BIOL 318 Immunology Lecture 2, September 9, 2024 PDF

BIOL 318 Immunology Lecture 2 Lecture by Andrea Verdugo Meza, PhD Candidate, MSc, BioEng Email: [email protected] September 9, 2024  What is happening in this figure? Learni...

BIOL 318 Immunology Lecture 2 Lecture by Andrea Verdugo Meza, PhD Candidate, MSc, BioEng Email: [email protected] September 9, 2024  What is happening in this figure? Learning outcomes By the end of this lecture, you will be able to understand: A. Triggers of the immune response B. The main cells and molecules involved in the immune response i. Granulocytes ii. Myeloid cells iii. Lymphoid cells iv. T cell receptor v. B cell receptor and immunoglobulins vi. Clusters of determination vii. Pathogen Recognition Receptors viii.Cytokines ix. Variable molecules C. The general effector mechanisms of the innate and adaptive immune response  Infectious agent Antigen presenting cell Lymphocytes Effector molecules Lymphoid organs Cells in human blood differ in number and life span How do immune cells arise? Immune cells arise in the bone marrow from a process called hematopoiesis Hematopoietic Stem Cells (HSCs) can differentiate into many types of blood cells o Red blood cells → Erythrocytes o White blood cells → Leukocytes (immune cells) o HSCs are constantly renewed and directed to differentiate into two major types of progenitors Myeloid progenitor cells Lymphoid progenitor cells Myeloid cells: Granulocytes Direct harm to pathogens Antiviral activity, antiparasitic activity Inflammation and allergies  Myeloid cells: Granulocytes The proteins in granules direct their function  Myeloid cells: Other cells Migrate into tissues and differentiate into macrophages They repair/remodel, phagocytose & destroy pathogens, present antigens Potent antigen- presenting cells; activate naïve T cells https://doi.org/10.1073/pnas.1000494107  Antigen Presenting Cells To present an antigen, the APC must ‘ingest’ it Ingestion = phagocytosis Macrophages are considered APCs https://www.biophys.uni-bayreuth.de/de/forschung/phagocytosis/index.html Dendritic Cells are specialized APCs https://doi.org/10.1073/pnas.0702449104 Immature dendritic cells capture antigen, then mature and migrate out of that location to another to present antigen to T cells Dendritic cells are the most potent antigen-presenting cells for activating naïve T cells  Antigen Presenting Cells Macrophages are specialized for phagocytosis, then present antigens to naïve T cells Lymphoid cells T cells, B cells, and ILCs are lymphoid cells How do we identify cells? Cell membrane proteins expressed by cells of the immune system are referred to as cluster of differentiation (CD) There is more than immune cells, let’s now talk about organs of the immune system Lymphoid organs Primary lymphoid organs: Where immune cells develop Secondary lymphoid organs: Where the immune response is initiated Tertiary lymphoid organs: Sites of infection Lymphoid organs: Primary lymphoid organs B cells develop in the bone marrow T cells develop initially in the bone marrow, but then migrate to the thymus to achieve full maturity Lymphoid organs: Secondary lymphoid organs Areas where lymphocytes: 1. Encounter antigen 2. Become activated 3. Undergo clonal expansion 4. Differentiate into effector cells Connected via the blood and lymphatic circulatory systems Circulating cells in the lymph are ultimately returned to the blood system Spleen Lymphoid organs: Secondary lymphoid organs Gut-Associated Lymphoid Tissue Barrier organs as lymphoid tissue Organized immune microenvironment Example: Gut-Associated Lymphoid Tissue (GALT) What do we know so far? The cells and organs of the immune system Although blood cell development is a necessary part of immune responses, it’s only a first step Multiple other organs and tissues of the body must receive those blood cells and interact with each other to achieve proper immune responses The immune response: the need of receptors and cytokines https://www.biophys.uni-bayreuth.de/de/forschung/phagocytosis/index.html https://doi.org/10.1073/pnas.0702449104 Cells interact and communicate via recognition and response Receptor-ligand interactions What do you remember from your cell biology class? Receptor-ligand interactions A cellular signal is any event that instructs a cell to change its metabolic state Signals are usually generated by the binding of a ligand to a complementary cell- bound receptor A cell can become more or less susceptible to actions of a ligand by increasing or decreasing expression of the receptor for that ligand Cell signalling often induces a change in the transcriptional program of the target cell Sometimes multiple signals through multiple receptors are required to effect particular outcomes: integration of signals Receptors of the immune cells T cell receptor (TCR) B cell receptor (BCR) MHC class I and MHC class II Cytokine receptors Chemokine receptors Pathogen Recognition Receptors (PRRs) Receptors of the immune cells T cell receptor (TCR) B cell receptor (BCR) MHC class I and MHC class II Cytokine receptors Chemokine receptors Pathogen Recognition Receptors (PRRs) Receptors of the immune cells Cell-bound T cell receptor (TCR) B cell receptor (BCR) MHC class I and MHC class II Cytokine receptors Soluble Chemokine receptors Pathogen Recognition Receptors (PRRs) Receptors of the immune cells T cell receptor (TCR) B cell receptor (BCR) MHC class I and MHC class II Cytokine receptors Chemokine receptors Pathogen Recognition Receptors (PRRs) Bind Pathogen Associated Molecular Patters (PAMPs) Receptors of the immune cells T cell receptor (TCR) B cell receptor (BCR) MHC class I and MHC class II Cytokine receptors Chemokine receptors Pathogen Recognition Receptors (PRRs) What is a cytokine? Proteins that mediate the effector functions of the immune system Other terms commonly used to describe particular cytokines: Monokines: Cytokines made by mononuclear phagocytic cells Lymphokines: Cytokines made by activated lymphocytes Interleukins: Cytokines mediate between leukocytes Chemokines: Small cytokines primarily responsible for leukocyte chemotaxis Cytokines: General characteristics Mediate and regulate immune responses Cytokine-signaling end results often induce a change in the transcriptional program of the target cell A cytokine signal is any event that instructs a cell to change its metabolic or proliferative state Pleiotropic: function is context-dependent Secretion is brief and self-limited Very potent: High affinity to receptors Produced by multiple cell types Cytokines Cytokines mediate the effector functions of the immune system They can act in several different ways Endocrine action―released into the bloodstream to effect distant cells Paracrine action―released to effect nearby cells Autocrine action―released, but then bind to receptors on the cell that produced them Cytokines are pleiotropic A cytokine may have different effects on different cells Cytokines and redundancy When different cytokines interact with the same receptor (with different affinities) and lead to the same response Cytokine redundancy is due to the nature of the cytokine receptor Cytokines synergism and antagonism A synergistic effect can occur when the effect of combined cytokines is greater than the separate effects of those cytokines added together An antagonistic effect can occur when one cytokine inhibits the effect of another cytokine  Cytokines: Cascade induction Cytokines bind to target cells causing a production of more cytokines, which then act on other target cells to produce even more cytokines This signaling cascade is referred to as the cytokine network The target cell response is complex and is dependent upon the cytokine signaling cascade within the cell Activity time Next class Wednesday, September 11, 2024 Pre-class quiz (Ch 4 Adaptive Quiz) Lecture 3, Innate Immunity (Chapter 4) In-class quiz with iClicker Discuss Assignment 1