LINES OF DEFENSE Physical Barriers, Innate Immunity, Acquired Immunity LINE OF DEFENSE FIRST LINE OF DEFENSE: PHYSICAL BARRIERS Skin and Mucosal Membrane The skin has a pH of 3–5 ● It produces acids that kill bacteria. ● Oil and sweat gland secretions make growth of pathogens on the skin difficult. ● The outer layer of skin cells also continually flake off carrying pathogens with them Skin and Mucosal Membrane Mucous membranes produce a viscous fluid called mucus that traps pathogens and foreign substances. Also contains Lysosomes Defence in the respiratory tract is aided by cells with cilia (singular: cilium) that sweep mucus and trapped particles Cilia in Lungs WHAT HAPPENS WHEN PATHOGENS GET PAST PHYSICAL BARRIERS? –>SECOND LINE OF DEFENSE: INNATE CELLS (Phagocytosis, Natural Killer cells, Inflammation, Fever) PHAGOCYTES Pathogen is detected by a class of WBCs called PHAGOCYTES. ● Recognise pathogens using the receptors present on the white blood cell’s surface. ● The pathogen is engulfed in a vacuole ● Vesicles containing lysozyme and other enzymes fuse with the vacuole, release their contents and destroy the pathogen. Neutrophils are a type of granulocyte normally found in the bloodstream. They are the most abundant type of phagocyte and the first responder to inflammation Neutrophils leave the bloodstream and reach the site of an infection by squeezing into the tissues. They rapidly engulf invaders Macrophages are tissue monocytes- they travel in the bloodstream and are attracted to infection sites where they move into tissues. They are also stationed in the spleen and lymph nodes. Macrophages act as scavengers and digest blood cells that have come to the end of their life-span, dead cells and debris ANTIGEN PRESENTATION Sometimes macrophages don’t fully digest pathogens. They can return part of the ingested pathogen to their cell surface into transmembrane proteins called MHC Class II It is displayed to other cells to produce antibodies and attack the pathogen –>SECOND LINE OF DEFENSE: INNATE CHEMICALS (Antimicrobial peptides and proteins) CHEMICAL INNATE IMMUNE RESPONSE The chemicals are: 1. Interferons 2. Complement system proteins 3. Cytokines. INTERFERONS Interferons are glycoproteins that inhibit the replication of viruses. Within hours of the onset of a viral infection, interferons are produced by the virus- infected cell. Interferons cause neighbouring uninfected cells to produce substances to stop themselves from being infected and inhibit viral replication. High concentrations of interferon limit the spread of the virus until a further immunological response can be mounted. COMPLEMENT PROTEINS ● Complement proteins circulate in the blood plasma in an inactive form. They are activated when they encounter antigens from pathogens such as bacterial cell walls Complement proteins join together to form a protein complex that punches holes in bacterial cell walls and plasma membranes ● These proteins ALSO attract phagocytes to the infection site and trigger inflammation CYTOKINES Cytokines produced mainly by T-cells and macrophages can stimulate the proliferation, maturation AND function of the other cells involved in defence. →SECOND LINE OF DEFENSE: INNATE CELLS AND CHEMICALS INFLAMMATORY RESPONSE AND FEVER MAST CELLS AND HISTAMINE When a pathogen gets passed the mucosal membrane, mast cells release histamine. Mast cells are a type of connective tissue cell that store histamine. Histamine causes: 1. Blood capillaries dilate and become more permeable or leaky 2. Results in redness and heat in the inflamed area. 3. Complement proteins and antibodies leave the blood and move to tissues 4. Macrophages and neutrophils are activated and they are attracted to the infection site 5. Capillaries leak fluid into surrounding tissues which causes swelling LOCALIZE VS SYSTEMIC INFLAMMATION In a localized inflammation, pus is typically formed. This is a fluid mixture of living white blood cells, dead microbes and cell debris that accumulates at the infection site. A severe injury (e.g. a stab or gunshot wound), tonsillitis, and appendicitis can cause a severe systemic inflammatory response. Systemic means a response throughout the entire body FEVER A fever is caused by special substances called pyrogens which are released by activated macrophages and are a metabolic product of pathogens Fevers can cause chills, body aches, a rise in blood pressure and increased capillary permeability. Bacteria can also produce pyrogens Fevers induce stress on pathogens and infected cells directly →SECOND LINE OF DEFENSE: INNATE CELLS NATURAL KILLER CELLS NATURAL KILLER CELLS ● Natural killer cells are lymphocytes that are able to recognise and destroy virus-infected cells and cells that have mutated to form tumours ● All body cells have a protein on their surface called a class I major histocompatibility complex (MHC) marker molecule ● Virus-infected cells and tumour cells stop expressing class I MHC molecules on their cell surfaces and the natural killer cells attack these cells releasing vesicles that contain pore-forming proteins which result in lysis of bacteria UNLIKE OTHER LYMPHOCYTES, THESE LYMPHOCYTES HAVE NO MEMORY