colonisation and invasion of the host

Question 1

what do the body’s defences do

Answer 1

• prevent microbes from getting into the body
• destroy microbes once they have got in

Question 2

the body’s 3 lines of defence

Answer 2

• non specific external defences (Physical, chemical, and biochemical barriers)
• non specific immune system
• specific immune system

Question 3

external defences

Answer 3

comprised of non specific physical, chemical and biochemical barriers

all the natural openings in the body and the skin have very good physical chemical and biochemical barriers to prevent organisms getting in.

Question 4

physical barriers - epithelia

Answer 4

the body is surrounded by an intact layer of skin and mucous membranes.
effective barrier against invasion by most pathogens and this is partly because these cells are held together really tightly.
So it’s very difficult to get in between them.

Question 5

stratified epithelia

Answer 5

in some places you have multiple layers of epithelial cells and that’s referred to as stratified epithelia.
○ And this tends to be the parts of the body that are most prone to attack or on the surface of the body.
○ So the skin is stratified epithelia.
○ In Your mouth you have stratified epithelia where you get mechanical damage.

Question 6

simple epithelia

Answer 6

a single layer of epithelial cells
- In the internal passageways of the body
- . So these are the mucosal surfaces and it’s where you’ve got absorption and secretion taking place And so you can only have a single layer of epithelial cells to allow those processes to take place.
- Obviously where you’ve only got a single layer of epithelial cells. It’s much easier for a pathogen to cross that barrier.

Question 7

squamous epithelia

Answer 7

really flattened cells.
○ So these are found on the outer surfaces outer layers of the skin,

Question 8

cuboidal epithelia

Answer 8

cube shaped

Question 9

the normal microbiota

Answer 9

the microbiota are microorganisms that live with the host in a symbiotic relationship and normally it’s mutually Beneficial and the organism doesn’t cause harm to the house.

in terms of our microbiota, it’s include viruses and fungi but by far the most predominant organisms are the bacteria and there are approximately 10 times more bacterial cells as mammalian cells in the human body

they constitute 200 times the genes in the human genome.
so that means they can add functionality.

Question 10

where does the microbiota occur

Answer 10

the microbiota is only present in parts of the body that are exposed to or communicate with the external environment.
- not found in normally sterile sites (blood lymph, pleural fluid, cerebrospinal fluid, peritoneal fluid, the bladder and kidneys, uterus, bones)

Question 11

how do microbiota provide defence

Answer 11

the microbiota can exclude potential pathogens and this is cause called colonization resistance.
- often they form a thick biofilm, which means that they cover potential adhesion sites for pathogens.
- So basically blocking sites for them to attach to
- They can also alter the physicochemical environment.
- also production of antagonistic substances
- also utilisation of available nutrients within a site

Question 12

external host defences - the skin

Answer 12

really effective structural barrier and this is because it’s made up of stratified squamous epithelia in the outer layers.
○ You also have a lot of dead cells and keratinized cells. These are really difficult to digest and the fact its stratified means organisms just can’t pass through
○ the skin is also dry and Low pH- again not good environment for organisms to grow and multiply in
○ because it’s on the outside of the body. It’s lower temperature. Most pathogens need a temperature of 37 degrees for optimal growth.
-You’ve got constant turnover of cells
- antibacterial secretiond
- resident microbiota
- Langerhans cells and skin associated lymphoid tissue

Question 13

sites more vulnerable to infection within the skin

Answer 13

within the skin the site that are more vulnerable to infection are where You’ve got natural indentation. So for example hair follicles and sweat glands and that’s because it’s a more moist. Environment
- these are areas are protected by antibacterial secretions (lysozyme, propionic acid and lactic acid) They lower the ph make the environment unfavorable for pathogens that usually require a neutral pH
○ and then phospholipase that breaks down lipids in the bacterial cell membranes.

Question 14

what helps if the organism does penetrate the skin

Answer 14

if an organism does penetrate the skin we have what’s called Skin Associated lymphoid tissue or salt
and this is a collections of lymphoid cells and it includes cells from the Adaptive and the innate immune systems such as phagocytes

Question 15

penetration of the skin

Answer 15

• Those that are able to cause infections of the skin usually colonise natural openings, like the hair follicles sweat glands sebaceous glands
  and the classic example is propionibacterium acnes that causes acne

Question 16

parenteral route of infection

Answer 16

• usually penetration requires some mechanical damage to the skin and this is referred to as a parenteral route of infection that the organism can penetrate through the skin.
  ○ so this can be caused by insect bites.
  ○ It can be an animal bite
  then most commonly, it’s just due to abrasions, wounds and burns but can also be catheters and surgery.

Question 17

external host defences - mucosal surfaces

Answer 17

these are all the internal surfaces of the body as well as the eyes.
- These are much more prone to infection because you only have a single layer of epithelial cells and they are also moist So they’re much better environments for organisms to grow
○ they are also 37 degrees C - optimal growth temperature.
- So you have to have really good defenses of the mucosal surfaces.

Question 18

defences at mucosal surfaces

Answer 18

in terms of the epithelial cells at mucosal surfaces, you have rapid cell turnover.
- gets rid of any organisms that happened to attach
- the cells are really tightly attached to each other by tight junctions and desmosomes, so it’s very difficult for organisms to pass between the epithelial cells.

Question 19

what other cells do mucosal surfaces contain with key roles in defence

Answer 19

goblet cells which produce mucus
-mucus is a glycoprotein matrix And it forms a protective barrier - It’s sticky So it’s difficult to get through
.
- You also have M cells which are interspersed amongst the epithelial cells called microfold cells - these are part of the mucosal Associated lymphoid tissue

-In the small intestine there are also paneth cells and these secrete antimicrobial proteins and peptides

Question 20

what does mucus contain

Answer 20

-it contains secretory IGA anti body produced by the adaptive immunity.
-It also has antibacterial proteins and peptides including lysozyme
-Also has a key defensive lactoferrin
-virtually all microbes require iron in over in order to grow and replicate
- lactoferrin binds iron really tightly so in response to an infection you produce more lactoferrin and that comes around and basically mops up all of the surrounding iron preventing growth of the pathoge
- Lactoperoxidase produces reactive oxygen species that are damaging - they damage membranes and DNA.

Question 21

function of Microfold cells in mucosal surfaces

Answer 21

these are part of the mucosal Associated lymphoid tissue
- they constantly monitoring the Lumen and they present antigens From that lumen into the underlying lymphoid cells, so they’re constantly sampling that for potential pathogens.
- you get collections of M cells distributed through the mucosa of the GI tract and these lymphoid cells include T cells and B cells, but you’ve also got dendritic cells neutrophils and macrophages.

Question 22

paneth cell funciton in mucosal surfaces

Answer 22

○ In the small intestine there are also paneth cells and these secrete antimicrobial proteins and peptides
What these do is punch holes in bacterial cell membranes

Question 23

external host defences - respiratory tract - resident microbiota

Answer 23

In the upper part of the respiratory tract, you’ve got a very complex resident microbiota And yet when you get down to the lungs the microbiota becomes much less complex -so there’s clearly mechanisms for preventing the travel of organisms down into the lungs

Question 24

external host defences - respiratory tract -turbinate baffles

Answer 24

○ these are the large sinus area at the back of the nose - So when you breathe through your nose this creates a turbulent airflow and what it means is that organisms then get trapped in the mucus at the back of The nose and back of the throat.
§ And so basically they get stuck in that mucus.
○ because you’ve got nose hair large particles also get stuck in there the nose hair

• and this is very protective.

Question 25

external host defences - respiratory tract -mucociliary escalator

Answer 25

§ have cilia- These Fine hairs constantly beat and waft and moving upwards.
§ So what happens is particles including bacteria gets stuck in the mucus and they start to form little balls in the mucus and then the hair whacks them upwards.

Question 26

external host defences - respiratory tract - alveolar macrophages

Answer 26

For organisms that do get down into the lungs, You’ve also got patrolling alveolar macrophages So phagocytes within the lungs that are able to engulf any organisms that end up there.

Question 27

pathogens mechanisms to inactive the cilia

Answer 27

some of the respiratory pathogens have mechanisms basically to attach to the epithelia to stop them being wafted by the Cilia.
e.g. Neisseria meningitidis

• some organisms actually produce toxins that inactivate the Cilia so they can’t move
  e.g. haemophilus influenzae

Question 28

external host defences - eyes

Answer 28

blinking
○ just mechanically remove particles from the eye.

We produce tears which contain mucus and so you’ve got all the antimicrobial properties of mucus

most eye infections are due to some sort of mechanical injury

Question 29

eye infections risks

Answer 29

in swimming pools You get a passage of fluid over the eyes and that again can lead to infections
- usually swimming pools are highly chlorinated, So it’s not an issue
- but the organism chlamydia trachomatis can cause eye infections and that can be transmitted in swimming pools that aren’t chlorinated.

also it’s a risk During birth. So as a baby passes through the birth canal passes through the cervix, if the mother has a chlamydial infection or another sexually transmitted disease then the eyes can get infected and if these infections are not treated quickly, they can lead to blindness

Question 30

external host defences - GI tract - mouth

Answer 30

• saliva (lactoferrin, lysozyme, phospholipase, slgA)

Question 31

external host defences - GI tract -STOMACH

Answer 31

low pH

proteolytic enzymes

Question 32

external host defences - GI tract - small intestine

Answer 32

-bile salts - act as a detergent
- fast flow/ rapid peristalsis
- mucus, sloughing of cells

Question 33

external host defences - GI tract - large intestine

Answer 33

• slow flow/ abundant resident microbiota
• mucus, sloughing of cells

Question 34

external host defences - GI tract

Answer 34

• peyers patches (mainly ileum and rectum)

Question 35

external host defences - urogenital tract

Answer 35

bladder
- flushing action of sterile urine
- lysozyme, lactoferrin, phospholipase, slgA
- low pH
- urethral sphincter

vagina
- resident microbiota - low pH
- sloughing of cells
- flow of vaginal fluid

cervical plug

Question 36

bacterial pathogens major strategies to colonise mucosal surfaces

Answer 36

• adherent bacteria bind to the apical pole of the epithelium
• invasive bacteria disrupt and invade the epithelium

Question 37

colonisation of mucosal surfaces - penetrating the mucus layer

Answer 37

• may lack surface proteins/ carbs that bind muffins
• motility and chemotaxis: ability to move through mucus or into spaces between mucin strands
• partially digest mucin: produce mucinases that catalyse the hydrolysis of mucopolysaccharides
• target M cells - M cells are phagocytic - they sample the lumen- mucus tends to be thinner over the M cells
• exploit neutral pH

Question 38

slgA proteases

Answer 38

-slgA molecules simultaneously bind bacterial antigens and interact with mucins
- protease cleaves lgA in hinge region
- very specific for slgA1

Question 39

bacteria - resisting antibacterial peptides

Answer 39

• LPS (gram negatives) - Defensins are positively charged so they just bind to the LPS so they don’t get to the bacterial membranes
• capsular polysaccharide layer - Coats the bacteria - Protects them so peptides cant get to them
• cytoplasmic proteins to counteract defensin permeabilisation
• iron acquisition mechanisms

Question 40

bacteria - resisting low pH

Answer 40

• produce urease
• acid tolerance response
• possess H+ pumps

Question 41

adherence - first step in the establishment of bacterial disease

Answer 41

adherence to host cell surfaces is often the first step in the establishment of bacterial disease
- for extracellular bacteria: allows bacteria to withstand mechanical clearing mechanisms
- for intracellular pathogens: often a prerequisite for uptake

Question 42

adhesins

Answer 42

bacterial components that mediate interactions between the bacterium and host cell surface

Question 43

what can engagement of host cell receptors do

Answer 43

• target a pathogen to a particular niche
• coopt underlying signalling pathways
• establish persistent infections
• induce invasion: invasion protects bacteria from immune detection and facilitates access to deeper tissues

Question 44

what does adherence to mucosal surfaces require

Answer 44

receptor and adhesin

adhesins: component of bacterial cel surface
- pili and fimbriae: rod-shaped macromolecular structure from chain of polymerised subunits of protein called pilin
- afimbrial: cell surface proteins or polysaccharides not organised in a rod-like structure

• usually interact in a complementary and specific manner
• a bacterium may possess a single adhesin or several distinct adhesins simultaneouslt

Question 45

what other surface molecules aid in adhesion

Answer 45

LPS

adherence can also be mediated by biofilms: involves an extracellular polysaccharide slime that allows colonisation of surfaces

Question 46

colonisation of host surfaces - invasion

Answer 46

• some bacteria can gain access to cells not normally phagocytic
• attach to cell surface and cause changes in cytoskeleton resulting in engulfment

Question 47

invasion - trigger mechanism

Answer 47

• Bacteria produce a needle like structure that they use to inject proteins into the host cell
• These needle structures are called type 3 secretion systems
• These inject proteins that cause massive cytoskeletal changes
  The host cell comes up and surrounds that bacteria and engulfs it

e.g type 3 secretion systems of shigella and salmonella

Question 48

invasion - zipper mechanisms

Answer 48

• express surface protein that binds eukaryotic surface receptors (invasins)
• triggers a cascade of signals that leads to the formation of a vacuole that engulfs the bacterium

e.g. internalins A and B of listeria monocytogenes binding to E cadherin