Immunology (Jeremy - Microbiome)

Question 1

Is is estimated that there are more microbes in your ‘…’ than there are human cells in your body

Answer 1

Intestine

Question 2

How do babies initially acquire their microbiome?

Answer 2

Vertical transmission

- Passage from mother to child

Question 3

What are some points of mother child contact that microbe contact can occur?

Answer 3

1) Mammary
- through breastfeeding

2) Cutaneous
- contact with skin

3) Vaginal
- passage through birth canal

Question 4

Name some factors that can reduce the acquisition of early microbiome

Answer 4

• Bottle feeding
• Early-life antibiotics
• Early/extensive bathing

Question 5

What is the microbiome?

Answer 5

Collectively all the microbes in the human body

- can include pathogenic microorganims

Question 6

Organisms of the microbiota come from which of the major domains of life?

Answer 6

All of them!!

• Bacteria, Eukarya and Archea
• Huge diversity

Question 7

Are the amounts of different microbes the same throughout the body?

Answer 7

No!

- Microbe amounts will vary depending on niches and selection pressures e.g. the low pH of the gut

Question 8

What project was undertaken to determine the human microbiome?

Answer 8

The NIH Human Microbiome Project

Question 9

What is the name for a microbe that is part of the microbiome but can cause disease when the individual is immunocompromised?

Answer 9

Opportunistic

Question 10

What factors can cause the microbiota to fluctuate?

Answer 10

• Diet (e.g going from eating meat to being vegetarian)
• Hygiene
• Hormones
• Age
• General health
• Drug therapies (e.g antibiotics)

Question 11

What is microbial antagonism?

Answer 11

• Bacterial biota benefit the human host by preventing the overgrowth of harmful microorganisms

Question 12

What are endogenous infections?

Answer 12

Infections caused by biota that are already present in the body

Question 13

What are the major barriers for microbes entering the gut?

Answer 13

• low pH
• saliva and bile
• immune system
• intestinal wall attachment
• varied diet (fluctuation in nutirent sources)

Question 14

Name some essential task of gut microbes

Answer 14

• Digestion
• Vitamin production
• Many others

Question 15

How do antibiotics influence the natural flora? What result can this have?

Answer 15

Kill the infectious bacteria but also disrupt the natural flora

Can cause problems such as yeast infections, digestive problems etc

Question 16

How can the gut flora modify chemotherapy drugs?

Answer 16

• Can modify drugs during metabolism
• Can have adverse effects such as an upset stomach
• Sometimes can improve the efficacy of the drug

Question 17

Name some diseases correlated with altered microbiota

Answer 17

• Obesity
• Childhood-onset asthma
• Inflammatory bowel disease
• Colorectal carcinoma
• Cardiovascular disease

Question 18

What is the gut-brain axis?

Answer 18

• Gut microbiome with a high inflammatory status is associated with increased anxiety like behavior
• Low inflammatory status gives low trait anxiety
• Treating anxious mice with antibiotics and recolonizing them with a low inflammatory gut microbiota reduces anxiety

Question 19

How can the intestinal microbiota regulate NFkB signalling?

Answer 19

• Bacterial PAMPS bind to TLRs on the surface of intestinal epithelial cells
• This activates MYD88 which signals to NFkB via IRAK1
• NFkB translocates to the nucleus and induces transcription of pro-inflammatory cytokines and chemokines

Question 20

How can the intestinal microbiota regulate adaptive immune activation

Answer 20

• Phagocytes such as DCs sample antigens from the intestinal lumen/epithelium
• M cells in the Peyers patch also sample antigens
• DCs acquire bacterial antigens
• DCs migrate to mesenteric lymph node for adaptive immune activation

Question 21

What are the effects of ‘peace-keeping’ bacteria such a SFB on the intestinal compartment?

Answer 21

• Stimulation of the innate immune response
• DC cells that obtain sampled antigens of these bacteria migrate the the T cell area and initiate CD4+ T cell responses
• Most notable is T reg production
• T reg cells migrate to the lamina propria of the villi
• Secrete IL-10 that suppresses the immune cell in the lamina propria
• Prevents large scale inflammation
• Small amount of inflammation left, called ‘physiological inflammation’ strengthens gut bacteria in immunocompetent hosts

Question 22

How does altered gut flora cause ‘pathological inflammation’?

Answer 22

• Less ‘peace-keeping’ bacteria
• More pathogenic bacteria
• Damage to epithelial barrier, bacterial penetrance
• Pathological inflammation

Question 23

Why is TLR-5 mediated sensing of gut microbiota necessary for antibody responses to seasonal influenza vaccination?

Answer 23

• Bacterial flagellin passes through lining of intestines into circulation
• Recognised by macrophages, activating TLR-5 signalling and subsequent B cell activation
• This increases antibody production