Roles of inflammation

Question 1

What are 5 signs of acute inflammation?

Answer 1

Heat (Calor)
Redness (Rubor)
Swelling (Tumour)
Pain (Dolor)
Loss of function

Question 2

What are the sites of local inflammation?

Answer 2

Local
Systemic (more serious)

Question 3

What are roles of inflammation?

Answer 3

1. To recruit effector molecules and cells to the site of the infection
2. To induce local blood clotting which traps pathogens and prevent their spread
3. To initiate tissue repair

Question 4

Inflammation is initiated by ?

Answer 4

1. Tissue Damage
2. Pathogen Recognition

Question 5

Tissue damage activates 4 systems which are?

Answer 5

1. Kinin system
2. Clotting system
3. Fibrinolytic system
4. Complement
   (first 3 systems lead to inflammation response)

Question 6

What does the kinin system do?

Answer 6

Enzymatic cascade leading to increased vascular permeability, vasodilation, pain and smooth muscle contraction

Question 7

What does clotting system do?

Answer 7

Increases vascular permeability and neutrophil chemotaxis

Question 8

What does the fibrinolytic system do

Answer 8

Complement activation

Question 9

What does complement do?

Answer 9

anaphylatoxins (C3a and C5a) bind to receptors on mast cells, causing degranulation. This releases histamine and other mediators

Question 10

What do macrophages and dendritic cells release upon pathogen recognition and phagocytosis?

Answer 10

1. prostaglandins and leukotrienes:
   ~Act as neutrophil and macrophage attractants
   ~increased vascular permeability
2. chemokines : recruit effector cells to the site of the infection
   ~Induce changes in cytoskeleton and increase adheviness of target cells
3. pro-inflammatory cytokines (IL-1, IL-6 and TNFa)

Question 11

Which immune cells play a role in inflammation?

Answer 11

Mast cells and basophils - release histamine

Question 12

What are some inflammation related effects?

Answer 12

1. Dilation of blood vessels leads to fall in blood pressure (dilation- less resistant to blood flow- the heart doesn’t have to pump as hard- therefore low pressure)
2. Increased vascular permeability leads to swelling
3. Chemotaxis of leukocytes

Question 13

How does inflammation causes increased vascular permeability, leading to swelling?

Answer 13

Usually our blood vessels are very tight which prevents leakage.
However when the immune system detects tissue damage or pathogens, it causes blood vessels to become leaky.
Immune cells release chemicals such as histamine, pro-inflammatory cytokines.
These chemicals act on the endothelial cells that line the blood vessels and cause cells to slightly shrink, which then creates a gap.
Through this gap, fluid, immune cells and proteins can leak out of the blood vessel into the surrounding tissue.
Thus the extra fluid in tissue causes swelling.

Question 14

What is meant by leukocyte extraversion?

Answer 14

It refers to when white blood cells leave the bloodstream and move into tissues during inflammation.

Question 15

What are CAMs?

Answer 15

Cell Adhesion Molecules (CAMs) are proteins on the surface of cells that help cells stick to each other and to their surroundings.

Question 16

Provide 4 different examples of Cams?

Answer 16

Mucins and Intergrins (expressed by leukocytes)
Selectins and ICAMs (expressed by vascular endothelial cells)

Question 17

What does the selectin bind to?

Answer 17

Mucins (expressed by leukocytes)

Question 18

What does integrin bind to?

Answer 18

IgCams expressed by endothelial cells.

Question 19

What is the function of selectins?

Answer 19

Selectins are expressed on endothelial cells.
They recognise and bind to sialyated carbohydrate structure, found on mucins (mucins are expressed by leukocytes)
This helps leukocytes slow down and roll along the endothelium.

Question 20

What is the function of IgCAMs?

Answer 20

IgCAMs are immunoglobins like molecules found on endothelial cells. They bind to integrins that are expressed by leukocytes.
This allows for firm adhesion of phagocytes to endothelium

Question 21

What is the function of mucins?

Answer 21

Mucins are glycolysated (sugar-covered) molecules found on leukocytes.
They have a sialyl-lewisX group, which act as binding sites for selectins on endothelial cells.

Question 22

What is the function of integrins?

Answer 22

Integrins are proteins on leukocytes that help them stick to the endothelial cells.
Usually they are inactive, but when leukocytes detect infection signals, integrins activate and bind to ICAMs on endothelial cells.

Question 23

What are 4 steps of leukocyte extraversion?

Answer 23

Rolling, Activation, Arrest and adhesion, Transendothelial membrane

Question 24

Describe the rolling stage of leukocyte extraversion?

Answer 24

In a healthy state, rolling is controlled by selectins (endothelial cells) and mucins (leukocytes). This allows leukocytes to loosely attach to the blood vessel wall but not stop completely.
During inflammation, cytokines and other inflammatory signals activate endothelial cells which causes increased expression of selectins.
Leukocytes which express mucins, now bind more efficiently to selectins, leading to slowed rolling.

Question 25

Describe the activation stage of leukocyte extraversion.

Answer 25

The activated endothelium produces chemokines. These chemokines bind to receptors on leukocytes, which activate the leukocytes. A signalling cascade inside leukocyte occurs. This activates integrins, which are needed for firm adhesion in next step.

Question 26

Describe the arrest and adhesion stage of leukocyte extraversion?

Answer 26

After the activation stage, integrins are activated. Activated integrings start clustering together in one area of the leukocyte membrane. This clustering increases the strength of binding to ICAM-1 on endothelial cells.

Question 27

Describe the transednothelial migration stage of leukocyte extraversion?

Answer 27

The leukocyte squeezes through the endothelial layer to enter infected tissues.

Question 28

What triggers integrin activation on leukocytes?

Answer 28

Chemokines from the inflamed endothelium bind to chemokine receptors on leukocytes, activating integrins

Question 29

Why don’t neutrophils bind to healthy endothelium?

Answer 29

Because selectins are not expressed in non-inflamed endothelium

Question 30

What are the first leukocytes to arrive at the site of the infection?

Answer 30

Neutrophils

Question 31

Which chemical signals attract neutrophils to inflamed endotheliums and how do they cause neutrophil activation and migration?

Answer 31

C5a (compelement protein fragment) Bacterial peptides Leukotrienes They bind to receptors on neutrophils, causing its activation and migration

Question 32

What is role of monocytes in healthy conditions?

Answer 32

Mococytes circulate in the blood. Even in the normal conditions, monocytes migrate at a lower rate across non-inflamed endothelium to replenish tissue resident macrophages, which help maintain tissue haemostasis

Question 33

What directs monocytes to the site of infection

Answer 33

Complement and bacterial peptide fragments

Question 34

Once monocytes arrive at the site of infection, what happens?

Answer 34

They differentiate into macrophages

Question 35

Which immune cells arrive at site of infection after neutrophils?

Answer 35

Monocytes

Question 36

Why do monocytes arrive at the site of infection much later?

Question 37

What are some pro-inflammatory cytokines

Answer 37

TNFa (tumour necrosis factor 1) IL6 (interleukin 6) IL1

Question 38

Give an example of anti-inflammatory cytokine

Answer 38

TGF-B1. Transforming growth factor beta 1

Question 39

What is the role of TNFa?

Answer 39

It activates macrophages and neutrophils, which in turn increases phagocytic activity and release of lytic enzymes into interstitial space, to destroy the pathogens

Question 40

How does TNF-α help contain infections locally?

Answer 40

It stimulates endothelial cells to initiate blood clotting in small local vessels, preventing the spread of pathogens

Question 41

Along with TNFa, what other cytokines initiate systemic and acute phase response? (Sytemic means Instead of just affecting the local site of infection, pro-inflammatory cytokines, trigger effects throughout the entire body. Acute means This is a rapid reaction by the immune system to fight infection and promote healing)

Answer 41

IL-1 IL-6

Question 42

How do pro-inflammatory cytokines initiate systemic responses. (4 ways)

Answer 42

IL-1, IL-6, and TNF-α act on the hypothalamus to raise body temperature. Fever helps slow pathogen growth and boosts immune function. IL-6 signals the liver to produce acute-phase proteins like: C-reactive protein (CRP) → marks pathogens for destruction in a process called opsonisation Fibrinogen → helps blood clotting to contain infection. TNF-α and IL-1 increase production of leukocytes More white blood cells = stronger immune defense IL-1 and IL-6 act on hypothalamus. which leads to increased synthesis of ACTH, which stimulates the adrenal glands to produce cortisol. Cortisol slows down inflammation to prevent damage from an overactive immune system.

Question 43

What is the role of TGFB-1?

Answer 43

* limits the inflammatory response by inhibiting the activation of monocyte derived phagocytes and lymphocytes activation, preventing excessive immune response * promotes tissue repair

Question 44

How does TGFB-1 promote tissue repair?

Answer 44

Stimulates fibroblast accumulation and proliferation (key for wound healing). Enhances the build-up of extracellular matrix (ECM), which helps restore tissue integrity.

Question 45

What 3 things can cause chronic inflammation?

Answer 45

1- When pathogens become resistant to immune defenses Some bacteria (e.g., Mycobacterium tuberculosis) can survive inside immune cells, leading to long-term infection and inflammation. 2- Autoimmune diseases The immune system mistakenly attacks the body’s own tissues, causing persistent inflammation (e.g., rheumatoid arthritis, lupus) 3- Cancer Tumor growth causes tissue damage and cell death, leading to continuous inflammation.

Question 46

What are 3 effects of chronic inflammation?

Answer 46

1- Continuous accumulation and activation of macrophages. Instead of helping, they start damaging tissues by releasing toxic molecules like reactive oxygen species (ROS) and enzymes. 2- Fibrosis In chronic inflammation, there is excessive fibroblast activity, too much ECM is produced. This thickens and stiffens the tissue, forming scars which can reduce organ function 3- Granuloma Activated macrophages are surrounded by activated lymphocytes (Some pathogens cannot be killed easily. Macrophages try to engulf and destroy them but fail. More macrophages and lymphocytes arrive at the site of infection. Macrophages fuse together to form giant cells but still unable to destroy pathogens. The body forms a protective barrier around the infected area. Macrophages, lymphocytes, and fibroblasts cluster together and surround the infection. The center of the granuloma may become necrotic (dead tissue) if it lasts too long. The pathogen is trapped inside, stopping it from spreading to other tissues. However, if the granuloma breaks down, the infection can reactivate and spread (like in tuberculosis). E.g. tuberculosis granuloma

Question 47

Define sepsis

Answer 47

overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure and death

Question 48

Define septicemia

Answer 48

Bacteria enter the bloodstream and spread throughout the body

Question 49

How does TNFa contribute to sepsis?

Answer 49

Normally, TNF-α helps fight infections But in sepsis, tissue macrophages release too much TNF-α, leading to uncontrolled systemic inflammation-

Question 50

What are the systemic effects of TNFa?

Answer 50

1) TNFa causes vasodilation, leading to a drop in blood pressure. This reduces blood flow to organs, which can result in shock. 2) Increased vascular permeability TNF-α makes blood vessels leaky, so plasma from blood vessels escapes into tissues. This further reduces blood volume, worsening low blood pressure. Less oxygen reaches organs → organ failure starts. 3) Blood clots in vessels Blood Clotting in Small Vessels → Blocked Blood Flow & Organ Failure TNF-α triggers clotting inside small blood vessels (disseminated intravascular coagulation, DIC). Tiny clots block oxygen supply to organs, leading to multiple organ failure.

Question 51

Provide a summary of how sepsis occurs.

Answer 51

1- Local Infection → Bacteria infect a specific area (e.g., lungs, skin, urinary tract). 2️⃣ Bacteria Enter Bloodstream (Septicemia) → Infection spreads through the blood. 3️⃣ Immune System Reacts → Immune cells release inflammatory signals (TNF-α, IL-1, IL-6). 4️⃣ Uncontrolled Inflammation (Sepsis) → Widespread inflammation causes low blood pressure, leaky blood vessels, and clotting. 5️⃣ Organ Damage & Septic Shock → Lack of oxygen leads to multi-organ failure and death if untreated.