Lecture 32: Introduction to the human microbiota & barriers to infection

Question 1

Human microbiota

Answer 1

Microorganisms on our body surfaces
Microbiota:
Groups of micro-organisms living in a specific environment

NOT usually harmful, often vital to health
An individual’s microbiota is usually unique-
Age / diet/ lifestyle/ time of year.

Indigenous human commensals-

Beneficial for bacteria and the host,
Provides some protection against pathogens

Question 2

The Gut Microbiome

Answer 2

Essential for breakdown of our food
Synthesise essential vitamins B12 and Vitamin K
Research suggests the gut microbiome is involved in obesity… allergies, mental health, immune disorders

Question 3

opportunistic pathogens

Answer 3

Our indigenous human commensals CAN cause harm when the status quo is perturbed

Question 4

Burns patients-

Answer 4

Pseudomonus aeruginosa (Gram –ve)

Question 5

Colonic bacteria

Answer 5

UTI eg E.coli (Gram –ve)

Question 6

Skin flora

Answer 6

wound infection eg Staphylococcus sp. (Gram +ve)

Question 7

Oral flora

Answer 7

Tooth decay eg Streptococcus sp. (Gram +ve)

Question 8

Normal human microbiota

Answer 8

Skin
Upper Respiratory tract: Nose and throat
Lower respiratory tract
Digestive system: Mouth (Oral cavity) stomach/ small intestine/ large intestine
Urinary tract
Adult female genital tract
The different environments in our body will have different colonisers or microbiota-

Question 9

Normal human microbiota: skin

Answer 9

Divided into 3 microenvironments:
- dry skin ( arms and legs)
- moist skin areas- (armpits)
- areas rich in sebaceous glands
Natural colonisers:
G+ve bacteria
(THICK CELL WALL- Resistant to drying)
- Staphylococcus, Streptococcus, Corynebacterium & Propionibacterium
Don’t usually cause disease.
BUT skin wound can lead to infection e.g. Staphylococcus aureus

Question 10

Upper Respiratory tract: Nose and throat

Answer 10

Extensive bacterial flora

Natural colonisers:
Streptococcus, staphylococcus,
Neisseria & Haemophilus

Mucosal surfaces (digestive system, respiratory tract etc )

The upper respiratory tract is the nose and throat.
It has a lot of different bacteria living on it
4 different genus listed here which commonly colonize the upper respiratory tract.

3 species of bacteria cause bacterial meningitis-
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenzae

Most people will have these 3 species living at the back of our throats some of the time.
They usually don’t cause any problems because of our non-specific barriers to infection.

Question 11

Lower respiratory tract

Answer 11

Lower respiratory tract : trachea, bronchi and lungs.
This is usually sterile-
It is a common site for infection – Chest infections/ lung infections-
common bacteria which cause these are Haemophillus species and Streptococcus species.

Tuberculosis is a serious lung infection caused by mycobacterium tuberculosis. This infection used to be uncommon, and despite the fact that we have antibiotics to treat it, it is currently increasing in prevalence-

Of all our mucosal surface the respiratory tract is the most susceptible to infection.

Question 12

Digestive system: Mouth (Oral cavity)

Answer 12

Complex microbial ecosystem > 600 spp. of bacteria.
Gingival groove - anaerobes
e.g. Bacteroides, Actinomyces
- cause gum disease
Tooth enamel – facultative aerobes
e.g. Streptococcus
- some spp. cause plaque & tooth decay
Cheeks & gums – facultative aerobes
e.g. Streptococcus
- some spp. colonise saliva

Question 13

Digestive system

Answer 13

In our Stomach in contrast to our mouth we have very few bacteria.
Least colonized part of the digestive system.
Strong acid conditions, enzymes and is highly mobile.
Helicobacter pylori –can exist in your stomach: Causes gastric ulcers and has been linked to cancer.

The small intestine:
The duodenum is still very acidic, a lot of digestive enzymes and highly mobile envioronment-
Low number of bacteria
The ileum
Less acidic, less enzymes, less motile : the numbers of bacteria increase.

The large intestine is the most heavily colonized part of the digestive system
In your large intestine -very little oxygen so all the bacteria are either anaerobes or facultative anaerobes

Examples of the 3 most common bacteria in your large intestine:
The most common is bacteroides fragilis-the most usual cause of appendicitis.

Enterococcus faecalis doesn’t cause any problems in your intestine.
If it moves from your large intestine
can cause infections in your heart (biofilms endocarditis

E. coli not usually a problem.
Some strains can cause gut infections, it can cause UTIs if it ends up in the urethra.

Know the trends not the numbers.

Question 14

Urinary tract

Answer 14

Kidneys Ureter and bladder are usually sterile in a healthy adult.

The Uretha is lightly colonized (not many bacteria) and the upper part is kept mainly sterile by the flushing effect of the urine.
It is a common site of infection.
The most common cause of Urinary Tract Infections is
E.coli

Question 15

Adult female genital tract

Answer 15

The Adult female genital tract has a complex microbiota.
Will depend on a womans age, whether they have undergone child birth, they are menopausal, diet etc.

Its an acidic environment.
Lactobacillus grows at a pH range of 5.5.- 6.5

Candida albicans (a yeast) exists happily in the vagina
If there is an overgrowth causes vaginal thrush.

Question 16

Non specific defences against infection
Indigenous microbiota
BARRIERS

Answer 16

Skin
Mucosal surface
Blood and tissues

Question 17

Probiotics

Answer 17

Live Microorganisms that
prevent / treat conditions
e.g. antibiotic-associated diarrhoea

Question 18

Prebiotics

Answer 18

Chemicals that induce
growth /activity of microorganisms
- promote health

(tablets and yoghurts)
A source microorganisms which can help prevent or treat conditions – they are ‘good bacteria’ which support or change your original gut bacteria. The microbial population remains healthy.
Mixed research on effect
Often suggested that they are taken after a course of antibiotics

Question 19

Commensals

Answer 19

Pathogen must compete with natural microflora for adhesion sites and food

Question 20

Our first line of defence are our

Answer 20

indigenous commensal bacteria.
They colonise your surfaces- so invading pathogenic bacteria find it harder to colonise.
-Compete for adhesion( attachment) sites and nutrients.

Question 21

Defences of skin

Answer 21

Epidermis
Sweat gland
Gland associated
with hair follicles
Skin associated
lymphoid tissue (SALT)

Question 22

Defences of skin-Epidermis

Answer 22

physical barrier
Dry, acidic
Shedding cells
Its hard for pathogenic bacteria to colonise.
Few infections of the epidermis.

Question 23

Defences of skin-Sweat gland and Gland associated
with hair follicles

Answer 23

both secrete an enzyme called lysozyme.
This can break down the peptidoglycan which makes up bacteria cell walls.
Gram +ve bacteria are more susceptible to this than gram –ve bacteria.

Question 24

Defences of skin-Skin associated
lymphoid tissue (SALT)

Answer 24

Invading pathogens are detected by lymphoid tissue which induces a local inflammatory response.

Question 25

Defences of mucosal surfaces

Answer 25

Mucus
Epithelium
Mucosal associated lymphoid tissue

Question 26

Defences of mucosal surfaces- Mucosal associated lymphoid tissue

Answer 26

SALT
Responds to any invading pathogens which breach this layer by inducing a local inflammatory response.

Question 27

Defences of mucosal surfaces- Epithelium

Answer 27

Physical barrier
Shedding cells
Cilia
Cilia
Indigenous bacteria
low colonisation

Lined by an epithelium- which is made up of tightly packed cells-
This provides a physical barrier, constantly being shed.
Parts of the digestive tract are lined with cilia which will waft invading pathogens back up the throat

Question 28

Defences of mucosal surfaces-mucus

Answer 28

Traps bacteria
Lysozyme kills G+ve bacteria
Lactoferrin binds iron
Lactoperoxidase kills bacteria

produced by submucosal glands
Contains mucin,
traps bacteria-
Mucus contains a number of chemicals –
Lysozyme which breaks down bacterial cell walls,
lactoferrin which binds iron-
lactoperoxidase which indirectly kills bacteria.

Question 29

Barriers to infection

Answer 29

trachea
lungs
digestive tract
genial tract
skin
eyes
stomach
urinary tract
blood and lymph

Question 30

Barriers to infection- trachea

Answer 30

Mucus and Cilia to move microbes out of the body

Question 31

Barriers to infection- lungs

Answer 31

Mucus and phagocytes prevent invasion

Question 32

Barriers to infection- digestive tract

Answer 32

normal flora, enzymes, (incl. Lysozyme) & bacteriocins prevent infection

Question 33

Barriers to infection- genital tract

Answer 33

normal flora, acidic environment

Question 34

Barriers to infection- eyes

Answer 34

washing by tears. Lysozyme

Question 35

Barriers to infection- skin

Answer 35

normal flora, sweat & antimicrobial fatty acids.

Question 36

Barriers to infection-blood and lymph

Answer 36

proteins beneath skin inhibit microbial growth

Question 37

Barriers to infection- stomach

Answer 37

Low pH inhibits microbial growth

Question 38

Barriers to infection- urinary tract

Answer 38

urine acidity and flushing prevents microbial growth

Question 39

Defences of Tissue & Blood

Answer 39

Transferrin binds to iron very tightly so unavailable for bacteria to use in growth.

Mannose binding lectin
A soluble factor produced in the liver following infection.
It binds to patterns on the surface of bacteria cells- they are not very specific
One end binds to the bacteria and the other end binds to receptors on macrophage,
The macrophages can now recognize and phagocytose the bacteria.
It also increases the activation of complement so it is acting as a positive feedback mechanism.

Question 40

Non specific defences

Answer 40

skin
mucosal surfaces
blood and tissues:
Granulocytes/monocytes
Phagocytosis
Complement
Transferrin
Mannose binding lectin

Question 41

Indigenous microbiota

Answer 41

skin
respiratory tract
digestive system
female reproductive system
urinary tract

Question 42

The complement system

Answer 42

It is present in the blood stream, as over 30 components which circulate in an inactive state.
The complement proteins become activated following an infection –
this is a biochemical cascade- the activation of some parts of the system lead to activation of the others

Once activated the complement system has 4 main functions
Lysis
Complement protein binds to the surface of target cell and lyse the cells by punching holes in their membrane, releasing the cytosol and killing them

Opsonization
The bacteria become coated in activated complement proteins, this makes it easier for phagocytic cells to recognize the bacteria as foreign invaders,
macrophage and monocytes have receptors for complement on their surface. They recognize the opsonized bacteria as something they should phagocytose.

Activation of inflammatory response:
1 The complement protein binds to receptors on white blood cells,
this stimulates the migration of the white blood cell from the blood into tissue where there is an infection

2. Degranulation
   Basophils and mast cells have complement receptors on their surface,
   Complement protein binds it activates the cells - causes degranulation, and the release of inflammatory mediators.
   (degranulation just means cells release pre-made granules they have stored inside them. These granules are ready made anti-microbial compounds)

The mediators then stimulate other immune cells to the site of infection.

Clearance of immune complexes
At the end of an infection, you have a lot complexes left in the blood which are a combination of antibody and antigen.
If they accumulate they cause problems-
Complement ensures they are removed by binding to these complexes, phagocytic cells then recognize them as something they should ingest and breakdown.

Question 43

Non-Specific Defences: Blood & Tissues

Answer 43

Mechanism to fight any bacterial infection which get into our blood or tissues-
These are not specific to any particular type of bacteria- non specific.
They respond to any non-self invader.

As part of your white blood cells there are a group of leukocytes - Polymorphonuclear (PMN) leukocytes also called (Granulocytes).
These circulate in the blood and recognise and mop up invading bacteria.
3 types of granulocyte
Neutrophilis- these are phagocytic cells,
Eosinophils – which release cytotoxic substances which kill bacteria
Basophils -when stimulated release inflammatory mediators like histimine which induces inflammation.

Monocytes are larger cells which circulate in the blood.
When they migrate into tissues they become macrophages
ingest and kill cells by phagocytosis,

Complement
- Transferrin
- Mannose-binding lectin