Exam III: Inflammation Part I

Question 1

Typical Inflammatory Reaction

Answer 1

The offending agent is located in extravascular tissues and recognized by host cells and molecules
Leukocytes and plasma proteins are recruited from the circulation to the site of offending agent
Leukocytes and proteins are activated and work together to destroy and eliminate the offending substance
Reaction is controlled and terminated
The damaged tissue is repaired

Question 2

Steps of Inflammatory Process

Answer 2

(1) recognition of the injurious agent
(2) recruitment of leukocytes
(3) removal of the agent
(4) regulation (control) of the response
(5) resolution (repair)

Question 3

Acute vs. Chronic: General

Answer 3

Acute or chronic inflammation
Depends on the nature of the stimulus
Effectiveness of the initial reaction in eliminating the stimulus or the damaged tissues

Question 4

Acute Inflammation

Answer 4

Rapid in onset/host response (minutes)
Short duration (hours or a few days)
Exudation of fluid and plasma proteins (edema)
Delivers leukocytes and plasma proteins to the sites of infection or tissue injury

Three major components:

1. Alterations in vascular caliber
2. Structural changes in the microvasculature
3. Emigration of the leukocytes (neutrophils)

Question 5

Chronic Inflammation

Answer 5

May follow acute inflammation
May be insidious in onset
Longer duration
Presence of lymphocytes and macrophages
Proliferation of blood vessels and fibrosis
Tissue destruction
Granulomatous inflammation is a subset of chronic inflammation

Question 6

Cardinal Signs of Inflammation

Answer 6

Rubor (redness)
Tumor (swelling)
Calor (heat)
Dolor (pain)
Loss of function (functio laesa)

Signs are typically more prominent in acute inflammation

Question 7

Stimuli for Acute Inflammation

Answer 7

Infections (bacterial, viral, fungal, parasitic) and microbial toxins- most common and medically important causes

Tissue necrosis: ischemia, trauma, physical, and chemical injury

Foreign bodies: impaled finger or foot with something = cuts can cause bad infections

Immune reactions: allergies

Question 8

Exudate

Answer 8

Inflammatory extravascular fluid
High protein concentration
Specific gravity > 1.020
Usually due to increased permeability

An inflammatory process caused by something causing increased vascularity to allow leukocytes to come in

Question 9

Transudate

Answer 9

Fluid with low protein concentration (albumin)
Specific gravity < 1.012
Permeability usually not increased (due to a pressure response)
changes in pressure= renal failure, liver failure, heart failure, etc.

Question 10

Edema

Answer 10

Excess interstitial fluid
Can be either an exudate or transudate

Excess INTERSTITIAL fluid/ vascular tissue; can be a pressure change or vascular change
Absorb water with sponge and stick needle in sponge you will not be able to get out the water because it is trapped in many compartments… same with patient, cannot just “drain” the fluid, need to restore lymphatic system

Question 11

Pus

Answer 11

Purulent exudate containing leukocytes (neutrophils), debris of dead cells, and microbes/bacteria

When you write in a patient chart that you found a pocket of pus = purulent exudate

Question 12

Hydrostatic and Colloid Pressure Changes

Answer 12

Normal: balance of hydrostatic and colloid osmotic pressure to keep plasma proteins to stay within the vessels

Transudate: fluid leakage caused by pressure change; proteins are still within the vessel; increased hydrostatic pressure due to venous outflow obstruction like in congestive heart failure; decreased colloid pressure due to decreased protein synthesis like in liver disease or increased protein loss like in kidney disease

Exudate: increased protein concentration because leakage of fluid and proteins outside of the vessels due to increased interendothelial spaces

Question 13

Steps of Inflammatory Process

Answer 13

Vasodilation with exudation leads to an outpouring of fluid with fibrin into the alveolar spaces, along with PMN’s. The series of events in the process of inflammation are:

1. Vasodilation: leads to greater blood flow to the area of inflammation, resulting in redness and heat.
2. Vascular permeability: endothelial cells become “leaky” from either direct endothelial cell injury or via chemical mediators.
3. Exudation: fluid, proteins, red blood cells, and white blood cells escape from the intravascular space as a result of increased osmotic pressure extravascularly and increased hydrostatic pressure intravascularly
4. Vascular stasis: slowing of the blood in the bloodstream with vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to collect and respond to the stimulus.

Question 14

Vascular Changes

Answer 14

Earliest manifestations of acute inflammation
Follows a transient constriction of arterioles
Lasts a few seconds
First involves the arterioles
Leads to opening of new capillary beds
Result is increased blood flow causing heat and redness (erythema) at the site of inflammation
Induced by the action of several mediators such as histamine and nitric oxide
Followed by increased permeability of the microvasculature causing an outpouring of protein-rich fluid into the extravascular tissues

Question 15

Loss of Fluid and Increase in Diameter of Vessels

Answer 15

Leads to slower blood flow, concentration of red cells in small vessels, and increased viscosity of the blood
Changes result in dilation of small vessels
Packed with slowly moving red cells

Increased vascular permeability created by inter-endothelial spaces
When protein rich fluid leaks out = slows down blood flow to get hemo-concentration (cells concentrate in inflammation so neutrophils can come), increased concentration of RBCs causing the blood to thicken= stasis
See leukocytes that start in center and migrate outwards to get into the vascular tissue; endothelial cells become activated by mediator depending on process occur and see leukocytes adhering to them

Question 16

As Stasis Progresses

Answer 16

Leukocytes (neutrophils) accumulate along the vascular endothelium
Endothelial cells are activated by mediators produced at sites of infection and tissue damage
Express increased levels of adhesion molecules
Leukocytes then adhere to the endothelium then migrate through the vascular wall into the interstitial tissue

Question 17

Hallmark of Acute Inflammation

Answer 17

Hallmark of acute inflammation= increased vascular permeability
Leads to the escape of a protein-rich exudate into the extravascular tissue causing edema

Question 18

Mechanisms of Increased Permeability

Answer 18

Contraction of endothelial cells
Results in increased interendothelial spaces
Most common mechanism of vascular leakage
Elicited by histamine, bradykinin, leukotrienes, the neuropeptide substance P, and many other mediators
Called the immediate transient response, which occurs rapidly after exposure to the mediator- usually short-lived (15-30 minutes)

Question 19

Endothelial Injury and Transcytosis

Answer 19

Endothelial injury
Results in endothelial cell necrosis and detachment
Direct damage to the endothelium from trauma, injury, or iatrogenic (physician cause)

Transcytosis
Increased transport of fluids and proteins through the endothelial cell
seen in transudate through endothelial cells without any other kind of damage

Question 20

Principle Mechanisms of Increased Vascular Permeability

Answer 20

Endothelium on basement membrane with leukocytes and plasma proteins; laminar flow causes white cells to be in the center of the vessels, but when blood flow slows down the cells start to tumble and come out of the endothelial cells

Retraction of Endothelial Cells: occurs in venules, short lived/rapid leakage of protein and fluid; induced by NO, histamine, and other mediators

Endothelial Injury: chemical, burn, toxin, etc. and causing the endothelial cells to die- can last longer (hours to days depending); rapid process and occurs in arterioles, capillaries and venules

Leukocyte-Mediated Vascular Injury: leukocytes adhere to endothlelial cells – hours and later stages of process; occurs in venules and pulmonary capillaries

Increased Transcytosis: occurs in venules and induced by VEGF; fluid can get to vascular lumen into surrounding tissue

Question 21

Responses of Lymphatics

Answer 21

Lymphatics and lymph nodes filter and police the extravascular fluids
Normally drain the small amount of extravascular fluid that leaked out of capillaries

Inflammation
Lymph flow is increased and helps drain edema fluid
Accumulates due to increased vascular permeability
Lymphatic vessels proliferate during inflammatory reactions
Lymphatics may become secondarily inflamed (lymphangitis)
Draining lymph nodes may become inflamed (lymphadenitis)
Hyperplasia of the lymphoid follicles (increase in cell #)
Increased numbers of lymphocytes and macrophages

Question 22

Recruitment of Leukocytes

Answer 22

Recruitment from the blood into extravascular tissues
Recognition of microbes and necrotic tissues
Removal of the offending agent

Question 23

Extravasation

Answer 23

Journey of leukocytes: vessel lumen to the interstitial tissue
Lumen: margination, rolling, and adhesion to endothelium via P and E-selections causing them to adhere and integrins cause them to go through the basement membrane
Migration across endothelium and vessel wall
Migration in the tissues toward a chemotactic stimulus

Question 24

Margination

Answer 24

Blood flow slows early in inflammation (stasis)
Hemodynamic conditions change (wall shear stress decreases)
More white cells assume a peripheral position along the endothelial surface
Rolling on the vessel wall- individual and then rows of leukocytes adhere transiently to the endothelium, detach, and then bind again
Cells finally come to rest at some point and firmly attach

Question 25

Leukocyte Migration

Answer 25

Transmigration or diapedesis Occurs mainly in post-capillary venules Chemokines act on the adherent leukocytes Stimulate the cells to migrate through interendothelial spaces toward the chemical concentration gradient Toward the site of injury or infection where the chemokines are being produced It crawls all the way along using its pseudopod to get to area of injury via chemokines (specific chemical mediators that have chemotactic signaling to the white cells) that bring leukocytes to the area or you would get crazy amounts of inflammation everywhere in the body

Question 26

Chemotaxis of Leukocytes

Answer 26

After exiting the circulation leukocytes emigrate in tissues toward the site of injury Chemotaxis: locomotion oriented along a chemical gradient Chemoattractants: exogenous substances, bacterial products, lipids, endogenous substances Chemical mediators: cytokines, components of the complement system, arachidonic acid (AA) Leukocyte movement: extending filopodia/pseudopods to pull the back of the cell in the direction of extension and migrate toward the inflammatory stimulus

Question 27

Leukocytic Infiltrate

Answer 27

Nature of the leukocyte infiltrate varies with the age of the inflammatory response and with the type of stimulus Acute inflammation: neutrophils predominate in the inflammatory infiltrate during the first 6 to 24 hours, but then replaced by monocytes in 24 to 48 hours When monocytes turn into tissue macrophages they survive longer and may proliferate in the tissues becoming the dominant population in chronic inflammatory reactions

Question 28

Exceptions in Leukocytic Infiltration Populations

Answer 28

Pseudomonas bacteria: cellular infiltrate is dominated by continuously recruited neutrophils for several days instead of only lasting 6-24 hours Viral infections: lymphocytes may be the first cells to arrive instead of neutrophils Hypersensitivity reactions and parasitic infections: eosinophils may be the main cell type

Question 29

Recognition of Microbes and Dead Tissue

Answer 29

Leukocyte recruitment to site of infection Must be activated to perform their functions Recognition of the offending agents Deliver signals Activate the leukocytes to ingest and destroy the offending agents and amplify the inflammatory reaction

Question 30

Trends of an MI

Answer 30

First 1.5 days = edema of tissues peaking at 12 hours First 2.5 days = neutrophil infiltration peaking at 24 hours Monocytes and Macrophages from beginning, but peak at 48 hours and slowly decrease population

Question 31

3 Steps of Phagocytosis

Answer 31

Clean up of inflammation 1. Recognition and attachment of the particle to be ingested by the leukocyte 2. Engulfment with subsequent formation of a phagocytic vacuole 3. Killing or degradation of the ingested material

Question 32

Engulfment & Degradation

Answer 32

After a particle is bound to phagocyte receptors: Extensions of the cytoplasm (pseudopods) Plasma membrane pinches off to form a vesicle (phagosome) Encloses the particle and fuses with a lysosomal granule Discharge of the granule's contents into the phagolysosome Final step in the elimination of infectious agents and necrotic cells occurs within neutrophils and macrophages Microbial killing involving ROS and reactive nitrogen species

Question 33

Microbial Killing

Answer 33

Can also occur through the action of other substances in leukocyte granules Granules contain many enzymes such as elastase, defensins, cathelicidins, and lysozymes, lactoferrin, major basic protein, and bactericidial Major basic protein: in eosinophil granules that is toxic to parasites

Question 34

Responses of Activated Leukocytes

Answer 34

Produce a number of growth factors to stimulate the proliferation of endothelial cells and fibroblasts, synthesis of collagen, and enzymes that remodel connective tissues Drive the process of repair after tissue injury

Question 35

Defects in Leukocyte Function

Answer 35

Inherited and acquired types Lead to increased vulnerability to infections Inherited defects in leukocyte adhesion and phagolysosome function

Question 36

Chédiak-Higashi Syndrome

Answer 36

Autosomal recessive condition Defective fusion of phagosomes and lysosomes in phagocytes causing susceptibility to infections Abnormalities in melanocytes (leading to albinism) Cells of the nervous system (associated with nerve defects) Platelets (causing bleeding disorders) Leukocyte abnormalities: Neutropenia (decreased numbers of neutrophils) Defective degranulation Delayed microbial killing

Question 37

Chronic Granlomatous Disease

Answer 37

Impairments of leukocyte function Inherited defects in microbicidal activity Chronic granulomatous disease: defects in bacterial killing that render patients susceptible to recurrent bacterial infection that starts during childhood Inherited defects in the genes encoding components of phagocyte oxidase Initial neutrophil defense is inadequate Granulomas: collections of activated macrophages that wall off the microbes Can occur all over the body which starts to replace functional tissue Example granulomas in the lungs can replace lung tissue and lungs cannot function properly

Question 38

Acquired Leukocyte Deficiencies

Answer 38

``` Acquired deficiencies—causes of leukocyte defects Bone marrow suppression Decreased production of leukocytes Seen following therapies for cancer Radiation and chemotherapy Marrow space is compromised by tumors Leukemias Metastatic from other sites ```

Question 39

Mediators of Inflammation: General

Answer 39

Mediators are generated either from cells or from plasma proteins Cell-derived mediators are normally sequestered in intracellular granules, and can be rapidly secreted by granule exocytosis: histamine in mast cell granules Synthesized de novo in response to a stimulus: prostaglandins, cytokines

Question 40

Mediators: Producing Cells & Plasma Derived

Answer 40

Cells that produce mediators: platelets, neutrophils, monocytes/macrophages, and mast cells, mesenchymal cells (endothelium, smooth muscle, fibroblasts), most epithelia Plasma-derived mediators Complement proteins, kinens Produced mainly in the liver Present in the circulation as inactive precursors Must be activated to acquire their biologic properties

Question 41

Active Mediators

Answer 41

Produced in response to various stimuli such as microbial products and substances released from necrotic cells, and proteins of the complement, kinin, and coagulation systems Activated by microbes and damaged tissues Ensures that inflammation is normally triggered only when and where it is needed

Question 42

Mediators are Short Lived

Answer 42

Once activated and released from the cell Quickly decay: arachidonic acid metabolites Inactivated by enzymes: kininase inactivates bradykinin Otherwise scavenged or inhibited Antioxidants scavenge toxic oxygen metabolites Inhibited: complement regulatory proteins break up and degrade activated complement components

Question 43

Vasoactive Amines

Answer 43

Two major vasoactive amines Histamine and Serotonin Stored as preformed molecules in cells and are Among the first mediators to be released during inflammation

Question 44

Richest Source of Histamine

Answer 44

Richest sources: mast cells Normally present in the connective tissue adjacent to blood vessels Found in blood basophils and platelets Present in mast cell granules Mast cells hangout in CT near the blood supply/vessels

Question 45

Action of Histamine

Answer 45

Causes dilation of arterioles Increases the permeability of venules Considered to be the principal mediator of the immediate transient phase of increased vascular permeability Producing interendothelial gaps in venules

Question 46

Serotonin

Answer 46

Preformed vasoactive mediator Actions similar to those of histamine Present in platelets Stimulated when platelets aggregate after contact with collagen, thrombin, adenosine diphosphate, and antigen-antibody complexes Platelet release reaction: key component of coagulation Present in certain neuroendocrine cells and gastrointestinal tract

Question 47

Arachidonic Acid Metabolites

Answer 47

Prostaglandins, Leukotrienes, and Lipoxins

Question 48

Arachidonic Acid (AA)

Answer 48

Arachidonic acid 20-carbon polyunsaturated fatty acid Derived from dietary sources Conversion from the essential fatty acid linoleic acid Does not occur free in the cell Normally esterified in membrane phospholipids Mechanical, chemical, and physical stimuli Release AA from membrane phospholipids through the action of cellular phospholipases such as phospholipase A2

Question 49

Eicosanoids

Answer 49

AA-derived mediators (eicosanoids) Synthesized by two major classes of enzymes 1. Cyclooxygenases- generate prostaglandins 2. Lipoxygenases- produce leukotrienes and lipoxins Bind to G protein-coupled receptors on many cell types Can mediate virtually every step of inflammation

Question 50

Prostaglandins

Answer 50

Produced by mast cells, macrophages, endothelial cells, and many others Involved in the vascular and systemic reactions of inflammation Produced by the actions of two cyclooxgenases Constitutively expressed COX-1 Inducible enzyme COX-2 COX 1 and 2- targets of anti-inflammatory meds If block COX 1- prevents some cancers because some are inflammatory to start with Divided into series based on structural features Coded by a letter: PGD, PGE, PGF, PGG, and PGH Subscript numeral: 1, 2 indicating the number of double bonds in the compound

Question 51

Most Important Prostaglandins in Inflammation

Answer 51

Most important ones in inflammation | PGE2, PGD2, PGF2α, PGI2 (prostacyclin), and TxA2 (thromboxane)

Question 52

Prostacyclin

Answer 52

Prostacyclin = PGI2 Vasodilator Potent inhibitor of platelet aggregation Markedly potentiates the permeability-increasing and chemotactic effects of other mediators Wants inflammation to continue so leukocytes can get through, increase chemotactic effect and inhibit platelet aggregation

Question 53

PGD2

Answer 53

Major prostaglandin made by mast cells along with PGE2 (which is more widely distributed) Causes vasodilation Increases the permeability of post-capillary venules Potentiating edema formation Chemoattractant for neutrophils

Question 54

PGF 2alpha

Answer 54

Stimulates the contraction of uterine and bronchial smooth muscle and small arterioles Vasoconstrictor

Question 55

PGE2

Answer 55

Hyperalgesic- makes skin hypersensitive to painful stimuli Involved in cytokine-induced fever during infections FEEEVER= PGEEEE 2… trick to remember; cannot even brush your hair because so painful

Question 56

Leukotrienes

Answer 56

``` Produced by lipoxygenase enzymes Secreted mainly by leukocytes Chemoattractants for leukocytes Vascular effects Will self perpetuate because recruits more leukocytes to the area of injury ```

Question 57

Leukotrienes: Three Different Lipoxygenases

Answer 57

1. 5-lipoxygenase: predominant one in neutrophils that converts AA to 5-hydroxyeicosatetraenoic acid Chemotactic for neutrophils Precursor of the leukotrienes 2. LTB4: potent chemotactic agent and activator of neutrophils and causes aggregation and adhesion of the cells to venular endothelium Generation of ROS and releases lysosomal enzymes 3. Cysteinyl-containing leukotrienes C4, D4, and E4 (LTC4, LTD4, LTE4) Intense vasoconstriction, bronchospasm and increased vascular permeability

Question 58

Lipoxins

Answer 58

Generated from AA by the lipoxygenase pathway Inhibitors of inflammation Two cell populations are required for their biosynthesis Leukocytes (esp. neutrophils): produce intermediates in lipoxin synthesis, and converted to lipoxins by platelets interacting with the leukocytes

Question 59

Principal Actions of Lipoxins

Answer 59

Principal actions of lipoxins 1. Inhibit leukocyte recruitment and the cellular components of inflammation 2. Inhibit neutrophil chemotaxis and adhesion to endothelium Inverse relationship between the production of lipoxin and leukotrienes Suggests that lipoxins may be endogenous negative regulators of leukotrienes May thus play a role in the resolution of inflammation

Question 60

Inhibition of Eicosanoid Synthesis

Answer 60

Anti-inflammatory drugs work by inhibiting the synthesis of eicosanoids: 1. Cyclooxygenase Inhibitors 2. Lipoxygenase inhibitors 3. Broad-Spectrum Inhibitors Modify the intake and content of dietary lipids Increasing the consumption of fish oil Polyunsaturated fatty acids in fish oil serve as poor substrates for conversion to active metabolites and excellent substrates for the production of anti-inflammatory lipid products Resolvins and protectins

Question 61

Cyclooxygenase Inhibitors

Answer 61

``` Cyclooxygenase inhibitors: Aspirin Non-steroidal anti-inflammatory drugs like Indomethacin Inhibit both COX-1 and COX-2 Inhibit prostaglandin synthesis ``` Inhibition of Eicosanoid Synthesis

Question 62

Lipoxygenase Inhibitors

Answer 62

Lipoxygenase inhibitors 5-lipoxygenase is not affected by NSAIDs (cyclooxygenase inhibitor) Inhibit leukotriene production (Zileuton) Block leukotriene receptors (Montelukast)- useful in the treatment of asthma Inhibition of Eicosanoid Synthesis

Question 63

Broad-Spectrum Inhibitors

Answer 63

``` Broad-spectrum inhibitors Corticosteroids Powerful anti-inflammatory agents Reduces the transcription of genes encoding COX-2, phospholipase A2, pro-inflammatory cytokines (such as IL-1 and TNF) Inhibit wound healing ``` Inhibition of Eicosanoid Synthesis

Question 64

Platelet Activating Factor (PAF)

Answer 64

Phospholipid-derived mediator Causes platelet aggregation Known to have multiple inflammatory effects Variety of cell types can elaborate PAF: platelets, basophils, mast cells, neutrophils, macrophages, and endothelial cells Causes vasoconstriction and bronchoconstriction At extremely low concentrations: induces vasodilation and increased venular permeability Causes increased leukocyte adhesion, chemotaxis, degranulation, and the oxidative burst Boosts the synthesis of other mediators (eicosanoids)

Question 65

Reactive Oxygen Species (ROS)

Answer 65

Oxygen-derived free radicals may be released extracellularly from leukocytes after exposure to microbes, chemokines, and immune complexes Production is dependent on the activation of the NADPH oxidase system Superoxide anion, hydrogen peroxide, and hydroxyl radical are major species produced within cells, and if combine with nitric oxide = reactive nitrogen species Causes tissue damage and oxygen derived free radicals Have many leukocytes to fix inflammatory process and release oxygen derived free radicals… good process occurring but also does damage to surrounding tissue

Question 66

Responses to Inflammation that Elicit ROS Release

Answer 66

Implicated in responses in inflammation: 1. Endothelial cell damage, with resultant increased vascular permeability 2. Injury to other cell types (parenchymal cells, red blood cells) 3. Inactivation of antiproteases (α1-antitrypsin)

Question 67

NO

Answer 67

Discovered as a factor released from endothelial cells Caused vasodilation called endothelium-derived relaxing factor Soluble gas: produced by endothelial cells, macrophages and some neurons Acts in a paracrine manner on target cells causing relaxation of vascular smooth muscle cells In vivo half-life of NO is only seconds: gas acts only on cells in close proximity to where it is produced Give NO to patient during MI to increase blood flow

Question 68

Actions of NO

Answer 68

Has dual actions in inflammation Relaxes vascular smooth muscle Promotes vasodilation Inhibitor of the cellular component of inflammatory responses Reduces platelet aggregation and adhesion Inhibits several features of mast cell-induced inflammation Inhibits leukocyte recruitment NO and its derivatives are microbicidal aka a mediator of host defense against infection Overall, NO released causing reduced platelets and leukocyte adhesion and vascular smooth muscle relaxation and vasodilation

Question 69

Cytokines

Answer 69

Proteins produced by many cell types Principally activated lymphocytes and macrophages Also endothelial, epithelial, and connective tissue cells Involved in cellular immune responses

Question 70

TNF and IL-1

Answer 70

Major cytokines that mediate inflammation Produced mainly by activated macrophages Secretion of TNF and IL-1 stimulated by endotoxin and other microbial products, immune complexes, physical injury, and a variety of inflammatory stimuli

Question 71

Actions of TNF and IL-1

Answer 71

Endothelium: induce a spectrum of changes referred to as endothelial activation Induce the expression of endothelial adhesion molecules Synthesis of chemical mediators, including other cytokines, chemokines, growth factors, eicosanoids, and NO Production of enzymes associated with matrix remodeling Increases in the surface thrombogenicity of the endothelium Augments responses of neutrophils to other stimuli like bacterial endotoxin

Question 72

TNF and IL-1: Endothelial Activation

Answer 72

Induce the systemic acute-phase responses associated with infection or injury Regulates energy balance by promoting lipid and protein mobilization and by suppressing appetite Sustained production contributes to cachexia Pathologic state characterized by weight loss and anorexia Accompanies some chronic infections and neoplastic diseases

Question 73

Chemokines

Answer 73

Act primarily as chemoattractants for specific types of leukocytes Two main functions: 1. Stimulate leukocyte recruitment in inflammation 2. Control the normal migration of cells through various tissues

Question 74

Chemokines: 4 Major Groups

Answer 74

``` Classified into four major groups According to the arrangement of the conserved cysteine (C) residues in the mature proteins 1. C-X-C chemokines (α chemokines) 2. C-C chemokines (β chemokines) 3. C chemokines (γ chemokines) 4. CX3C chemokines ```

Question 75

C-X-C chemokines (α chemokines)

Answer 75

One amino acid residue separating the first two conserved cysteine residues **Act primarily on neutrophils** IL-8 is typical of this group Secreted by activated macrophages, endothelial cells, and other cell types Causes activation and chemotaxis of neutrophils, with limited activity on monocytes and eosinophils Most important inducers are microbial products and other cytokines, mainly IL-1 and TNF

Question 76

C-C chemokines (β chemokines)

Answer 76

First two conserved cysteine residues adjacent | Generally attract monocytes, eosinophils, basophils, and lymphocytes but NOT neutrophils

Question 77

C chemokines (γ chemokines)

Answer 77

Lack two (the first and third) of the four conserved cysteines Lymphotactin **Relatively specific for lymphocytes**

Question 78

CX3C chemokines

Answer 78

Contain three amino acids between the two cysteines Fractalkine: two forms Cell surface-bound protein Soluble form

Question 79

Lysosomal Constituents of Leukocytes

Answer 79

Neutrophils and monocytes contain lysosomal granules Neutrophils have two main types of granules 1. Smaller specific (or secondary) granules 2. Larger azurophil (or primary) granules

Question 80

Neuropeptides

Answer 80

Secreted by sensory nerves and various leukocytes Play a role in the initiation and propagation of inflammation Substance P and neurokinin A: family of tachykinin neuropeptides produced in the central and peripheral nervous systems ``` Biologic functions: Transmission of pain signals Regulation of blood pressure Stimulation of secretion by endocrine cells Increasing vascular permeability ```