Term
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Definition
Protective response to remove the initial cause of the bodily insult. Also remove necrotic cells and tissues from the insult.
Happens in a living place with other biochem processes-not a vacuum. |
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Term
| Acute/Chronic Inflammation |
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Definition
First and fast
Usually PMNs first there. (neutophil)
Happens later
Mononuclear cells predominate like the lymphocyte or monocyte
Viral infections don't really have much of a PMN response. Mostly lymphocytic response. |
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Term
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Definition
Calor- HEAT
Rubor- REDNESS
Tumor- SWELLING
Dolor- PAIN
Functio Laesa- LOSS OF FUNCTION |
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Term
| Systemic Effects of Imflammation |
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Definition
1. Fever medicated by IL-1/TNF
2. Somnolense, malaise and anorexia
3. Hypotension
4. Acute phase reactants made in the liver- increased synthesis of complement and clotting factors (like IL-6)
5. More PMNs made (leukocytosis) with a "left shift"
6. Elevated ESR |
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Term
| Left shift and Elevated ESR in Acute Phase Reaction |
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Definition
Increased polymorphonuclear leukocytes- left shit where immature premature PMNs move from the one marrow compartment into the peripheral compartment.
Simple test for imflammatory response. The red cells stick together and act as larger profile bodies and they sediment in the serum faster than do individual cells. |
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Term
| What things participate in imflammation? |
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Definition
| circulating cells, plasma proteins, vascular wall cells, CT and ECM |
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Term
| More about what participate in inflammation. (Cells) |
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Definition
1. Vessel- PMNS, Lymphocytes,Platelets, Monocytes, Eosinophil/Basophil
2. CT Matrix- Endothelium and Basement Membrane (collagen IV, laminin, fibronectin, proteogycans, elastic fibers)
3. CT cells- Mast cells, Fibroblasts, Macrophages |
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Term
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Definition
1. Acute imflammatory response.
2. Granulocytes have lobulated nucei. Attached by a thin strand of cytoplasm
3. Mature from cells with polylobed nuclei.
4. COARSE granules (toxic granulations)
5. Hazy blue cytoplasmic patch which is dilated ER called Dohle Body. (indication of cell released as response to an inflammatory challenge) |
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Term
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Definition
1. Acute imflammatory response.
2. Granulocytes have lobulated nucei. Attached by a thin strand of cytoplasm
3. Mature from cells with polylobed nuclei.
4. COARSE granules (toxic granulations)
5. Hazy blue cytoplasmic patch which is dilated ER called Dohle Body. (indication of cell released as response to an inflammatory challenge) |
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Term
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Definition
1. Both part of the acute resonse
2. PARASITE infections
3. (e) nucleus bilobed or trilobed with orangish blocky rather than larger granules
4. Basophil- major source of histamine.
5. Both travel together a lot bc Eosinophils carry antihistamines to balance out.
6. Basophil smaller. Nuceus without lobes and cytoplasm with block even larger dark purple granules. |
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Term
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Definition
1. Hallmarks of chronic inflammation.
2. Nucleus of lyphocyte is rounded and slightly irregular and larger in diameter.
3. Little cytoplasm in lymphocyte. (indistinct)
4. Monocytes are larger than lyphocyte and have more irregular nuclei with more cytoplasm.
(look at monocytes by size, amount of cytoplasm and irregularity of nucei) |
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Term
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Definition
1. Make Igs
2. Oval shape, elliptical cells with their nuclei located off to one pole (long axis)
3. Clearing in the cytoplasm around the nucleus called the HOF- Golgi
4. Nucleoplasm- nuclear chromatin is in larger blocks- not finely dispersed.
5. CLOCK FACED CHROMATIN |
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Term
|
Definition
1. Not usually found in the peripheral circulation
2. Macrophage has a smaller nucleus compared to cytoplasm
3. Eat up debris. |
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Term
| Acute and Chronic Inflammation differences (MAIN) |
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Definition
Acute: lasts for a short time (minutes to a few days), fluid and plasma protein= EXUDATE, mostly a PMN (neutrophilic response)
Chronic- Lasts longer (days to years), lyphocytes and macrophages predominate, Associated vascular proliferation(new blood vessels), scarring, NOT always proceeded by acute inflammation |
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Term
| Viral infection does NOT HAVE neutrophilc response (fact) |
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Definition
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Term
| Immediate and early response to injury |
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Definition
1. Components- vascular changes like vasodilation and increased vascular permeability
2. Cellular events like cellular recruitment and activation (emigration of PMNS from microcirculation to the site of injury) |
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Term
| Vascular changes in acute inflammation |
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Definition
1. Vascular dilation causes erythema and warmth- rubor and calor
2. Extravasation of plasma fluid and protein causes edema- tumor
3. Emigration of leukocytes to site of injury- tumor |
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Term
Exudate vs. Transudate
TRANSUDATE FIRST!!!!!!!!! |
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Definition
EXUDATE: protein rich in the interstial space with a specific gravity greater than 1.0201. Contains Leukocytes and is mostly associated with acute imflammation
TRANSUDATE: Increased fluid in the interstial space (EDEMA) which is protein poor (specific gravity less than 1.012. Its relatively ACELLULAR. |
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Term
| Increased vascular permeability: Immediate Transient Response |
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Definition
Creation of gaps between endothelial cells by contraction of those cells.
Post capillary venules.
Reversible change due to the action of vasoactive mediators like histamine and LTs on the endothelial cells.
They shrink a little and create gaps between cells- leakage. |
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Term
| Increased vascular permeability: Endothelial Cell Retraction |
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Definition
Organization of endothelial cytoskeleton.
Venules and capillaries under effect of cytokines like IL-1 and TNF and hypoxia.
Seen over 4-6 hours ad may persists upto a day.
REVERSIBLE. |
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Term
| Increased vascular permeability: Direct Endothelial Injury (Immediate Sustained Response) |
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Definition
Vessels injured by burns/toxins/chemicals- the endothelial cells actually die.
Arterioles, Capillaries or Venules.
Endothelaial cells undergo necrosis , cell death and detachment and fall away leaving large gaps and holes that leak.
PERMANENT response. |
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Term
| Increased Vascular Permeability: Leukocyte Dependent Endothelial Injury |
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Definition
| Leukocytes carry chemical for killing and dissolving pathogens/dead tissues. They can leak out as they travel through vessels and tansmigrate. Cargo into endothelium. Mostly in VENULES (pulmonary). |
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Term
| Increased Vascular Permeability: Increased Transcytosis |
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Definition
| Materials can pass though the endothelial cell without any damage/injury. VENULES. Mediated by VEGF. |
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Term
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Definition
1. First cell to arrive in acute imflamm
2. Can dwell for long periods in abscesses
3. Short life span of about a day.
4. Phagocytic (esp. pyogenic cocci)
5. Have lysosomes in granules- suppuration and liquifaction of tissue. |
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Term
| Parts/Steps in Neutrophil killing/phagocytosis |
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Definition
1. Engulfs bacteria into phagosome. Primary granule attaches containing acid phosphatase, Myeloperoxidase and esterase.
2. Secondary granule comes that has lysozyme, collagenase. Here, Oxygen radicals are formed- oxidative burst.
3. Killing and dissolving of the invader. Exocytosis into tissues and circulation |
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Term
| Sequence of events in leukocyte emigration |
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Definition
Margination
Rolling
Adhesion
Transmigration |
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Term
Margination
Rolling
Pavementing |
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Definition
Leukocyte accumulation at the periphery of blood vessels
Leukocytes are pushed out of the central axial column by flowing blood- MEDIATED BY SELECTINS
Leukocytes line up along the blood vessel wall. |
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Term
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Definition
Surface receptors that bind to SUGAR domains- LECTINS.
Loose and transient adhesions that are involved in rolling of PMNS along hte endothelial surface.
E- endothelium
P- endothelium and platelets
L- most leukocytes |
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Term
| Adhesion and Transmigration |
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Definition
- PMNS stick to the endthelial surface
- Diapedesis is when PMNs move between endothelial cells and through the basement membrane into the extravascular spaces.
MEDIATED by molecules of IG-superfamily on endothelial cells that interact with the integrins on PMN cell surface. |
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Term
Adhesion Molecules (IG supefamily and Integrins)
STRONGER INTERACTION |
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Definition
1. IG Superfamily: Endothelial adhesion molecules
ICAM-1 and VCAM-1
Induced by cytokines like TNF/IL-1
2. Integrins: Leukocyte transmigration heterodimeric glycoproteins
LFA-1 and MAC-1 bind to ICAM-1
VLA-1 binds to VCAM-1 |
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Term
Transmigration through endothelial and basement membrane is NOT passive. Mediated by PLATELET ENDOTHELIAL CELL ADHESION MOLECULE 1
PCAM-1 on the endothelial cells |
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Definition
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Term
| Chemotaxis and aCTIVATION |
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Definition
Movement of cells or organisms in response to chemicals.
Migration of Leokocytes towards sites of injury along a chemical gradient.
(soluble bacterial products, Complement C5a, LTB4 or cytokines like IL-8) |
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Term
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Definition
Happens when Chemotactic molecules bind to cell surface receptors.
G-protein coupled activation of Phospholipase C
Membrane PIP2 is hydrolyzed into DAGand IP3
IP3 INCREASES intracellsular Calcium causing PSEUDOPOD assembly. |
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Term
| Activation of Leukocytes (modulated by many chemicals and other factors) |
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Definition
1. Activation of protein kinase C
-degranulation and secretion of lysosomal enzymes
-generation of oxidative burst
2. Activation of Phospholipase A2
-arachidonic acid metabolites |
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Term
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Definition
Recognition and attachments
Engulfment
Killing and Degradation |
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Term
Recognition and Attachment
(part of phagocytosis) |
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Definition
Opsonins: IgFc, C3b and collectins
Bind to FcR;CR 1/2/3; and C1q
respectively
HELP TO RECOGNIZE A PARTICLE AS SOMETHING THAT SHOULD BE ENGULFED AND KILLED AND DEGRADED. |
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Term
ENGULFMENT
(part of phagocytosis) |
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Definition
Triggered by binding of opsonized particles.
Psuedopods extend to form phagocytic vacuole.
Membrane of vacuole fuses with the membrane of a lysosomal granule to form phagolysosome. |
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Term
KILLING AND DEGRADATION
Part of phagocytosis |
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Definition
Oxidative burst forms reactive O2 species- H2O2
Azuophilic granules contain MPO- HOCl (perchlorate)
Dead microorganisms are degraded by lysosomal acid hydrolases |
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Term
| Chemical mediators of Inflammation are? |
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Definition
Plamsma derived mediators or cell derived mediators
Certain common charateristics- usually bind to cell specific receptors to produce their effect. They may stimulate the release of secondary effector molecules. Mediator function is highly regulated!!! |
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Term
| Types of PLASMA DERIVED CHEMICAL MEDIATORS |
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Definition
-Complement
-Kinins
-Coagulation Factors (clotting and fibrinolysis)
All three circulate as inactive precursors!!!! |
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Term
| Details about cell-derived chemical mediators |
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Definition
Normally made in intracellular granules.
Secreted upon activation- like histamine from mast cells.
OR made de novo in response to a certain stimulus- like prstaglandins |
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Term
| TYPES of chemical mediators (lots) |
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Definition
Vasoactive amine- (histamine and serotonin)
Neuropeptids
Plasma proteases (kinins, clotting, complement)
Arachidonic acid metabolites
Plateley activating facor
Cytokines
IL-1 and TNF
Chemokines
NO and O2 free radicals
Lysosomal constituents |
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Term
| VASOACTIVE AMINES- HISTAMINE |
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Definition
1. Preformed
-Histamine exits mast cells in preformed packets (also in platelets and basophils)
- Release triggers include trauma, heat/cold, binding of IgE to Fc, C3a and C5a, substance P and cytokines like IL-8
- Causes arteriolar dilation and the immediate phase of increased vascular permeability. IMPORTANT!!!! |
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Term
| VASOACTIVE AMINES- SEROTONINS |
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Definition
Preformed vasoactive mediator
5-hydroxytryptamine
Platelet dense body granules
Released during platelet aggregation
Effects are just like HISTAMINE |
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Term
|
Definition
Important chemical mediators in inflammation.
Substance P
usually small peptides
transmit PAIN signals
Regulate vascular tone
Nerve fibers that secrete neuropeptides are prominent in the lung and GI. |
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Term
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Definition
Seen in the kinin system, complement system and clotting system
ALL THREE systems linked by Hageman factor (Factor XII) - made in the liver and activated by collagen, BM or platelets |
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Term
| Plasma Proteases- COMPLEMENT SYSTEM |
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Definition
1. Vascular effects- C3a and C5a are anaphylatoxins that increased vascular permeability/ activate lipoxygenase pathway
2. Leukocyte activation, adhesion and chemotaxis- C5a activates leukocytes and is chemotactic for granulocytes and monoytes
3. Phagocytosis- C3b and C3bi act as opsonins for neutrophils and macropahages
4. C3 and C5 can be activated by lysosomal hydrolases and plasmin- self perpetuating cycle of neutrophil emigration |
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Term
| SUMMARY OF PLASMA PROTEASES |
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Definition
Central role of Hageman Factor (XIIa)activated 4 systems (kinin, clotting, fibronolytic and complement)
Bradykinin, C3a and C5a contribute to vascular permeabilty
C5a imp for chemotaxis
Thromnbin has many effects
Kallekrein and Plasmin amplify the system by feedback activation of Hageman factor |
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Term
| ARACHIDONIC ACID METABOLITES (general info) |
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Definition
AA- component of phospholipid cell membrane
Clyclooxygenase pathway- PGs and TXA2
Lipoxygenase pathway- LTs
Lipoxins- natural endogenous negative regulators of LT actions |
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Term
1. Lipoxygenase pathway responsible for vasocontriction, bronchospasm and increased vessel permeability.
2. 5-HETE and LTB4 involved in chemotaxis
3. Cyclooxygenase pathway -vasodilation and inhibition of platelet aggregation via PGI2 (prostcyclin) and TXA2 causes platelet aggregation and vasoconstriction
PGd2/PgE2 and PGFa2 potentiate edema via vasodilation |
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Definition
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Term
| ARACHIDONIC ACID (functions and the types of metabolites) |
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Definition
Vasoconstriction- TXA2, LTC4, D4 and E4
Vasodilation- Prostacyclin (PGI2), PGE1, PGE2, PGD2 and lipoxins
Increased vascular permeability- LTC4, D4 and E4
Chemotaxis and leukocyte adhesion- LTB4 ad lipoxins |
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Term
| PLATELET ACTIVATING FACTOR |
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Definition
1. PAF- can aggregate platelets and cause degranulation
2. Phospholipid derived mediator
3. Can also cause VASCONSTRICTION and BRONCHOCONSTRICTION
4. 100 times more potent than histamine in inducing vasodilation and increased vascular permeability |
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Term
| What are cytokines? (imp in the imflammatory response) |
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Definition
Polypeptides made by many cell types.
"messenger molecules of the immune system"
Modulate function of other cells
Include colony stimulation factors, ILs and chemokines
Secretion typically transient and highly regulated.
Effects are pleiotropic- diff. cells are affected differently by the same cytokine. |
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Term
| Autokines, Parakines and Endokines (types of cytokines) |
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Definition
act on same cell that makes it
acts on cells closeby
acts systemically via bloodstream |
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Term
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Definition
1. Both made by activated macrophages (secretion stimulated by endotoxin, ab-ag complexes, toxins, injury and other inflammatory mediators)
2. Both activate endothelial cells and tissue fibroblasts
3. TNF causes aggregation and activation of neutrophils- hypotension in septic shock.
IL-1/TNF induce systemic acute phase responses- FEVER, LETHARGY, HEPATIC SYNTHESIS, CACHEXIA, ACTH RELEASE, NEUTROPHILIA) |
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Term
| Chemokines (subgroup of cytokines) |
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Definition
Activators and chemoattractants for leukocytes
Recruit particular cell populations
Two major groups
1. CXC alpha chemokines: IL-8, attract neutrophils
2. CC beta chrmokines: attract monocytes, macrophages and eosinophils |
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Term
| Nitric Oxide (functions) IMP!!! |
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Definition
Half life of seconds
used by macrophages to kill macrobes and tumor cells
Relaxes smooth muscle cells in blood vessels
Antagonizes all stages of platelet activation
Reduction of leukocyte recruitment |
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Term
|
Definition
Made from L-arginine, molecular oxygen, NADPH and other co-factors by the enzyme nitric oxide synthase (NOS)
endothelial, neuronal and cytokine inducible (eNOS, NNOS, iNOS) |
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Term
| Oxygen-derived free radicals |
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Definition
1. Made via NADPH oxidase pathway
2. Released by neutrophils and macrophages in response to chemotactic agents, immmune response or phagocytic activity.
3. Can amplify imflammation by increasing chemokines, cytokines and adhesion molecule expression
4. Negative effects- thrombosis, increased permeabilty and direct cell injury
5. Antioxidant protective systems- catalase, superoxide dismutase |
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Term
| Oxygen-derived free radicals |
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Definition
1. Made via NADPH oxidase pathway
2. Released by neutrophils and macrophages in response to chemotactic agents, immmune response or phagocytic activity.
3. Can amplify imflammation by increasing chemokines, cytokines and adhesion molecule expression
4. Negative effects- thrombosis, increased permeabilty and direct cell injury
5. Antioxidant protective systems- catalase, superoxide dismutase |
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Term
|
Definition
1. Acid Proteases- need acidic pH for their activity, usually only active within phagolysosomes
2. Neaural Proteases-
-found in ECM in the form of elastase, collagenase and cathepsin
- they cause deforming tissue injuries by release and destruction of elastic and collagen tissues
- can cleave C3 and C5 and thus, activate them
- Antiproteases are present in tissues to check and help reverse the action of neural proteases- like alpha-2-macroglobulin and alpha-1 antitrypsin |
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Term
When you get an injury, mediators can lead to either acute or chronic injury.
ACUTE can lead to resolution, abscess formation or healing (regeneration and scarring) It can also go into chronic inflammation.
CHRONIC inflammation (persistent infections, persistent toxins or autoimmune disease) only leads to Healing (with regen and scarring) |
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Definition
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Term
|
Definition
Inflammation of prolonged duration (weeks, months, years)
INfiltration with mononuclear cells- macrophages, lymphocytes and plasma cells
Tissue destruction!!!
Repair, angiogenesis and fibrosis |
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Term
| What are the things that can cause chronic inflammation? |
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Definition
viral infections
persistent microbial infections
prolonged toxic agent exposure
autoimmune diseases |
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Term
| What activates macrophages? |
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Definition
Come from circulating monocytes.
SEcretion of acid and neural proteases, plasminogen acticator, complement components, coagulation factors, arachidonic acid metabolites and reactive O2 species. Also, Il-1/TNF |
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Term
| Activated T cell gives signals (INF_gamma) to monocyte/macrophage and activates it. This then participates in fibrosis and tissue injury. |
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Definition
|
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Term
| Besides macrophages, what other cells do you see in chronic inflammation? |
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Definition
Lymphocytes- viral infections
Plasma cells- rheumatic arthritis and syphilis
Eosinophils- parasites!!! and allergic inflammation
Mast cells- allergic inflammation and TB |
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Term
| Details of Granulomatous Inflammation |
|
Definition
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