Inflammation

Question 1

Inflammation

Answer 1

1. response to cell & tissue injury by vascularized tissue
2. elicted to protect host
3. By eliminating necrotic debris
4. By eliminating initial cause

Question 2

Features of Inflammation

Answer 2

• protective response
• Vascular= vasodilation & perm
• Cell= inflammatory cells (neutrophils, macrophages & lymphocytes)
• Via plasma proteins & cytokines
• Outcome elimination or persistence= chronic inflammation

Question 3

Steps in Inflamm Response

Answer 3

1. recognize injurious agent
2. recruit leukocytes
3. remove agent
4. regulation of response
5. resolution & repair

Question 4

Acute inflammation

Answer 4

1. heat
2. redness
3. swelling
4. pain
5. loss of function

Question 5

Acute Inflammation

Answer 5

Question 6

Vascular events in acute inflamm

Answer 6

alter vascular caliber & increase BF

Extravasation of plasma fluid & protein (leakage)

Question 7

Cell events in acute inflamm

Answer 7

Leukocyte immigration & phagocytosis

*neutrophils first then macrophages*

Question 8

Etiology of Inflammation

Answer 8

1. microorg- bac, viral, fungal, parasitic
2. tissue necrosis- uric acid, ATP, DNA, DNA binder HMGB-1
3. hypoxia- mediatoer HIF1-a, effectors eg VEGF
4. physical- trauma, thermal, chem
5. foreign- splinter, dirt, suture
6. immune- hypersensitivity, inappropriate immune rxn

Question 9

Normal/Transudate/Exudate

Answer 9

Question 10

Mechanism of Increased vascular perm

Answer 10

1. Endothelial contraction- via his, bradykinin, leukotrienes, NO, SP. 15-30 min or 2-12 hr (sunburn)
2. direct endothe injury- burns, UV, neutrophil damage

Question 11

Increase Transcytosis

Answer 11

in venules

induced by VEGF

Question 12

Exudate

Answer 12

Vasodilation

Increase blood viscosity

Decrease Colloid osmotic P

increased vascular perm

• transport
• nutrition
• make appropriate ground for neutrophils

Question 13

Exudate

Answer 13

1. fluid of acute inflammation
2. high protein
3. contain cell debris
4. sp gravity >1.02

abscess

Question 14

Transudate

Answer 14

1. ultrafiltrate of blood plasma; increase hydrostatic P
2. low protein
3. no cells
4. sp gravity <1.012

ascites

Question 15

Lymphatics

Answer 15

• lymph flow increased to drain edema from extravascular space
• lymph drainage can also transport microbes in extensive inflammation

Lymphangitis- inflammation of lymph channels

lymphadenitis- inflammation of draining LN

Question 16

Neutrophils

Answer 16

1. from BW
2. highly motile
3. in tissue 24-48 hours
4. high phagocytic capacity
5. effective killers of bac

• use NADPH/Phagocyte oxidase= makes O2-*
• Myeloperoxidase= makes HOCl*
• NO oxidase= makes OONO-*
• Fenton= makes OH*

Question 17

Leukocytes in inflammation Steps

Answer 17

1. margination
2. rolling
3. activation
4. adhesion
5. pavementing
6. emigration
7. diapedesis
8. chemotaxis
9. phagocytosis

Question 18

Leukocytes

Answer 18

Question 19

P selectin on Endothelial Mem

Answer 19

Allows for rolling when bound; neutrophols, lymph & monocytes:

• to Sialyl Lewis X modified proteins on leukocytes

Question 20

E selectin on endothelial mem

Answer 20

Allows for rolling & adhesion; neutrophils, T lymphocytes & monocytes, when:

• bound to sialyl lewis X modified prot on leukocyte

Question 21

GlyCam-1, CD34 on endothelial

Answer 21

Allows for rolling, neutrophils & monocytes :

• when bound to L-selectin on leukocyte

Question 22

ICAM-1 on endothe

Answer 22

Adhesion, arrest, transmigration; neutrophils, mono & lymphocytes

• when bound to CD11/CD18 integrins (LFA-1, Mac-1) on leukocyte

TNF & IL-1 activation of neutrophils

Question 23

VCAM-1 on endothelial

Answer 23

Adhesion of eosinophils, moncytes & lymphocytes

• when bound to VLA-4 integrin on leukocyte

Question 24

CD31 on endoth

Answer 24

Transmigration of all leukocytes aided by PECAM-1 on endothelial cell as well:

• when bound to CD31 on leukocyte

Question 25

Chemotaxis

Answer 25

Escaped leukocytes reach injury site Chemoattractans * exogenous- bac agents N-formylmethionine terminal aa * endogenous- chemokines, C5a, leukotriene B4

Question 26

Inflammation

Answer 26

Question 27

Recognition & Attachment

Answer 27

* C3b & IgG= opsonins * Aid in phagocytosis

Question 28

Phagocytosis

Answer 28

Bidn to R on leukocyte Engulf Fusion of lysosome with phagocytic vacuole Destroy ingested particles- enz, ROS & nitrogen species Use O2-\*, HOCl\* and OH\* and OONO\* Granule contents may be exocytosed Imp enz= MPO, iNOS and Phagocyte oxidase!

Question 29

Phagocytosis

Answer 29

Question 30

O2 indep mechanisms of killing

Answer 30

1. lysozymes- from neutrophil granules destroy microbe mem 2. major basic prot- from eosinophil granule kill prasite 3. bactericidal perm increasing prot BP- cationic prot that strongly increases cell wall permeability 4. defensins- in primary granules of neutrophils, can kill fungi & viruses & bac

Question 31

Activated Macrophages

Answer 31

1. Microbial prod- cytokines, IFNg, TLR ligands activate M1 (clasically activated macrophage) * show inflamation! * IL-1,12-23, chemolines * ROS, NO, lysosomal enz 1. helminths, IL-13 and IL-4 activate alternatively activated macrophage M2 * anti inflammtory & woulnd repair * IL-10, TGFB

Question 32

Leukocyte Induced injury

Answer 32

* tissues around leukocytes get injured * reperfusion injury in MI * autoimune & allergic responses * activated luekocytes that don't distinguish self/non self 1. lysosomal enz 2. ROS 3. cytokines

Question 33

Acute Leukocyte Induced Injury Inflamm Disorders

Answer 33

1. acute resp distress yndrome- neutrophils 2. acute transplant rejection- lymphocytes, Y & complement 3. Asthma- eosinophils & IgE 4. Glomerulonephritis- Y & complement, neutrophils & monocytes 5. Septic shock- cytokines 6. vasculitis- Y & complement, neutrophils

Question 34

Chronic Leukocyte Induced Injury Inflamm Disorders

Answer 34

1. Arthritis- lymph, macrophages & Y 2. asthma- eosinophils, IgE & other leukocytes 3. atherosclerosis- macrophages 4. chronic transplatn rejection- lymphocytes & cytokines 5. pulm fibrosis- macrophages & fibroblasts

Question 35

Genetic Defects In Leukocyte function

Answer 35

1. leukocyte adhesion def 1- defective leukocyte adhesion due to CD11/CD18 B chain mutation 2. def 2- def leukocyte adhesion due to mut in fucosyl transferase needed for ligand syn for selectins 3. chronic granulomatous disease- decrease ox burst 4. x-linked- phagocyte oxidase in mem 5. autsomal recessive- phagocyte oxidase in cytoplasm 6. MPO def- decreased microbe killing, no H2O2 sys 7. Chediak-Higashi syndrome- decreased due to mut affecting prot of lysosomal mem traffic.

Question 36

Chediak Higashi Syndrome

Answer 36

LYST albinism n. defects neutropenis defective degranulation Leukocyte giant observed

Question 37

Acquired Defects

Answer 37

1. BM suppression: tumors, radiation & chemotherapy- defect in producing leukocytes 2. Thermal injury, diabetes, malignancy, sepsis, immunodef- defect in chemotaxis 3. Hemodialysis, DM- defect in adhesion 4. Leukemia, anemia, sepsis, diabetse, neonates, malnutrition- defect in phagocytosis & microbicidal activity

Question 38

Inflammation

Answer 38