Ch.2 Acute Inflammation pt.2 Flashcards
(95 cards)
1
Q
Derived from monocytes circulating in the blood
A
Macrophages
2
Q
Macrophages injest organims via ____?
A
Phagocytosis
3
Q
Phagocytosis in macrophages is faciliateted by what?
A
Opsinins
4
Q
What helps destroy phagocytosed materials in macrophages?
A
Lysosyme & 2nd granuales
5
Q
Macrophges can either 1. or 2.
A
- Promote resolution & healing if balance restored
- Recruit more help
6
Q
Secretion of anti-inflmmatroy cytokines IL-10 and TGF-Beta by macrophages signales what?
A
Balance restored, promoting healing
7
Q
What cytokiene is secreted by macrophages if there is continued inflamation and persistant pus formation
A
IL-8
8
Q
What may follow acute inflammation if the issue is not resolved?
A
Abcess formation
9
Q
Macrophages, active antigen presenters and activate + regulate what?
A
Chronic inflmation
CD4+ Helper T cells
10
Q
Activation of what kind of cell via antigen prensentation from macrophages secrete cytokienes that promote chronic inflammation?
A
CD4+ Helper T cells
11
Q
Macrophages are the link bewteen what?
A
Innate & adaptive immunity
12
Q
_____ have the principle ligan Sialyl-Lewis X
A
Selectins
L-selectin, E-selectin, P-selectin
13
Q
____ have the principle ligand ICAM-1 expressed
A
Integrings
LFA-1, MAC-1, VLA-4, a4b7
14
Q
___ are important causes of injury to normal cells and tissues
Occures during normal defesne agaisnt microbs **esp those resistant*
Ex. Mycobacteria
A
Leukocytes
15
Q
leukocyte-mediated tissue injury is release of the contents of ___ and ____
A
Lysozymes and Granules
16
Q
A
16
Q
Cells that secrete cytokienes like IL-17 that recruit neutrophils and stimulate production of antimicrobial peptides that directly kill microbes.
A
Th17 cells
Kind of T-cell
17
Q
Cells that are mportant in reactions to helminthic parasites and in some allergic disorders
A
Eosinophills
(can cause cell damage)
18
Q
critical cells of allergic reactions.
A
mast cells and basophils
19
Q
What kind of inflmmatory mediator ?
Released from intracellular granules (e.g.,amines) or are synthesized de novo (e.g., prostaglandins and leukotrienes, cytokines) in response to a stimulus.
A
Cell-derived mediators
Produced locally by cells at site inflam. or derived from ciruclating
20
Q
What are the three major cell types that produce mediators of acute inflammation?
A
- Tissue macrophages
- Dendritic cells
- Mast cells
21
Q
What kind of inflmmatory mediator?
Complement protiens
A
Plasma-derived mediator
produced mainly in the liver and circulate as inactive precursors.
22
Q
produced only in response to various stimuli, including microbial products and substances released from necrotic cells, which ensures that inflammation is triggered only when and where it is needed.
A
Acitve Mediators
23
Q
Receptors found in innate immune system effectors (mac & dend) that detect foreign molecular patterns
A
Toll like receptors
24
Antigen presentors, cotrol what to process and send out necessary signals
| Just the umbrella term
Regulators
25
They respond to stimulus
| Just umbrella term
Effector
| ex. Macrophages & Dendritic cells
26
Commo structural patterns found on many foreign microbs
Pathogen Associated Molecular patterns (PAMPS)
| Ex. Cell membrane, dsRNA ssDNA, Proteins (flagella, techoic acid).
27
# This is an example of what?
CD14 (a co-receptro fro TLR4) can identify a specific PAMP fond in LPS of gram (-) bacteria.
Toll Like receptors
28
TLR actiavtion results in upregulation of what?
Nuclear transcription Factor
| NF-kB, activates immune response + promote inflmation
29
What gives TLR a link in mediation of both acute & chronic inflamation?
They are housed on lymphocytes
| Which are adaptive immunity effector & regulators
30
# What are the 2
lipid mediators produced from **arachidonic acid (AA)** present in membrane phospholipids **that stimulate vascular and cellular reactions in acute inflammation**
Prostaglandins & Leukotrienes
31
20-carbon polyunsaturated fatty acid that is released from **membrane phospholipids**through the action of cellular phospholipases, mainly **phospholipase A2**
Arachindroic Acid
32
# AA mediator is produced by what?
Generate prostaglandins
Cyclooxygenases
33
# AA mediator is produced by what?
Produce leukotrienes and lipoxins
5- Lipooxgenanses
34
produced by mast cells, macrophages, endothelial cells, and many other cell types and are **involved in the vascular and systemic reactions of inflammation.**
Prostaglandins
35
# What Cyclooxygenase?
produced in response to **inflammatory stimuli** and is also constitutively **expressed in most tissues**, where it may have homeostatic functions
COX-1
| Cyclooxygenase
36
fluid and electrolyte balance in the kidneys, cytoprotection in the GI tract
| Homeostatic function of tissues where ___ is found
COX-1
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induced by **inflammatory stimuli **and thus generates **prostaglandins i**n inflammatory reactions but is **low or absent in most healthy tissues.**
COX-2
| Cyclooxygenase
38
Major Prostiglandins made by mast cells, cause **vasilodation** + increased membrane permability of post-cap venules.
| (potentiant exduatio resulting in edema)
PGD2 and PGE2
| PGDis a chemoattractant for neutrophuls.
39
**Platelets** contain the enzyme thromboxane synthase, which produces _____ the major eicosanoid (AA mediator) in these cells.
TxA2
| Potent platelet-aggregating agent and **vasoconstrictor.
40
vascular endothelium lacks thromboxane synthase. Instead, it contains this enzyme____, which produces ____
prostacyclin synthase; produces Prostacyclin PGL2
| ***vasolidator, inhibitor of paltlet agregation, prevent thrombosis**
41
Prostoglandins are in invloved in the pathogenesis of ___ and ____
Pain & Fever
42
# Derived from Prostoglanding G2/H2
* **Induce** platlet agregation
* Potent **vasoconstrictor**
* Induce vascular smooth muscle proliferation
* Proatherogenic
Thromboxone A2
| TXA2
43
# Derived from Prostoglanding G2/H2
* **Inhibit** platlet agregation
* Induce **vasolidation**
* **inhibit** vascular smooth muscle proliferation
* ANTI-athrerogenic
* Gut protection
* Renal blood flow regulation
Endothelial Prostacyclin
| PGL2
44
produced by leukocytes and mast cells by the action of lipoxygenase and are i**nvolved in vascular and smooth muscle reactions** and leukocyte recruitment.
Leukotrienes
45
# Activation of ___ examples
1. Prevent closure of ductus arteriosis in newborns with cyanoic heart defects
2. Tx of NSAID induced gastric ulcers
3. Reduction of pulmonary hypertension
4. Induction of childbirth
5. Vasodilation of digits for treatment of severe Raynaud disese or critical limb ischemia
6. Management of glaucoma
7. Tx of erectile dysfunction
Activation of Prostiglandins
46
The ____ pathway yields hydroperoxyeicosatetraenoic acid (HPETE) and its derivatives
5-lipoxygenase pathway
47
# What does this do?
Zileuton
| Used for tx of chronic asthma
Inhibit leukotriene synthesis
48
LTC4, LTD4, LTE4
| These leukotrienes do what?
Increase broncial tone
*intense vasoconstriction
* bronchospasm (important in asthma)
* increased permeability of venules.
49
# What does medicatio do?
Monetlukast & Zafirlukast
| For allergic asthma & alergic rhinitis
Prevent **action of leukotrienes** responsible for increase in bronchial tone
| LTC4, LTD4, LTE4
50
# What leukotriene?
produced by neutrophil and some macrophages and is a **potent chemotactic agent and activator of neutrophils**
LTB4
| neutrophils arrive B4 others remember!
51
# In leukotriene synthesis
____ gives rise to leukotrienes
5-HPETE
52
Also generated by AA through lypoxygenase pathway.
**supress inflamation; inhibit neutrophil chemotaxis, no recruitment of leukocytes**
Lipoxins
53
# Principle action of Arachidonic Acid Metabolites in Inflammation
Prostaglandins PGI2 (prostacyclin), PGE1, PGE2, PGD2
Vasodilation
| Big blood vessles
54
# Principle action of Arachidonic Acid Metabolites in Inflammation
Thromboxane A2 (COO pathway) , leukotrienes C4, D4, E4
Vasoconsriction
| Small vessels
55
# Principle action of Arachidonic Acid Metabolites in Inflammation
Leukotrienes C4, D4, E4
Increased vascular permeability
| (exxudation & dev of edema in PG) ( Bronchospasm in leukotrienes)
56
# Principle action of Arachidonic Acid Metabolites in Inflammation
Leukotriene B4
Chemotaxis, leukocyte adhesion
| Activate neutrophil, chemotaxis bring inmore.
57
Aspirn & NSAIDs ex. Ibuprofen.
| Inhibit COX-1 & COX-2
Cyclooxygenase inhibitors
| = prostaglandin synthesis blocked
58
Why are asprin and NSAIDs good at treating pain and fever?
They block COX-1 and COX-2 which prevents prostaglandin syntheis.
| Aspringirreverisbly inactiavted COO
59
# What kind of inhibitiors:
may increase the risk of cardiovascular and cerebrovascular events:
**Impairs PGL2** (antitrhombotic)
while **ignoring COX-1 mediated production of TxA2** which promotes plate aggregation
| *only used to treat arthritis & pre-op pain in pt. with zero cardio. ris
Selective COX-2 inhibitors
60
Anti-inflammatory agents like glucocorticoids and corticosteroids are what?
Lipoxygenase inhibitors
61
Broad spectrunm antiinflamatory drugs.
Reduce transcription of genes encoding COX-2, Phospholipase A2..
Corticosteroids
| Contain Cortisol
62
A major vasoactve amine that stored as a **preformed molecule in the granules** of mast cells, blood basophils, and platelets
| Vasoacivte= affect diameter of blood vessles
Histamine
| Rapidly released when cells are aitvated
63
What kind of cell has the richest source of histamine?
Mast cells
| **normally found in connective tisssue next ot blood vessels**
64
What 5 things can activate Histamines?
1. Trauma
2. Complement C3a & C3b
3. Cell surface IgE cross-linking by hapten/antigen (allergy)
4. Cytokiene IL-1
5. Neuropeptides
65
What happnes when histamines are activated?
Degranulation of mast cell
| *histamine was already fromed*
66
What occurs if there is a mass degranulation of mast cells?
Anaphylactic **SHOCK**! Mass release of histamine; high vasodialation= **hypotension**
67
What is the immeidte response of histamine?
Vasodialation of arterioles+ increased vascular permeability.
68
What are the complement fragments C3a and C5a called?
| They actiavte degranulation of mast cell; release histamine
Anaphylatoxins
69
# What kind of drug?
drugs that treat inflammatory reactions, such as allergies, bind to and block the H1 receptor
Antihistamines
70
71
**Vasodialation** & **increased vascular permeability** causes what symptoms of inflmation?
What are their key-mediators?
* Redness (rubor)
* warmth (calor)
Both caused by histamines, prostaglandins & bradykinins
72
# What symptom of inflmmation?
When fluids escape from post-capillary venules into interisital space
Swelling (tumor)
73
What key mediator of inflmation will act on the **integrity** of the Blood vessel, which causes endothelial cell contraction and **tissue damage, resulting in endothelial cell dissruption**
Histamines
74
Is congestive heart faliure inflmmatory?
| Stagnation fo blood in heart
NO. b/c **permeability of vessels is not affected **. It is a transudate, fluid escaping due to pressure diffrences.
75
How do prostogladinds like PGE2 affect pain?
| What is a major player?
They** dont cause pain, **they **lower threshold** of pain i.e you feel more pain.
Bradykinin is major player in making action potential
| Pain is peripheral!
76
Lower concentrations of Bradykinn & histamine results in what?
Activation of nociception= more painful stimuli
77
Substances that induce fever
Pyrogens
| ex. Bacterial products like LPS
78
Pyrogens stimulate leukocytes to release cytokienes ___ and ___
IL-1 & TNF
| Acute Phase Response
79
Following pyrogen stimulaton of leukocytes (**macrophages 3-4 days** post intial infection) to **release IL1 & TNF** the production of _____ is **upregulated** via increased cyclooxygenease acitvity.
| Occurs in perivascular cells of hypothalamus
Prostaglandins, specifcally PGE2
80
PGE2 does what to the body?
Fever!
| Lowers threshold.
81
WHere does temperature control occur?
Perivascular cells of the hypothalamus
| Fever is CNS
82
NSAIDS including aspring reduce fever how?
Inhbit cyclooxygense COX-1 and COX-2 therefor no prostoglandin syntheiss (no PGE2)
83
**proteins** produced by many cell types (principally activated lymphocytes, macrophages, and dendritic cells, but also endothelial, epithelial, and connective tissue cells) that **mediate and regulate immune and inflammatory reactions
Cytokines
84
# What cytokienes?
serve critical roles in leukocyte recruitment by promoting adhesion of leukocytes to endothelium and their migration through vessels.
| Mainly acitvated by macrophages & dendritic cells
TNF & IL-1
85
Systemic effect of TNF & IL-1
Induce fever and Leukocytosis (send out lots of mature leukocytes, high leveles)
86
sustained production of ____ contributes to cachexia, a pathologic state characterized by weight loss and anorexia that accompanies some chronic infections and cancers.
TNF
87
# What kinds of drugs? What is downside?
effective in the treatment of chronic inflammatory diseases, particularly rheumatoid arthritis, psoriasis, and some types of IBD
TNF antagonist.
Pt. more suseptible to **mycobacterial infection** b/c of reduced ability of macrophages to kill intracellular microbes
88
Synthesis of acute pase protiens, induced by TNF & IL-1in the liver.
Hepatic Syntheis
89
TNF & IL-1increase the expression of ____ molecules in the endothelium of blood vessels
Adhesion moleules
90
IL-1 and TNF reduce the thromboresistant properties of endothelium, thus promoting ______
| Vasodialation + increased permeability
Thrombosis
91
This cytokinene raises hear rate, lower blood pressure due to vasodialation b/c of increased circulation of Neutrophils
TNF
92
family of small (8 to 10 kD) proteins that act primarily as chemoattractants for specific types of leukocytes
Chemokines
93
Chemokines **bind to proteoglycans** and are thus displayed at high concentrations on the ____ of **endothelial cells** and in the **extracellular matrix**
Surface
94
What are 2 main function of Chemokines?
1. Inflamtion; bind leukocyte receptors & stimulate inegrin dependent attachement to endothelium or migration (chemotaxis) of leukocyte to damaged tissue
2. Maintain tissue architecture
