Lecture 2 Cellulitis / complementary system

Question 1

In terms of bacteria size, it can sometimes migrate into the sweat gland. This happens all the time; however, we tend to not get infected all the time. Why is this the case?

Answer 1

Because not all bacteria can survive under human conditions or affect human skin.

• To effect the epithelial cells it has to be the correct type of bacteria.

Question 2

what type of bacteria can affect the human skin?

Answer 2

The 2 types of bacteria that causes skin infection is S. pyogenes and S. aureus.

Question 3

how can S.pyogenes damage the cells?

Answer 3

S.pyogenes interacting with the epithelial cells in the sweat glands. It damages the cells by releasing bacterial Toxins called cycolysins.

Question 4

After damage, what is the first line of defence?

Answer 4

The first line of defence is the macrophages and the dentretic cells. Cells near by marocphages and dendretic cells that eat all the debris and infection. These cells will wonder off and communicate with helper T-cells.

Question 5

what are the main types of chemical released when damage has occurred?

Answer 5

• IL-8 is a very potent attracter of neutrophils

- IL-1 are a very potent attracter of T-cells and macophages / dentretics cells.

Question 6

In response to the chemical being released:

Answer 6

Endothelial cells part of the blood vessel increase there receptors, and these receptors are P-selectin and CAM. They are sticky receptors. The concentration of the receptors are higher when they are closest to the chemicals being released. The concentration gradient of receptor decreases as you move further away in the vessels.

Question 7

how are neutrophils transported to the site of infection?

Answer 7

The receptors on the endothelial cells attract the neutrophils. The neutrophil are more likely to stick and attract to where the CAM adhesion molecules are highly concentrated. This is celled chemoatttraction.

Question 8

what happens when the endothelial cells open up?

Answer 8

The opening of endothelial cells enables the neutrophil to leak out to the area of damage. The neutraphils travel via chemoattractions to the chemicals released by the epithelium. Specifically attracting to IL-8

Question 9

why are neutrophils important?

Answer 9

The netrophills are the main immune cells that are recruited earlier during the infection to come along and phagocytose bacteria

Question 10

what are the function of macrophages and dendritic cells ?

Answer 10

The macrophages and dendretics cells take what they have eaten and present it to helper T-cells

Question 11

what is the function of Neutrophils?

Answer 11

The Neutrophils main task is to eat the bacteria and kill it.

This process if happening in the space of hours.

Question 12

When do symptoms occur?

Answer 12

Once, the cells are damaged, that it a sign of when symptoms starts to occur.

Question 13

Define Diapedis.

Answer 13

• Diapedis is defined as the way neutrophil change the cellular shape and squeeze through the endothelial space.

Question 14

what are the 3 triggers of the complementary system?

Answer 14

1. The largest trigger is the antibody
2. The second trigger is from the recognition of human carbonhydrates and carbonhydrates that bacteria consist.
3. he third trigger is by complements spontaneously forming on cells surfaces.

Question 15

what is the complementary system?

Answer 15

• The complement system is doing stuff that augment the immune response (via chemical release at epithelial cells)
• It’s job is to amplify the normal immune response
• It triggers the complement pathway and there are 3 triggers. All these trigger come together to enhance the normal immune response.

Question 16

describe the trigger of antibodies associated to the complementary system.

Answer 16

The largest trigger is the antibody. When the antibody recognizes and bind to the bacterial antigen. This is an intense trigger for the complement system to kick in.

Question 17

describe the trigger of recognition of human carbohydrates associated to the complementary system.

Answer 17

The second trigger is from the recognition of human carbonhydrates and carbonhydrates that bacteria consist. One of the carbonhydates is called mannose. The is a protein made from out livers that circulate around allows mannose to bind on to and this protein is called Lectin. This is a good trigger for the complementry system. These bacterial sugars are also recognised by our immune cells, epithelial cells, and endothelial cells. Recognised by things like the Toll like receptor

Question 18

describe the trigger of spontaneous complement associated to the complementary system.

Answer 18

The third trigger is by complements spontaneously forming on cells surfaces. If that happens on human cells, there are things on our cells to turn it off. But if it happens on a bacterial cell, the complementary casecade is continuous until the bacteria is killed

Question 19

what is the function of C3 in the complementary mechanism?

Answer 19

• The 3 tirggers wants to form C3 covertase
• C3 convertase is an enzyme
• Its function is to convert C3

The enzyme C3 convertase converts complement C3 → C3a and C3b.

• C3b is important
• A human cannot live without C3b

Question 20

why is C3b important?

Answer 20

C3b is a very important opsonin that has an essential acitivity to tag bacteria. The reason why this is important is because of its function. It has the ability to coat the antigen or bacteria with antibodies and complementry protein. This coating allows for the enhancement of immune cells like neutrophils, dendretics, and macrophages to recognise the antigen/bacteria and phagocytose it.

Question 21

What is the function of C3a?

Answer 21

C3a helps blood vessels to open up and improve the delivery od neutrophils to the infection site.

Question 22

Which C protein has the same function as C3a?

Answer 22

C5a helps blood vessels to open up as well

Question 23

Some of the C3b binds to the C3 convertase and convert further to form C5 Covertase. what is the function of C5 convertase?

Answer 23

C5 cleaves and converts further to C5a and C5b.

Question 24

why is C5a important?

Answer 24

C5a is a chemotactic protein along with IL-8.They attract Neutrophils

Question 25

What is the function of C5b?

Answer 25

C5b binds onto other complementry factors such as C6 → C9 and forms a complex called the “Membrane attack complex — MAC” This function lyses bacteria that are gram negative because they ahve a really thin cell wall.

Question 26

why can’t MAC kill S.pyogenes and S. Aureus ?

Answer 26

MAC cannot lyses S.pyogenes and S. Aureus because these bacteria are gram POSITIVE with a thick cell wall.

Question 27

what is the end result after the activated complementary system?

Answer 27

• Blood vessel opening to deliver more oxygen, more nutrients, more neutriphils etc.
• The skin becomes RED.
• More tissue build up and swelling caused by opening up the blood vessels and lymphatics.

Question 28

Why do people with cellulitis experience pain?

Answer 28

Pain comes from the nerve fibers stimulating from the proteins particulary the immune cells. C5 a can stimulate a nerve fiber to the brain. Sending pain signals to the brian, and communicating there is a problem.

Question 29

what kind of Organism causes Stuart illness (Cellulitis)?

Answer 29

Streptococcus Pyogenes

Question 30

what are Streptococcus Pyogenes ?

Answer 30

Gram positive cocci

Question 31

What diseases can Streptococcus Pyogenes cause?

Answer 31

pharyngitis

rheumatic fever

Question 32

who discovered streptococci could be classified based on the carbonhydrates held on their cell walls?

Answer 32

Rebecca Lancefield 1895-1981

Question 33

What did Rebecca Lancefield demonstrate?

Answer 33

She demonstrated that S.pyogenes (Gp - A streptococcus) caused rheumatic fever.

Question 34

what organism causes Boils and Furuncles?

Answer 34

Straphylococcus aureus

Question 35

How does bacteria cause infection and avoid the human immune system?

Answer 35

• There are some of the toxin/ proteins released from the bacterial cells.
• e.g. Streptolysins (protein)
• S.pyrogenes and S.aureus have the capcity to avoid the immunes → infection arising

Question 36

Problems of soil bacteria?

Answer 36

• Soil bacterial do not have any ability to avoid the Human immune system which allows the immune system to kill it.
• Cannot interact with human cells and the capacity to kill human cells

Question 37

S.pyrogenes and S.aureus has the ability to bind to adhesins. what happens next
?

Answer 37

S.pyrogenes and S.aureus may coat it self in a sugary capsule. This prevents C3b antibodies from binding to it. Which leads to the possibility of neutrophil not being triggered to the bacteria.

Question 38

What is another way of bacteria resisting to our immune system?

Answer 38

Bacteria can release C5a peptidase that degrades C5a reducing chemotaxis, and this decreases the ability for Neutrophils to attract C5a and transport to the site of infection.

Question 39

how does bacteria us M proteins to avoid the immune system?

Answer 39

M proteins on the bacterial surface can bind to factor H. Factor H is a human proteins. The function of factor H prevent and inhibits the complementry systems. So the bacteria can use the human proteins to turn off the complementry system.

Question 40

What is the clinical diagnose of cellulitis?

Answer 40

Diagnosis is largely based on appearance of the lesion.

Question 41

what are the treatment for cellulitis?

Answer 41

• Supportive care to maintain ‘normal’ physiology
• rest and elevation - helps with pain and discomfort
• analgesia
• antimicrobial drugs

Question 42

what antibiotic is the best for cellulitis? and why?

Answer 42

Treatment fo cellulitis= Flucoxacillin
According to research, it is better to use an anitbody that kills aganist S.pyogenes and S.arueus. So, the resolution was to use a drug that mainly treated S.aureus because it also treats S.pyogenes. However, if you use penicillin to treat S.pyogenes it is be somewhat effective for the 85-90% of S.pyogene but it won’t kill the rest of the 10-15% S.aureus because S. aureus is resistant to penicillin.