immunology - acute inflammatory response 2

anti-histamine/mast cell stabilizers (drops)

zaditor

NSAIDs (drops)

prolensa

steroids (drops)

PredForte

chemical mediators and regulations

- cell-derived

produced locally by cells at site of inflammation

in intracellular granules until activation and secretion

synthesized in response to stimulus

examples of cell derived chemical mediated and regulations

histamines, vasoactive amines, arachidonic acid metabolites, platelet-activating factor, cytokines, ROS, nitric oxide, lysosomal enzymes of leukocytes, neuropeptides

chemical mediators and regulations

- plasma protein-derived

come from circulation, inactive precursors

- manufactured in liver, proteolytic cleavage to activate

complement, coagulation, kinin systems

histamine

- produced by ...

- stimulus ?

- actions ?

ocular drug?

1. many cell types, mast cells, basophils, platelets

2. injury, immune reactions, anaphylatoxins, leukocyte-derived neuropeptides, cytokines

3. vasodilation, increased vascular permeability

4. zerviate (zyrtec for the eye)

arachidonic acid metabolites

prostaglandins, leukotrienes, lipoxins

sources of AA metabolites

leukocytes, mast cells, endothelial cells, platelets

AA metabolites metabolism via 2 enzymatic pathways

1. cyclooxygenase --> prostaglandins and thromboxanes

2. lipooxygenase --> leukotrienes and lipoxins

sterioids inhibit which step

stops pathway 'before it begins'

inhibits metabolism of arachidonic acid by blocking PHOSPHOLIPASES

what do NSAIDs block? prevents what

CYCLOOXYGENASE

prevents production of prostaglandins

role of prostaglandins in inflammation

important mediator for inflammation

acetaminophen (tylenol) vs ibuprofen

A: reduces pain and fever

I: reduces pain, fever, and inflammation

who should you NOT recommend ibuprofen to ?

GIT disease / ulcers, and those on anti-coagulants

is tylenol an NSAID?

NO

is ibuprofen an NSAID?

yes!

vasodilation is mediated by

prostaglandins (+prostacyclin)

increased vascular permeability is mediated by

prostaglandins, leukotrienes

chemotaxis, leukocyte adhesion is mediated by

leukotrienes, HETE (hydroxyeicosatetraenoic acid)

pain and fever is mediated by

prostaglandins

anti-inflammatory drugs

NSAIDs

- examples

- inhibitors?

aspirin, ibuprofen, acular (drop)

COX-1 COX-2 (cyclooxygenase) inhibitors

inhibit cyclooxygenase and thus prostaglandin production

anti-inflammatory drugs

steroids

- examples

- inhibit?

prednisone (oral), PredForte (topical), Prednisolone acetate (topical)

inhibit activity of phospholipase A2 (inhibits release of AA from membrane lipids)

"pro-inflammatory" drugs

Xalatan (latanoprost), Lumigan, Travatan Z, Vyzulta, rocklatan

function of "pro-inflammatory" drugs

prostaglandin analogs to increase uveoscleral outflow

pro-inflammatory drugs may be used to treat _____

glaucoma

why be cautious of pro-inflammatory drugs

bc pt may have inflamed eyes all the time if taking

dont prescribe if pt has history of uveitis

cell-derived mediators

platelet-activating factor

phospholipid-derived via phospholipase A2

monocytes, basophils, endothelial cells, platelets

all-inclusive mediator of acute inflammation

cell-derived mediators

cytokines

immune and inflammatory messengers

interleukins (IL-#), tumor necrosis factor, IL-1 and IL-6, chemokines

role of chemokines

allows for communication between WBCs

recruit leukocytes to inflamed areas, organizers of cells in lymphoid tissues

role of TNF and IL-1

endothelial cell activation in immunity and inflammation

___ agonists treat chronic inflammatory diseases (ex: rheumatoid arthritis)

TNF

_________(3): kill microbes and can potentiate tissue injury

ROS, NO, lysosomal enzymes

reactive oxygen species

phagocytes, immunity and inflammation, recruiters, communicators, and destroyers

nitric oxide

short lived, soluble, free radical gas, many cell types and functions

lysosomal enzymes

leukocytes, destroyers

neuropeptides

vasoactive, transmit pain signals, secreted by nerve fibers

how does NO help with glaucoma

lowers IOP in normal and POAG eyes

three systems of plasma protein-derived mediators

complement, kinin, coagulation

complement system functions in ____ & ____

inflammation and immunity

mechanism of complement system

activation --> opsonization of microbe --> phagocytosis and destruction --> inflammatory response

generation of anaphylatoxins

complement system:

activation of C3 - cleavage via 3 pathways which are...?

1. classical: antigen-antibody complex + C1

2. alternative: microbial cell wall components + properdin + factors B and D

3. lectin: lectin in plasma binds to microbes

pathway of C3 convertase cleaving C3--> C3a and C3b

C3b + microbe surface --> C5 convertase cleaves C5 --> C5a and C5b

C6-C9 assembly

MAC: membrane attack complex generated

which cause generation of anaphylatoxins?

C3a and C5a

_____ are more mediators of inflammation

complement system

what do anaphylatoxins do?

cause release of histamine from mast cells

leukocyte activation --> adhesion and chemotaxis

what is augmented when C3b attaches to microbe surface?

phagocytosis

function of MAC and C9

creates "hole" in bacterial cell membranes

mechanism of new geographic atrophy treatment

intravitreal complement inhibitor

syfovre inhibits complement factor C, stopping a vital step in the complement cascade, which promotes inflammation

GA is associated with?

AMD

coagulation and kinin systems function/mechanism

during blood clotting --> generation of some activated molecules --> inflammatory roles

MAKES BRADYKININ

role of bradykinin

increased vascular permeability, arteriolar dilation, pain

major contributors:

vasodilation

prostaglandins, histamine

also- NO, PAF, bradykinin

major contributors:

increased vascular permeability

histamine, prostaglandins, anaphylatoxins, leukotrienes

also- bradykinin, PAF

major contributors:

chemotaxis and leukocyte activation

TNF, IL-1, chemokines, anaphylatoxins, leukotrienes

also- bacterial products, PAF

major contributors:

fever

IL-1, TNF, prostaglandins

major contributors:

pain

prostaglandins, bradykinin

major contributors:

tissue damage

lysosomal enzymes, ROS