Interactions between the gut microbiota and immune system
A healthy microbiota may be critical for the immune system to function correctly.
The immune system is composed of two main parts:
- Non-specific immune system: this defends us against all pathogens in the same way no matter what they are. For instance, physical barriers like skin or chemicals in blood that react to anything deemed ‘foreign’.
- Adaptive immune system: this is specific and tests cells to see if they are foreign and then mounts a defence against those considered pathogens. It does this with the help of T-Cells and Cytokines to tell the immune system how to respond.
The adaptive immune system has to process and recognise all cells that it comes into contact with and then directs cells to attack pathogens. It also has a memory which is why it is called adaptive. Once it comes into contact with a pathogen, it can remember it so it can react more quickly in the future.
Vaccines train the adaptive immune system. They present the immune system with de-activated pathogens so it reacts more quickly to real pathogens and we don’t get as sick.
There are 2 responses with the adaptive immune system:
- Humoral response: this targets pathogens found outside of human cells i.e. in the blood (bacteria, worms, fungus). B-cells tag pathogens as invaders. Helper T-cells recognise projections on pathogen cell walls called Antigens and direct B-cells to create other proteins (antibodies) that latch on to the antigen and identify pathogens. It tags pathogens for other immune cells to destroy.
- Cell-mediated immunity: targets pathogens found inside cells i.e. viruses. Cells with pathogens inside them send signals. T-cells recognise these and send signals to cells to self-destruct. The gut microbiota interacts constantly with the immune system.
Remember that microbes are foreign. They are not our own cells yet we have then in and on our body
The immune system has to recognise they are foreign but not pathogenic, therefore the adaptive immune system constantly monitors the gut microbiota using a variety of cells located in the wall of the intestine. It tests microbiota to see what is there and stimulates the secretion of antibodies called Immunoglobulin A (IgA). This is specific to certain microbes and used by B-cells to tag pathogenic invaders.
When the immune cells in the gut secrete IGA in response to certain microbes, it influences the composition of the gut microbiota and protects beneficial microbes from host immune attacks.
There is a theory that the only reason we have an adapted immune system is to identify and tolerate microbial residents.
The microbiota incites the immune system to make IGA antibodies.
New-borns have far fewer cells that can secrete IGA compared to an individual with a fully developed microbiota, therefore microbiota stimulates the immune system. Also, germ-free mice lack immune activity and only colonization of the gut with bacteria can restore it. Mice without a developed gut microbiota are more susceptible to infection.
Beneficial gut microbes contain chemicals that attack pathogens and incite T-cells to react to pathogens.
Gut microbes affect the immune function outside of the gut.
Antibiotic use may reduce immune function in response to the flu virus.
Hygiene hypothesis: reduced immune function as a result of the immune system not being trained properly.
Exposure after birth affects the immune system but only in the critical infant period and not after. Gut microbes are not always beneficial. If the abundance of certain types change, it can lead to health problems.
Gut microbes can do damage if they get out of the gut. The gut lining and immune cells keep microbes out of the gut where they are healthy for us but they can get out and become an infection. The innate immune system attacks anything that crosses into the body from the gut. The adaptive immune system targets specific bacteria with antibodies. How do microbes get out? Eating certain foods causes inflammation which in turn causes a leaky gut.
Contained and helpful microbes vs loose and unhelpful microbes!
In this condition we see a virus that attacks CD4 T-cells (helper T cells within the immune system).
People think that the immune system is suppressed in cases of HIV but this is true only in part. There can also be a hyper-reaction causing inflammation. HIV sufferers have dramatically different microbes and live with compromised gut microbes leading to various diseases such as metabolic and cardiovascular disease.
Microbes that disappear in HIV patients are the microbes that induce T-reg cells.
HIV knocks out CD4 T cells resulting in:
- Decreased anti-inflammatory bacteria
- Increased pro-inflammatory bacteria
This results in inflammation which results in metabolic disease.
In HIV patients we see enriched Prevotellacae and decreased Bacteroides.