Innate Immunity Part 2 PDF

Innate pt.2 Pathogen recognition receptor (prr's) Phagocytic receptors - Is also called as primitive pattern recognition receptor -cell surface receptors that bind the pathogen - Internal defense system...

Innate pt.2 Pathogen recognition receptor (prr's) Phagocytic receptors - Is also called as primitive pattern recognition receptor -cell surface receptors that bind the pathogen - Internal defense system initaites a signal leading to the release of effector ◆ Design to recognize molecules that are unique to infectious organisms molecules (cytokines) - Macrophages and dendritic cell between 10-15 % are in - macrophages this tissue this are the most important cell in' recognition of have cell surface receptors that recognize PAMPs pathogen containing mannose -able to distinguish pathogen from normally present molecules in body by means of receptor known as PRRS which are found on : Toll like receptors T cell Monocyte - set of transmembrance receptors that recognize different Eosinophil types of PAMPs Epithelial cell Mast cell Neutrophil - found on : o macrophages o dendritic cells Mechanism: o neutrophils Important in second one of defense once pathogen attaches to o epithelial cells phagocyte cell it becomes activated able to eliminate and engulf microorganism Once the tea is activated it will release chemical signal which Is Calle cytokines at chemokine : This two are chemical messenger that gives signal to other phagocytic cell types in that area of infection it can also triggered adaptive immune response -Able to distinguish self from non self by recognizing PAMPS only present on microoganism Toll like receptors – bind to particular substances - host immune response will produce chemokine and cytokine that will rapidly acute phase reactants (APR’s) activate the immune response - soluble factors that contribute to the innate immune response – Neutrophil are recruited to area of stimulus increasing Normal serum constituent due to infection, trauma to the Capillary permeability tissue Dendritic cells and macrophages become more - indicators of inflammation effective due to an increase in adhesion molecule expression on their cell surfaces. o positive APRs – increase in concentration during inflammation These processes enhance phagocytosis & destroy more o negative APRs – decrease in concentration during pathogen before disease set in inflammation Secreted prr’s -molecules that circulate in blood and lymph -Circulating protein bind with PAMPS Triggers complement cascade → opsonization of the pathogen phagocytosis  C-reactive protein alpha a1-anti trypsin – Somehow act as antibodies capable of - general plasma inhibitor of proteases released from o opsonization – coating of foreign particles leukocytes – esp. elastase o precipitation o agglutination - regulates expression of pro inflammatory cytokines o activation of complement by the classical pathway – Main substrate: Phosphocoline o TNF o Interleukin-1 S o IL-6 – Best indicator of inflammation – Most widely monitored haptoglobin - binds irreversibly to free hemoglobin released by intravascular hemolysis - acts as antioxidant to provide protection against oxidative damage Note: recent research ng CDC increase level of CRP denotes myocardial infraction , trauma , cardiovascular disease mediated by free hemoglobin – Easily destroyed at 56 °C at 30 mins fibrinogen clot -increases the strength of a wound & stimulates Serum amyloid A (SAA) endothelial cell adhesion & proliferation – critical to healing process -other major protein whose concentration can increase almost a thousandfold in response to infection/injury -The apolipoprotein produced in liver; 11,685 molecular weight Dalton - appears to act as a chemical messenger; activates monocytes & macrophages to then produce products that increase inflammation - increases significantly more in bacterial - contributes to localized inflammation in coronary artery disease Mannose-binding protein (mbp) – Trimer acts as opsonin (calcium dependent) – Widely distributed in mucosal surface throughout the body – Similarities to complement C1q – Complement proteins -overall function is mediation of inflammation - major functions o opsonization o chemotaxis o cell lysis  Inflammation Phagocytosis – When pathogen penetrates outer layer of innate immunity – Main purpose of inflammatory response is to attract cells & humoral and cellular mechanism works together to create pathogen by means of phagocytosis inflammation APR-acute reactant note : phase – This is the overall reaction of body to injury invasion of - enhance phagocytosis infectious agent – Most active cell in phagocytosis Neutrophil Monocytes primary objectives : Macrophages Localized and eradicate the irritant & repair surrounding Dendritic cells tissue. Steps in phagocytosis #Y POX1A Can induce inflammation Classic step: ICED INITIATION -> CHEMOTAXIS -> ENGULFMENT -> DIGESTION note : Rodaks RECOGNITION & ATTACHMENT -> INGESTION -> KILLING & five cardinal signs o rubor – redness DIGESTION -> EXTRACELLULAR TRAPS o calor – heat o dolor – pain TURGEONS o tumor – swelling o functio laesa – loss/diminished function CHEMOTAXIS -> ADHERENCE -> ENGULFMENT -> PHAGOSOME FORMATION -> FUSION -> DIGESTION & DESTRUCTION : Stages  Other important information in phagocytosis Chemotaxis: Cell are attracted to site of inflammation by chemical substance chemokines Note: that without this chemotactic substance movement of cell are random Job syndrome -Abnormal chemotactic activity Lazy leukocyte -Abnormal and random chemotactic activity Boy den chamber assay -test to detect chemotactic activity Positive chemotaxis -migration is toward the stimulation Negative chemotaxis -Migration is away from site of stimulation Natural killer cells -Do not express marker of either t/b cells : arise in common lymphocyte progenitor -Have the ability to kill Target cell nit host prior exposure - major function o capable of recognizing any foreign cell o represent the first line of defense against virally infected cells & tumor cells o can destroy virally infection cells/tumor cells without/no MHC restriction (MHC- unrestricted cytolysis) orantigen presentation - once activated by IL-2 → lymphoine killer activated cells (LAK) major producers of cytokines – interferon-gamma & TNF-α that help to recruit T cells -expresses/possesses o CD16 o CD56 o CD94 -Half life : 7 - 10 days