1. DR. SYEDA SALEHA HASSAN LECTURE 3: INNATE IMMUNITY BIOT 307 1-09-2014

2. LECTURE OBJECTIVES Understand the concept of innate immunity Describe the characteristics of the response Understand recognition processes Describe the cells involved and their effector functions

3. INNATE IMMUNITY Innate immunity is a non specific defense mechanism that a host uses immediately or within several hours after exposure to antigen 0-4 hours Innate immunity (natural immunity) 4-96 Early, induced response >96 hours Acquired immunity (adaptive immunity)

4. CHARACTERISTICS This is the immunity you are born with! Designed to be very fast- within hours Ancient evolution-components of innate immunity found in invertebrates-amoeba, snails, fruit flies Responds exactly the same way every time Uses a handful of molecules to recognise that infection is present Induces and directs the acquired immune response

5. COMPONENTS OF THE INNATE IMMUNE SYSTEM Physical/anatomical barriers Skin, GI tract, respiratory tract, mucosal epithelia Secreted compounds Antibacterial compounds, complement, natural antibodies, cytokines Cellular components Phagocytes, NK cells

6. GOALS OF THE IMMUNE SYSTEM Prevent entry of the pathogen!

7. PATHOGEN PREVENTION Skin: dry outer protective layer, difficult for pathogens to penetrate, fatty acid production inhibits microbes on skin Respiratory tract: cells joined tightly together- tight junctions, cilia, mucus GI tract: peristalsis, hydrochloric acid production, low pH

8. PATHOGEN PREVENTION Tears, sweat, saliva: lysozyme, destroys bacterial walls GI tract: acid hydrolysis, bacterial digestion/degradation Microbial competition: bacteria that normally live in the body can prevent the pathogen from growing Skin-Staphylococcus epidermis GI tract-lactobacilli

9. GOALS OF THE INNATE IMMUNE SYSTEM Recognise the pathogen

10. THE INNATE IMMUNE RESPONSE DOES NOT RECOGNISE EVERY POSSIBLE ANTIGEN Recognises a few highly conserved molecular structures present in many different microorganisms Pathogen Associated Molecular Patterns=PAMPS Present in the microorganism but not the host Essential for the survival of the pathogen e.g. Lipopolysaccharide from Gram negative bacteria

11. LIPOTEICHOIC ACID FROM GRAM NEGATIVE BACTERIA Peptidogly- can found in bacterial cell walls ds RNA unique to most viruses

12. PATTERN RECOGNITION RECEPTORS=PRR 1.Collectins 2.Toll like receptors

13. COLLECTINS Family of proteins present in solution Collagen-like region and a lectin like region=collectin Collagen-like region interacts with effector parts of the immune system Lectin region binds to sugar molecules on surface of pathogen e.g. mannose

14. TOLL LIKE RECEPTORS (TLR) Toll proteins first identified in the fruit fly Drosophila melanogaster At least 11 mammalian homologues

15. TOLL LIKE RECEPTORS

16. EFFECTOR MECHANISMS OF THE INNATE IMMUNE RESPONSE Phagocytosis Cytokine/chemokine production Inflammation Pathogen destruction

17. PHAGOCYTOSIS Monocyte/macrophage-Mature from circulating monocytes found in large numbers in the GI tract, lung, liver, spleen. Relatively long-lived. Neutrophils-Short-lived, found only in blood.

18. PHAGOCYTOSIS Recognition of the pathogen by receptors on the phagocyte leads to ingestion and destruction Receptors: PRR Complement receptors

19. KILLING MECHANISMS OF MACROPHAGES & NEUTROPHILS Reactive oxygen intermediates (more in neutrophils) Following phagocytosis there is an increase in oxygen uptake i.e. respiratory burst Oxygen is reduced by NADPH oxidase to form hydroxyl radicals and hypochlorite DNA damage and alterations in bacterial membranes

20. KILLING MECHANISMS OF MACROPHAGES AND NEUTROPHILS Reactive nitrogen intermediates (more in macrophages) L-arginine to L-citrulline generates NO radicals Catalysed by the enzyme inducible nitric oxide synthase (iNOS, NOS2) induced by cytokines and bacterial componen ts

21. CYTOKINES “Intracellular messengers” Proteins that are produced by many cells in the body that control immune defences by binding to specific receptors Can be activating or deactivating IL-1 (interleukin 1), IL-6 (interleukin 6) causes inflammation and fever TNF-α(tumour necrosis factor α) causes fever and macrophage activation IL-12 causes CD4 T cell differentiation

22. CHEMOKINES Class of cytokines with chemoattractant properties Promote inflammation by enabling cells to adhere to the surface of blood vessels and migrate to the infected tissue IL-8 produced by macrophages and endothelial cells MCP (monocyte chemoattractant protein)

23. INTERFERONS Type I interferons (IFN-Υand IFN-β) Produced in response to virally infected cells Natural killer cells-kill virally infected cells and tumour cells, responsive to TNF-αand IL-12. Produce IFN-Υ. Critical cytokine-activates macrophages, upregulates MHC molecules, together with IL-12 stimulates differentiation of CD4 Th1 cells