BIOL 1003 Innate Immunity and Inflammation Student Notes PDF

BIOL 1003 2-1 Innate immunity 2-2 Adaptive Immunity 2-3 Defects in Mechanisms of Defence Branches of Immunity Innate (natural/native) immunity First line of defense Physical + Biochemical Second line of defense Inflammation Adaptive (acquired) immunity Third line of...

BIOL 1003 2-1 Innate immunity 2-2 Adaptive Immunity 2-3 Defects in Mechanisms of Defence Branches of Immunity Innate (natural/native) immunity First line of defense Physical + Biochemical Second line of defense Inflammation Adaptive (acquired) immunity Third line of defense B + T cell mediated ‘memory’ responses Innate: Physical & Chemical Barriers Epithelial cell-derived physical barriers: Skin (~2m2) Linings of the gastrointestinal, genitourinary, and respiratory tracts (~32m2) Tight Junctions Sloughing off of cells Skin Turnover die quick shed quick Mucus and cilia NB 14 TEEN 28 Coughing and sneezing 50 84+ Flushing Vomiting Innate: Physical & Chemical Barriers Epithelial cell-derived chemical barriers: Secrete saliva, tears, ear wax, sweat, and mucus Antimicrobial peptides -cathelicidins, collectins pH barrier Skin pH = 3-5 (from FA+LA) Stomach pH = 1.5-3.5 (from HCl) Thermal barrier -Skin is 33-370C Figure 6.1 Inflammation: Second Line of Defense Inflammation (-itis): The sum of host responses to damage in vascular tissue Caused by a variety of materials Infection, mechanical damage, ischemia, nutrient deprivation, temperature extremes, radiation, etc. Cardinal features of inflammation 1) Redness 2) heat 3) swelling 4) pain 5) loss of function – Goals: – Limit extent of tissue damage 5 Ls of Inflammation – Destroy invading microorganisms LIMIT – Initiate adaptive immune response LETHAL – Initiate clearing of debris/healing of wound LYMPHO CLEAR HEAL  Figure 6.2 Inflammatory response Vascular response: Blood vessel dilation (more blood, slow flow) Expansion of the capillary bed  Figure 6.2 Inflammatory response Vascular response: Increased vascular permeability and leakage (exudate) White blood cell adherence to the inner walls of the vessels and migration through the vessels (Pools and infiltrates into tissues) Inflammatory response Tissue response: Uniform across all members of a species Non specific- Recognizes broad classes of organisms No memory- 2nd response is same as 1st Sequential, cross-recruitment of defense, clotting, and healing factors Acute Inflammatory Response 1. Cellular Injury 2. Activation of plasma systems 3. Release of Autocoids subcellular components Plasma Protein Systems All contain inactive enzymes (proenzyme/zymogen) Sequentially activated First proenzyme is converted to an active enzyme Substrate of the activated enzyme becomes the next component in the series Plasma Protein Systems FP=fibrinopeptides Figure 06-04 Plasma Protein Systems - Complement Complement system (C= complement component) Straddles Innate and Active immunity Can destroy pathogens directly Activates or collaborates with every other component of the inflammatory response Pathways: Classical (Ag-AB) Lectin (Mannan-binding lectin binds sugars in the bacterial coat) Alternative Plasma Protein Systems - Complement End goal: (1) opsonization -Opson (Gr) = ‘seasoning’ docking sites for macrophages to eat target (2) anaphylatoxin (histamine release from Mast cells) Histamine: vascular hyperpermeability (endothelial contraction + vasodilation) (3) leukocyte chemotaxis (4) cell lysis (MAC) Plasma Protein Systems Coagulation (clotting) system Forms a fibrinous meshwork at an injured or inflamed site 1) Traps microorganisms and foreign bodies at the site (stops spread, concentrates immune response) 2) Forms a clot that stops bleeding 3) Provides a framework for repair and healing Main substance is an insoluble protein called fibrin Extrinsic pathway Intrinsic pathway FP=fibrinopeptides Plasma Protein Systems Kinin system Functions to activate and assist inflammatory cells Primary kinin is bradykinin Causes dilation of blood vessels, pain, vascular permeability, and leukocyte chemotaxis Cellular Mediators of Inflammation Cellular components: Granulocytes Platelets Monocytes (Macrophage, Dendritic) Lymphocytes (T,B,NK) WBC NEVER Neutrophils LET Lymphocytes MONKEYS Monocyte EAT Eosinophil BANNANAS Basophil Cellular Mediators of Inflammation Cell surface receptors: Also: DAMPs Recall: Primary immune system recognizes broad classes of microorganisms Pathogen-associated molecular patterns (PAMPs) PAMPs detected by WBC with: Pattern recognition receptors (PRRs) Complement receptors Toll-like receptors Cellular products: Cytokines (Traffic lights for immune function) Cytokines Interleukins (IL) Produced primarily by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation Many types Examples: IL-1 is a pro-inflammatory cytokine IL-10 is an anti-inflammatory cytokine Cytokines The 5 ‘A–tions’ of IL 1) Attraction (chemotaxis) 2) Adhesion (regulates attachment to site) 3) (in)Activation (enhance or suppress response) 4) Amplification (induce proliferation and maturation of leukocytes) 5) Adaptation (development of acquired immunity) Cytokines Interferon (IFN) Protects against viral infections Produced and released by virally infected host cells in response to viral double-stranded RNA Types: IFN-alpha and IFN-beta Induce production of antiviral proteins IFN-gamma Increases microbicidal activity of macrophages Cytokines - IFN Cytokines Tumor necrosis factor-alpha (TNF-α) Secreted by macrophages in response to PAMP and toll-like receptor recognition -Induces fever by acting as an endogenous pyrogen -Increases synthesis of inflammatory serum proteins -Causes muscle wasting (cachexia) and intravascular thrombosis Cytokines Chemokines Attract leukocytes to site of inflammation Synthesized by many cells (macrophages, fibroblasts, endothelial cells) Leukocytes Mast Cells Cellular bags of granules located in the loose connective tissues close to blood vessels Skin, digestive lining, and respiratory tract Basophils are a lot like mast cells but are found in blood Degranulation: release histamine and chemotactic factors Migrating De-graunlating mast cell Chemokines immune cells Mast Cells Activation Physical injury, chemical agents, immunologic processes, and toll-like receptors Chemical release in two ways 1) Degranulation 2) Synthesis of lipid-derived chemical mediators Histamine Vasoactive amine that causes temporary, rapid constriction of the large blood vessels and the dilation of the post-capillary venules Retraction of endothelial cells lining the capillaries (leads to edema) Receptors: H1 receptor (pro-inflammatory) H2 receptor (anti-inflammatory) Mast Cell Degranulation Chemotactic factors: Neutrophil chemotactic factor Attracts neutrophils Eosinophil chemotactic factor of anaphylaxis (ECF-A) Attracts eosinophils “INTRUDER ALERT!” Mast Cell Synthesis of Mediators Leukotrienes Product of arachidonic acid from mast cell membranes Similar effects to histamine (lasts longer) Prostaglandins Similar effects to leukotrienes; they also induce pain Aspirin and some other nonsteroidal anti-inflammatory drugs (NSAIDs) block the synthesis of prostaglandins Platelet-activating factor Similar effect to leukotrienes and platelet activation Leukocytes Dendritic cell Phagocytosis Process by which a cell ingests and disposes of foreign material Phase 1: Extravasation Marginationàpavementing Adherence of leukocytes to endothelial cells Diapedesis Emigration of cells through the endothelial junctions Phagocytosi s Phase 2: Phagocytosis Steps: Adherence Engulfment Phagosome formation Fusion with lysosomal granules Destruction of the target “Adherence to English produces fine diction” Adherence, Engulment, Produce, Fusion, Destruction (Phagosome)(Lysosome) Tissue Leukocytes Dendritic cell  Lym Dendritic cell Tissue Leukocytes ph oc yte Dendritic cells Antigen An APC in peripheral organs and skin Cinderella (1950) Connects innate and adaptive immunity 1- Recognize and phagocytose foreign material 2- Migrate through lymph vessels to lymphoid tissues and interact with lymphocytes to generate an adaptive immune response Acute and Chronic Inflammation Acute (Local) Self limiting Vascular changes leak circulating components into the tissue Heat, swelling, redness, pain Exudative fluids Exudative Fluids Serous exudate Watery exudate: indicates early inflammation Fibrinous exudate Thick, clotted exudate: indicates more Sir Fib, he purrs. advanced inflammation What a clod that bloody puss! Hemorrhagic exudate Exudate contains blood: indicates bleeding Purulent exudate (suppurative) Pus: indicates a bacterial infection Sir Fib, he purrs. (serous) (fibrinous) (hemorrhagic) (purulent) What a clod that bloody puss! (Water) (Clot) (blood) (pus) Acute Inflammation (systemic) 1) Fever Caused by exogenous and endogenous pyrogens Act directly on the hypothalamus 2) Leukocytosis Increased numbers of circulating leukocytes Left shift – immature : mature neutrophils in blood count 3) Acute phase reactants (↑ plasm proteins) C-reactive protein Fibrinogen Haptoglobin Amyloid Ceruloplasmin, etc. Chronic Inflammation Inflammation lasting 2 weeks or longer Often related to an unsuccessful acute inflammatory response Other causes of chronic inflammation: High lipid and wax content of a microorganism Ability to survive inside the macrophage Toxins Chemicals, particulate matter, or physical irritants Chronic Inflammation Chronic Inflammation Characteristics: Dense infiltration of lymphocytes and macrophages Granuloma formation (wall off) Epithelioid cell formation Giant cell formation