L2

Question 1

Inflammatory Phases ?2

Answer 1

Two overlapping phases of inflammation occur
simultaneously explain the cardinal signs:
A. Vascular changes: (dilatation, permeability
and slow blood flow)
B. Cellular changes: influx of cells and their exit
from vessels into interstitial tissue

Question 2

List the cellular events in acute inflammation? 5

Answer 2

1. Leukocyte margination & rolling
2. Leukocyte Adhesion
3. Transmigration
4. Chemotaxis
5. Phagocytosis & degradation

Question 3

1. Margination ?

Answer 3

The reasons for loss of the normal axial stream.
The normal axial stream: The blood cells in the center
and plasma in the margin.

Question 4

The reason for loss of the normal axial stream: ?3

Answer 4

1. Stasis (slowing down) of circulation due to vasodilation of the blood vessels.
   2.loss of the negative charges on the surface of the leukocyte.
2. RBCs stick to each other (small cluster) displacing leukocyte (WBCs) to the periphery near the endothelial cells margination of leukocyte.

Question 5

Rouleaux?

Answer 5

RBCs stick to each other

Question 6

cellular events in acute infulmmation, cont.1-Rolling

Answer 6

WBCs roll over the endothelium, during this process activation of both WBCs and endothelial cells which adhere loosely& transiently by cell surface adhesion molecules

Question 7

adhesion molecules ?

Answer 7

e.g. selectin (CD62), which includes:
* E-selectin: located in Endothelial cells.
* P-selectin: located in Platelet & endothelial cells.
*L-selectin: located in Leukocytes.

Question 8

How local process of rolling happend?

Answer 8

When endothelium (injured or activated) by chemical mediators
like histamine& thormbin, selectins will be up-regulated on that site only, leading to local process of rolling

Question 9

Selectins [CD62]?

Answer 9

• The weak and transient adhesions involved in rolling are mediated by the selectin family of adhesion molecules.
• Selectins are receptors expressed on leukocytes and endothelium.

Question 10

Integrins [ICAM1]?

Answer 10

-Transmembrane glycoproteins
-Receptors expressed on leukocyte (Integrins), ligand on endothelial
cells
Firm & stable attachment of leukocytes to endothelial cells at sites of inflammation.(adhesion)

Question 11

cellular events in acute infulmmation, 3.Transmigration / Emigration (diapedesis).

Answer 11

➢ leukocytes start to migrate outside the blood vessels by squeezing between endothelial cells at intercellular junction.

➢ Activated WBCs assume amoeboid shape and amoeboid movement , then crawl over the endothelial lining till reaching the intercellular junction, pierce the basement membrane by secreting collagenase enzyme that degrades basement membrane and tissue.

Question 12

Platelet-Endothelial Cells Adhesion Molecule-1
What its do?

Answer 12

[PECAM1 – CD31] control the binding events that are needed for transmigration.

Question 13

Timing of Inflammatory Cells?

Answer 13

➢ Neutrophils predominate in the inflammatory infiltrate during the first 24 hours and are replaced by monocytes after 24 hours.

➢ Monocytes in tissue are called macrophages.

Question 14

Type of migrating inflammatory cells is depends on ?

Answer 14

Type and age of the inflammation :
Neutrophils: in acute inflammation esp. in first 24h
Monocytes :in chronic inflammation and after 24h

Question 15

Why neutrophil is the prominent type of WBCs in ACUTE inflammation?

Answer 15

-The commonest type of WBCs in the blood.
-Response quickly.
-Adherent firmly.
-Live for short period & die by apoptosis within 24-48 hours

Question 16

neutrophil is the prominent type of WBCs in ACUTE inflammation,but There are some exceptions as: ?

Answer 16

-Viral infection: lymphocytes will be the most prominent one.
-Allergy & hypersensitivity: eosinophils will be the most prominent.
-pseudomonas infection: neutrophils will last for several days.

Question 17

cellular events in acute infulmmation, 4. Chemotaxis?

Answer 17

• A process by which leukocytes migrate toward sites of infection or injury (a directed movement) by chemotaxins that released at sites of tissue injury such as cytokines, complement components.
• Occurs after extravasation from the blood

Question 18

The chemical mediators responsible for chemotaxis?

Answer 18

1.Bacterial products, Infectious products (Exogenous).
2.Cytokines .
3.Components of the complement system, particularly C3a & C5a.
4.Cell membrane products particularly, leukotriene B4 (LTB4).
(2,3,4 Endogenous)

Question 19

Leukocytes activation:

Answer 19

Once the leukocytes have been recruited, they must be activated to do their function,the activation occurs as a result of stimulation of WBCs by:
Microbes
Necrotic cells
Chemical mediators

Question 20

Activation of leukocytes will reslt in :

Answer 20

-phagocytosis of the causeative antigen
-intracellular destruction of the phagocytoed particles:by reactive oxygen&nitrogen species and lysosomal enzymes.
-extracellular destruction of particles: by the same mechanism of intracellular one.
-Production of more mediators: as arachidonic acid products and cytokinss to amplify&maintain the inflammatory process till the causative agent disappear.

Question 21

cellular events in acute infulmmation, 5. Phagosytosis:?

Answer 21

It is cellular process of phagocytes of engulfing organisms such as bacteria by the cell membrane to form an internal phagosome.

Using specific surface receptors that:
•Directly recognize the dead tissue.
•Indirectly recognize the microbes through Opsonin.

Question 22

Steps of phagocytosis:?

Answer 22

1 Recognition & attachment of the bacteria to the ingesting leukocyte.
2 Engulfment with subsequent formation of a phagocytic vacuole.
3 Killing & degradation of ingested material.

Question 23

Opsonin?

Answer 23

-Host proteins that coat the causative agent to make it recognizable by WBCs to be targeted.
-The process of coating the microbes with opsonins is called (opsonization).
Opsonization: It is coating of the bacterial surface by opsonin which binds to specific receptors on leukocyte to facilitate its phagocytosis.
-opsonins are either already made&present in human blood or produced during the process of inflammatiom.

Question 24

The important opsonins are:

Answer 24

➢ IgG → recognized by Fc receptor on WBCs surface.
➢ C3b → recognized by complement 1 & 3 receptor.
➢ Collectin → recognized by C1q receptor.

Binding for opsonized particles triggers engulfment and
induces cellular activation that enhances degradation of ingested microbes.

Question 25

In engulfment:

Answer 25

1 Pseudopods are extended around the object.
2 Form a phagocytic vacuole (phagosomes).
3 The membrane of phagosomes fuses with the membrane of lysosomes resulting into phagolysosome.

Question 26

Killing and Degradation of Microbes

Answer 26

This process needs microbicidal substance which
already made within the lysosomes. The most important microbicidal substances are: -Oxygen-dependent mechanism in microbial killing (Reactive oxygen species (ROS)). Fr
-Oxygen-Independent mechanism of microbial killing ( Lysosomal enzymes )

Question 27

Oxygen-dependent mechanism in microbial
Reactive oxygen & nitrogen species

Answer 27

Engulfment stimulate production of ROS (oxidative/Respiratory burst)
الجزيئات الناتجه من البلعمه
• Superoxide O2, and H2O2
• H2O2 -MPO (halide system, is the most efficient bactericidal system in neutrophils).
• NO

Question 28

Degradation Oxygen-independent mechanism of microbial killing:
Now, dead microbes degraded by enzymes called ??

Answer 28

“lysosomal acid hydrolase ”.
الانزيمات الرئيسيه هي
1. Elastase: degradation of bacteria.
2. Major basic protein (in eosinophil): cytotoxicity for parasite.
3. Defensins: holes in the wall of the microbe (in general).

Question 29

Secretion of microbicidal substances in extracellular space:?

Answer 29

Microbicidal substance make case injury to the host cells therefore they are usually produced in and limited to the phagocytic vacuole to control them.

Unfortunately, few amount of these substance are found in the extracellular space

Question 30

Secretion of Microbicidal Substances in Extracellular space:

Answer 30

The possible Mechanisms for this finding are:
● Phagocytic vacuoles remain transiently open to the outside.
● The causative agent can NOT be engulfed: as immobile immunocomplex diseases.
● The membrane of the phagosome is damaged due to ingestion of potentially injurious substances: as silica.

Question 31

Neutrophil extracellular traps (NETs)

Answer 31

-Are extracellular fibrillar network produced by neutrophils.
-in this process the neutrophils die and their nuclear chromatin embedded with granular proteins (anti-microbial).
-these traps will provide high concentration of antimicrobial proteins and prevent the spread of the infection.
-it is belived that these traps are the source of the ANA in some systemic diseases as SLE.

Question 32

Fate of Acute inflammation?

Answer 32

1-Regression: followed by healing (Resolution).
2-Progression & spread to the surrounding tissue
e.g. rupture of an abscess into skin surface or nearby tissues. Blood Spread ….pyemia, toxemia, septicemia, bacteremia. Lymphatic spread …lymphangitis & lymphadenitis.
3-Chronicity: occur when the causative organism is partially overcomed.
4-Complications of healing:
Fibrosis-scar
Chronic ulcer
Sinus
Fistula
Keloid
Fibrous adhesion