immune mechanisms in disease processing

what type of response will chemical mediators produce in response to injury?

1. cellular response

2. vascular response

what are the two groups of chemical mediators of inflammation?

1. cellular derived

2. plasma derived

cellular derived

pre-made mediators released from cells after stimulation or lysis

what are some examples of cells that release pre-made mediators in cellular derived chemical mediators?

1. inflammatory cells

2. platelets

3. vascular endothelium

plasma derived

soluble cascade system with activated subunits that have wide ranging inflammatory effects

what are the categories of cell derived chemical mediators?

1. lipid mediators

2. cytokines and chemokines

3. vasoactive amines

4. lysosomal components with inflammatory cells

what does the phospholipid bilayer break down into from inflammatory insult?

1. arachidonic acid

2. phospholipase A2

what will phospholipase A2 be further broken down into from inflammatory insult?

arachidonic acid

what can arachidonic acid be further broken down into?

1. COX-1

2. COX-2

3. Lipoxygenase

what enzymes are associated with COX-1?

1. thromboxanes

2. prostaglandins

what enzymes are associated with COX-2?

prostaglandins

what enzymes are associated with lipoxygenase?

leukotrienes

COX-1 is expressed in...

healthy animals with roles in cell protection of mucosal cells and renal function; will also be increased during inflammation

COX-2 is expressed...

during inflammation only

what do thromboxanes expressed during inflammation cause?

1. vasoconstriction

2. platelet aggregation (coagulation)

what do prostaglandins expressed during inflammation cause?

1. fever

2. pain

3. loss of function

4. vascular response

5. cellular response

what reactions do we most see leukotrienes associated with?

hypersensitivities and allergies

what reactions can leukotrienes cause?

1. smooth muscle contraction

2. vascular response

3. cellular response

4. mucous secretion (catarrhal exudate)

mucopurulent

catarrhal and purulent exudate

what do interleukins and interferons respond to?

1. infection

2. inflammation

3. hypersensitivities

4. sepsis

5. cancer

6. reproduction

what cells produce interleukins and interferins?

1. white blood cells

2. endothelial cells

3. fibroblasts

what is the cellular target for cytokine IL-1?

activation of phospholipase A2; stimulates acute phase proteins

if you had an animal with fever and neutrophilia, what cytokine may you use to treat?

IL-1

which cytokines are involved in acute inflammmation?

1. IL-1

2. TNF-alpha

which cytokines are involved in immune system activation?

1. IL-1

2. TNF-alpha

3. INF-gamma

what is the cellular target of TNF-alpha?

1. activation of neutrophils and endothelial cells

2. stimulates production of other cytokines

which cytokine could be associated with shock?

TNF-alpha

what is the cellular target for INF-gamma?

activates macrophages and lymphocytes

which cytokine is involved in chronic inflammation?

INF-gamma

what is the cellular target of IL-10?

immune system supression

chemokines

a subclass of cytokines; activate specific cells and creates "radar" for how to get to their site of inflammation

what is the cellular target of IL-8?

neutrophil

what is the cellular target of eotaxin (CCL10)?

eosinophils

what is the cellular target of CCL1?

lymphocytes

what is the cellular target of CCL2?

lymphocytes and monocytes

what is the cellular target of CCL17?

lymphocytes

what is the cellular target of CCL22?

lymphocytes

what is the cellular target of monocyte chemoattractant protein 1 (MCP-1 and CCL2)?

monocytes

fever

a sign of inflammation but not necessarily infection

what are fevers believed to increase the efficiency of?

1. leukocytes and iron sequestration

2. impair replication of microorganisms

3. stimulate acute-phase imflammation

what type of fever will you have during acute infection?

high fever

what type of fever will you have during chronic infection?

low grade fever

what cytokine is expressed during acute inflammation?

IL-1

what is produced by phospholipid bilayer cleavage and phospholipase 2?

arachidonic acid

what part of the brain controls the body's temperature and set-point?

hypothalamus

what is produced by COX-1 and COX-2 enzymes and produces many of the cardinal signs of inflammation?

prostaglandins

what are stimuli to produce a fever?

1. infection

2. immune mediated

3. prolonged catheters

what chemical mediators are involved in making a fever?

1. IL-1

2. TNF-alpha

3. IFN-gamma (later)

during a fever what does teh arachidonic acid pathway result in?

increased prostaglandin synthesis

what is the result of increased prostaglandin synthesis during a fever?

1. temperature set-point on hypothalamus is increased

2. muscle contractions

3. increased metabolic rate

what produces vasoactive amines?

WBC, endothelial cells, platelets

what are examples of vasoactive amines?

1. histamine

2. serotonin

3. nitric oxide

what do vasoactive amines result in?

vasodilation locally (increased vascular permeability) or systemically

what is important to understand about vasoactive amines?

immediate and short lived

what are lysosomal components within inflammatory cells important for?

intracellular and extracellular digestion of pathogens, dead cells, and debris

what type of inflammatory cells are involved with lysosomal activity?

1. phagocytes

2. degranulating cells

what are the two type of inflammatory cell responses (lysosomal components)?

1. phagocytosis

2. degranulation

what cells are involved in phagocytosis?

neutrophils and macrophages

what cells are involved in degranulation?

1. neutrophils

2. eosinophils

3. mast cells

4. basophils

what is important to understand about mast cells and basophils in terms of degranulation?

do not act directly

what groups of lysosomal components are most likely to contribute to liquefactive necrosis?

1. enzymes

2. reactive oxygen species

what are the groups of lysosomal components?

1. enzymes

2. antimicrobial peptides

3. reactive oxygen species

lysosomal enzymes are...

non-specific in the break down of cellular structures

what cells are lysosomal enzymes?

mainly neutrophils but also eosinophils + enzyme

what are the advantages to lysosomal enzymes?

1. kill and degrade microbe

2. aid in wound debridement

3. facilitate cellular migration

what are the disadvantages to lysosomal enzymes?

1. exacerbate inflammation and tissue damage

2. delay reepithelialization

3. impair collage deposition

4. reduce wound strength

what are included in antimicrobial peptides?

defensins (neutrophils) and major basic protein (eosinophils

antimicrobial peptides...

specifically target pathogens

reactive oxygen species

free radicals produced by inflammatory cells and endothelial cells

what do free radicals cause in the host cell?

oxidation of membrane lipids and proteins and damage of the cellular components leading to oxidative stress and eventual cell death

Dr. Fonseca's experimenting in the lab with a new workout powder. He wants to increase blood flow to his pecs. Which mediator would be least useful to drop in his orange juice?

thromboxane

3 multiple choice options

what are the two plasma derived inflammatory mediators?

1. complement cascade

2. clotting cascade

the complement system is comprised of activated proteins that...

1. attack pathogens directly

2. enhance vascular and cellular inflammatory responses

what proteins in the complement cascade are considered anaphylatoxins?

C3a and C5a

what is the function of anaphylatoxins?

initiate the vascular and cellular response to inflammation

what proteins in the complement cascade are considered opsonization?

C3b

what is the function of opsonization proteins?

initiate enhanced phagocytosis by neutrophils and macrophages

what pathways of the complement cascade would be effected by a C3 defiency?

decreased activity of alternative and common pathways

what specific functions would be effected by a C3 deficiency?

1. decreased MAC attack complex

2. decreased anaphylatoxins

3. decreased opsonins

what pathway would be effected by a C1 deficiency?

loss of classical pathway

what are the two pathways of the clotting cascade?

1. intrinsic pathway

2. extrinsic pathway

what stimulates the intrinsic pathway of the clotting cascade?

contact activation of platelet plug to subendothelium

what stimulates the extrinsic pathway of the clotting cascade?

damaged tissue

what is the final product of clotting cascade?

fibrin

what is important to understand about fibrin in the clotting cascade?

it is also a tissue exudate

when is the fibrinolytic system activated?

at the same time as clotting cascade to degrade fibrin and blood clots

what does plasmin do in the fibrinolytic system?

cleave C3 of the complement system to create more MAC complexes

what would prothrombin and activated partial thromboplastin being increased signify?

clotting disorder, specifically babesia

why does babesia cause hemolytic anemia?

protozoa infects and completes life cycle in RBC of host

how do we get from infection to a clotting disorder?

inflammation, coagulation, and fibrinolysis keep recirculating during a severe infection leading to "disseminated intravascular coagulation"

what does disseminated intravascular coagulation cause?

widespread consumption of clotting factors and fibrinolysis; the body cannot keep up to make enough so then massive bleeding cannot be stopped without intervention