Immunity across life Flashcards
How does immunity change with ageing?
Rapidly increases from birth, peak between 18-25 years.
Risk of infection is low for people under the age of 60 where it then starts to quickly increase.
Immunity begins to gradually decrease after the peak at 25, with a more rapid decrease at around 45 years of age.
There is a larger decrease if there has been illness, infection or operation.
Microbiota composition quite stable until old age, unless diet change and/ or antibiotic use. The development in early years is crucial for the composition of bacteria in the gut as the patient grows up.
In older age microbe diversity decreases which means there is less bacteria to fight infections, which decreases immune response.
This is said to be due to different factors such as diet, stress, inflammation and any health conditions.
How can breastfeeding aid immune development?
Pre-birth immunity?
IgG or IgA in breast milk potentially coats bacteria and may influence postnatal microbiota or immunity
Bacterial metabolites translocation from the gut to mammary glands
- can also translocate to placenta, which can help modulate the gut microbiome before birth
Bacterial metabolites at the maternal-foetal inferface drive epigenetic changes impacting foetal immunity, e.g. SCFA from maternal gut
Maternal IgG is involved in transplacental transfer of bacteria which impact offspring
Can help reduce risk of serious conditions later in life such as diabetes, stroke, cardiac infarction
Healthy maternal status helps to promote a healthy microbiome in their children
What provides antibodies to the baby during pregnancy and after birth?
What are these antibodies?
What is the development over pregnancy and breastfeeding?
IgG and IgA
- very affective to kill bacteria and viruses
IgG represents approx 75% if serum antibodies in humans
After birth the baby will start to produce antibodies itself after exposure to microbes that can stimulate all lines of defence to make these immunoglobulins.
Have full range by 4-5years
Main source from human milk
- increases during pregnancy
- after birth begins to decrease
Describe immunity status after birth?
Why is illness likely?
In neonates, the first line of defence is not full developed this means
- Physical barriers are immature e.g. thin skin, low sebum production –> more likely to suffer skin infections
- No micorbial flora to guard against pathogens
- Short length of respiratory tree –> easy access of pathogens to lungs –> plugging of respiratory tree by mucus-traps pathogens –> can lead to respiratory infection
- Less cough and sneeze reflex
Second line of defence
- Low number of neutrophils, macrophage, monocytes, dendritic cells
- Increase natural killer cells –> this is not higher than adults, when taking into account the smaller volume of blood they are in higher concentration
- Complement proteins are lower
- Phagocytosis, opsonisation, superoxide production, cytokines down-regulated –> lower ability to produce free radicals
Third line of defence
- Decreased relative B-cell, T-cell and immunoglobulin concentration
Having a weak immune system in early stages of life allows bacterial microbes to colonise the baby’s gut, skin, mouth and lungs. Studies have shown this weak immune system is deliberate. Learning to manipulate the system could lead to treatments for infections in newborns and perhaps even improve the way babies are vaccinated
What is the composition of colostrum vs milk vs cows milk?
Human colostrum (first 5/7 days after delivery)
- Total protein –> 23g/l
- Immunoglobulins –> 19g/l
- Fat –> 30g/l
- Lactose –> 57g/l
- Calcium –> 0.5g/l
Human breast milk
- Total protein –> 11g/l
- Immunoglobulins –> 0.1g/l
- Fat –> 45g/l
- Lactose –> 71g/l
- Calcium –> 0.3g/l
Cows milk
- Total protein –> 31g/l
- Immunoglobulin –> 1g/l
- Fat –> 38g/l
- Lactose –> 47g/l
- Calcium –> 1.4g/l
What are the bioactive compounds found in human milk?
- Immune cells (100billion cells/ day)
- Human Alpha-lactalbumin Made Lethal –> a protein complex between albumin and folic acid. Can have an antimicrobial activity
- Lactoferrin
- Eryhthropoietin –> hormone produced in renal gland to create new blood cells
- Bacteria –> unknown if it is full functional or not, whether antibodies alter the functionality
- microRNA and mRNA
- Growth factors –> hormones, enzymes
What antimicrobial proteins are found in human milk?
Lactoferrin
- Not usually found in formula milk
- Chelates iron and blocks siderophilic bacterial (need iron) growth
- Blocks absorption of bacteria and adhesion of viruses
- A protein
- Decrease in concentration after 2-3 days
sIgA
- Binds to microbial antigen and blocks adhesion enhances phagocytosis
- High in colostrum over first few days, then rapid decrease
Lysozyme
- Promotes bacterial cell wall lysis (similar to antibiotics, ‘natural antibiotics’)
- Help the body have a stronger response against harmful bacteria
- Increases sIgA
Alpha lactalbumin
- Useful in killing bacteria that causes respiratory infections such as Strepococcus Pneumonia
- Can identify abnormal malignant cells and induce apoptosis
- HAMLET protein –> Human Alpha-lactalbumin Made Lethal –> a protein complex between albumin and folic acid. Can have an antimicrobial activity
Lactahedrin
- Blocks binding of rotavirus
C3
- Precursors of opsonins –> up-regulate T and B cell function (2nd line of defence, main protein controlling the compliment system)
- Enhance immune cells
- Up-regulate inflammatory response
Casein
- Inhibits adhesion of various bacteria
- Promotes growth of bifodobacteria
- Can be prebiotic
What is lactoferrin?
A antimicrobial component of human milk
- Not usually found in formula milk
- Chelates iron and blocks siderophilic bacterial (need iron) growth
- Blocks absorption of bacteria and adhesion of viruses
- A protein
Discuss sIgA in human milk?
sIgA in human milk are active against many viruses including enteroviruses, herpes virus, respiratory syncytical virus, rotavirus, rubella
- Many bacteria are targeted by sIgA in human milk e.g. E Coli, Salmonella, Campylobacter
- Function by binding directly microbials antigens blocking the adhesion, enhancing phagocytosis, modulating local immune function and contributing to the infant immune system development.
- Functions indirectly through anti-inflammatory properties which prevents adherence of microorganisms without activating the complement cascade
Why is human milk not sterile?
Contains a continuous supply of commensal, mutualistic and/ or potentially probiotic bacteria to the infant gut. The bacteria could protect the infant against infections and contribute to the maturation of the immune system.
Studies suggest that some bacteria present in the maternal gut could reach mammary gland during late pregnancy and lactation.
Modulation of the gut microbiota during pregnancy and lactation could have a direct effect on infant health.
What are the differences between breast-fed and formula fed infants in terms of immunity?
Have different composition of microbiome
Breast-fed infants
- The digestive tract is colonised primarily by Bifidobacteria –> higher abundance
- Has antimicrobial factors that lower the growth of facultative anaerobes
- Intestinal lumen is acidified more easily because human milk does not serve as an efficient buffer –> lower pH
Formula-fed infants
- The digestive tract is colonised predominantly by Bacteroides with some Bifidobacteria. Higher abundance of Bacteroides
- More complex flora consisting largely of facultative and obligate anaerobe, such as enterobacteria, streptococcus and clostridium
- Intestinal lumen is closer to a neutral pH
How does maternal gut bacteria travel to the infant?
Gut bacteria from the maternal gut leaves through a mesenteric lymph node and enters the entero-mammary pathway through the lymph/blood circulation and binds to the mammary gland epithelium where is then is transported to the mammary microbiota and into the colostrum/ milk microbiota where it is then given to the infant via breastfeeding.
What are the main factors determining the composition of breastmilk?
- Environmental factors
- Maternal diet
- Use of antibiotics
- Maternal genetics
- Lactation period
- Gestation period
- Maternal body composition/ physiological status before and during pregnancy
- Infant sex
All can contribute to composition of fatty acids, phospholipids, proteins etc in milk.
Diet and environmental factors are the most influential, also Maternal body composition/ physiological status before and during pregnancy
What are the potential pre-biotics in breastmilk?
Nitrate and nitrite
Found in colostrum
- Higher levels of nitrate than nitrite
Even higher in some formula milks
Nitrite can be converted to nitrate
Nitrite at high levels can be toxic
What is the hygiene hypothesis?
The decreasing incidence of infections in western countries at the origins of the increasing incidence of both autoimmune and allergic diseases.
The hygiene hypothesis is based upon epidemiological data, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation
Mechanisms are complex
Include decreased consumption of homeostatic factors and immuno-regulation involving T cells and some changes in microbiota, especially in inflammatory bowel disease
Allergic disorders/ autoimmune disorders related to
- Westernised countries
- Small family size
- Intestinal microflora-stable
- High antibiotic use
- Good sanitation
- Good access to medical services
- Low orofaecal burden
Non allergic disorders related to
- Developing countries
- Large family size
- Rural homes, livestock
- Intestinal microflora-variable, transient
- Low antibiotic use
- Poor sanitation
- High orofaecal burden –> contamination
- Lack of medical access and medical development
- High helminth burden
- Variation in diet could cause differences in microbiome
