Immunology (Jeremy - Microbiome) Flashcards
Is is estimated that there are more microbes in your ‘…’ than there are human cells in your body
Intestine
How do babies initially acquire their microbiome?
Vertical transmission
- Passage from mother to child
What are some points of mother child contact that microbe contact can occur?
1) Mammary
- through breastfeeding
2) Cutaneous
- contact with skin
3) Vaginal
- passage through birth canal
Name some factors that can reduce the acquisition of early microbiome
- Bottle feeding
- Early-life antibiotics
- Early/extensive bathing
What is the microbiome?
Collectively all the microbes in the human body
- can include pathogenic microorganims
Organisms of the microbiota come from which of the major domains of life?
All of them!!
- Bacteria, Eukarya and Archea
- Huge diversity
Are the amounts of different microbes the same throughout the body?
No!
- Microbe amounts will vary depending on niches and selection pressures e.g. the low pH of the gut
What project was undertaken to determine the human microbiome?
The NIH Human Microbiome Project
What is the name for a microbe that is part of the microbiome but can cause disease when the individual is immunocompromised?
Opportunistic
What factors can cause the microbiota to fluctuate?
- Diet (e.g going from eating meat to being vegetarian)
- Hygiene
- Hormones
- Age
- General health
- Drug therapies (e.g antibiotics)
What is microbial antagonism?
- Bacterial biota benefit the human host by preventing the overgrowth of harmful microorganisms
What are endogenous infections?
Infections caused by biota that are already present in the body
What are the major barriers for microbes entering the gut?
- low pH
- saliva and bile
- immune system
- intestinal wall attachment
- varied diet (fluctuation in nutirent sources)
Name some essential task of gut microbes
- Digestion
- Vitamin production
- Many others
How do antibiotics influence the natural flora? What result can this have?
Kill the infectious bacteria but also disrupt the natural flora
Can cause problems such as yeast infections, digestive problems etc
How can the gut flora modify chemotherapy drugs?
- Can modify drugs during metabolism
- Can have adverse effects such as an upset stomach
- Sometimes can improve the efficacy of the drug
Name some diseases correlated with altered microbiota
- Obesity
- Childhood-onset asthma
- Inflammatory bowel disease
- Colorectal carcinoma
- Cardiovascular disease
What is the gut-brain axis?
- 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
How can the intestinal microbiota regulate NFkB signalling?
- 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
How can the intestinal microbiota regulate adaptive immune activation
- 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
What are the effects of ‘peace-keeping’ bacteria such a SFB on the intestinal compartment?
- 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
How does altered gut flora cause ‘pathological inflammation’?
- Less ‘peace-keeping’ bacteria
- More pathogenic bacteria
- Damage to epithelial barrier, bacterial penetrance
- Pathological inflammation
Why is TLR-5 mediated sensing of gut microbiota necessary for antibody responses to seasonal influenza vaccination?
- 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
