SI2101 Immunology I PDF - University of Galway

SI2101 Immunology I Dr. Louise Horrigan Physiology [email protected] University ofGalway.ie Learning To learn: Objectives of Functions of the immune system Today’s Lecture Cells and tissues of the imm...

SI2101 Immunology I Dr. Louise Horrigan Physiology [email protected] University ofGalway.ie Learning To learn: Objectives of Functions of the immune system Today’s Lecture Cells and tissues of the immune system Role of cytokines The two main branches of immune system Innate immunity Adaptive immunity Functions of innate immunity Phagocytosis Complement Natural Killer Cells Functions of immune system Infectious diseases Cancer fighting Promotes wound healing and tissue regeneration Elimination of cell debris An antigen is any molecule or structure that provokes an immune response University Anti-gen = antibody generating ofGalway.ie  Tissues of the Immune System Primary lymphoid organs –Where immune cells are formed and mature –Bone marrow –Thymus Secondary/peripheral lymphoid organs –Where immune cells are concentrated and function –Lymph nodes –Spleen –Mucosal immune system Cells of the immune system Some cells circulate between the blood and the tissues, while others are resident in the tissues Circulating cells (can also enter tissues) Neutrophils, monocytes/macrophages, eosinophils, lymphocytes Resident in the tissues (sentinel cells) Dendritic cells, macrophages, mast cells University ofGalway.ie Cells resident in the tissues Dendritic cell (detects pathogens and presents Mast Cell (allergy them to lymphocytes) and defence against helminths) Macrophage (phagocytosis) Cytokines: Important effectors of immune function Small Proteins (5 – 20kDa) Secreted by cells and function in an autocrine and paracrine manner Bind to specific receptors on cells Interleukins (IL-1 – IL-22); Interferons (IFN-a, b, g); tumour necrosis factors (TNF-a, b); transforming growth factor-b (TGF-b) Each immune cell secretes a characteristic profile of cytokines that can determine that cell’s function Cytokines drive and orchestrate immune responses University ofGalway.ie Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45(2):27– 37. University doi:10.1097/AIA.0b0 ofGalway.ie 13e318034194e  Physical barriers eg. skin, lysozyme in secretions Innate Phagocytosis immunity Natural Killer Cells Complement (plasma proteins that stimulate immune reactions when activated) Inflammatory mediators and antimicrobial peptides released from innate cells Antibodies Adaptive B cells (B lymphocytes) immunity Cell-mediated Immunity T cells (T lymphocytes) Cells of the innate and adaptive branches Innate Adaptive Monocytes/Macrophages Lymphocytes Neutrophils B cells Eosinophils T cells Basophils Mast cells Dendritic cells Natural Killer cells University ofGalway.ie Features of innate/natural immunity  We are born with it  It is always present and functional  Can respond immediately  Instructs the adaptive immune system  Recognises non-self in a non-specific manner  Has no ability to remember pathogens or to improve with experience University ofGalway.ie Features of Adaptive/Acquired Immunity  Not born with it  Develops (adapts) throughout a lifetime  Slower to respond than innate system  Recognises antigens with high specificity  Has a memory function University ofGalway.ie Timescale for innate and adaptive responses School Institute Name to go here Innate Immune System University ofGalway.ie Pathogen recognition by cells of the innate system Non-specific Innate cells express Pathogen Recognition Receptors (PRRS) Eg. Toll-like receptors Bind to pathogen-associated molecular patterns (PAMPs) Structures on microbes Shared by groups of microbes eg. Lipopolysaccharide present on all Gram negative bacteria University ofGalway.ie Innate immune recognition of bacterial cell wall components Gram-negative bacteria Gram-positive bacteria Slide by R. Ceredig  Identical Toll-like receptors recognise a common structure on different microbes TLR Innate Cells  Innate Functions: Phagocytosis & Destruction of Pathogens Neutrophils & macrophages are most important phagocytes Following infection, these cells can leave the blood and travel to site of infection Phagocytosis involves Recognition Ingestion Digestion https://www.youtube.com/watch?v=2d1SFqJJeVY University ofGalway.ie Phagocytosis 19 Image from: Phagocytosis and the actin cytoskeleton R.C. May, L.M. Machesky Journal of Cell Science 2001 114: 1061-1077; Image provided for that article by Philippe Montcourrier and Philippe Chavrier.  Complement 30 plasma proteins normally circulating in an inactive state Become activated at sites of infection and trigger a series of inflammatory events C3 is the central component Classical pathway Inflammation C3a Alternative pathway C3 Opsonisation C3b Lectin pathway Terminal pathway (MAC)  Classical Pathway Pathogen C3a C3 C3b C4b2a = C3 convertase Activated by antigen-antibody complex Inhibitors on host cells C3b Pathogen b Kolev M, Friec GL, and Kemper C. Complement — tapping into new sites and effector systems. Nature C4b2a3b = C5 convertase Reviews Immunology 14: 811, 2014.  C5a C3b C5 Pathogen C5b C5 convertase MAC Kolev M, Friec GL, and Kemper C. Complement — tapping into new sites and effector systems. Nature Reviews Immunology 14: 811, 2014. Membrane Attack Complex Causes disruption of fluid balance leading to lysis of pathogen https://en.wikipedia.org/wi ki/Complement_membran e_attack_complex#/media/ File:Membrane_Attack_Co mplex_(Terminal_Comple ment_Complex_C5b- 9).png https://creativecommons.o rg/licenses/by-sa/3.0/ Functions of Complement Opsonisation may be the most important function Activated complement proteins bind to surface of pathogens and make them more amenable to phagocytosis eg. C3b, C4b Inflammation C3a, C4a and C5a are mediators of inflammation Bind to receptors on neutrophils, macrophages, mast cells, basophils, endothelial cells Cell lysis Membrane attack complex University ofGalway.ie Natural Killer Cells Lymphocytes (10 – 15% of blood lymphocytes) Recognise if a cell has been invaded by a virus or if a cell has become cancerous These cells have lost or modified surface structures Kill infected cells through release of Perforin Punches holes in cell membrane Granzyme Enters cells via perforin pore Induces apoptosis (cell death) pathway University ofGalway.ie Summary of main points Where and what is the immune system? Cells and tissues Cytokines drive and orchestrate immune responses Innate and adaptive branches Differences between the two branches and how they work together Phagocytosis is an important function of innate immunity Neutrophils and macrophages eliminate pathogens by phagocytosis Process and functions of complement Natural Killer Cells use perforin and granzyme to target pathogens University ofGalway.ie