Higher Human Biology Unit 3 – Neurobiology and Immunology Section 21 – Non-Specific Immunity

a) Non-Specific Body Defences We will be learning… To describe both physical and chemical first line defences To describe the structure and function of epithelial cells as a physical barrier To state that chemical secretions include tears, saliva, mucus and stomach acid To state that chemical secretions are produced in response to invading pathogens To define a pathogen as a bacterium, virus or other organism that can cause disease.

First Line Defences The body defends itself against disease causing organisms (pathogens), some toxins, and cancer cells by using its immune system. This can be in the form of a physical defence or a chemical defence. Immunity is the ability of the body to resist infection by a pathogen or to destroy the organism if it succeeds in invading and infecting the body.

What are Pathogens? Fungus Bacteria Virus A pathogen is an microorganism that can be seen only with the aid of a microscope and that typically consists of only a single cell. Typically they cause disease in the host. There are three main types of microorganisms. Fungus Bacteria Virus https://www.youtube.com/watch?v=1EkehFkhWf4

Destroying Invading Pathogens – Self or Non-Self? On the surface of a cell membrane, there are many proteins partially embedded in the lipid bilayer. Some of these proteins are called antigens and allow our immune system to recognise our own cells. Invading bacteria and viruses which would cause disease (pathogens) have different antigens – non-self.

Physical First Line Barriers – Non-Specific Saliva Washes microbes from the teeth and mucous membranes of the mouth Tears Wash away irritating substances and microbes Lysozyme kills many bacteria Skin Provides a physical barrier to the entrance of microbes. Acidic pH discourages the growth of organisms Sweat and oil gland secretions kill many bacteria Respiratory Tract Mucous traps Cilia sweep away trapped organisms Stomach Acid kills organisms Large Intestine Normal bacterial inhabitants keep invaders in check Bladder Urine washes microbes from urethra

Physical Barrier - Epithelial Cells of the Stomach Epithelial cells are our first line of defence against infection. They line the surfaces and cavities of the entire body and form a physical barrier against infection. The stomach is lined by a mucous membrane . The lining is always covered by a layer of thick mucus that is secreted by epithelial cells.

Physical Barrier - Epithelial Cells of the Skin The skin provides a physical barrier of dry, dead cells and mildly acidic conditions. These cells cover almost the entire surface of the body. They grow constantly upwards and outwards from the bottom layer of stem cells. By around 14 days they have become dead cells which flake off taking any bacteria or pathogens with them. Epithelial cells also produce secretions such as enzymes, hormones and lubricating fluids that can defend against infection.

Chemical First Line Barriers Some tissues are specialised to secrete specific substances, such as enzymes, hormones and lubricating fluids, to defend against infections.

Chemical Defence - Mucus The goblet cells in the trachea secrete mucus which, being a sticky substance, is able to adhere to foreign particles, thus holding them on the surface. This adhesion allows the cilia which line the bronchi to sweep the mucus, with its entrapped particles, up into the pharynx where it is swallowed. Antimicrobial chemicals are also found in the mucus, secreted by the epithelial linings of the respiratory and upper gastrointestinal tracts.

Chemical Defence - Tears Tears contain an enzyme called lysozyme that destroys the cell walls of some bacteria. As the tears are produced and the eyelid blinks, the surface of the eye is cleaned and the pathogens are washed away.

Chemical Defence - Saliva Helps moisten and break down food to ease swallowing. Saliva helps remove oral waste and cavity- causing bacteria, protects teeth from decay by neutralizing harmful acids. After a tooth is cleaned, its enamel surfaces become coated with a salivary protein film called the pellicle. The pellicle supports the attachment of free- floating bacteria. The more bacteria attach to one another, the more they “attract” other bacteria, creating large clumps that are easier to swallow and eliminate.

Chemical Defence – Stomach Acid Your stomach lining also secretes hydrochloric acid, which creates the ideal conditions for the protein-digesting enzymes to work. The potent hydrochloric acid kills bacteria, protecting your body from harmful microbes which can enter your body in food.

b) The Inflammatory Response We will be learning… To fully describe the inflammatory response To describe the role of histamine when released from mast cells To describe how increased blood flow leads to an accumulation of phagocytes and clotting elements at the site of infection

What is the Non-Specific Inflammatory Response? The inflammatory response is triggered when something breaks the skin.

The Inflammatory Response-mast cells (second line of defence). Inflammation is a common response to bee/wasp stings Chilblains – inflammation of the toes (or other extremities) caused by prolonged exposure to moisture and cold. Acne – inflammation of the skin caused by bacteria in the pores Tonsillitis – inflammation of the tonsils

Inflammatory Response-Mast Cells (second line of defence). This operates when the body suffers a physical injury or invasion by microbes. Following injury mast cells are activated and release large volumes of histamine which is a chemical that dilates blood vessels that lets them fill up with blood.

What Happens at the Site of Infection? Mast cells are made from the same stem cells that make white blood cells and are found in connective tissue throughout the body. Blood vessels in the injured area vasodilate and fill full of blood which makes the area swollen, red and inflamed. The tissues become swollen because the capillaries become more permeable and tissue fluid leaks out.

What are Mast Cells? A cell found in connective tissue, which releases histamine and other substances during inflammatory and allergic reactions. Mast cells are located at the boundaries between tissues and the external environment, for example, at mucosal surfaces of the gut and lungs, in the skin and around blood vessels. Mast cells are key players in the inflammatory response as they can be activated to release a wide variety of inflammatory mediators.

Role of Histamine Once released from its granules, histamine produces many varied effects within the body, including the contraction of smooth muscle tissues of the lungs, uterus, and stomach; the dilation of blood vessels, which increases permeability and lowers blood pressure; the stimulation of gastric acid secretion in the stomach;

Cytokines attract white blood cells called phagocytes to the area and the release of antimicrobial proteins or clotting elements to the damaged area. Histamines are also released which cause the capillary to vasodilate and become more permeable. Look at the following animation: Video

c) Phagocytes We will be learning… To describe the process of phagocytosis To fully explain the role of phagocytes in recognising and destroying pathogens To describe the role that phagocytes play in attracting more phagocytes by the release of cytokines To define the term cytokine

Phagocytes Phagocytes are cells which will engulf and digest a foreign particle such as bacteria. They recognise the foreign antigen molecules on its surface then bind with the bacterium and engulf it by endocytosis. The process of phagocytosis is carried out by a type of white blood cell called a phagocyte.

How do Phagocytes Recognise Pathogens? Phagocytes can move and when they detect chemicals released by a pathogen or detect antigens present on the surface of a pathogen they move towards it. The pathogen is engulfed(taken in to the cell) and the cell membrane folds in to form a vacuole with the pathogen inside it. Lysosomes which are vesicles filled with digestive enzymes fuse with the vacuole and release their digestive enzymes into it. The pathogen is broken down and the products are absorbed by the phagocyte. .

How do Phagocytes Destroy Pathogens? Once the bacterium is inside the phagocyte, lysosomes fuse with the vesicle, digesting the bacterium. VIDEO Pus is dead bacteria and phagocytes that can form at a site of injury

How do Phagocytes attract other Phagocytes Cytokines are released by the phagocyte and they attract more phagocytes to continue the battle. Cytokines attract more phagocytes to the damaged tissue and these engulf pathogens by phagocytosis and clean up the injured site. Fast delivery of anti-microbial proteins to the infected site which amplify the immune system. Rapid delivery of blood clotting chemicals to the injured site to prevent other microbes entering and to start repair.

Role of Cytokines NK cells and phagocytes also release cytokines after contact with a pathogen. These molecules move in the blood and stimulate the specific immune response by activating lymphocytes.

Natural killer cells Natural killer (NK) cells are found in the blood and are constantly looking for signs of an infection. They can also release cytokines but they have an important role in destroying a pathogen-infected cell. They look for a cell which has not got the normal surface antigens or self antigens and knows that it must be infected. It then destroys it with self-destructive enzymes perforating the plasma membrane, bursting it, a process called apoptosis.

NK cells are not phagocytic. Non-specific cellular responses-natural killer cells (second line of defence) NK cells are not phagocytic. They attack virus-infected cells in general and cancer cells.

The NK cells releases molecules of a protein which forms pores in the target cells of the membrane . Signal molecules from the NK cell can then enter the target cell and trigger a genetically controlled series of events. The target cell produces cell destructive enzymes and the cell’s DNA and vital proteins are broken down and destroyed and the cell dies. This is called a programme of cell death and is called apoptosis.

Questions Name a secretion made by the epithelial cells lining the inside of the body. What name is given to the immediate response of the body to a cut? What are mast cells? Why do the capillaries vasodilate? What general name do we give disease-causing organisms? Describe what an antigen is made of and where it is found. What is the name of the cell signalling molecule produced by many immune cells? Describe the process of phagocytosis. What are NK cells? Describe the stages involved in apoptosis.

Answers Name a secretion made by the epithelial cells lining the inside of the body. What name is given to the immediate response of the body to a cut? What are mast cells? Why do the capillaries vasodilate? What general name do we give disease-causing organisms? Describe what an antigen is made of and where it is found. What is the name of the cell signalling molecule produced by many immune cells? Mucus Inflammatory response Cells found under the epithelium containing histamines and cytokines Histamines causes this Pathogens An antigen is a protein marker found on the cell membrane surface Cytokine

Answers Describe the process of phagocytosis. 9. What are NK cells? 10. Describe the stages involved in apoptosis ( cell death ) Phagocyte recognises antigen on surface of pathogen as ‘non self’ Phagocyte attaches to antigen Phagocyte engulf pathogen into vacuole/vesicle Lysosomes containing digestive enzymes bind with vacuole/vesicle. Pathogen digested - Natural Killer Cells which recognise damaged or cancerous cells NK cell produces protein which punctures cell membrane of cell NK protein binds to ‘suicide gene’ in nucleus of cell Proteins produced by ‘suicide gene’ destroy cell

a) Non-Specific Body Defences Now I can….. Describe both physical and chemical first line defences Describe the structure and function of epithelial cells as a physical barrier State that chemical secretions include tears, saliva, mucus and stomach acid State that chemical secretions are produced in response to invading pathogens Define a pathogen as a bacterium, virus or other organism that can cause disease.

b) The Inflammatory Response Now I can….. Describe the inflammatory response Describe the role of histamine when released from mast cells Describe how increased blood flow leads to an accumulation of phagocytes and clotting elements at the site of infection

c) Phagocytes Now I can….. Describe the process of phagocytosis Explain the role of phagocytes in recognising and destroying pathogens Describe the role that phagocytes play in attracting more phagocytes by the release of cytokines Define the term cytokine

substance released by mast cells that causes the inflammatory response Word Definition Cytokines category of defence proteins secreted from cells; involved in signalling to other cells Histamine substance released by mast cells that causes the inflammatory response Inflammatory Response response to damage or infection involving vasodilation and cytokine release Mast Cells cells that produce histamine in response to tissue damage Non-Specific Defence general response to infection, including phagocytosis Epithelial Cells A type of cell that lines the surfaces of your body. They are found on your skin, blood vessels, urinary tract, and organs Pathogen Anything that can cause disease e.g. bacteria Antigen is a foreign molecule recognised by a lymphocyte Vasodilation the dilatation of blood vessels, which decreases blood pressure Phagocytes a type of white blood cell within the body capable of engulfing and absorbing bacteria and other small cells and particles.

Describe non-specific defences that the body uses to protect itself from pathogens The skin prevents the entry of pathogens / is a physical barrier. Epithelial cells (in cavity linings) produce (protective chemical) secretions Description of one non-specific defence e.g. mucus in windpipe / acid in stomach / lysozyme or anti- bacterial substances in tears / coughing or sneezing /blood clotting The inflammatory response is caused by the release of histamine from mast cells Vasodilation / increased capillary permeability / increased blood flow (occurs) Increased blood flow / secretion of cytokines results in the accumulation of phagocytes It also results in the delivery of antimicrobial proteins / clotting elements to the site Phagocytes recognise surface antigens/ protein markers on pathogens They then destroy the pathogen by engulfing it / by phagocytosis Natural killer (NK) cells induce the pathogen to destroy itself / apoptosis (The NK cells cause) the pathogen to produce digestive / self-destructive enzymes 12 Phagocytes / NK cells release cytokines that stimulates the (specific) immune response 10 marks