Unit 2 Flashcards
What is inflammation?
a protective response involving host cells, blood vessels, and proteins and other mediators that is intended to eliminate the initial cause of cell injury, as well as the necrotic cells and tissues resulting from the original insult, and to initiate the process of repair
How does inflammation accomplish its protective function?
diluting, destroying, or otherwise neutralizing harmful agents. Removes dead and injured cells and initiates tissue repair
The goal of the inflammatory reaction is to bring which cells to the site of infection or tissue damage?
Leukocytes and plasma proteins
What are the two types of inflammation?
Acute and or chronic
Which system transports leukocytes and plasma proteins to the infection site?
Circulatory system
Inflammation does have its downside however, It can cause secondary damage to normal tissue via
Virulent microbes, prolonged chronic infections and via innapropiate immune response
When injure or infection is detected, what happens?
Macrophages, dendritic cells and or mast cells secrete cytokines and attract plasma proteins to regulate or induce inflammation
What are the five steps of inflammation?
recognie the injury, recruit leukocytes, remove agents via phagocytosis, regulate the response and resolve/repair tissue
What are the cardinal signs of inflammation?
Rubor, calor, tumor, dolor, and functio laesa
Inflammations are typically, _____ (self limiting) when the pro inflammatory mediators are inactivated and the antiinflammatory mediators are activated
Short lived
What is an acute inflammation?
an inflammation that has a rapid onset and could last anywhere between minutes and days
what are the signs of acute inflammation?
Systemic signs, edema, neutrophils infiltrate cells, but no fibrosis
What is chronic inflammation?
Insidious form of inflammation and usually has an onset of days to years. It shows few systemic signs such as angiogenesis and fibrosis
In accute inflammation, in which day is the neutrophil activity most prevalent?
first day
In chronic inflammation which day/days has more monocyte and macrophage activity?
Day 2
What are the stimuli for accute inflammation?
infection, trauma, ischemia, necrosis, foreign bodies, and hypersensitivity reactions
What do leukocytes and plasma proteins do after they are stimulated (in acute inflammation)?
destroy microbes and celullar debris
What are the components of acute inflammation?
Vascular changes and leukocyte recruitment + activation
How do cells recognize harmful agents?
pattern recognition receptors
What are pattern recognition receptors?
Macrophages, dendritic cells and mast cells that recognize non-self molecular patterns
What are the two types of pattern recognition receptors?
Toll like receptors and inflammasome
What type of infections pathogens are recognized by Toll like receptors and where are they located?
All types of infectious pathogens and they are located in the plasma membrane
What type of pattern receptor recognizes products of dead cells and crystals and where is it located?
Inflammasome and they are located in the cytoplasm
Usually vessels alter to allow better flow and permeability of ____ and proteins to ____
Cells and proteins to target tissues
What does vasodilation entail?
Increase in blood flow
What could vasodilation cause during inflammation?
Erythema and calor in target area
What would an increase in permeability cause in inflammation?
An increase in fluid transport to target tissue
An increase in viscosity or stasis would cause _____ to collect along the vascular wall and then ______into tissue. This process is known as _____
Leukocytes, migrate, diapedesis
An increase in permeability would reverse osmotic gradient and then would fill the interstitial space with fluid causing what?
Edema
What are the mechanisms for increasing permeability?
Endothelial cell contraction , endothelial necrosis, and leakage from angiogenesis
What is the most common mechanism for increasing permeability in vessels?
endothelial contraction
What does endothelial contraction lead to and how does it dlead to it?
leads to intercellular gaps in postcapillary venules by binding histamine to specific receptors
What does endothelial necrosis entail?
basically vascular leakage by burns and or infections. This damage persists until repaired
What does leakage from angiogenesis entail?
vessel sprouts remain leaky until proliferating endothelial cells mature sufficiently to form intercellular junctions.
inflammation, lymph flow is increased and helps drain ___ ____ leukocytes, and cell debris from the extravascular space.
Edema fluid
What is lymphadenopathy?
A general disorder of lymph nodes
What is lympadenitis?
Inflammation of the lymph node leading to an increase in size
What is lymphangitis?
inflammation of the lymphatic channel
What do leukocytes actually do when delivered to target tissue?
Kill microbes, remove celullar debris. It also may lead to injury of the inflammation is prolonged or excessive
What are the 4 steps toward leukocyte recruitment?
(1) margination and rolling along the vessel wall; (2) firm adhesion to the endothelium; (3) transmigra- tion between endothelial cells; and (4) migration in inter- stitial tissues toward a chemotactic stimulus
What happens during margination and rolling?
Basically the RBC push the leukocytes out of the central canal and into the walls of endothelium causing them to interact with it by accumulating (margination) Once the endothelial cells are activated they express adhesion molecules to which the leukocytes attach and detach and sort of tumble (rolling)
What protein mediates Margination and rolling?
Selectins
Which protein mediates firm adhesion?
Integrins
What happens when leukocytes adhere to endothelium walls and start rolling?
they detect changes in the endothelium and can thus start the next step of repair once change is detected
Chemotaxis
Leukocyte activation results in the enhancement of the following functions:
Phagocytosis, destruction of phagocytosed molecules, liberation of substance
The process through which Leukocytes bind and ingest most microorganisms and dead cells by means of specific surface receptors is known as
Phagocytosis
What are opsonins?
receptors that recognize host proteins and coat microbes to tag them for phagocytosis
What are the most import ant opsonins?
Antibodies of the immunoglobulin G (IgG) class, break- down products of the complement protein C3, and plasma carbohydrate-binding lectins called col- lectins
Leukocyte induced tissue injury in inflammation occurs because _____ ____ ____ cant distinguish between tissues
White blood cells
In certain infections that are persistent such as tuberculosis the autoimmune response does ____ than the ______
more damage; microbe
An example of tissue injury due to leukocytes might be an infarct. In this situation what may happen due to inflammation?
it may prolong and exacerbate the injurious con- sequences of the ischemia, especially upon reperfusion
What are the 3 possible outcomes of inflammation?
Resolution: Regenation and repair, Chronic inflammation ,and/or scarring
What happens during Resolution of inflammation?
the injured tissue is capable of regenerating, the usual outcome is restoration to structural and functional normalcy
When structural and functional normalcy in the cell are being restored what must occur?
neutralization, decay, or enzymatic degradation of the various chemical medi- ators; normalization of vascular permeability; and ces- sation of leukocyte emigration, with subsequent death (by apoptosis) of extravasated neutrophils.
Phagocytes and lymphatic drainage of lymph are both key players in this outcome of inflammation because they eliminate detritus from the “battlefield”
(actual quote from the book )
Resolution
(after restoration of normalcy) Leukocytes secrete _______ that initiate the subsequent repair process, in which new blood vessels grow into the injured tissue to provide nutrients
cytokines
What stimulates the proliferation of fibroblasts and collagen being layed down in order to fill defects ?
growth factors
If inflammation still persists due to the offending tissue not being removed and exceeding the capacity for adaptability of the cell, inflammation persists in a more insidious fashion. this is also known as
Chronic inflammation
What is scarring?
type of repair after substantial tissue destruction or when inflammation occurs in tissues that do not
regenerate, in which the injured tissue is filled in by connective tissue.
What is fibrosis?
In organs in which extensive connec- tive tissue deposition occurs in attempts to heal the damage or as a consequence of chronic inflammation. This process can significantly impede function
What are the morphologic patterns of acute inflammation?
Serous, Fibrinous, suppurative or purulent and ulcerative
What is serous inflammation?
characterized by the outpour- ing of a watery, relatively protein-poor fluid that, depend- ing on the site of injury, derives either from the plasma or from the secretions of mesothelial cells lining the perito- neal, pleural, and pericardial cavities.
What is fibrinous inflammation?
occurs as a consequence of more severe injuries, resulting in greater vascular perme- ability that allows large molecules (such as fibrinogen) to pass the endothelial barrier.
What is characteristic of fibrinous inflammation?
Fibrinous exaudate
What is suppurative inflammation?
Localized infection of pus-forming organishs such as Staph. aureus
What is an abscess?
A focal collection of pus that may be caused by seeding of pyogenic organ- isms into a tissue or by secondary infections of necrotic foci
What do abscesses typically have?
a central, largely necrotic region rimmed by a layer of preserved neutrophils with a surrounding zone of dilated vessels and fibroblast proliferation indicative of attempted repair.
what is ulcerative inflammation?
a local defect, or excavation, of the surface of an organ or tissue that is produced by necrosis of cells and sloughing (shedding) of necrotic and inflammatory tissue
Where are ulcers most commonly encountered?
the mucosa of the mouth, stomach, intestines, or genito- urinary tract and the subcutaneous tissues of the lower extremities in older persons who have circulatory disturbances predisposing affected tissue to extensive necrosis.
What are two others types of inflammation?
Granolumatous or pseudomembranous
What is a granulomatous inflammation?
A pattern of chrnoinc inflammation caused by activated macrophages and lymphocytes that wall off an area
The most common type of granulomatous inflammation?
TB
What kind of Granulomas are caused by TB?
Caseating granulomas
inflammatory mediators may be produced locally by cells at the site of inflammation, or may be derived from circulating inactive precursors that are acti- vated at the site of inflammation (True or false?
True
How do most mediators of inflammation act?
By binding to specific receptors on different target cells
What are the types of cell derived inflammatory mediators?
Vasoactive amines, arachidonic acid metabolites, Cytokines, Reactive oxygen species, Lysosomal enzymes, and neuropeptides
When are vasoactive amines activated and where do they come from?
They are activated during acute inflammation and they are derived from mast cells, platelets,endotheliums and WBCs
What are the two types of vaso active amine inflammatory mediator?
Histamine and serotonin
When is histamine released?
In response to physical injury (trauma/heat), Immune response dealing with IgE antibodies, in response to anaphylotoxins, leukocyte derived histamine releasing proteins, neuropeptides, and certain cytokines
What does histamine cause?
Vasodilation and increases vascular permeability
What is serotonin?
a preformed vasoac- tive mediator found within platelet granules
when is serotonin released?
during platelet aggregation
What does serotonin induce?
vasoconstriction during clotting
What are Arachidonic acid metabolites?
Products derived from the metabolism of AA also known as Eicosanoids
Where do Acid metabolites come from?
Leukocytes, mast cells, endothelial cells and platelets
What do prostaglandins and leukotrienes do?
They are vasodilators and contribute to pain and fever caused by inflammation. They are also chemotaxis
NSAIDs are medications that affect ______ ______ and reduce pain and fever due to that
Prostaglandin synthesis
What are lipoxins?
A type of Metabolite that inhibits chemotaxis
What do cytokines do?
Increase WBC production and contribute to Adhesion and well as migration
where do cytokines come from?
Mast cells, endothelial cells, macrophages
What are the most important cytokines?
Il-1 and 6, TNF and chemokines
Where do ROS’s come from?
Neutrophils and macrophages
What do ROS do?
Kill and degrade microbes
What is an example of an ROS and whats its function?
Nitric oxide. It is a vasodilator and microbe killer
Where do lysosomal enzymes come from and what do they do?
They come from neutrophils and monocytes and they kill microbes and degrade tissue
What do neuropeptides do?
Initiate inflammation, transmit pain and regulate vascularity
What are the plasma protein derived mediators of inflammation?
Complement proteins, coagulation proteins and kinin system
What do complement proteins do?
They are plasma proteins and are very important in opsonization and inflammation.
They are vasodilators and increase vascular permeability
They help WBC get to where they need to go
What are coagulation proteins?
Proteins that come from the liver (hageman factor) and are activated by Exposed collagen or platelets
What do coagulation proteins stimulate?
Complement system, the kinin system, and clotting
What do coagulation proteins activate?
Thrombin which leads to clotting
What does the Kinin system lead to ?
Bradykinin production it is a vasodilator and it increases vascular permeability
What is chronic inflammation?
inflammation of prolonged duration (weeks to years) in which continuing inflammation, tissue injury, and healing, often by fibrosis, proceed simultaneously
How may chronic inflammation arise?
Persistent infection by microbes that are hard to eradicate, Immunesuppression (aids), hypersensitivity reactions
What is chronic inflammation characterized by?
Mononuclear leukocyte cells are there after or around 48 hours, tissue destruction and fibrosis, and angiogenesis and repair
What are the dominant cells at the site of chronic inflammation?
Macrophages
What are the functions of macrophages?
- Eliminate microbes & dead cells
* Initiate angiogenesis & fibrosis
What are macrophages activated by during chronic inflammation?
Endotoxis, cytokines and foreign bodies
What is another chronic inflammatory cell which sustains chronic inflammation and relate to adaptive and innate immunity?
Lymphocytes
What could stimulate lymphocytes?
Bacterial/viral infxns., autoimmune rxns (RA)
What is a classically activated macrophage?
macrophages that produce lysosomal enzymes, NO, and ROS, all of which enhance their ability to kill ingested organisms, and secrete cytokines that stimulate inflammation
What is an alternative activated macrophage?
the macrophages that are not actively microbicidal; instead, their principal role is in tissue repair. They secrete growth factors that promote angiogenesis
What are the systemic effects of inflammation?
Production of cytokines causes Acute Phase reactions and fever
What is an acute phase reaction?
A reaction in which we experience malaise, elevated heart rate, elevated blood presure, anorexia, somnolecne and anhidrosis
What causes fever?
Pyrogens related to prostaglandin synthesis
When we have a high C reactive protein what does that mean?
C reactive protein is usually a telltale sign of inflammation
What is leukocytosis?
elevated count of WBCs and is extremely common with bacterial infeactions
During leukocytosis there is an elevated number of immature cells and they tend to
Shift to the left
What are leukemoid reactions?
Reactions that mimic leukemia in which the blood leukocyte is very high commonly happens in TB
What is leukopenia?
too low WBC count (HIV/AIDS, chemotherapy)
