LESSON 1: INFLAMMATION & ALLERGY Flashcards
is a complex dynamic response of tissues to damaging noxious stimuli.
Inflammation
it comprises interrelated vascular & cellular changes in affected tissue;
acute inflammation
acute inflammation aims to?
- Remove
- Neutralized
- Repair
what are the 5 cardinal sign of inflammation?
- pain
- altered functions
- redness
- increase temperature
- swelling
PAIN is due to what?
stimulation of local receptors
this is due to reduced activity.
altered function
redness is due to what?
transient hyperemia
increase of temperature is caused by?
increase blood flow
swelling is cause by?
increase vascular permeability
what are the 2 main components of acute inflammation?
- Innate non-immunological response
- Acquired immunological response
in this event circulating neutrophils adhere to the swollen endothelial cells.
Margination
when margination happens this event will be the next, neutrophils actively migrate through the basement membrane vascular epithelium passing into the area of tissue damage
emigration
this migration process is called what??
chemotaxis
chemotaxis is caused by the attraction of _____ to chemotoxins produced in the site of tissue damage
luekocytes
give me the 3 function of acute inflammation
- to dilute (weakend)
- to eliminate (get rid)
- to remove inflammatory debris (clean)
leukocytes are classified into 2, what are those?
- Polymorphonuclear
- Mononuclear
the main cellular events in acute inflammation is caused by?
chemical mediator
during inflammation the endothelial cell of small arterioles are activated to secrete?
- Nitric oxide& prostcycline
- Endothelin, plasminogen activator, platelet-activation factor, thromboxane A2, angiotensin 2, cytokines
endothelial cell function also in _____ which occurs in wound repair, chronic inflammation & cancer.
Angiogenesis
what is the meaning of angiogenesis?
formation of new blood vessels
_______ is the first line of defense
neutrophils
_______ have the capacities similar to those of the neutrophils & release the number of potent granule that can damage multicellular parasites
eosinophils
______ are similar in many aspects of many mast cells; it secrete histamine. but found on circulating blood.
basophils
this _____ are like basophil but can only be found in tissue, it can be activated to secrete histamine.
mast cells
_____ enters the area of inflammation at a larger stage, several hours after the polymorphs; this is associated by chemokines.
monocytes/macrophages
macrophages bind with bacterial ________ that generate & release cytokines that act on vascular endothelial cells to further increased vascular permeability, attract other leukocytes & cause fever
lipopolysaccharide
this ______ involved primarily in blood coagulation & in inflammation.
platelets
platelets is also called _____?
thrombocytes
platelet or thrombocytes generate this 3 substance, what are these?
- Thromboxane A2
- Platelet-activating factor radicals
- pro-inflammatory cationic proteins
what are the neurons that are stimulated in an inflamed areas releasing neuropeptides.
Type C & Ab fibers
what are the functions of type c & ab fibers?
- transmit pain impulses to CNS
- generate chemical mediators (kinins, serotonin) during inflammation
_____ are cell that are specialized lymphocytes that are active in non-immunological reactions.
Natural killer cells
Natural killer cells kills what?
- target cells such as; virus-infected cells
- cancer cells
this____ molecules normally present in normal cells inhibit NK cells by acting on the inhibitory receptors on the NK cells themselves.
MHC
What are the components of exudate ?
- Fluid
- Fibrin
- Neutrophils
- Macrophages
this component of exudate contains salts & high concentratiom of proteins inlcuding immunoglobulins & mediators
Fluid
fluid is predominant in what type of exudate?
serous exudate
this component of exudate is a high molecular weight filamentous insoluble protein
fibrin
fibrin is predominant is what type of exudate
fibrinous exudate
in purulent exudates what cells are present ?
- Neutrophils, Macrophages, Lymphocytes
inflammatory exudates is composed of 5 substances what are those?
- fluid
- electrolytes
- proteins
- cellular elements
- inflammatory mediators
this 2 substances can diffuse into the area of inflammation to support the macrophages
- glucose
- oxygen
immunoglobulin in the exudates may act as?
opsonins
responsible for body production-the humoral immune response
B-Cells
responsible cell mediated immune reactions
T-cells
specialized non-T & non-B lymphoid cells that are active in non-immune innate response
Natural killer cells
This phase involves the production of B cells & T cells from uncommitted lymphocytes.
The induction phase of immunological response
the antigen molecules are presented to the lymphocytes by the?
Antigen-presenting cells (APC)
The APC engulf & process the antigen & present it to uncommitted ______ also known as t-helper precursor, in association with HMC
CD4 + T helper lymphocytes
the CD4 develop this _____, a cytokine which act on the same cells causing their proliferation, producing clones of activated T cells (Th0) give rise to 2 subsets which are the (Th1 & Th2)
Interleukins-2
IL-12 is produced by?
APC
IL-4 is produce by?
some Th0
what does Th1 controls?
it controls cell-mediated responses
Th1 secrete this______ which, activates CD8+ to become cytotoxic cells that kill virally infected host cells.
interferon-gamma (IFN-Y)
IL-4 is derived from ______ cells that inhibit Th1 function
Th2 cells
what does Th2 pathway controls ?
it controls antibody humoral-mediated responses
IFN-y is derived from ____, that inhibits Th2
Th1
this phase involves how the cells that is produce in induction phase, acts to eliminate antigens. This acts may be (antibody or cell mediated)
The effect phase of the immunological response
______ can form a link between a parasite & eosinophils, which are the able to damage or kill the parasite.
Antibody
______ can attach to mast cells & basophils to stimulate these cells to release histamine & other inflammatory mediators
IgE
2 FUNCTIONS OF ANTIBODY or IMMUNOGLOBULINS
- to recognize & interact with specific antigens
- to activate one or more, the host’s defense system
the tissue reacts though ?
vascular & cellular changes
are substance mediated by the body & act near the sites of their synthesis, & sometimes called local hormones
AUTOCOIDS
histamine is derived from?
histidine
blood of this 2 animals is relatively histamine
goat & rabbit
while the blood of this 4 animals is relatively low in histamines.
horse, dog, cat, rat
histamine is stored mainly in _____, which are abundant to:
1. Gastrointestinal mucosa
2. Bronchial mucosa
3. Skin
mast cells & basophils
Non-mast-cell histamine is secreted by _____ in the stomach & by _____ neurons in the brain.
Histaminocytes & Histaminergic
in allergy ______ is release as a result of interaction of the antigen & the antibody IgE on the surfaces of mast cells & basophils.
Histamine
the prescence of _____ stimulates the production of IgE, which then binds to the surface of receptors in mast cells.
Antigen
______ activates phospholipase C in the mast cell membrane, which catalyzes the breakdown of membrane phospholipids resulting in the relese of:
1. diacyglycerol
2. inositol-1,4,5-triphosphate
antigen-antibody complexes
3 physiological roles of histamine
- Histamine secreted by histaminoyctes, regulates gastric acid secretions
- Histamine secreted by histaminergic neurons acts as neurotransmitter in the CNS
- Histamine secreted by mast cells act as mediators of early inflammatory reactions
what are the 3 response to histamine?
- red spot
- Flare
- whale
a few millimeters around the site of injection is due to immediate direct vasodilator effect of histamine.
RED SPOT
A bright red irregular outline from the original red spot due to reflex dilation of the adjacent small vessels.
FLARE
A localized edema due to leakage of plasma fluid through the abnormality permeable walls of the small blood vessels
WHEAL
______ histamine receptors mediates most inflammatory & are antagonized by the classical anti-histamines.
h1
what is the agonist of h1 receptor
histamine
what is the antagonist of h1 receptor
mepyramine
______ receptor of histamine, that has a role in gastric acid secretions, an action blocked by specific H2 antagonist
H2 receptor
what is the agonist of h2 receptor?
histamine dipamrit
what is the antagonist of h2 receptor?
cimetidine
what is the agonist of h3 receptor?
(R)- methyl histamine
what is the antagonist of h3 receptor
thloperamide
what are the drugs to use to prevent release of histamine by inhibiting the responses of sensitized cells basophils to specific antigen: E.T.C
- epinephrine
- theophyline
- chromolyn sodium
drugs to for physiologically antagonize histamine effects: E.T.A
- epinephrine
- theophyline
- aminophyline
is poorly absorbed from the gut, usually given inhalation as nebulized solution or powder
Cromolyn sodium
how many % of cromolyn sodium is absorb?.
10%
how many % of cromolyn sodium is excreted in I bile & urine
50%
is better absorbed than cromolyn sodium
Nedicromyl
what is the mechanism of action of cromolym sodium?
- stabilized mast cells
2, prevent histamine release
these xanthine derivates are bronchodilators used in the management of attack of bronchopasm.
Theophylline ethylene diamine
Theophylline ethylene diamine has a 3 positive effects:
- Chonotropic
- inotropic effects
- Mild diuretic effects
Mode of action of Theophylline ethylene diamine:
- Inhibit phosphodiesterase, enzyme that catalysis the breakdown of cyclic AMP
- they cause relaxation on smooth muscle,
unwanted effects of Theophylline ethylene diamine:
- Anorexia
- Nausea & vomitting
- Nervousness & tremors
- Sometimes-fatal cardiac arrythimias
More significant clinical action of Theophylline ethylene diamine;
- Depression of release of certain neuropeptides
- Antagnosm of tachynin receptors
- Inhibition of platelet activating factor interaction w/platelets & eosinophils
what are the drugs that inhibit microsomal cytochrome P450 enzymes: Ery,Cip,Allo,Flu,Cim
- Erythromycin
- Ciprofloxacin
- Ca2+ channel blockers
- Allopurinol
- Fluconazole
- Cimetidine
what are the drugs the induce cytochrome P450
that derease the therapeutic effect of drugs.
- Phenobarbital
- Phenytoin
this drug causes pheripheral vasoconstriction, bronchodillation & cardiac stimulation; effects that counter histamine effects.
Epinephrine
2 reasons why H1 antihistamine are not widely used in animals:
- Antihistamine have varying effectiveness in animals
- glucocorticoids are available & are more effective
Cyproheptadine also blocks?
5-HT receptors
has weak alpha-adrenoreceptor blocking action
Promethazine
a nontoxix metabolite of Terfenadine & is now available for use.
Fexofemadine
How does arachidonic acid is released?
- Activated phospholipase C
- Increase in cytosolic Ca2, that will stimulates phospholipase A2 & release of arachidonic acid
the prostaglandin are also called prostanoids, because they share the chemical features of hypothetical substance. What are those?
- 20 carbon prostanoic acid
- 5-member cyclopentane ring
- 2-hydrocarbon side chains
are not stored in tissue but are rapidly formed & release when tissue is damaged.
Prostaglandins
is invloved in the regulation of biosynthesis of prostaglandins by causing the release of the precursur arachidonic acid.
Phospholipase A2
what are the 2 majory enzymes that use arachidonic acid as a substance:,
- Cyclooxygenase
- Lipoxygenase
arachidonic acid is converted by ______ to cyclic endoperoxidase, (pgg2 & pgh2), these endoperoxidase have a short half-life of 30-45 sec.,
CYCLOOXYGENASE
2 identified cyclooxygenase isoenzymes:
- COX-1
- COX-2
inhibition of this _____ is believed to underline the most significant “side effects” of non-steroidal anti-inflammatory drugs. ex. aspirin drugs
COX-1 or cyclooxygenase -1
on the other hand, is induced during inflammation, & inhibition of COX-2 accounts for the therapeutic action of NSAIDs
COX-2 or cyclooxygenase -2
Arachidonic acid is also converted by lipoxygenase 3 HPETE namely:
- 15-HPETE
- 12-HPETE
- 5-HPETE
what is the complete name of HPETE?
hydroperoxy-cicosatetraenoic acid
unlike the 2 HPETE, this ____ serves as a substrate for the enzyme leukotriene synthase & is further transformed into various leukotrienes
5-HPETE
what are the various leukotrienes in 5-HPETE
- LTA4
- LTB4
- LTC4
- lTD4, LTE4, LTF4
_____ are leukotriens are the slow-acting substance of anaphylaxis (SRS-A), they are 1000x as potent as histamine in increasing vascular permeability.
LTC4 & LTD4
What are the roles of (PG) prostglandin in inflammation:
- Metabolic effects
- Oppose the action of another PG
- Cause edema
- Function enhnace during phagocytosis
- PGE is chemotactic for leukocytes
- Produce fever themselvesm
- Do not cause pain, but can sensitize
- Chemical stimulation so that pain can be magnified.
this causes vasodilation, inhibition of platelet aggregation, relaxation of gut & uterine muscle, modify pituitary hormone release.
PGD2 w/ receptor DP
this causes myometrial contraction leutolysis bronchochonstriction
PGF2 w/ receptor F
this causes vasodilation, inhibition of platelet aggregation, renin release & natriuresis
PGI2 w/ receptor IP
this causes vasoconstriction, platelets aggregation & bronchoconstriction
TXA2 w/ receptor TP
in PGE w/ receptor EP1 they causes:
- Bronchoconstriction
- Contraction of gut muscle stimulation of intestinal fluid secretion
in PGE w/ receptor EP2 they causes:
- Stimulation of intestinal fluid secretion
- Relaxation of gut muscle
in PGE w/ receptor EP3 they causes:
- Contraction of intestinal muscle
- inhibition of gastric acid secretion
- Increase gastric mucus secretion
- inhibition of lipolysis
- inhibition neurotransmitter release
- contractionof pregnant uterus
is a powerful chemotactic agent for a bit neutrophils & macrophages.
LTB4, on specific LTB4 receptor
LTB4 does?
- increase the formatiom of membrane adhesion molecules
- production of toxic oxygen products
- release of granules enzymes
while LTD4 & LTC4 causes:
- increase respiratory mucus secretions
- reduced blood pressure
- coronary vessel constriction
- wheals & flare
- increase nasal vascular permeability
PGE & PGF are rapidly metabolized in the lungs by _______. The depression of capacity of the lungs to metabolized PG’s may result in increased levels of PE2 & PGF2A
Prostaglandin dehydrogenase
the factor that inhibit prostaglandin dehydrogenase include:
- Nitrate
- Irradiation
- Bacterial endotoxins
are heterogenous group of compound which are often chemically unrelated.,
NSAID’s or Non-steroidal anti-inflammatory drugs
what are the prototypes of NSAID’s ?
aspirin, hence they are called aspirin-like drugs
what are the clinical used of NSAID’s?
- Analgesic
- Antipyretic
- Anti-inflammatory
in veterinary medicine, NSAID’s are used for tx. of:
- acute inflammation of m. skeletal system
- non-immune inflammation of m.skeletal system & anaphylactic reaction in cattle
- equine colic
- acute resp. disease in calve & pigs
______ is used to reduce thromboembolosus, fromation associated w/ heartworm disease in dog & w/ hypertrophic cardiomyopathies, it has the ability to prevent platelet aggregation.
Aspirin
aspirin is usually administered orally & converted into?
salicylic acid
similar to aspirin, less commonly used. cannot be given to animals less than 30 days old,
sodium salicylate
used systemically in the management of non-ulcerative keratitis in the horse
flunixin & phenybutazone
used externally as a counter-irritant
methylsalicylic acid
recommended in horses for treatment of inflammatory conditions, involved in lameness & pain such as tying up syndrome:
Naproxen
a simple derivative of phenylpropionic acid, metabolized in the liver & may cause gastro. irritation & bleeding.
ibuprofen
inhibits both cylooxygenase & some lipoxygenase
ketroprofen
it’s usually not included w/ NSAID’s for it’s devoid of anti-inflammatory effects but retain antipyretic 7 analgesic effects
paracetamol
is a small molecule, a powerful cause of vasodilation & increase vascular permeability. important re-active oxygen intermediary, also mediate cell & bacterial killing
Nitric oxide
is a polar lipid release from leukocytes & cause platelet aggregate
platelet activating factor
are polypeptide production release by connective tissue & activated lymphocytes & monocytes
Cytokines
is a non-peptode (arg-pro-pro-gly-phe-ser-pro-phe-arg)
bradykinin
while this type of kinin systems has an additional lysine & amino terminal
kallidin
is used in treatment of acute pancreatitis & carcinoid syndrome
aprotinin
blood clotting is initiated by activation of ?
hageman factor (factor xii)
what is the best anti-inflammatory agent ?
Heparin