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Summary Infections and Disorders
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The document summarizes the theory of all lectures from the course Infections and Disorders.
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INFECTIONS AND DISORDERSINFLAMMATION AND HYPERSENSITIVITY
Inflammation is a normal process characterised by harmful side effects. In inflammation, there is a primary
contact with an antigen. It may be removed by a primary (innate) immune response, but in some cases the
antigen persists and results in chronic inflammation. This results in a secondary (specific) immune
response. Chronic inflammations occur when there are inadequate feedback mechanisms, chronic
stimulations or when the antigen persists. This may result in destructions of neighbouring cells that should
not be destroyed.
Antigens that cause inflammation can be microbes, microbial products, viral infected cells, wastes, some
nutrients, “danger signals”.
Inflammation causes harmful side effects, such as cell and tissue damage, pathologies or even death.
Inflammation is usually, but not always, immune mediated à it means it is caused by an altered immune
response. When you have an exaggerated response to an “innocent antigen” (e.g. pollen, some food), we
talk about hypersensitivity instead of inflammation (an allergic reaction).
Characteristics of inflammation à pain, swelling (due to vasoconstriction), redness (due to vasodilation),
function loss (due to vasopermeability), fever, increased blood flow.
NB: inflammation is NOT the same as infection à infection refers to the entrance of antigens/microbes in
the organism, inflammation is the consequence of infection. Inflammation can be septic (internal, and no
infection) or aseptic (caused by microbes).
During inflammation, chemotaxis occurs à inflammatory cells are recruited, e.g. neutrophils (granulocytes),
monocytes. They are attracted by dead cells, antigens, chemokines (certain cytokines, messenger
molecules) or immune complexes (antigen+antibody).
During inflammation, also diapedesis of immune cells occurs à they leave blood vessels and enter the
surrounding tissue where infection occurs, and they cause inflammation and damage to tissue or
dysfunctioning of cells.
Steps of inflammation:
1. There is an infection in the body caused by bacterium or non-healthy cells (PAMP=microbial
molecules)
2. The complement system is activated; when C5a (anaphylatoxin) is activated it binds to receptors on
mast cells and activates them.
3. Mast cells release histamine, leucotrienes and other molecules that induce
vasopermeability/vasoconstriction/vasodilation, which cause decreased blood flow.
4. Thanks to decreased blood flow, leukocytes in blood can stop in the site of infection instead of
being transported away by blood flow.
5. At the same time, macrophages also detected the microbe and produce IL-1 (interleukin-1,
messenger molecule that attracts other cells of the immune system). IL-1 stimulates the endothelial
cells of blood vessels to secrete molecules like selectins and preformed-CAMS.
6. These molecules bind to receptors on leukocytes in the blood, so leukocytes can bind to the
endothelial cells of blood vessels and migrate in the infected tissue.
7. Leukocytes destroy the microbe and accumulate in the tissue, causing a reddish swelling à
inflammation.
Many diseases are related to inflammation, e.g. mastitis, obesity, covid, Alzheimer, asthma, pneumonia.
,When inflammation occurs, in blood and tissues you find higher levels of gamma-interferon, IL3/6/8/18,
insulin, glucose, leptin, prostaglandins, fatty acids omega 6.
Anti-inflammatory components are IL10 and 6, TGF-beta, TNF receptor, albumin, fatty acids omega 3,
natural auto-antibodies.
Natural-auto antibodies NAAb à auto antibodies are antibodies that you produce and “attack” your own
cells and tissues. High levels of natural auto-antibodies can be beneficial, as they can result in lower renal
and cardiovascular disease in humans, higher chance of survival in sheep. Low levels of NAAb are related to
diabetes, schizophrenia, depression, uterine inflammation, mastitis, liver inflammation. In summary, they
can protect you against inflammation.
Covid 19
Its corona is made of so called Spike proteins on the surface. On this protein there is the epitope where the
antibodies against it will bind.
The virus binds with the spike proteins to ACE2 receptors on epithelial cells in the lungs. The
problem with the variants of covid is that the spike protein have a different charge, and they can bind more
strongly.
Normally, viruses trigger in the organism an anti-viral interference response to eliminate it;
however, covid is able to block it so it is not recognised but causes a hyperinflammation. With covid it was
also observed Antibody Dependent Enhancement à it means that macrophages that should destroy the
antibody attached to the virus become overactivated, and start producing cytokines that make the situation
even worse with inflammation.
Food allergy and intolerance
We have 2 m2 of skin, 80m2 of lung tissue and 350m2 of gut tissue.
Reminder: the innate immunity is very fast and is made by phagocytes, dendritic cells, natural killer cells.
The adaptive immunity is made by T cells and B cells that produce specific antibodies. It is slower.
The primary immune response occurs when you infected with an antigen for the first time; you produce
non-specific antibodies against it. in the meantime, memory B cells “remember” about this antigen so when
you encounter it for the second time, your B cells can produce specific antibodies against it and in higher
amounts à secondary immune response, which is faster. Another difference is that the primary response
produces IgG and IgM antibodies, while the secondary produces mainly IgG.
The immune response is not constant during life à in young and old people for example hare much more
susceptible to death due to influenza. This because in these people the immune system is using more
energy to avoid possible inflammation, and uses less energy to provide a proper response to other
problems.
In our body we have about 1.5kg of microbes, especially in the gut so also the immune responses occur
mainly here (70%). Our annual food intake 750kg/year; in some cases, the immune system is into alarm
even when there is nothing wrong in your food.
NB: during life, the microbes in the gut are not the same. For example, the fetus is probably almost sterile,
but as soon as it is born, bacteria will get into its organism e.g. by simply passing in the vagina (so it takes
the microbes from the mother) or by breast feeding because milk contains nutrients that are used by
certain bacteria. In children, there are more different bacteria with solid feeding. In adults, there are
,complex and unique microbes. In old people, the diversity of microbiota decreases and there may be
altered species.
Food modulates immunity at four levels in the gut:
1. Microbiota composition and metabolites (outgrowth and adhesion pathogens)
2. Interaction with epithelium (cytokine production and barrier function)
3. Local activation of immune cells (local effects)
4. Migration of immune cells or uptake in blood (systemic/distant effect)
Dendritic cells in the gut mucosa are the cells that decide if the immune systems should react to a certain
food (hypersensitivity/allergy) or microbe, or if to stay tolerant.
Development of allergic symptoms à dermatitis on skin, food allergy in the gut, rhinitis/hay fever in the
nose, or asthma in the lungs.
There are many types of allergens: foods, fungi, trees, grasses, herbs, insects (bees, wasps), mites, animals,
drugs. Allergens are usually proteins, resistant to acid hydrolysis and to proteases (enzymes).
General concepts of allergy:
- Hypersensitivity à undesirable effects against a foreign stimuli; stimuli are usually tolerated and
are not harmful
- Allergy à it is a form of hypersensitivity caused by an (excessive) reaction of the immune system to
a substance
- Intolerance à it is not caused by the immune system, e.g. lactose intolerance is due to the lack of
the enzyme that breaks lactose down
- Hyperreactivity à excessive irritability, due to a physical stimuli e.g. smoke, dust, perfume, cold air.
Prevalence of food allergy is not known precisely; it depends on genetic factors, age, dietary habits.
The major food allergens according to the EU, and that should be declared in food, are 14 and include
gluten, peanuts, tree nuts, celery, mustard, eggs, milk, sesame, fish, crustacean, molluscs, soya, sulphites
and lupine.
A study found that allergies and diseases associated with chronic inflammations are increasing in the
population. This might be explained by the hygiene hypothesis à the decreased number of infections at
young age results in changes in the structure and activity of the immune system, and this enables a higher
development of allergic diseases.
It was found that children living in a farm, drink non-treated cow milk, that have pets, that go to
kindergarten have less allergies. Also eating food with probiotics and mycobacteria can reduce allergies.
We can develop immunotherapy to block the activation of immune cells against the allergens, so we don’t
have an allergic reaction.
NB: there is a strong interaction between gut and brain. This interaction occurs with molecules and with
nerves, such as the nervus vagus, so signals can go directly from brain to the gut. This means that if a
person is very stressed or has something wrong in the brain, it can affect its gut activity, or vice versa.
Consequently, also the immune system may be affected by such situations.
BACTERIOLOGY
, History of bacteriology
Bacteriology started around 1600-1700 with Anthonie van Leeuwenhoek. He was able to observe bacteria
with a microscope with magnification up to 450x and with one lens. He first observed bacteria associated
with disease in the pus of smallpox (vaiolo). Other microbiologists were Pasteur and Koch, that studied
microbes of specific diseases.
Pasteur found that bacteria and yeast make fermentation in food; found that heat is a preservation
technique (pasteurisation); he found that weakened bacteria can be used for vaccination; he gave evidence
for the germ theory of disease; he rejected the theory of spontaneous generation of bacteria (which said
that they can generate a caso from non-living material e.g. cadavers, dust).
Koch made a lot of work on cultivation of bacteria and developed solid culture medias to grow them. He
identified the causal agents of anthrax, tuberculosis and cholera. He developed the Koch’s postulates and
studied tropical diseases e.g. malaria. He got a Nobel prize in 1905. Koch’s postulates were used to
determine if a microorganism is the cause of a certain disease:
1. The microorganism must be found in all organisms suffering from the disease to be its cause, but
not in healthy organisms
2. The microorganism must be isolated from a diseased organism and grown in a pure culture.
3. The culture organism should cause the disease when introduced in a healthy organism
4. The microorganism must be reisolated from the inoculated host and identified as being identical to
the original specific causative agent.
Limitations of the postulates à not all pathogens can be cultured, not all pathogens can cause disease in all
animals.
The first bacterial genome was sequenced in 1995.
Main developments in microbiology:
- Microscopy
- Culturing techniques to grow bacteria in liquid culture or pure culture
- Antiseptic techniques, to work in a sterile environment
- Molecular biology, e.g. genome sequencing to identify the genes that cause disease and that cause
antibiotic resistance in the bacterium, and in vivo technology
Classification of bacteria
There are 5x1030 bacteria on Earth, divided in 3 million species of which 3500 are described. They are very
small, around 0.1-10 micrometers. They are classified based on morphological characteristics (e.g. shape,
inside of cells), growth characteristics (e.g. what environmental conditions they need to grow), biochemical
properties, and molecular techniques.
To study them, you have to take a sample from an infected individual and then culture it in the lab. You can
culture them on the Petri plates in two ways: semi-quantitative if you make horizontal lines, or
quantitative if you make zigzag lines.
Steps to study them:
1. Make a pure culture
2. Study morphology
3. Study biochemical properties, antigenic properties and growth characteristics
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