{"id":6536,"date":"2026-06-03T13:26:28","date_gmt":"2026-06-03T17:26:28","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=6536"},"modified":"2026-06-09T15:22:58","modified_gmt":"2026-06-09T19:22:58","slug":"complement-system-interferons-and-cytokines","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/complement-system-interferons-and-cytokines\/","title":{"raw":"Section 3: Complement System, Interferons, and Cytokines","rendered":"Section 3: Complement System, Interferons, and Cytokines"},"content":{"raw":"

The Complement System<\/strong><\/span><\/h3>\r\n

The complement system<\/strong> consists of 50+ plasma proteins produced by the liver<\/strong> that circulate the blood in an inactive state and play a crucial role in the immune system.\u00a0 There are three complement pathways in which these proteins are activated in a domino-like chain reaction called a complement cascade during infection or injury.\u00a0 All three complement pathways converge on three shared outcomes:\u00a0 (1) opsonization<\/strong> via C3b to enhance phagocytosis; (2) formation of Membrane Attack Complexes (MAC)<\/strong> that create pores in bacterial cell walls, causing swelling and rupture; and (3) activation of mast cells and basophils<\/strong> to release pro-inflammatory mediators.<\/span><\/p>\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Classical Pathway<\/strong><\/span><\/td>\r\nTriggered by antibodies<\/strong> forming complexes with pathogen surface antigens.\u00a0 C1 binds two antibodies to start the cascade (C1 \u2192 C2 \u2192 C3, etc.)\u00a0 C3b attaches to the pathogen as an opsonin;<\/strong> C5-9 assemble into MAC pores<\/strong>.\r\n\r\nThese activated complement protein complexes attract white blood cells for further defense and induce mast cells and basophils to release pro-inflammatory mediators (e.g. histamine).<\/td>\r\n<\/tr>\r\n
Lectin Pathway<\/strong><\/span><\/td>\r\nMannose-Binding Lectin (MBL)<\/strong> is produced by the liver,<\/strong> MBL binds to mannose (a sticky adhesive sugar on the surface of bacteria, yeasts, viruses, and protozoa) and initiates a similar cascade.\r\n\r\nExamples of pathogens that can be bound by MBL:\u00a0 Salmonella, Streptococci, Candida albicans,<\/em> HIV, SARS-CoV-2, influenza A, and Leishmania<\/em> (protozoa transmitted by sand fly bite in tropics & subtropics).<\/td>\r\n<\/tr>\r\n
Alternative Pathway<\/strong><\/span><\/td>\r\nIndependent<\/strong> of antibodies and lectin, though initiates the same 3 outcomes as the Classical and Lectin Pathways (opsonization, MAC,<\/strong> and activation of mast cells and basophils<\/strong>)\r\n\r\nComplement proteins bind directly to pathogens.<\/strong> bonds that are stabilized by properdin<\/strong> (a complement factor released by leukocytes),\r\n\r\n.<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n

Interferons<\/strong><\/span><\/h3>\r\n

Interferons (IFNs)<\/strong> are a type of cytokine\u00a0(signalling glycoproteins)<\/strong> released by almost all cell types during any infection.\u00a0 Their name reflects their primary function;\u00a0 interfering with viral replication<\/strong>.\u00a0 Over 20 IFN genes exist.\u00a0 Some produce anti-viral proteins (AVPs)<\/strong>; some act as endogenous pyrogens<\/strong> (inducing fever); and interferons can cause muscle pain<\/strong>, body aches,<\/strong> and flu-like symptoms<\/strong>.\u00a0<\/span><\/p>\r\n\r\n\r\n[caption id=\"attachment_2335\" align=\"alignnone\" width=\"300\"]\"Interferons<\/a> Interferons released from infected cells are able to: (1) induce AVP enzyme production in neighbouring cells to interfere with viral replication, (2) bind to \"death receptors\" of neighbouring cells triggering apoptosis, and (3) stimulate WBC activation.[\/caption]\r\n\r\n\r\n\r\n\r\n\r\n
Alpha interferons (Type I)<\/strong><\/span><\/td>\r\nProduced by virally-infected host cell<\/strong>s.\r\n\r\nInduce AVP production<\/strong> in neighbouring cells to block viral RNA\/DNA replication.\r\n\r\nTrigger apoptosis<\/strong> in infected neighbouring cells.\r\n\r\nStimulate NK cells<\/strong> and macrophages.<\/strong>\r\n\r\nIncreases MHC I expression.\u00a0 MHC is<\/strong> used by all cells to present non-self antigens to T cells (activating T cell specific immunity).<\/span><\/td>\r\n<\/tr>\r\n
Beta interferons (Type I)<\/strong><\/span><\/td>\r\nProduced by fibroblasts<\/strong> (a common stromal\/mesenchymal\/connective tissue cell).\r\n\r\nAnti-inflammatory<\/strong>; released in preparation for healing after infection.<\/td>\r\n<\/tr>\r\n
Gamma interferons (Type II)<\/strong><\/span><\/td>\r\nReleased by activated NK and T cells<\/strong>.\r\n\r\nStimulate macrophage activity<\/strong>.\r\n\r\nIncreases MHC II expression<\/strong> in APCs (macrophages and dendritic cells).\u00a0 MHC II is used in presenting non-self antigens to T cells (activating T cells specific immunity).<\/span><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n

Cytokines<\/strong><\/span><\/h3>\r\n

Cytokines<\/strong> are signalling glycoproteins produced by most cells of the body - macrophages, B cells, T cells, mast cells, endothelial cells, fibroblasts and other stromal (mesenchymal\/connective tissue) cells.\u00a0 Some cytokines participate in innate (non-specific) defense; others in adaptive (specific) immune responses.\u00a0 Four main categories:<\/span><\/p>\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Interferons<\/strong><\/span><\/td>\r\nAs described above.\u00a0 Main roles; interfere with viral replication<\/strong>, activate NK cells, T cells, and macrophages<\/strong>, acts as endogenous pyrogens<\/strong>, slow inflammation in preparation for healing.<\/td>\r\n<\/tr>\r\n
Chemokines<\/strong><\/span><\/td>\r\nInduce chemotaxis<\/strong> - directed migration and recruitment of WBCs to infection or injury sites.<\/td>\r\n<\/tr>\r\n
Lymphokines<\/strong><\/span><\/td>\r\nProduced by T lymphocytes<\/strong> to:\u00a0 (a) attract macrophages; and (b) stimulate B lymphocytes.<\/td>\r\n<\/tr>\r\n
Interleukins<\/strong><\/span><\/td>\r\nProduced by helper T cells<\/strong>.\u00a0 Functions:\r\n\r\n(a) activate macrophages<\/strong>.\r\n\r\n(b) stimulate fever (act as endogenous pyrogens);<\/strong>\r\n\r\n(c) stimulate T and B cell differentiation<\/strong>;\r\n\r\n(d) stimulate hematopoietic cells<\/strong> to produce more WBCs.<\/strong><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n

<\/h3>","rendered":"

The Complement System<\/strong><\/span><\/h3>\n

The complement system<\/strong> consists of 50+ plasma proteins produced by the liver<\/strong> that circulate the blood in an inactive state and play a crucial role in the immune system.\u00a0 There are three complement pathways in which these proteins are activated in a domino-like chain reaction called a complement cascade during infection or injury.\u00a0 All three complement pathways converge on three shared outcomes:\u00a0 (1) opsonization<\/strong> via C3b to enhance phagocytosis; (2) formation of Membrane Attack Complexes (MAC)<\/strong> that create pores in bacterial cell walls, causing swelling and rupture; and (3) activation of mast cells and basophils<\/strong> to release pro-inflammatory mediators.<\/span><\/p>\n\n\n\n\n\n
Classical Pathway<\/strong><\/span><\/td>\nTriggered by antibodies<\/strong> forming complexes with pathogen surface antigens.\u00a0 C1 binds two antibodies to start the cascade (C1 \u2192 C2 \u2192 C3, etc.)\u00a0 C3b attaches to the pathogen as an opsonin;<\/strong> C5-9 assemble into MAC pores<\/strong>.<\/p>\n

These activated complement protein complexes attract white blood cells for further defense and induce mast cells and basophils to release pro-inflammatory mediators (e.g. histamine).<\/td>\n<\/tr>\n

Lectin Pathway<\/strong><\/span><\/td>\nMannose-Binding Lectin (MBL)<\/strong> is produced by the liver,<\/strong> MBL binds to mannose (a sticky adhesive sugar on the surface of bacteria, yeasts, viruses, and protozoa) and initiates a similar cascade.<\/p>\n

Examples of pathogens that can be bound by MBL:\u00a0 Salmonella, Streptococci, Candida albicans,<\/em> HIV, SARS-CoV-2, influenza A, and Leishmania<\/em> (protozoa transmitted by sand fly bite in tropics & subtropics).<\/td>\n<\/tr>\n

Alternative Pathway<\/strong><\/span><\/td>\nIndependent<\/strong> of antibodies and lectin, though initiates the same 3 outcomes as the Classical and Lectin Pathways (opsonization, MAC,<\/strong> and activation of mast cells and basophils<\/strong>)<\/p>\n

Complement proteins bind directly to pathogens.<\/strong> bonds that are stabilized by properdin<\/strong> (a complement factor released by leukocytes),<\/p>\n

.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Interferons<\/strong><\/span><\/h3>\n

Interferons (IFNs)<\/strong> are a type of cytokine\u00a0(signalling glycoproteins)<\/strong> released by almost all cell types during any infection.\u00a0 Their name reflects their primary function;\u00a0 interfering with viral replication<\/strong>.\u00a0 Over 20 IFN genes exist.\u00a0 Some produce anti-viral proteins (AVPs)<\/strong>; some act as endogenous pyrogens<\/strong> (inducing fever); and interferons can cause muscle pain<\/strong>, body aches,<\/strong> and flu-like symptoms<\/strong>.\u00a0<\/span><\/p>\n

\"Interferons<\/a>
Interferons released from infected cells are able to: (1) induce AVP enzyme production in neighbouring cells to interfere with viral replication, (2) bind to “death receptors” of neighbouring cells triggering apoptosis, and (3) stimulate WBC activation.<\/figcaption><\/figure>\n\n\n\n\n\n
Alpha interferons (Type I)<\/strong><\/span><\/td>\nProduced by virally-infected host cell<\/strong>s.<\/p>\n

Induce AVP production<\/strong> in neighbouring cells to block viral RNA\/DNA replication.<\/p>\n

Trigger apoptosis<\/strong> in infected neighbouring cells.<\/p>\n

Stimulate NK cells<\/strong> and macrophages.<\/strong><\/p>\n

Increases MHC I expression.\u00a0 MHC is<\/strong> used by all cells to present non-self antigens to T cells (activating T cell specific immunity).<\/span><\/td>\n<\/tr>\n

Beta interferons (Type I)<\/strong><\/span><\/td>\nProduced by fibroblasts<\/strong> (a common stromal\/mesenchymal\/connective tissue cell).<\/p>\n

Anti-inflammatory<\/strong>; released in preparation for healing after infection.<\/td>\n<\/tr>\n

Gamma interferons (Type II)<\/strong><\/span><\/td>\nReleased by activated NK and T cells<\/strong>.<\/p>\n

Stimulate macrophage activity<\/strong>.<\/p>\n

Increases MHC II expression<\/strong> in APCs (macrophages and dendritic cells).\u00a0 MHC II is used in presenting non-self antigens to T cells (activating T cells specific immunity).<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Cytokines<\/strong><\/span><\/h3>\n

Cytokines<\/strong> are signalling glycoproteins produced by most cells of the body – macrophages, B cells, T cells, mast cells, endothelial cells, fibroblasts and other stromal (mesenchymal\/connective tissue) cells.\u00a0 Some cytokines participate in innate (non-specific) defense; others in adaptive (specific) immune responses.\u00a0 Four main categories:<\/span><\/p>\n\n\n\n\n\n\n
Interferons<\/strong><\/span><\/td>\nAs described above.\u00a0 Main roles; interfere with viral replication<\/strong>, activate NK cells, T cells, and macrophages<\/strong>, acts as endogenous pyrogens<\/strong>, slow inflammation in preparation for healing.<\/td>\n<\/tr>\n
Chemokines<\/strong><\/span><\/td>\nInduce chemotaxis<\/strong> – directed migration and recruitment of WBCs to infection or injury sites.<\/td>\n<\/tr>\n
Lymphokines<\/strong><\/span><\/td>\nProduced by T lymphocytes<\/strong> to:\u00a0 (a) attract macrophages; and (b) stimulate B lymphocytes.<\/td>\n<\/tr>\n
Interleukins<\/strong><\/span><\/td>\nProduced by helper T cells<\/strong>.\u00a0 Functions:<\/p>\n

(a) activate macrophages<\/strong>.<\/p>\n

(b) stimulate fever (act as endogenous pyrogens);<\/strong><\/p>\n

(c) stimulate T and B cell differentiation<\/strong>;<\/p>\n

(d) stimulate hematopoietic cells<\/strong> to produce more WBCs.<\/strong><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

<\/h3>\n

Media Attributions<\/h2>