Innate Immunity PDF

THE INNATE IMMUNITY Sunday, October 8, 2023 10:17 PM INFLAMMATION: → Innate, nonspecific response to tissue injury → Causes: redness, swelling, painful and produce a hot temperature (heat) ○ The heat felt is an inflammatory response: begins locally § If It can't be...

THE INNATE IMMUNITY Sunday, October 8, 2023 10:17 PM INFLAMMATION: → Innate, nonspecific response to tissue injury → Causes: redness, swelling, painful and produce a hot temperature (heat) ○ The heat felt is an inflammatory response: begins locally § If It can't be stopped right away it can became systematic (whole body will feel it, like in the joints) → Recruitment of phagocytes to invaded or injured area. If infection is causing the inflammation its: 1. Isolate, destroy, or inactivate the invaders - going to be attacked to kill it so it doesn't spread 2. Remove debris - before repair the site needs to be cleaned 3. Prepare for subsequent healing and repair - repair → Tissue damage is what causes inflammation to start → Twisting the ankle is an example of inflammation that isn't external → Goal of inflammation is to repair tissue damage (and remove pathogen if one is present) → Resident tissue (like macrophages, dendritic cells) ○ Macrophages activate inflammatory response ○ … ingest pathogens ○ … have cytokines and histamine = vasodilation (widen tube) Picture Description: 1. A break in the skin introduces bacteria, which reproduce at the wound site. Activated resident macrophage engulf the pathogens and secrete cytokines and chemotaxis - Macrophages are first defenders - Have receptors to recognize its identity as a virus - Cytokines and chemotaxins will activate nearby cells and alert the whole system and recruit additional cells 2. Activated mast cells release histamine 3. Histamine dilates local blood vessels and widens the capillary pores. The cytokines cause neutrophils and monocytes to stick to the blood vessel wall - Phagocytes that are recruited are: neutrophiles and monocytes which will both start phagocytosis and some monocytes will also differentiate into macrophages 4. Chemotaxins attract neutrophils and monocytes, which squeeze out b/w cells of the blood vessel wall, a process called diapedesis, and migrate to the infection site. Will eat pathogen 5. Monocytes enlarge into macrophages. Newly arriving macrophages and neutrophils engulf the pathogens and destroy them → Inflammatory response is similar no matter what the triggering event (Pathogens or sterile) ○ Initiated by resident tissue macrophages -> release cytokines and chemokines b/c macrophages won't be able to handle the pathogen alone ○ Mast cells are activated -> release histamine ○ Localized vasodilation: blood vessel increase in size (diameter) § Increased capillary permeability (space b/w epithelial cells) § Localized edema (swelling and pain) § Walling-off the inflamed area □ If an area is exposed to air □ Prevent loss of blood and from additional foreign pathogens from entering → Inflammatory response is similar no matter what the triggering event (pathogens or sterile) ○ Emigration (recruitment from the blood) of leukocytes = neutrophils and monocytes ○ Leukocyte proliferation ○ Marking of bacteria for destruction by opsonins (complement) § Process of opsonization: compliment proteins will attach themselves to the surface of the pathogen and coat them. This makes it easier for phagocytosis to occur smoothly CYTOKINES: → Can Kill microbes directly → STAR PLAYERS, POTENT: several chemicals (i.e. interleukin (IL) 1, interleukin 6, TNF bring about a diverse array of effects ○ Produced between leukocytes ○ Allows increased of metabolism, increase heat and body temperature ○ Can be made by muscle cells ○ Tumor Necrosis Factor Alpha → EP (endogenous pyrogen) induces fever in the body ○ When local it is not felt that much ○ When they are released systemically they decrease concentration of iron, make more heat than ATP ○ We can handle heat better than the pathogen ○ EP will go to your liver and hypothalamus → Decrease plasma concentration of iron: bc pathogen relies on our iron → Stimulates release of acute phase proteins (e.g. CRP) → Trigger clotting and anticlotting systems → Each cytokine can have multiple jobs and some can overlap: meaning some cytokines ca have different functions but can have a common job → Chemokines are the ones that are told to come to the site MORE ABOUT INFLAMMATION → Ultimate goal -> tissue repair → Cell division replaces lost cells with same kind of cells → In non-regenerative tissue (nerve and muscle) ○ Lost cells are replaced with scar tissue § Activate fibroblast: ECM: collagen fibers are used → Prolonged, unwanted, chronic inflammation: can cause Alzheimer's disease, atherosclerosis, asthma, diabetes, cancer ○ Solution: NSAIDs (nonsteroid anti-inflammatory drugs), glucocorticoids, steroids → Interferons: antiviral effects (indirect) -> limit viral spread ○ Type of cyokines ○ Potent against viral infections ○ Interfere with the virus: block the virus from hijacking the cell or kill the cell that is infected with the virus THE COMPLEMENT SYSTEM → Nonspecific response → Composed of plasma proteins that are produced by the liver and circulate in inactive form → Three mechanisms of activation: 1. Spontaneous activation on microbial surfaces - Coat pathogen - Fastest way (within minutes) - Occurs only near the surface of the pathogen, cascade effect 2. Binding to carbohydrates chains present on surfaces of microorganisms but not on human cells - Mannose is a type of glucose - And is found on our cells as well as on the surface of pathogens but it is distributed differently so some complement proteins can recognize the mannose configuration and activate 3. Activation by antibody binding to antigens on pathogens - Longest to take place → Causes destruction of pathogen by two mechanisms: 1. Forms membrane attack complexes (MAC) that punch holes in the pathogen - Complex of compliment proteins and punches a hole 2. Enhances the uptake of the pathogen by phagocytes (opsonization) DENDRIIC CELL (DC) → Bridge to innate and adaptive → Sit in tissue, drink fluid, takes pathogen, cut up pathogen into smaller peptides and gets combined with a MHC protein then presents it on the surface of the cell. Then it leaves the site of infection and goes to a secondary lymphoid organ. Presents to T-cells → Tissue residents cells with a unique star-shaped morphology → Immature DC in tissue have very high ability to internalize particular (micropinocytosis) ○ Happy sitting drinking → Professional APC (antigen presenting cell) → Encounter with pathogen causes maturation of DC -> mature DC → T cells have o receptors that can see the pathogen directly so they need to be activated