Bacterial infections and immune system

Question 1

Define infection

Answer 1

invasion and multiplication of microorganism in the body causing local or/and systemic injury due to toxins, replication or aberrant host immune responses

Question 2

How does bacteria cause infection (steps)

Answer 2

1- Entry is through mucosa of respiratory, GI and urogenital tract or through wounds in skin
2- Attachment to host cell
3-Proliferation
4- Invasion of host tissue
5- Toxin release which causes damage to the host

Question 3

Details of helicobater pylori?

Answer 3

1- Helicobacter pylori has an outer membrane consisting of LPS.
LPS is an endotoxin, which is released when bacteria dies or lyses.
2- Most infections occur in childhood and about 80% are asymptomatic
3- It is an acute infection which resolves within 2 weeks.

Question 4

Alongside endotoxin, Which exotoxin does H. pylori produces?

Answer 4

vacuoulating cytotoxin A

Question 5

What is H.pylori associated with

Answer 5

Chronic H.pylori is associated with:
- gastritis (inflammation of stomach lining)
- duodenal ulcers and stomach ulcers
- distal gastric adenocarcinoma
- primary gastric lymphoma

Question 6

Define NETosis

Answer 6

Special process where neutrophils release web like structures called NETs into the environment

Question 7

What is NET made of?
5 things

Answer 7

DNA, NET-associated proteases, Histones, ROS-generating enzymes, antimicrobial peptides

Question 8

What’s the function of DNA

Answer 8

traps the pathogens

Question 9

What’s the function of NET-associated proteases

Answer 9

inactivate and kill pathogens by cleaving their virulence factors

Question 10

What’s the function of histones

Answer 10

Disintegrate pathogen’s cell membrane

Question 11

What’s the function of ROS-generating enzymes

Answer 11

causes oxidative attack

Question 12

Whats the function of antimicrobial peptides

Answer 12

Restricts fungal growth by sequestring iron needed for fungi to survive.

Question 13

Define remnant NETs

Answer 13

Leftover pieces of DNA, histones and enzymes from old NETs.

Question 14

Why are remnant NETS dangerous?

Answer 14

They act like danger signals to the immune system as the body can mistakenly treat NET components as if they’re foreign leading to:
Chronic inflammation
Autoimmune diseases

Question 15

What are examples of diseases linked to remnant NETS

Answer 15

Cardiac infarction (heart attack)
DVT
Astherosclerosis
Diabetes
SLE

Question 16

What is the main protective mechanism against extracellular bacteria and toxins

Answer 16

Humoural Response

Question 17

How is humoural response against bacteria carried out?

Answer 17

Removal of bacteria
* Opsonisation by Ab and complement (e.g. C3b)
(Fc receptors and complement receptor (CR) on neutrophils and
macrophages → ↑phagocytosis
* Lysis by the complement (classical,
alternative, lectin) through formation of MAC
* C3a and C5a (anaphylatoxins) – local inflammatory response:
↑ mast cell degranulation → lymphocytes and neutrophils extravasation

Question 18

What is intracellular bacteria and how does it get inside host cell

Answer 18

Bacteria which live inside host cells to survive and grow.
Through phagocytosis

Question 19

What are 2 types of intracellular bacteria

Answer 19

Intravesicular
Cytosolic

Question 20

Whats’s the function of intravesicular bacteria

Answer 20

blocks the fusion of endosomes/ phagosomes with lysosomes

Question 21

Function of cytosolic bacteria

Answer 21

Breaks out of endosomes (vesicle which forms once pathogen is phagocytosed) into cytosol

Question 22

What are the main mechanism of defence agaisnt intracellular bacteria

Answer 22

Cell-mediated response
NK cells
Macrophages
Dendritic
CD8

Question 23

Give an example of intracellular bacteria

Answer 23

Mycobacterium tuberculosis

Question 24

How many deaths in TB responsible for?

Answer 24

20% of all deaths

Question 25

How is TB spread

Answer 25

by inhalation of droplets containing TB bacilli

Question 26

How is TB bacilli ingested

Answer 26

by alveolar macrophages

Question 27

What does bacilli prevent formation of? and what does that cause?

Answer 27

formation of phagolysosome. This leads to proliferation within macrophages. Macrophages lyse and release large no of bacilli

Question 28

How does the immune system try to control the infection

Answer 28

through the formation of granuloma (tubercule)

Question 29

What does tubercule contain

Answer 29

~ predominantly macrophages ~ few lymphocytes ~ CD8 cells

Question 30

What is potential target for TB vaccine

Answer 30

CD8 cells boosting the activity of these cells as these are the responsible for killing internalised bacteria

Question 31

Macrophages release lytic enzymes in response to TB, what does this cause?

Answer 31

~ Destruction of nearby healthy cells ~ Circular region of necrotic tissue (as immune response intensifies, the tissue around macrophages undergoes necrosis) ~ Caseous (cheese like) necrosis- type of tissue death that is seen in tuberculosis because of the immune response to the bacteria. It appears as a soft, crumbly material resembling cheese. Overtime caseous necrosis can undergo calcification, making it visible on X-ray

Question 32

Give some examples of evasion of immune responses by bacteria?

Answer 32

Phagocytosis evasion Complement Adaptive immunity (T cells) Manipulation of cytotoxicity Manipulation of antibody responses

Question 33

How does bacteria evade phagocytosis

Answer 33

Some bacteria have capsules which covers PAMPS e.g. pneumunococcus These resist opsnonisation by antibodies and complement and eventually phagocytosis Capsuled bacteria have pilli with adhesion molecules to attach to host cells Some produce exotoxins which block endocytosis Some inhibit formation of phagolysosome by preventing fusion of phagosome and lysosome Some escape phagolosome by lysing phagosome mebrane Some block the loading of MHC-2 on APCs, or reduce the expression Some may interfere with host gene expression e.g. blocking the expression of immune genes so no inflammatory response

Question 34

Evasion of adaptive immunity. Which signalling pathway does Helicobacter block

Answer 34

IL-2 No activation of T cells Weaker immune response

Question 35

Which bacteria releases IgA proteases and what does it do

Answer 35

Heamophilis influezae cleaves IgA, allwoing bacteria to stick to mucosal surfaces to gain entry and colonise

Question 36

Which receptors do some bacteria have which prevent immune cells from binding to Ab?

Answer 36

Fc receptors Bind to fc region of Ab Immune cells can't bind No phagocytosis, no opsonisation

Question 37

How does bacteria evade complement

Answer 37

capsule prevents complement from attaching to it- resistant to MAC Some bacteria like streptococcus produce C5a peptidase which causes proteolysis of C5a Gram + bacteria resistant due to thick peptidoglycan layer