Week 5 Lec 1.pdf

Infection and Immunity BIOL341/982 Overview of Immunity I 1  Learning Outcomes Define immunity Distinguish between different types of lymphoid tissues and define their roles in immunity Distinguish between innate and adaptive immunity D...

Infection and Immunity BIOL341/982 Overview of Immunity I 1  Learning Outcomes Define immunity Distinguish between different types of lymphoid tissues and define their roles in immunity Distinguish between innate and adaptive immunity Distinguish between different types of immune cells and define their roles in immunity 2  Reading Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Chapters 20-23. Karp, G. Cell and Molecular Biology, 7th ed. John Wiley & Sons, 2013. Chapter 17. Additional Reading Murphy, K, Travers P, Walport, M. Janeway’s Immunobiology, 7th ed. Garland Science, 2008. Chapter 1. Kindt, TJ, Goldsby, RA, Osborne, BA. Kuby Immunology, 6th ed. WH Freeman and Company, 2007. Chapters 1 and 2. Qi, H, Kastenmüller, W, Germain, RN (2014). Spatiotemporal Basis of Innate and Adaptive Immunity in Secondary Lymphoid Tissue, Annual3 Review of Cell and Developmental Biology 30:141-167  Immunity Is the state of protection within a host against infectious microorganisms (pathogens) and cancers Depends on the ability of the host to distinguish non-self (foreign) from self molecules Molecules which invoke an immune response are termed antigens Immunology is the study of immunity 4  Antigens Antigens are molecules which are recognised by the immune system Immune molecules (antibodies or T-cell receptors) recognise only a portion of an antigen - called epitopes (or antigenic determinants) Antigens can contain more than one epitope and thus can bind different immune molecules 5 Cf: Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Fig. 21.5.  Immunity May be against: Pathogens - viruses, bacteria, fungi, protozoa and multicellular parasites Tumours (immune surveillance) Self tissues or organs (autoimmunity) Allergens (hypersensitivity) Transplanted tissues or organs (host vs. graft; graft vs. host) 6 7  Human lymphoid tissues Primary and secondary lymphoid tissues (left hand side lymphatic system not shown) 8 Cf: Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Fig. 20.3A.  Lymphoid tissues Primary lymphoid tissues - sites where leukocytes (white blood cells) form and mature: Bone marrow Thymus Secondary lymphoid tissues - sites where leukocytes encounter and respond to foreign antigen: Lymph nodes (“glands”) Spleen Mucosa-associated tissues (MALT) in gut, nasal cavity, bronchii 9  Bone marrow Site of haematopoiesis: haematopoietic stems cells give rise to progenitor cells that can differentiate into the various blood cells Site of B-cell differentiation (T-cells differentiate in the H&E stain CD34+ cells (stem cells) thymus) CD38+ cells (plasma cells) CD20+ cells (B cells) Antibody secreting B-cells (plasma cells) are: short lived (2-4 days) in the lymph node; (b-d) Red staining indicates positive cells. Adapted from Zhao et al., Cell Mol Immunol, 9: 11-19, 2012. long lived in the bone marrow 10 Circulation of lymphocytes 11  Revision Leukocytes form and mature in what general type of lymphoid tissue? Leukocytes encounter and respond to antigen in what general type of lymphoid tissue? Examples of primary lymphoid tissues include? Examples of secondary lymphoid tissues include? Mucosa-associated lymphoid tissue (MALT) is associated with what tissues? 12  Immunity Can be divided into two arms: Innate (or natural) immunity Adaptive (or acquired) immunity 13  Innate and adaptive immunity Innate Adaptive Response time Minutes to hours Days Specificity and Limited and fixed Highly specific; highly diverse; diversity improves during immune response Response to Identical to primary More rapid than primary repeat infection Memory None Persistent Self/nonself Non-self (breakdown in Non-self (breakdown in self/nonself discrimination homeostasis leads to discrimination leads to autoimmune autoinflammatory disorders) disorders) Main Physical/chemical barriers (e.g. B-cells, T-cells, components skin, antimicrobial peptides); DCs, macrophages; Monocytes, macrophages, Antibodies; granulocytes, DCs, NK cells, T-cell receptors innate lymphocytes; Pattern recognition receptors 14 Modified from Kindt, Goldsby, Osborne. Kuby Immunology, 6th ed. WH Freeman and Company, 2007. Tables 1-3 and 3-1.  Responses to infection 15 Cf: Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Fig. 20.1. Adaptive immune response to infection 16  Revision The immune system recognizes what general type of molecules starting with A? Name the two arms of the immune system. The innate immune system responds faster than the adaptive immune response. True or false? The specificity and diversity of the innate immune system is greater than that of the adaptive immune. True or false? The adaptive immune response but not the innate immune response develops immunological memory. True or false? List some main components of the adaptive immune response.  Cells of the immune system Mast cell Monocyte Macrophage Neutrophil Eosinophil Dendritic cell Basophil Myeloid NK cell progenitor T cell Bone Pluripotent Lymphoid marrow haematopoietic progenitor cell B cell Plasma cell18 Adapted from Karp, G. Cell and Molecular Biology, 6th ed. John Wiley & Sons, 2008, Fig. 17-5. Cf: Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Fig. 20.2. 19 Cells of the Immune System 20 21  B-cells (B-lymphocytes) Antibody production T-cells (T-lymphocytes) Cytotoxic, helper and regulatory effector functions http://science.sciencemag.org/content/sci/suppl/2017/05/10/356.63 38.eaal3118.DC1/aal3118_CaiSM_mov1.mov From Caiet al., Science, 356: 598, 2017. 22 Cf: Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 8th ed. Garland Science, 2008. Fig. 20.4.  Two arms of adaptive immunity Cell- mediated Humoral (T cells) (B cells and antibodies) Often requires T cell help 23 See Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Fig. 21.14.  Humoral immunity Mediated by B-cells that produce antibodies Antibodies recognise epitopes of antigens Antibodies are secreted proteins called immunoglobulins (Ig) Ig comprise 5 classes: IgM, IgD, IgG, IgA, IgE Antibodies have various functions: neutralisation, opsonization and complement activation 24  Cell-mediated immunity Involves T-cells that express specific cell surface receptors (TCRs) TCRs recognise antigenic epitopes associated with major histocompatibility complex (MHC) molecules on the surface of cells Three types of T cells, each with a different function: cytotoxic, helper and regulatory 25  Lymphocytes recognise antigen via unique receptors B-cell T-cell 26 Cf: Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Fig. 21.5.  Antibodies directly recognise antigen; TCRs recognise antigen fragments bound to MHC molecules 27  Antibodies have various effector functions 28 Cf: Pommerville, JC. Alcomo’s Fundamentals of Microbiology, 10th ed. Garland Science, 2014. Fig. 21.8.  T-cells have various effector functions Cytotoxic Helper 29  Revision Name the two arms of the adaptive immune response. Humoral immunity involves what proteins produced by B-cells? List 3 key effector functions of antibodies. Cell-mediated immunity predominately involves what type of lymphocyte subset? T-cells recognize antigen by what cell-surface receptors? The TCR recognizes antigen (antigenic peptide) bound to what kind of cell-surface receptors? List 3 key effector types of T-cells. 30  Summary Immunity is the state of protection against pathogens (and cancers) Primary lymphoid tissues are sites where leukocytes form and mature Secondary lymphoid tissues are sites where leukocytes encounter and respond to antigen Immunity is divided into innate and adaptive immune responses Adaptive immunity is divided into humoral and cell- mediated immunity Immune responses are carried out by leukocytes with specialised functions 31