ANSC 40300 Lecture 2B PDF

Dr Kieran Meade Associate Professor of Immunobiology UCD College of Health and Agricultural Sciences ANSC40300 MSc in Animal Science...

Dr Kieran Meade Associate Professor of Immunobiology UCD College of Health and Agricultural Sciences ANSC40300 MSc in Animal Science L2B: Innate Immune System www. immunobiology.ie 1 Lecture content – lecture 2 Topic Title 2A Why is Evolution relevant? 2B What is the innate immune system? 2C What is the adaptive immune system? 2D Mans influence on livestock – relevance for immunity? 2 Failure to protect = no survival The earliest life forms needed to survive long enough to reproduce or the species would die out Think of primitive life forms and ask yourself how do they protect themselves against infection? Horseshoe crab secretes Tough exoskeletons to Echinoderms secrete mucus glycoproteins through pores prevent bacterial entry with antimicrobial peptides to immobilize bacteria 3  All these early mechanisms are called innate Invertebrates use three major defence mechanisms: bacteria 1. Opsonisation – complement proteins in blood ‘tag’ invaders for destruction The complement system comprises plasma proteins that can be activated either directly by pathogens or indirectly via antibody-bound pathogens, resulting in a cascade of reactions on the pathogen's surface that produces active components with diverse effector functions. 2. Phagocytosis – ‘to eat’ by cells called phagocytes which have opsonin receptors. examples of opsonins - mmunoglobulins (Ig), complement components, mannose binding lectin (MBL), and C-reactive protein (CRP). Phagocytes express receptors that recognize and interact with opsonins. Foreign material is engulfed into a vesicle called a phagosome and enzymes from the lysosome are phagocyte cells - a type of added (they fuse to form a immune cell engulfs phagolysosome) to digest and excrete it. 4 https://www.youtube.com/watch?v=_AqnnDs6H1I All these early mechanisms are called innate 3. Antimicrobial peptides -AMPs are small peptides that widely exist in nature and kill bacteria, fungi, parasites and viruses. They are positively charged whereas bacteria membranes are negatively charged. Over time we have learnt that these also affect our own immune cells – this is known as immunomodulation and so we refer to these as Host Defence Peptides (HDPs). host defence peptides are naturally occurring peptides that combat infection. they are short cationic amphiphatic peptides The immunomodulatory role of AMPs encompasses their impact on nearby cells, the recruitment and activation of additional cells, the facilitation of responses to pathogenic microorganisms, and the resolution of the inflammatory process, thereby demonstrating a systemic effect. DOI: 10.1038/nrmicro1098 5 All these early mechanisms are innate As all modern (extant) life evolved from these early invertebrate life forms – these defence mechanisms have been retained because they are effective. They are referred to as universal defence mechanisms in the animal kingdom. As life forms became more complex, more specialised immune mechanisms arose (i.e. in vertebrates). Adaptive immunity arose around the time of ‘jawed vertebrates’. Mammals (milk producers) are a group fo vertebrates consist of three orders – the egg layers (monotremes), - the marsupials (pouched mammals) and - eutherians (or placental mammals). 6 Innate immunity in vertebrates AMPs from frogs are We are primarily concerned with the immune systems now used as a cream in the third order (placental mammals) – unless you for diabetic plan on farming platypuses or kangaroos? foot ulcers! BUT other vertebrate non-mammalian species (fish and chicken immunity) are also very important for Very effective drugs used in the agricultural industry. human medicine originally came form the sea snail, Also, for the pharmaceutical industry, solutions form for example, but are now made any order will do nicely! Think CRISPR. synthetically! 7 What do we mean by innate immunity? The innate immune system is the body's first line of defense against foreign molecules entering the body. It acts very quickly: For instance, it makes sure that bacteria that have entered the skin through a small wound are detected and destroyed rapidly. Similar to Biosecurity on a farm – Bioexclusion (keep things out) and Biocontainment The functions of the innate immune system are: (Contain infection if it does get in) 1. Exclusion - Protection offered by the skin and mucous membranes 2. Containment and elimination - Protection offered by the immune system cells (defense cells) and proteins It consists of physical weapons (skin); chemical weapons (enzymes) and biological weapons (immune cells) 8 Skin is a physical barrier - exclusion 1. The skin is the largest organ in the body and protects against internal passage of foreign material… 2. But there are routes in and out through the skin which are high risk portals – these are usually coated with mucus (hence referred to as mucus membranes 3. Mucus membranes need added protection 9 ‘Good’ bacteria also help exclude ‘bad’ bacteria so not everything is killed! Skin and mucus membranes tolerate healthy bacteria (also known as commensals) as these help exclude the overgrowth of bad bacteria. However, you can have too much of a good thing and these need to be kept in check too! Think of your intestine or the rumen in cattle 10 DOI: 10.1186/1475-2859-12-71 Components of innate immunity https://www.learninsta.com/basic-concepts-of-immunology/ 11 Evolution of innate immune cells Epithelial cells are usually the first cell to detect infection and they start the response cascade These are adaptive cells They then communicate with innate cells The most common innate cells in blood are neutrophils and macrophages. Reference: Peprotech Inc, 12 2021 Test yourself 1. What do we mean by innate immunity? 2. Do you understand how changes in gene families evolved over evolutionary time to give rise to differences between species? 3. Do you understand the importance of the epithelial cell? These are immune cells too! 4. Do you know examples of innate immune cells and innate immune mechanisms? 13