Phagocytosis (ingestion of foreign substance) against colonization and infection by pathogen - Defensins - Antimicrobial peptides - e.g. sweat glands produce a form of these to kill microbes on the skin - Lysozymes - Destroys cell walls of bacteria via the breaking of bonds between sugar molecules - Sebum - Oily substance secreted by sebaceous glands in the dermis - 2 methods of antimicrobial function - Keeps skin pliable so it is more resistant to injury - Lowers skin pH to around 5 - Inhibits bacterial growth - **Mucous Membranes** - Mucous secreting membranes cover all body cavities that are open to the environment - i.e. respiratory, gastrointestinal (GI), genitourinary (GU), and reproductive tracts - Respiratory tract contains - Goblet cells - Secrete mucous which trap microbes - Ciliated cells - Cilia beat to propel microbe containing mucus out of the respiratory tract - GI tract - High acidity (low pH) of the stomach kills most microbes - Saliva in the mouth contains lysozymes, enzymes which break down bacterial cell walls, and other antimicrobial molecules - GU/Reproductive tract - Mucous membrane provides a physical barrier to infection - Urine flushes microbes out of the urethra - Vaginal acidity helps to prevent microbial colonization - Eyes - Lacrimal glands produce lysozymes in tears **Normal Microbial Flora** - Microbial flora refers to the normal microbial life that exists on and within a body at any given time - Most microbial life is harmless and beneficial to humans - e.g. In the human gut. E. coli produces Vitamin K as a byproduct of its metabolic reactions, which human cells can then utilize - Normal microbial life consumes available nutrients and makes life inhospitable to other microbes\` - Also able to change pH which creates an environment hospitable to existing microbial life **Innate Genetic Immunity** - Some individuals are born with genes that offer them protection from certain pathogens - Examples - HIV Immunity - About 1% of population has a mutation in the CCR5 receptor (a receptor on T cells) - This is the site by HIV enters T cells - This mutation prevents HIV from entering the T cells - Malaria Immunity - Patients with Sickle Cell Disease are immune from malarial infection due to the shape of their red blood cells **[The Body\'s Second Line of Defense]** - This occurs when the 1st line of defense is breached and is carried out by different cells and chemical mediators **Leukocytes** (White Blood Cells) - Granulocytes - Basophils - Release histamine in inflammatory response - Eosinophils - Targets parasites - Play a role in asthma and some allergic reactions - Neutrophils - Phagocytosis - Agranulocyte - Lymphocyte - B cell - involved in adaptive immunity - T cell - involved in adaptive immunity - NK (natural killer) cell - Targets virally infected cells and cancer cells - Monocyte - Macrophage - Phagocytosis - Leukocytes are produced in the red **bone marrow** of the skeleton **Phagocytosis** - The consumption of a pathogen - Primarily performed by neutrophils and macrophages - Occurs in 5 steps - Chemotaxis - Certain microbial components, chemicals released from damaged tissues and **chemokines** released by other white blood cells attract neutrophils and macrophages - Adherence - Once the macrophages and neutrophils arrive they attach themselves to the offending pathogen - Ingestion - Once attached the cell coats the pathogen in a membrane to form a **food vesicle** called a **phagosome** - Brings phagosome inside itself - Death of Pathogen - An organelle called the Golgi Body creates a vesicle containing **hydrolytic enzymes and digestive chemicals which break down many types of molecules** - **Called a Lysosome** - Lysozyme vesicle fuses with phagosome to create a **phagolysosome** - Phagolysosome contains toxic **oxygen radicals, various digestive enzymes, and creates an acidic environment** (pH 5.5) by actively pumping in H^+^ from cytoplasm - These factors effectively \"digest\" engulfed microbes - Elimination - Remnants of pathogen removed via **exocytosis** **Opsonization** - Process by which a pathogen is covered by antibodies or complement proteins to make it easier to be recognized by phagocytic cells **Eosinophils** - Attach to surface of parasitic helminths (worms)and secrete toxins which weaken/kill the parasite - Increased \# of eosinophils in blood is usually symptomatic of parasitic infection or allergic inflammatory response **NK Cells** - Create toxic proteins, called **porforins**, which destroy the cell membrane of virally infected cells, certain tumor cells, and some varieties of parasite **Interferon (INF)** - Protein molecules released by host cells released in the presence of several pathogens, particularly viruses - - Virally infected cells produce a small protein that spreads to neighboring cells and induces them to produce antiviral proteins that prevent viral replication from occurring - Type I Interferons - Alpha (**INF-α**) - Secreted by monocytes, macrophages, and some lymphocytes - Beta (**INF-β**) - Secreted by fibroblasts - Act within hours of infection - Mechanism of action - Viral replication in host cell triggers gene expression of INF - INF binds to neighboring, uninfected cells - Binding triggers production of antiviral proteins (AVP) - AVP remain dormant until host cell becomes virally infected - AVP becomes active and stops protein synthesis by degrading mRNA - Inhibits viral replication - Affects hosts cellular metabolism negatively but typical antiviral state lasts just a few days - Long enough for cells to get rid of virus - Short enough for cell to survive without protein production - Type II Interferons - Gamma (**INF-γ**) - Secreted by T lymphocytes and NK cells - Takes days to weeks to be produced - Has smaller role in viral infections - Important in regulation of immune cell activity - Mechanism of action - Stimulates macrophage activity → ↑ phagocytosis - Stimulates increased NK cell activity **Complement System** - A system of about 30 proteins, produced by the liver, which circulate through the bloodstream in an inactivated state - Can induce killing via opsinization (leads to phagocytosis) or cell lysis. - Activation of complement occurs in a cascade in which each component initiates the next step in the pathway - 2 Primary Pathways - Classic Pathway - **Adaptive** (specific) **immunity** - This pathway activated by antigen antibody complex (formed when an antibody joins with an antigen on a pathogen) - Alternate pathway - **Innate** (nonspecific) **immunity** - This pathway activated by pathogen recognition - Results in formation of a large protein called a membrane attack complex (**MAC**) which creates a hole in the cell wall of bacteria causing lysis of the bacterial cell - Has a greater effect on Gram (-) cells due their thinner cell walls **Inflammation** - Inflammation serves to localize the effects of injury (infection, toxin), minimize these effects, and destroy the pathogen when possible. It also sets the stage for tissue repair - ***Cardinal signs of inflammation:*** Rubror (redness), Calor (heat), Tumor (swelling), Dolor (pain) and Functio laesa (impaired function). - Stages of Inflammation - Injury releases chemical mediators, especially **histamine,** which cause **vasodilation** (increase in the size of a blood vessel), increased blood flow (**hyperemia**), and increase in **vascular permeability** - Increased permeability will allow fluid to leak from the vessels into tissues and causes **edema** (swelling) - Pain may be caused by release of chemical mediators, nerve irritation by toxins or pressure on nerves from edema fluid - Vasodilation and hyperemia will deliver clotting factors to the site of injury, or phagocytic cells -- a process known as **phagocytic mobilization** -- to destroy invading pathogens. This sets the stage for repair **Fever** - A temperature \> 37C (98.6F) - The hypothalamus of the brain serves as the \"thermostat\" for the body - When certain chemical mediators known as **pyrogens** are detected they trigger the hypothalamus to increase the body\'s temperature - Pyrogens include bacterial toxins, cytoplasmic contents of bacteria released on cell lysis, antigen-antibody complexes, chemicals released by white blood cells, etc\... - Increased temperature that occurs with fever interferons and other chemicals toxic to bacteria and inhibit microbial growth in some pathogens