[P] Week 2: Inflammation and Repair - Part 1 Flashcards by Geno Alinsub

It is fundamentally a protective response of the body to combat offending agents that we encounter in day-to-day life

Inflammation

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Can inflammation be harmful?

YES. The inflammatory process could also damage the normal tissues; may be adjacent
or may also lead to other disease entities like
autoimmune diseases

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what is the mechanism of inflammation (just give the overview)

a complex reaction between blood vessels and the contents, particularly the WBCs or leukocytes

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Inflammation is divided into 2 categories, enumerate

Acute
Chronic

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what is the purpose of inflammation?

rid the host of both the initial cause of the injury and its consequences

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inflammation has been described even in the
Egyptian times by the ____

Papyrus

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who mentioned the 4 cardinal signs of inflammation? and what are those

Celsus

Rubor (redness)
Calor (warmth)
Tumor (swelling)
Dolor (pain)

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who added the fifth cardinal sign and give the sign

Virchow

5th - Function laesa (loss of function)

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Match

inflammation is not a disease but a response to an offending stimulus
described phagocytosis
described the concept of chemical substance with chemo attractance
1st noted an inflamed blood vessel

A. John Hunter
B. julius Cohnheim
C. Elie Metchnikoff
D. Sir Tomas Lewis

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Acute or Chronic

Onset: Rapid
Short duration
There is more prominence of local & systemic signs

Acute

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Acute or Chronic Inflammation

The inflammatory cells are more of mononuclear, macrophages, and
lymphocytes
Associated with response of the tissues
Associated with tissue necrosis

Chronic

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Acute or Chronic Inflammation

Usually associated with
more manifestation (Exudation of fluid and plasma protein)
Emigration of leukocyte (neutrophils)

Acute Inflammation

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Enumerate the Steps of Inflammatory Response

Recognition
Recruitment
Removal
Regulation
Resolution / Repair

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INFLAMMATORY RESPONSE - Recognition

The body must be able to recognize the?

offending agents

im offended. ganon

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INFLAMMATORY RESPONSE - Recognition

Engagement of the receptors leads to the production of?

mediators of inflammation

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INFLAMMATORY RESPONSE - Recognition

enumerate the recognition mechanism of microbes and damaged cells

Cellular Receptors
Sensors of cell damage
Other cellular receptors involved in inflammation
Circulating proteins

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INFLAMMATORY RESPONSE - Recognition

what are the cellular receptors

TLRs or TOLL-like receptors

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INFLAMMATORY RESPONSE - Recognition

how does the cellular receptors express their receptors?

Cells express receptors in the:
- plasma membrane (for extracellular microbes)
- endosomes (for ingested microbes)
- cytosol (for intracellular microbes)

this enable the cells to sense the presence of foreign invaders in any cellular compartment.

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INFLAMMATORY RESPONSE - Recognition

where is the “sensors of cell damage” can be located or present

cytosolic receptors which can detect the level of uric acid, ATP, decreased intracellular K+

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INFLAMMATORY RESPONSE - Recognition

Cytosolic receptors can activate a multiprotein cytosolic complex
called?

INFAMMASOME

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INFLAMMATORY RESPONSE - Recognition

Infammasome indusces the production of?

cytokine interleukin-1 (IL-1)

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INFLAMMATORY RESPONSE - Recognition

All cells have cytosolic receptors, such as?

NOD-like receptors (NLRs), that recognize diverse molecules that are liberated or altered as a consequence of cell damage

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INFLAMMATORY RESPONSE - Recognition

Many leukocytes (WBCs) express receptors for the ____ of antibodies and for complement proteins

Fc tails

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INFLAMMATORY RESPONSE - Recognition

Some proteins and Fc portion of antibodies could be ____ or
____ the offending agent

taggy or
opsonizing

When opsonized, the WBC can recognize these molecules or offending agents (recall hema)

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# INFLAMMATORY RESPONSE - Recognition The ____ reacts against microbes and produces mediators of inflammation

Complement system

# INFLAMMATORY RESPONSE - Recognition this circulating proten recognizes microbial sugars and promotes ingestion of the microbes and the activation of the complement system?

Mannose-Binding Lectin ## Footnote Other proteins called **COLLECTINS** also bind to and combat microbes

# INFLAMMATORY RESPONSE Since blood perfuses every tissue, leukocytes and proteins such as complement can be delivered to any site of microbial invasion or tissue injury.

Recruitment

# INFLAMMATORY RESPONSE The inflammatory cells needed to combat the offending agents should go to the area of the offending agents

Recruitment

# INFLAMMATORY RESPONSE - Removal Removal of the stimulus for inflammation is accomplished mainly by?

**phagocytic cells** which ingest and destroy microbes and dead cells

# INFLAMMATORY RESPONSE - Removal this is the process wherein the inflammatory cells are at the location of the offending agents and get rid of them

Phagocytosis/killing.

# INFLAMMATORY RESPONSE - Regulation Regulation of the response is important for?

terminating the reaction when it has accomplished its purpose

# INFLAMMATORY RESPONSE - Regulation TOF Inflammation can be harmful

**True** we want to regulate the presence of these inflammatory cells to minimize damage to normal tissues

# INFLAMMATORY RESPONSE In this process the injured tissue is replaced through regeneration of surviving cells and filling of residual defects with connective tissue (scarring)

Resolution / Repair

# INFLAMMATORY RESPONSE - Resolution / Repair We hope for a complete healing of the injury in that area but the healing may be brought about by repair together with healing of tissues plus _____

Fibrosis

Enumerate the Stimuli of Acute Inflammation

- Infections and Microbial toxins - Tissue necrosis - Foreign Bodies - Immune Reaction

What are the three major components of acute inflammation?

1. Alterations in vascular caliber 2. Increased permeability of the microvasculature 3. Emigration of leukocytes from the microcirculation

# Acute Inflammation Alterations in vascular caliber leading to an?

increase in blood flow

# Acute Inflammation Increased permeability of the microvasculature enabling plasma proteion and leukocytes to?

leave the circulation

# Acute Inflammation their accumulation in the focus of injury, and their activation to eliminate the offending agent

Emigration of leukocytes from the microcirculation

# Acute Inflammation The vascular reactions of acute inflammation consist of

1. Changes in vascular flow and caliber 2. Increased vascular permeability 3. Responses of lymphatic vessels and lymph nodes

# Reaction of blood vessels in acute inflammation denotes an excess of fluid in the interstitial tissue or serous cavities; it can be either an exudate or a transudate

EDEMA

# Reaction of blood vessels in acute inflammation a purulent exudate, is an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells, and, in many cases, microbes

PUS

# Exudate or Transudate The escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities

Exudate

# Exudate or Transudate essentially an ultrafiltrate of blood plasma that is produced as a result of osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability

Transudate

# Exudate or Transudate extravascular fluid that has: - high protein concentration - high specific gravity - increase in vascular permeability due to infection

Exudate

# Exudate or Transudate a fluid with: - low protein content (most of which is albumin) - little or no cellular material - low specific gravity

Transudate

# Exudate or Transudate 1. Associated with changes in pressure (hydrostatic and plasma colloid oncotic pressure) 2. Associated more with infection

1. Transudate 2. Exudate

# Changes in vascular flow and caliber **Vasodilation** is induced by the action of several mediators, notably?

HISTAMINE

# Changes in vascular flow and caliber what is the presentation of vasodilation?

increased blood flow, which is the cause of he **at and redness (erythema)** at the site of inflammation

# Changes in vascular flow and caliber Vasodilation is quickly followed by

increased permeability of the microvasculature

# Changes in vascular flow and caliber The loss of fluid and increased vessel diameter lead to ?

**STASIS:** - slower blood flow - concentration of red cells in small vessels - increased viscosity of the blood

# Changes in vascular flow and caliber is seen as vascular congestion andlocalized redness of the involved tissue

Stasis

# Changes in vascular flow and caliber As stasis develops, blood leukocytes, principally neutrophils accumulate along the vascular endothelium or at the sides of the blood vessels

Margination

a hallmark of acute inflammation

Increased vascular permeability

increased vascular permeability are composed of the foillowing, enumerate

1. Contraction of Endothelial Cells 2. Endothelial injury 3. Increased transport of fluids and CHON: transcytosis

# Increased vascular permeability resulting in opening of interendothelial gaps is the most common mechanism of vascular leakage.

Contraction of endothelial cells

# Increased vascular permeability Contraction of endothelial cells is elicited by?

histamine, bradykinin, leukotrienes, and other chemical mediator

# Increased vascular permeability Contraction of endothelial cells are called the ____ because it occurs rapidly after exposure

immediate transient response | usually short-lives (15 to 30 mins)

# Increased vascular permeability In some forms of **mild injury,** vascular leakage begins after a delay of

2 to 12 hours and lasts for several hours or even days ## Footnote may be caused by contraction of endothelial cells or mild endothelial damage

# Increased vascular permeability Endothelial injury resulting in?

endothelial cell necrosis and detachment

# Increased vascular permeability Increased transport of fluids and CHON

Trancytosis

# Increased vascular permeability Trancytosis are induced by?

Induced by VEGF (vascular endothelial growth factor); venules

# Responses of lymphatic vessels Lymphatics drain the small amount of ____ ____ that seeps out of capillaries in the healthy state

extravascular fluid

# Responses of lymphatic vessels In inflammation, lymph flow is?

increased and helps drain edema fluid

# Responses of lymphatic vessels with inflmmation, the lymphatics may become? (may sakit)

- secondarily inflamed (**lymphangitis**) - draining lymph nodes (**lymphadenitis**).

# Leukocyte Recruitment Changes in the blood flow and vascular permeability results in?

**leukocyte extravasation–** the leakage of WBC from the veins into the surrounding tissue

# Leukocyte Recruitment This ensures that the inflammatory cells will go out and “meet” the offending agent.

Leukocyte extravasation

# Leukocyte Recruitment what are the wbc capable of phagocytosis

neutrophils and the macrophages the inflammatory cells that are more important are those with the capability of combating the offending agents

Enumerate the steps of "journey of Leukocytes"

1. Margination 2. Rolling 3. Adhesion 4. Migration 5. offending agent producing the chemotactic stimulu

# journey of Leukocytes During stasis, with vasodilation and congestion, there is ____ of leukocytes at the periphery of the vessel walls

MARGINATION

# journey of Leukocytes vessel wall, there will be an interaction between the vessel and the white cells. This interaction is termed as ____, which consists of the alternating attachment and detachment of the leukocytes from the vessel

ROLLING

# journey of Leukocytes This rolling action will continue until there is a firm ____ to the endothelium

ADHESION

# journey of Leukocytes The leukocytes will then ____ across the endothelium and vessel wall

Migrate

# journey of Leukocytes From the vessel wall, the leukocytes will continue to migrate to the tissues, towards the offending agent producing the ____ ____, or to the site of injury

chemotactic stimulus

# Leukocyte Adhesion to The Endothelium Stasis occurs, which slows the flow of blood resulting to more?

more **leukocytes** at the periphery or the margination site

# Leukocyte Adhesion to The Endothelium Leukocytes bind or adhere to the wall ____, then detaches

Transiently | mabilis lang, short tiome

# Leukocyte Adhesion to The Endothelium Rolling is mediated by the following ligands that may be present, such as?

- Leukocyte (L-) selectins - Endothelial (E-) selectins - Platelet (P-) selectins

# Leukocyte Adhesion to The Endothelium this molecule functions for firm adhesion (enumerate the adhesion molecules)

**Integrins:** - Vascular Cell Adhesion Molecule (VCAM) - Intercellular Adhesion Molecule (ICAM)

# ENDOTHELIAL-LEUKOCYTE ADHESION MOLECULES Match the following Endothelial: 1. P selectin 2. E selecting 3. GlyCAM-1, CD34 4. ICAM-1 5. VCAM-1 Leukocyte A. L-selectin B. Integrin (LFA-1) C. Sialyl-Lewis X D. Integrin (VLA-4)

1. C 2. C 3. A 4. B 5. D

# ENDOTHELIAL-LEUKOCYTE ADHESION MOLECULES state the role 1. P-selectin and Sialyl-Lewis X 2. E-selectin and Sialyl-Lewis X 3. GlyCAM-1, CD34 and L-selectin 4. ICAM-1 and Integrin (LFA-1) 5. VCAM-1 and Integrin (VLA-4) A. Rolling (NMT) B. Ahesion, Arrest, Transmigration (NMT) C. Adhestion (EMT) D. Rolling and Adhesion (NMT) E. Rolling (NM)

1. A 2. D 3. E 4. B 5. C

# LEUKOCYTE MIGRATION THROUGH THE ENDOTHELIUM the exit of the cell through the vessel wall | pwede rin ata entrance

Transmigration or diapedesis occurs

# LEUKOCYTE MIGRATION THROUGH THE ENDOTHELIUM It is mediated by what adhesion molecules?

Platelet Endothelial Cell Adhesion Molecule (PECAM-1), or CD31

# LEUKOCYTE ADHESION DEFICIENCIES Defect in the biosynthesis of B2 chain

Leukocyte Adhesion Deficiency Type 1

# LEUKOCYTE ADHESION DEFICIENCIES Absence of Sialyl-Lewis X

Leukocyte Adhesion Deficiency Type 2

Once the cells are out of the vessels, they will go through?

Chemotaxis

defined as locomotion along the chemical gradient toward the site of injury

chemotaxis

# CHEMOTAXIS OF LEUKOCYTES Both exogenous and endogenous substance can act as?

chemoattractants

# CHEMOTAXIS OF LEUKOCYTES The most common exogenous factors are?

- bacterial products including peptides with N-formylmethionine terminal amino acids - some lipids

# CHEMOTAXIS OF LEUKOCYTES Endogenous chemoattractants include several chemical mediators such as?

- cytokines–particularly of the chemokine family (IL-8) - components of the complement system (C5a) - arachidonic acid metabolites–mainly leukotriene B4 (LTB4)

# CHEMOTAXIS OF LEUKOCYTES All these chemotactic agents bind to this specific receptor?

seven (7) transmembrane G-protein-coupled receptors

# CHEMOTAXIS OF LEUKOCYTES TOF The nature of the plasma cell infiltrate varies with age of inflammatory response and type of stimulus

F (not plasma cell, should be LEUKOCYTES)

# CHEMOTAXIS OF LEUKOCYTES predominate in most forms of **acute inflammation**–during the first 6 to 24 hours, making them short-lived.

Neutrophils

# CHEMOTAXIS OF LEUKOCYTES replace neutrophils in cases of **chronic inflammation** which may last from 24 to 48 hours.

Monocytes

# CHEMOTAXIS OF LEUKOCYTES Pseudomonas bacteria, the cellular infiltrate is dominated by

**neutrophils** for several days

# CHEMOTAXIS OF LEUKOCYTES In viral infections

**lymphocytes** may be first to arrive

# CHEMOTAXIS OF LEUKOCYTES In some hypersensitivity reactions

Lymphocytes, macrophages, and plasma cells are dominan

# CHEMOTAXIS OF LEUKOCYTES In helminthic infections and allergic reactions

eosinophils may be the main cell type

# PHAGOCYTOSIS AND CLEARANCE OF OFFENDING AGENT The two major phagocytes are

**neutrophils** and **macrophages**

# PHAGOCYTOSIS AND CLEARANCE OF OFFENDING AGENT Revolves around the recognition of microbes or dead cells which induces several response in leukocytes that are collectively called

LEUKOCYTE ACTIVATION

# LEUKOCYTE ACTIVATION Results from signaling pathways that are triggered in leukocytes resulting in? enumerate

- Increased **cytosolic calcium** - Activation of enzymes such as **protein kinase C** and **phospholipase A2**

[P] Week 2: Inflammation and Repair - Part 1 Flashcards

(101 cards)