Chemical Mediators by akashyap


									Chemical Mediators Arachidonic acid – derived from cell membrane (from fats) Histamine: major source is mast cells and basophils – used in allergic reactions (IgE)  leads to increased vascular permeability – acts on H1 receptors H2 receptors found in stomach – use H2 blockers in peptic ulcers Serotonin: in platelets – released when cell injury so platelets aggregate  leads to increased vascular permeability Action of histamine and serotonin is very similar Nitric Oxide: from Endothelial cells – need inducible form which comes about from exposure to injurious agent  leads to relaxation and vasodilation Protaglandins Cell damage from membrane phospholipids causes release of arachidonic acid PGI2: prostocyclins Pro-inflammatory and anti-inflammatory action If need inflammation in a site – proinflammatory action goes up Anti-inflammation: needed to bring down inflammation Both groups are found in arachidonic acid derivatives Prostaglandin group: vasodilation and increased vascular permeability Leukotriene group: If inflammation not stopped it can bring about destruction of cells – normal cells are not always recognized (called bystander injury) How do you prevent this? NSAID = nonsteroidal anti-inflammatory drugs COX1: why do we need this?*** COX2: inhibitors for this Use NSAIDs and steroids to bring down inflammation – form backbone of treatment (bronchial asthma, autoimmune diseases) Corneal injury – scar formation will lead to formation of white background (problem since cornea should be transparent to allow light into eye)  leads to blurring of vision

Need steroids especially where you don’t want fibrosis Autoimmune disorders : where immune system acts against itself – thinks it is a foreign object – therefore produces inflammation Hypersensitivity: when person is hypersensitive to some certain substance, causes release of mediators and inflammation occurs – may lead to angioneurotic edema (edema in larynx, blocks airway), anaphylactic shock, etc which may lead to death Cytokines: IL-1, IL-6, TNF  induce fever and cause release of acute phase reactants from liver (C reactive protein) – get fever with any inflammatory disease (increased temperature- due to release/presence of cytokines) Oxygen derived free radicals: see this in neutrophils – action: destruction of microbes  if released extracellulary can damage the host Lysosomal constituents of neutrophils: granules – MPO, lysozyme  when released can destroy tissue Plasma derived mediators: 4 interconnected mediator producing system – tissue damage can occur if activated C5A and C3A: what are they? Alternate pathway: microbial surfaces Classical pathway: C1 (don’t worry about this) Complements in inflammation: C5A and C3A – act in inflammation as …???**** C3BA: phagocytosis Membrane attack complex (MAC): formed by complex of C5-9 – go to bacterial surface and destroy it C5B: attachment of and series of multiples actions – go to microbe, coat it and destroy it (MAC) C5A: also helps in chemotaxsis Chemical mediators cause: Vasodilation – increased permeability – chemotactic factors – pain Systemic effects of acute inflammation: fever, leucocytosis (increased WBC count), acute phase reactants – Creactive proteins produced by liver which have a generalized anti-inflammatory effect In chronic diseases: chronic inflammation – deposited in tissues – leads to amyloidosis Chronic inflammation: long duration of inflammation – macrophages seen Treponema palidum: Mycobacterium tuberculosis:

Macrophages can engulf the bacteria but cannot destroy it because the cell wall contains particular acid that resists digestion Exposure to irritant non-living foreign material that cannot be removed = asbestosis (long thread like that enters respiratory tract when inhaled – enters up to alveoli – ingested by alveolar macrophages – resistant material therefore indigestible – macrophage itself gets killed, therefore fiber remains intact – ultimately asbestosis body is formed in which there is deposition of iron and protein) Giant cells formed (fallen body type) – tries to injure the suture material  what are giant cells? *** Why is autoimmune disease chronic? Because the antigen is always there, not removed Tuberculosis – primary: when person is first exposed to Tb antigen, production of immunity + production of hypersensitivity; secondary: infection does not spread, it is contained, but because of the hypersensitivity there is great inflammation and production of fibrosis (tissue destruction) – chronic inflammation is debilitating disorder Acute inflammation: there can be complete resolution – tissue can go back to original state Activated T cell which leads to production of interferol gamma – activates a macrophage which becomes activated macrophage In TB macrophage becomes an epithelioid cell (more cytoplasm with differently shaped nucleus) Becomes a cycle – t cells – macrophages – in turn activate the t cells  goes on until agent is removed by drugs Tissue injury and fibrosis (by production of growth factors) Tissue macrophage is dominant player in chronic inflammation 1. 2. 3.  Recruitment: from peripheral blood to the site of inflammation Macrophages undergo division and increase in number Have to become immobilized – cant go back to the blood These three steps lead to collection of macrophages

Special type of inflammation = chronic granulomatous inflammation – presence of distinctive pattern known as granuloma Granuloma: granule like a tumor (small) Multinucleate giant cells – seen in granulomas – with epithelioid cells which have abundant cytoplasm compared to a macrophage and also the nucleus gets a peculiar shape (slipper shaped nucleus) Normally macrophages have an oval-shaped nucleus

In Tb there is caseous necrosis (chalky or cheesy) – surrounded by modified macrophages (epithelioid cell) with a giant cells and surrounding it is a lymphoplasma cytic cup and a fibrous wall around it  confides the infection to a small area

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