Intro to the Immune System I and II PDF

Intro to the Immune System I and II 24/10/23, 7:14 PM Intro to the Immune System I and II Innate immunity • Natural immunity that is present from birth and is generally non-specific • Includes physical barriers, inflammatory mediators, complement proteins, acute phase proteins, immune cells etc....

Intro to the Immune System I and II 24/10/23, 7:14 PM Intro to the Immune System I and II Innate immunity • Natural immunity that is present from birth and is generally non-specific • Includes physical barriers, inflammatory mediators, complement proteins, acute phase proteins, immune cells etc. Barriers to infection Skin • • Physical barrier - tightly packed, highly keratinized cells Physiological factors ◦ ◦ • Low pH (5.5) Low oxygen tension Sebaceous glands – hydrophobic oils, lysozymes, ammonia Mucus • • Mucous membranes line all body cavities that are in contact with the external environment • Secretory IgA Mucus traps bacteria and contains lysozymes and defensins that directly kill invading pathogens Commensal bacteria • Compete with pathogens for resources and produce fatty acids and bactericidins that stop pathogens growing Cytokines • Interferons released by virally infected cells signal to neighbouring uninfected cells: ◦ Destroy RNA and reduce protein synthesis ◦ Undergo apoptosis • Interferons also activate immune cells e.g. NK cells Macrophages • Phagocytose bacteria 1. PRRs on macrophages bind to PAMPs on pathogen, which signals the formation of the phagocytic cup 2. Cup extends around the pathogen and pinches off – phagosome 3. Phagosome fuses with lysosome – phagolysosome 4. Pathogen killed and contents degraded 5. Debris released into extracellular fluid 6. Pathogen-derived peptides expressed on special cell surface receptors (MHC-II) 7. Pro-inflammatory mediators released (TNF⍺) - acute inflammation Mast cells • Deal with pathogens too large for phagocytosis https://galvanized-borogovia-4fa.notion.site/Intro-to-the-Immune-System-I-and-II-5f57deedceb74e9089c0a4025e2d9466 Page 1 of 3 Intro to the Immune System I and II 24/10/23, 7:14 PM • When PRRs on mast cell bind to PAMPs on pathogen, the mast cell is stimulated to release pre-formed pro-inflammatory substances such histamine and tryptase – degranulation • As this happens, the mast cell also begins to produce pro-inflammatory substances (histamine, TNF, chemokines, leukotrienes) • Associated with allergy Neutrophils Transendothelial migration is the recruitment of neutrophils to the site of infection/damage during acute inflammation: 1. Loss of intravascular fluid in the presence of inflammation causes slower blood flow, allowing neutrophils to undergo margination • Neutrophils travel close to endothelial cells instead of centre of the vessel 2. Neutrophils can then encounter and bind to adhesion molecules expressed by the endothelial cells (e.g. selectins, ICAM-1) 3. Neutrophils migrate across the endothelium via diapedesis 4. Once in the tissues, the neutrophils travel to the exact site of injury via chemotaxis 5. Neutrophils are then activated by PAMPs and pro-inflammatory mediators such as TNF⍺ Killing mechanisms • Phagocytosis: phagolysosomal killing (like macrophages) via production of reaction oxygen species (ROS) • • Degranulation: release of anti-bacterial granules NETs: release of a net-like structure that traps pathogens, leading to phagocytosis Modes of ingestion • Receptor mediated endocytosis: molecules bound to membrane receptors are internalized ◦ • • Important in the generation of adaptive immunity Pinocytosis: ingestion of fluid of surrounding cells Phagocytosis: bacterium engulfed by cell surface NK cells • Lymphocytes involved the rejection of tumors and virally infected cells • Respond to levels of MHC class I – virally infected and cancerous cells have reduced levels • Kill by degranulation – release perforin • Produce IFN𝛾 Dendritic cells • Act as a bridge between the innate and acquired immune system • Express antigens on their cell surface and present them to T cells – antigen presenting cells Basophils • Granules contain histamine etc. • Act as effector cells in allergic reactions Eosinophils • Associated with allergy https://galvanized-borogovia-4fa.notion.site/Intro-to-the-Immune-System-I-and-II-5f57deedceb74e9089c0a4025e2d9466 Page 2 of 3 Intro to the Immune System I and II 24/10/23, 7:14 PM Complement system • Activated in response to inflammation and creates a cascade of chemical reactions AlternativePathway C3 Acute C3b+C3a inflam MBLPathway C5 -*CSb+C5a opsonisation MAC ClassicalPathway IgM&IgG 3pathwaysofcomplement systemactivation: Phagocytosis &killing Pathogen killing 1.Classicalpathway 2.MBLpathway 3.Alternativepathway 1. C3 is cleaved into the active C3a and C3b 2. C3b can then cleave C5 into C5a and C5b 3. C3b can then amplify the reaction via the alternative pathway, causing more C3 to cleave into C3a and C3b 4. C5b (along with other factors) produces the membrane attack complex, which inserts into cell walls and destroys the cell by letting salt and water in 5. C3a and C5a are responsible for acute inflammation (they are anaphylatoxins) Acute phase proteins • Proteins produced by the liver whose plasma concentrations increase or decrease in response to inflammation • • C3 - involved in complement CRP - activates complement via classical pathway ◦ ◦ • Very rapidly increased during inflammation Very short half-life - decreases rapidly once well MBL - activates complement via MBL pathway Enhancement of the immune system • The innate response can be enhanced by antibodies • Complement system - classical pathway activated by IgM and IgG • IgG acts as opsonins https://galvanized-borogovia-4fa.notion.site/Intro-to-the-Immune-System-I-and-II-5f57deedceb74e9089c0a4025e2d9466 Page 3 of 3