UM1010 Immunology 1 VLE PDF

Introduction to Immunology Dr Geraldine O’Connor [email protected] HA210  Overview of Immunology in Year 1 Immunology as a clinically Lesson Plan important discipline...

Introduction to Immunology Dr Geraldine O’Connor [email protected] HA210  Overview of Immunology in Year 1 Immunology as a clinically Lesson Plan important discipline Basic Concepts in Immunology The challenges The defences Overview of Year 1 Immunology Introduction Mucosal Immunology 1/Immunopathology Innate Immunity Vaccination Adaptive Immunity Mucosal Immunology 2  Role of the Immune System in Health and Disease Roles of the Immune System Immunology in Medicine Antibody Vaccines Therapy Blocking Cytokine cytokine therapy therapy Organ Immune transplan- suppre- tation ssion Adoptive Allergen Cell desentisi- Therapy tation  The Challenges Microbes are ubiquitous in nature, extraordinarily diverse, rapidly evolve to exploit opportunities to infect hosts and to evade their immune systems. Adopt different lifestyles e.g. some microbes hijack cellular machinery to replicate and spread. Intracellular pathogens include viruses (influenza, coronavirus) and intracellular bacteria (listeria) and intracellular parasites (malaria, toxoplasma). When Things go Wrong  1. Physical and Chemical Defences Physical Barriers Chemical Barriers Physical and Chemical Barriers  Skin Barrier Function β-defensins and cathelicidins (cationic peptides) produced by keratinocytes in the stratum spinosum are stored in lamellar bodies and secreted into the intercellular space as an antimicrobial agent.  Barrier Functions Across the Body Production of a variety of chemical substances that are microbicidal or inhibit microbial growth e.g. lysozyme, stomach acid, digestive enzymes. Antimicrobial peptides (defensins) are secreted by epithelial cells and phagocytes and disrupt the cell membranes of bacteria and fungi and some viral envelopes. 2. Innate and Adaptive Immune Responses  Overview of Immune System The immune system consists of the tissue, organs, cells, molecules and genes responsible for protection from (infectious) disease Innate and Adaptive Immunology Innate defences: Immediate response from mechanisms in place before an infection occurs. Recognition of infection via receptors that recognise structures that are common to groups of pathogens (e.g. lipopolysaccharide (LPS) of gram-negative bacteria) Adaptive Response: Stimulated by exposure to specific pathogens. Reacts to a large number of different structures (antigen: A molecule/structure recognised by the adaptive immune system), that are specific to a particular pathogen Innate and Adaptive Immunity  The Immune Response Barrier Function Innate Immunity Adaptive Immunity  3. Cells of the Immune System  Immune Cells A variety of different types of white blood cell (leukocytes), including neutrophils, macrophages, T cells, B cell etc each with a specialised function and role in the immune system  Innate Cells: Macrophages Patrols in the tissues Macrophages subsets in different tissue are given their own name (e.g. Kupffer cells in liver) Phagocytosis Phagocytosis: the internalisation of particulate matter by a process of engulfment, eventually forming a vesicle (phagosome) containing the ingested material Important in the elimination of potential pathogens and other foreign material, but also cell debris, apoptotic cells, and damaged tissue Phagocyte come from the Greek “to eat” and –cyte meaning cell  Steps of Phagocytosis iNOS= inducible nitric oxide (NO) synthase ROS= reactive oxygen species Phagocytosis In Action Opsonisation Some microbes (esp. those with capsules) are difficult to phagocytose. Opsonisation is the coating of microbe with proteins, such as antibodies or complement, that facilitate phagocytosis. Acute phase proteins produced by the liver e.g. C reactive protein (CRP) will bind to phosphocholine on bacteria and act as an opsonin. These proteins are recognised by specific receptors on the surface of the phagocyte. Phagocytes Phagocytes 1. Macrophages 2. Granulocytes: Neutrophils, eosinophils, and basophils Primary function is to engulf and destroy pathogen 3. Immature dendritic cells Primary function is activation of adaptive immunity (more on this later) Phagocytic Mechanisms Innate Immune Cells: Neutrophil Granulocyte Most abundant white blood cell in peripheral blood – multilobed nucleus Not generally found in tissues but can be recruited Typically have a short lifespan after activation Innate Immune Cells: Monocyte Agranulocyte ~10% of White blood cells in peripheral blood Not classified as a granulocyte Innate Immune Cells: Eosinophil Granulocyte Found in low numbers in the blood Granules contain enzymes that can attack the cell wall of parasites, but will also cause damage to host tissue Innate Immune Cells: Basophil Granulocyte Found in low numbers in the blood Granules contain potent inflammatory mediators, aiding in the defence against parasites Innate Immune Cells: Mast cells Granulocyte Not found in the blood, but in the tissues Similar to basophils, granules contain potent inflammatory mediators, aiding in the defence against parasites. Involved in allergic responses Innate Immune Cells: Natural Killer cells Lymphocyte Part of the innate immune system Can kill host cells – e.g virally infected cells or transformed (malignant) cells. Production of chemical mediators (cytokines) NK Cell Activation I NK cells can be activated by the engagement of activating receptors CD16 on NK cells binds to antibodies and activates the NK cell to kill the antibody-coated cell. This process is called antibody-dependent cell cytotoxicity (ADCC) NKG2D on NK cells binds to NKG2D ligands that are upregulated to cellular and metabolic stress e.g. infection and cancer and leads to death of the cell. NK Cell Activation II NK cells can be activated by the loss of molecules (MHC class I) from unhealthy cells. MHC Class I is present on all nucleated cells and engages inhibitory receptors (Killer Immunoglobulin-like receptors, KIR) on NK cells. MHC Class I can be downregulated in viral infection and in cancer. This process is known as “missing self” Natural Killers In Action MBBS Learning Outcomes Over the first three Immunology sessions we will address: Recognise the role of the immune system in defence against invasion by foreign matter and list individual components of the immune system Distinguish the function of immune cell types and other arms of the immune system Distinguish the role of immune response in disease prevention Distinguish the components of the lymphatic system and describe their role in host defence Reading List Both available via Clinical Key