Components of the Innate Response – Humoral Elements PDF

Components of the innate response – Humoral elements Learning Objectives On completion of this session you should be able to - Define humoral elements of innate immunity, encompassing soluble factors like cytokines, chemokines, antimicrobial peptides, complement proteins, acute phase protei...

Components of the innate response – Humoral elements Learning Objectives On completion of this session you should be able to - Define humoral elements of innate immunity, encompassing soluble factors like cytokines, chemokines, antimicrobial peptides, complement proteins, acute phase proteins, and collectins. Components of the Innate Response – Humoral Elements Several groups of soluble molecules contribute to the innate response 1. Cytokines: Cytokines have local and systemic effects Several are important mediators e.g i) IL-1. (Macrophages, endothelial cells and some epithelial cells) Activates vascular endothelium, activates some lymphocytes*, stimulates IL-6 production (and APP) and induces fever Components of the Innate Response – Humoral Elements ii) IL-6. (Macrophages, endothelial cells, T cells*) Increases antibody production and induces class switching* Induces production of acute phase proteins (APPs) from the liver Components of the Innate Response – Humoral Elements iii) TNF-a. (Macrophages, T cells*) Activates vascular endothelium Increases vascular permeability Activates neutrophils Induces fever Induces apoptosis Stimulates fat and muscle catabolism (cachexia) Mediates septic shock Components of the Innate Response – Humoral Elements iv) IL-12. (Macrophages, DCs) Stimulates IFN-g from T cells* & NK cells Mediates T cell activation* v) Interferons (IFN) Three types IFN-a, IFN-b, produced by most cells and IFN-g, produced by immune cells Anti-viral activities IFN-a and -b produced in response to dsRNA Components of the Innate Response – Humoral Elements Inhibit viral replication by degrading viral RNA and inhibiting translation Increase MHC class I expression to aid recognition of infected cells Protect neighbouring cells IFN-g produced by T cells and NK cells Activates macrophages, stimulates Th1 cell differentiation* and antibody class switching* Components of the Innate Response – Humoral Elements vi) Chemokines Chemoattractant factors and include: IL-8. (Macrophages) Chemoattractant for neutrophils, basophils & T cells* Macrophage chemoattractant factor 1 (MCP-1) Produced by macrophages, neutrophils and endothelial cells Chemoattractant for monocytes Components of the Innate Response – Humoral Elements 2. Lipid mediators Include prostaglandins, leukotrienes, platelet activating factor (PAF) Produced by macrophages and mast cells Produced from arachidonic acid which is converted to prostaglandins by cyclooxygenases (COX-1 and COX-2) or leukotrienes by 5-lipoxygenase Increase vascular permeability, increase vascular dilation, increase smooth muscle contraction, increase endothelial cell adhesiveness Components of the Innate Response – Humoral Elements Components of the Innate Response – Humoral Elements 3. Antimicrobial peptides Expressed by epithelial cells and neutrophils 29 – 35 amino acids long 3 groups: a) a-defensins b) b-defensins c) cathelicidins Components of the Innate Response – Humoral Elements 1) Neutrophils express all 3 types and epithelial cells express according to location 2) Antimicrobial peptides have widespread activity 3) Bind to acidic phospholipids, enter membranes and form pores 4) Host cells protected as sialic acids carried away from surface 5) Need high concentrations of antimicrobial peptides (1mM +) 6) Some microbes alter cell surface to confer resistance against these peptides Components of the Innate Response – Humoral Elements 4. Collectins & Ficolins 2 families of proteins Mucosal surface and in serum Bind carbohydrate configurations on microbes Recognise carbohydrate patterns that distinguish host and microbe (pathogen associated molecular patterns PAMPs) Components of the Innate Response – Humoral Elements Ficolins bind to N-Acetylglucosamine (GlcNAc) residues Collectins e.g. mannose binding lectin (MBL) binds mannose residues Opsonise pathogen and activate complement cascade Key immune components MBL deficient individuals exhibit a 6-fold greater risk of meningococcal disease Components of the Innate Response – Humoral Elements 5. Acute Phase Proteins (APPs) TNF-a, IL-1 and IL-6 stimulate production of APPs by hepatocytes Two important APPs: i) C-Reactive protein (CRP) Binds phosphorylcholine portion of bacterial and fungal cell walls Opsonises pathogen and can activate complement proteins ii) Mannan binding lectin (MB-lectin) Acts as an opsonin for monocytes Activates complement cascade (Overlap between collectins and APPs) Components of the Innate Response – Humoral Elements 6. Complement Group of serum proteins activated by both innate and adaptive responses Termed complement as they ‘complement antibody function’ Important innate mechanism Activated through a sequential cascade activation of complement proteins Activated by 3 pathways: i. Classical (adaptive/innate) ii. Mannan Binding Lectin (MBL) (innate) iii. Alternative (innate) Consider in detail later Summary 1. Humoral elements of innate immunity include soluble factors that play crucial roles in defending against pathogens. 2. Cytokines and chemokines regulate immune cell communication and movement 3. Antimicrobial peptides directly kill microbes 4. Complement proteins enhance pathogen clearance; 5. Acute-phase proteins modulate inflammation 6. Collectins aid in pathogen recognition and clearance. 7. Together, these factors provide a robust and immediate immune response to infections.