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56 Cards in this Set
- Front
- Back
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What is the purpose of inflammation?
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To protect the body by eliminating the initial cause of cell injury.
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Is inflammatioin part of the innate immunity or adaptive immunity?
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Innate
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What types of cells and tissues play an important role in inflammation?
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- Leukocytes
- Plasma proteins - Vascular cell wall cells - ECM cells |
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Acute inflammation
- Duration? - Characterized by? |
- Minutes to days
- Exudate - Neutrophils |
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Chronic inflammation
- Duration? - Characerized by? |
- Days to years
- Lymphocytes and macrophages - Vascular proliferation - Fibrosis (scarring) |
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Name the cardinal signs of inflammation?
What are they a result of? |
- Calor (heat)
- Rubor (redness) - Tumor (swelling) - Dolor (pain) - Functio laesa (loss of function) The first three (calor, rubor and tumor) are a result of vascular changes and recruitment. The last two (dolor and functio laesa) are a result of mediator elaboration and leukocyte-mediated cell damage. |
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Why/When does an acute inflammation turn into a chronic inflammation?
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When the injurious agent cannot be quickly eliminated.
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Where do the inflammatory mediators originate from?
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- Plasma proteins
- Various cells _Macrophages |
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What do the five R's tell us?
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They tell us about the steps of the infalmmatory response:
- Recognition of the injurious agent - Recruitment of leukocytes - Removal of the injurious agent - Regulation of the response - Resolution (resolution) |
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Acute inflammation is designed so as to...?
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Deliver leukocytes and plasma proteins to the site of injury.
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What are the two major components of acute inflammation?
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- Vascular changes:
-- Vasodilation -> Resulting in increased blood flow -- ↑ Vascular permability ->Permits plasma proteins to leave circulation - Cellular events -- Cellular recruitment and activation (neutrophils) |
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What stimuli may trigger acute inflammation?
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- Infections
- Trauma - Tissue necrosis - Foreign bodies (splinteres, dirt, etc.) - Immune reactions (immune-mediated inflammatory disease) -- Often have features of chronic inflammation |
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Erythema?
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Redness
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What are the vascular changes of acute inflammation and what is their effect?
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- Vasodilation (arteriolar)
-- ↑ Intravascular blood flow -> Engoregemnt of down-stream capillary beds -> ↑Hydrostatic pressure -> Rubor, calor and tumor - ↑ Vascular permeability -- Exudation -> Concentration of RBC's -> Slowing of blood flow -> STASIS. ---The statis provides a good environment for the leukocytes, which want to attach to and transfer out of the blood vessels. |
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The extravasated fluid of acute inflammation, is it an transudate or an exudate?
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- Exudates are typical of inflammation!
However, the first fluid to be extravasated because of inflammation is a transudate. This is why: The vasodilation leads to increased blood flow and engorgement, both of which result in an increase of the hydrostatic pressure. Later (when the vascular permeability is increased) the fluid becomes an exudate. The increased vascular permeability contributes much more to the extravasation than the increased hydrostatic pressure. Furthermore, once exudate starts extravasating the osmotic balance (which forces fluid INTO the vessels) is decreased, promoting an even larger extravasation. |
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What mechanisms cause the ↑ vascular permeability in acute inflammation?
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- Endothelial cell contration
-- Most common cause -- Postcapillary venules -- IMMEDIATE TRANSIENT RESPONSE --- 15-30 min --- Reversible --- Histamine, bradykinin, leuketrienes, etc. -- Delayed TRANSIENT RESPONSE --- Changes in cytoskeleton --- TNF, IL-1 --- 4-6h after initial trigger --- May persist for 24h or more. - Endothelial injury -- IMMEDIATE SUSTAINED RESPONSE --- Begins immediately after injury --- Hours to days --- Venules, capillaries, arterioles -- DELAYED PROLONGED LEAKAGE --- Delay of 2-12h --- Last for hours or days --- Venules or capillaries --- Mild to moderate thermal injury, certain bacterial toxins, x- or ultraviolet radiation - Leukocyte-mediated endothelial injury -- Leukocyte accumulation along the vessel wall -Increased transcytosis --VEGF (vascular endothelial growth factor) - Leakage from new blood vessels -- Repair invloves angiogenesis -- Many VEGF receptors -> ↑Transcytosis. |
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How are the lymphatic vessels involved in the inflammatory response?
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- They transport the excess interstitial fluid but may also transport the infectious agent and the lymphatics may beceome secondarily inflamed (lymphangitis), as may the draining lymph nodes (lymphadenitis)
Red streaks near a skin wound is a diagnostic sign of lymphangitis. Painful and enlarged lymph nodes signify lymphadenitis. |
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What is the sequence of events in the recruitment of leukocytes?
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(1) Margination (assisted by stasis)
(2) Adhesion and rolling on endoth. (selectins) (3) Firm adhesion to endoth. (integrins) (4) Transmigration (5) Chemotactic migration in tissue |
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What type of selectins are there?
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- E-selectins: expressed on endoth.
- P-selectins: on endoth. and platelets - L-selectins: on most leukocytes |
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- When are selectins expressed on endoth.?
- What effect does this have? |
- E- or P-selectins are only expressed on endoth. which has been exposed to inflam. mediators.
- The binding of leukocytes is restricted to endoth. at sites of infection or tissue injury (where inflam. mediators are produced) |
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Where are intergrins found and where are intergrin ligands found?
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Integrins - leukocytes
Integrin ligands - endothelium |
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If integrins and integrin ligans are present at all times, what stops leukocytes from forming strong adhesions with endoth.?
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The integrins are found on leukocytes in their low-affinity form onless the leukocyte has been activated by chemokines; then it expresses the high-affinity form.
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What activates leukocytes?
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Chemokines: chemoattractant cytokines
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What is the role of endothelium when it comes to firm adhesion w/ leukocytes?
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The endoth. can also be said to be "activated". However, the activating cytokines are different: TNF and IL-1.
Upon activation, the endoth. increases it's expression of ligands, such as ICAM-1 and VCAM-1. |
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What is the mechanism of migration?
Where does it occur? |
It occurs between intercellular junctions OR through endothelial cytoplasm. This movement of leukocytes can also be called diapedesis.
It occurs in the venules of the systemic circulation or capillaries of the pulmonary circulation. |
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How does the inflammatory infiltrate change with time?
Why? Are there any exceptions? |
First 6-24h: neutrophils
24-48h: monocytes There are several reasons: (a) There are more neutrophils in the blood (b) The neutrophils respond more rapidly to chemokines (c) The neutrophils can attach more firmly to the selectis on the endoth. (d) Neutrophils "die" within 24-48h. Monocytes survive longer. Yes: - Pseudomonas: neutrophils continously - Viral infections: lymphocytes may be first - Hypersens.: Eosinophils may be first. |
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What enables leukocytes to recognize microbes or other signs of infection?
What happens when a leukocyte rocognizes an inflammator mediator? |
Toll-like receptors (TLR's)
It becomes activated. |
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What does leukocyte activation entail?
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- Phagocytosis
- Production of substances that destroy phagocytosed microbes and dead tissue -- Lysosomal enzymes -- Reactive oxygen and nitrogen species - Production of mediators that amplify the inflam. response. -- Arachidonic acid metab. -- Cytokines |
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What role do opsonins play?
What are opsonins? How do leukocytes react to a opsonized microbe? |
The role of opsonins is very improtant because the coat and tag microbes (opsonization), thereby targeting them for phagocytosis by leukocytes.
- IgG antibodies - C3 breakdown prod. (complement) - Collectins The engulfment "reflex" of leukocytes is triggered. Furthermore, if the microbe is opsonized by IgG or C3, recognition of this by a leukocyte also triggers enchanced degradation of ingested microbes. |
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How do leukocytes kill ingested microbes?
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Through lysosomal enzymes and the formation of ROS.
- Lysosomal: Myeloperoxidase +Cl- =>HOCl, a powerful oxidant and antimicrobial agent Once the microorganisms are dead, they are degraded by lysosomal acid hydrolases: elastase etc. There are also other ways of killing the bacteria. |
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What substances are mostly resp. for the negative effects of leukocyte-induced tissue injury?
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- Lysosomal enzymes
- ROS and RNS |
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What may cause leukocytes to secrete the contents of their lysosomal granules into the extracellular milieu?
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- Regurgitation during feeding: when the phagolysosome stays partially open to the outside.
- Frustrated phagocytosis: when attempting to phagocyte something that is difficult to phagocyte e.g. immune complexes on flat surfaces. - Phagocytosis of potentially injurious substances that may damage the phagolysosome mebrane e.g. urate crystals. |
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What stimulates the oxidative burst?
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Phagocytosis.
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What are the outcomes of acute inflammation?
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- Resolution
-- Restoration to histological and functional normalcy - Progression to chronic inflam. -- If offending agent is not removed -- Can lead to restoration or svcarring - Scarring or fibrosis -- When inflam. in tissues that do not regen. -- Fibrosis - When fibrinous exudates do not become competely absorbed and are organized by ingrowth of CT. -- Abcesses --- If extensive neutrophilic infiltrates --- Pyogenic (pus forming) organisms. --- SCARRING is normally the outcome. |
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Explain "serous inflammation".
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Outpouring of watery, relatively protein-poor fluid.
E.g. Skin blister from burn. Fluid within the serous cavity is called an "effusion". |
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Explain "fibrinous inflammation".
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Occurs as a consequence of more sever injuries in which larger molecules, such as fibrinogen pass the endothelial barrier.
Such exudates may be cleared completely, leading to resolution. If not cleared completely, the result is ingrowth of blood vessels and fibroblast (organization) leading ultimately to scarring which may have considerable harmful effects. Is common in the lining of body cavities, e.g.mininges, pericarium and pleura. |
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Explain "suppurative (purulent) inflammation".
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An inflammation in which there are large amounts of pus. This pus may be spread or collected locally in abcesses.
Certain organism are more prone to cause suppurative infalmmation, such as staphylococci, and are referred as pyogenic. Pus consists of neutrophils, necrotic cells and edema fluid. |
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Define "ulcer".
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A local defect or excavation of the surface of an organ or tissue due to necrosis and sloughing.
Can only occur when tissue necrosis and resultant inflammation occurs near or on a surface. A lot of neutrophils in margins during acute stage. The neutrophils are replaced by lymphocytes, macrophages and plasma cells when chronic. |
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Descibe an abcess histologically.
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- Central, largely necrotic region
- A rim of preserved neutrophils surrounding the central region w/ dilated vessels and fibroblastic prolif. indicative of early repair. |
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What is the funtion of lipoxins?
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As inhibitors of inflammation.
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What does PAF (Platelet-Activating Factor) cause?
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- Platelet aggregation and degranulation
- Vasoconstriction - Bronchoconstriction |
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Name a few cytokines of acute inflammation.
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- TNF
- IL-1 - Chemokines - Interferon-γ (IFN-γ) - IL-12 |
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What is the principal role of TNF and IL-1 in inflammation?
Do they have any other, yani, secondary roles in inflammation. |
Endothelial activation.
Systemic acute-phase reaction: - Fever - Lethargy - Hepatic synthesis of various acute-phase proteins - Metabolic wasting (cachexia) - Neutrophil release into the circulation |
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What are the two main functions of chemokines?
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- Leukocyte recruitment in inflammation
- Normal anatomic organization of cells in lymphoid and other tissues. E.g. the segregation of T and B lymphocyters in different areas of lymph nodes and spleen. |
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How is NO related to macrophages?
How is NO related to endothelial cells? |
Macrophages use it as a cytotoxic metabolite for killing microbes and tumor cells.
They synthesize it and it causes smooth m. relaxation and vasodilation. |
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Explain the differnet isoforms of NOS (Nitric Oxide Synthase).
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Type I (nNOS)
- Constitutively expressed in neurons w/ no significant role in inflammation Type II (iNOS) - Inducible in macrophages and endothelial cells - Respons. for NO prod. in inflammatory reactions - Also present in hepatocytes, cardiac monocytes and resp. endothelium. |
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What is the role of the complement system in inflammation?
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- Vascular effects
-- C3a and C5a: the anaphylatoxins. They are called so because they mimic the action on mast cells; the main cellular effectors of the severe allergic reaction called anaphylaxis. --- C5a also activates lipooxygenase pathway of AA metab. - Leukocyte activation, adhesion and chemotaxis -- C5a -Phagocytosis -- C3b opsonizes microbes, augmenting phagocytosis. |
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Chronic inflammation
How long does it last? What occurs in the chronically inflamed tissue (unlike acute inflam.)? What is characteristic of it? |
Weeks to months to years.
Active inflammation, tissue injury and healing proceeds simultaneously. - Infiltration w/ mononuclear cells, including macrophages, lymphocytes and plasma cells - Tissue destruction: largerly induced by the products of the inflammatory cells. - Repair, involving angiogenesis and fibrosis. |
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In which settings does chronic inflam. arise?
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- Persistent infections by microbes that are difficult to eradicate.
-- Most viral infections - Immune-mediated inflammatory diseases (hypersensitivity diseases) -- E.g. autoimmune diseases: in which the eliciting antigens cannot be eliminated. |
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Can neutophils be seen in chronic inflam.?
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Yes!
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Define "granulomatous inflammation".
What is the purpose of the granuloma? What type of disease can give rise to granumomtous inflam.? |
A type of chronic inflammation in which aggregates of macrophages assume an epithelioid appearance. These aggregates surround a central area of caseous necrosis. Lymphocytes may also be present in together with the macrophages.
To "wall-off" the offending agent, thus being a defensive mechanism. However, fibrosis of granulomas may cause organ dysfunction, e.g. TBC. - TBC - Leprosy - Syphilis - Cat-scratch disease - Sarcoidosis - Crohn's disease (granulomatous colitis) - Sutures, splinters, etc. (foreign body granulomas) |
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Acute phase reaction (systemic inflam. response syndrome)
What are its most important mediators? What clinical pathological changes occur? |
-TNF, IL-1 and IL-6
- Fever -- IL-1 and TNF (endogenous pyrogens) increase the levels of COX in the hypothalamus. PGE2 stimulates the prod. of neurotransmitters that reset the temp. to a higher point. - Elevated plasma levels of acute-phase protein -- CRP, fibrinogen and serum amyloid A (SAA) protein. -- Liver -- IL-6 -- Opsonize and fix complement (CRP ans SAA) -- RBC's form stacks (rouleaux) (fibrinogen) ===> Erythrocyte sedimentation rate (ESR), a test for systemic inflam. response!!! - Lukocytosis -- Especially in bacterial infections -- Bacterial infections -> Neutrophilia -- Viral infections -> Lymphocytosis - ↑HR, ↑BP, chills, etc. |
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Put the following inflammatory responses in proper order:
- Neutrophils - Edema - Macrophages |
Edema, neutrophils, macrophages
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What types of exudate can inflammation give rise to?
Give examples of where this may occur. |
- Serous - skin blister
- Fibrinous - pericarditis - Purulent (suppurative) - abscess - Haemorrhagic In a way, the type depends on degree of vascular wall permeability. |
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How can purulent inflammation be further sudividied?
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- Superficial
-- Limited: in a body cavity - Empyema. E.g. pleural empyema. -- Extensive - Pyorrhea. E.g. Gonococcal pyorrhea of the urethra. - Deep -- Limited - Abscess. E.g. Brain abscess. -- Extensive - Phlegmon. E.g. in skeletal mm. |
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Purulent inflam.
Panaritium? Paronychia? Furunculus? Carbunculus? Hordeolum? |
- Subcut. phlegmon of the fingertip
- Phlegmon of the nail fild - Purulent inflam. of hair capsule - Numerous furuncles close to each other - Furuncle of eyelash |
