9. Complement System/ Chronic& Acute Inflammation Flashcards
Complement system
A collection of circulating proteins
Functions:
Opsinization - attach to microbes and flag them for phagocytosis (C3b)
Inflammation- C3a and C5a are anaphlytoxins
Cell lysis through formation of MAC (C6-9)
Activation of the Classical complement cascade
Classical : IgM or IgG binding to pathogen = C1 Complex
C1 cleaves C2 and C4 into C2a and C2b/ C4a and C4b
C3 convertase is formed (C4bC2b)
Cleaves C3 - C3a (anaphlytoxin) and C3b
C3b binds to C3 convertase (C3bC4bC2b) and becomes C5 convertase
Cleave C5 into C5a (anaphytoxin) and C5b
C5b involved in formation of MAC (C6-9)
Lectin/ atlternative pathway of a complement activation
Lectin: C3b flags microbe
Want to continue to cleave C3bs to continue to flag microbes - opsinization
MAC is eventually formed
Lectin: Mannonse binding Lectin initiates activation
Reactions of Blood vessels due to acute inflammation
Changes in blood flow caliber
Vasodilation: induced by histamine (increase permeability)
Stasis of blood flow: slow movement of blood vessels
Neutrophils accumulate along endothelium
Response of lymphatic vessels and nodes due to acute inflammation
Inflammation directly induces lyphangiogenic factors in immune cells and inflamed tissue
Lymphaniogenic factors:
Act on local lymphatic vessels - developing new vessels and vessel dilation
Act on local blood vessels - recruiting macrophages - express lymphangiogenic growth factors such as VEGF (vascular endothelial growth factors - cause blood vessels to sprout)
Reactions of leukocytes in acute inflammation
Movement of leukocytes from vessel lumen to tissue intersititum can be divided into sequential phases:
- Rolling adhesion to endothelium
- Diapedesis- migration through epithelium
- Migration in tissue toward chemotactic stimuli
Receptors expressed on endothelial cells and leukocytes are TNF and IL-1
Selection and Integrins
Cell adhesion molecules (CAMs) - allow leukocytes / WBCs to bind to endothelial cells
Outcomes of acute inflammation
Resolution
Fibrosis- fibroblasts making
excessive collagen
Chronic inflammation
Chronic inflammation
Response to prolonged inflammation
Causes of chronic inflammation
Persistent infections
Hypersensitivity/autoimmune diseases
Prolonged exposure
Major cell types in chronic inflammation
Phagocytes (macrophages)
Lymphocytes
Role of macrophages in chronic inflammation
Have phagocytosis function
Initiate tissue repair and participate in scar formation (fibrosis)
Secrete TNF, IL-1 and ROS causing inflammation and tissue injury
Present antigens on T-lymphocytes
Role of lymphocytes in chronic inflammation
Lymphocytes and macrophages interact in a bidirectional way
Activated macrophages activate T cells and in turn activated T cells can activate macrophages
Granulomatous inflammation
Characterized by local accumulation of activated macrophages (granuloma) surrounded with lymphocytes and the central nervous system
Types of granulomas
Foreign body - induced by particles that can be phagocytosed
Immune granulomas - formed by T cell mediated responses to persistent microbes or self antigen
Tuberculosis
Cause Myobacterium tuberculosis
Reaction: case acting granuloma (tubercule) with central necrosis ‘
Foreign body granuloma
Crohn’s disease (IBD)
Cause: immune reaction against intestinal bacteria
Tissue reaction: non-case sting granulomas in wall of intestine with chronic inflammation
Immune granuloma
Systemic effects of inflammation
Cytokines TNF and IL-1 involved in systemic changes
Fever: result of prostaglandin production in hypothalamus
Acute Phase proteins: increase in these are considered an acute phase reactant, useful biomarker, made in liver and found in RBCs
Leukocyte- increase WBCs
Acute phase reactions (APR)
Increase of these proteins in blood
Fibrinogen - seen in erythrocytes sedimentation rate - attaches to RBCs and causes them to sediment
Serum Amalyoid A (SAA) - attach to cell wall of bacteria (opsinization)
C-reactive Protein (CRP) attach to cell wall of bacteria (opsinization) marker for cardiovascular disease (MI)
Onset: acute vs chronic
Acute: fast, minutes
Chronic: slow, weeks/months
Cellular filtrate: acute vs chronic
Acute: mainly neutrophils
Chronic: monocytes/macrophages and lymphocytes
Tissue injury/fibrosis: chronic vs acute
Acute: mild and self limited
Chronic: severe and progressive
Disorder: acute vs chronic
Asthma and arthritis
Acute: asthma
Chronic: arthritis
