This document includes my personal lecture notes from lectures 1 through 24, the PO lecture on cancer is included as well. The document may be a bit long but there is overlap between the lectures.
CBI lecture notes
IMU – lecture 1 and 2
There has been knowledge on the concept of immunity from 1347 and onwards. People knew that
someone who survived the plague was more likely to survive.
The first clear reference to immunology was in china, they exposed people to a disease before they
got a disease.
Information in the immunology field develops very rapidly.
An immune response can either be against infectious microbes or against the modified self.
Each area of the body is drained by lymph nodes to which lymph fluid is sent. The spleen is a kind of
filter of the blood and contains a lot of immune cells as well.
Primary lymphoid organs: bone marrow and thymus (respectively B and T cells). In primary organs
immune cells can develop.
Secondary lymphoid organs are locations where immune cells go to/seed once they have developed.
Symptom of a throat infection:
Fever
Headache
Throat pain
Most symptoms are not caused by a microbe or virus but by the response of the immune system.
In the body mucosal surfaces are a combat zone, viruses and bacteria try to get in and the immune
system tries to keep them out.
In general, you've got an epithelial cell layer under which blood vessels and other cells are laid.
Overlying epithelial cells is a layer of mucus, this is difficult to penetrate, AMPs antimicrobial peptides
can be made by goblet cells in the mucus and these can kill of pathogens as well.
Once a virus enters the nose or throat it encounters the epithelial surface and encounters toll like
receptors.
TLRs have functions recognizing all kinds of molecules. In the cytosol there are also toll like receptors
(NLRs) present. Toll like receptors recognize different classes of microbes.
What does TLR4 recognize? Is a classic exam question
This figure should be known.
,First a TLR recognizes a pamp, then an intracellular cascade starts, and alarm molecules are
transcribed.
Damage to the epithelial layer also sound the alarm because chemicals inside cells suddenly are
outside cells, mainly acute phase proteins are released which upregulate proteases that kill bacteria.
Such proteins are an indication of inflammation.
There are innate and adaptive immunity.
Innate immunity is the first response, it reacts quickly but it is not very specific, there is no memory
for the specific pathogen. However, a few years ago it was discovered there is a type of training in
the innate response, so after multiple encounters a response will be more fiercely.
Sometimes activation of adaptive immunity is not necessary. However sometimes it is needed.
Adaptive immunity includes B cells and T cells.
Phagocytes are recruited to the site of infection. They are already in the site or come from the blood
through a process of extravasation. These cells will then recognize microbes and viruses usually by
toll-like receptors. There is a pathogen associated molecular pattern and a pattern recognition
receptor. So PAMP and PRR. PRR is the receptor on the host site. The phagocytes ingest the microbe
which also involves different receptors and mediators. Usually a phagosome fuses with a lysosome,
this causes the pH. is the phagosome to drop and everything in it will be killed (the phagosome is the
bubble in the phagocyte in which the microbe is eaten).
Phagocytes are also called granulocytes. It’s the same thing. There are
Neutrophils
Basophils
Eosinophils
Neutrophils are usually the first responders; they have a lobed nucleus and they have all sorts of
granules inside. They can quickly migrate to the site of infection. They are terminally differentiated
and have a relatively short half-life.
Neutrophils can also from nets. They can eat a lot of bacteria, but they can also explode, and sticky
insides will be spilt out into the environment trapping all sorts of bacteria and viruses. They are part
of the innate immune system.
Basophils play a role in the clearance of parasites; it is short lived as well and can direct T cell
differentiation. The main difference from neutrophils is that they are more specified towards allergy
and responses.
Eosinophils is more involved with inflammation and allergy.
Granulocytes release toxic substances into their surroundings, and they can phagocytose.
Granulocytes are short lived fast responders.
Monocytes are mainly found in the blood. They can become macrophages once they get the right
signals and enter the blood. So, monocytes are in the blood macrophages in the tissue. Monocytes
and macrophages are professional antigen presenting cells. They help clean the mess neutrophils
leave behind. They can present the pathogen they phagocytose which is their main important
function.
They can produce NTF IL1, IL12 cytokines which influence inflammation and enhanced adaptive
immunity. They can also produce factors that promote healing.
Dendritic cells are very specialized. They are basically macrophages 2.0. they are very good at taking
up antigens. They develop in the bone marrow from a hematopoietic stem cell.
,Dendritic cells have very long dendrites, they can even penetrate the epithelial cell layer. For
example, in the gut they can stick a dendrite into the gut and sense the lumen. They can for example
take up beneficial bacteria in the lumen and they induce tolerance to these bacterial, so they are
very importance in tolerance to certain bacteria.
In contrast to phagocytes they can present small peptides of a killed microbe. They basically ask
naive t cells if what they found is either good or bad.
Acetylcholine activates muscles and this causes shivering.
Noradrenaline activates brown adipose tissue and induces vasoconstriction of blood vessels. Fish
have a sort of behavior fever because they tend to swim to warm water when they are infected this
is induced by a TNF signal. Some viruses can even block this. TNF-alpha is meant to induce a
temperature increase if not hindered by certain pathogen.
Toll like receptors can sense pathogens and they are in and outside cells. Once activated first
phagocytes and granulocytes are recruited (innate cells). Macrophages arrive a little later.
Typical exam questions
What is an AMP? Peptides released by epithelial cells and innate cells that have an antibiotic like
function.
What is NOT true about macrophages? They are numerous in blood
They do secrete reactive oxygen species; they can secrete NF alpha and IL12 and are professional
APCs
Which antigens are recognized by the following toll-like receptors 2 4 and 9? Lipoproteins LPS and
DNA.
The level of detail is quite high.
IMU – Lecture 3 and 4
Epithelial cells make different factors to recruit cells from the surrounding lamina propria and from
surrounding blood vessels. Cells can sense the gradient of such factors and use this as a guide to get
to the right spot.
, leukocytes stick to the blood vessel wall and start rolling. Leukocytes get higher affinity receptors
and start to bind stronger. Therefore, they stick better. The adhesion becomes stable and from here
on the leukocyte can migrate into the endothelium.
Antigen presenting cells seek out specific locations to present found antigens. The body has locations
where such cells can meet a lot of T cells.
Innate vs. acquired immunity:
Innate
o Can also be trained, but is not called memory
o Early response
Adaptive response
o Matures over time and affinity increases
o Repeated exposure will lead to memory and more rapid clearance after multiple
encounters with the same antigen
o Later response, it takes a while to get antibodies
How does antigen presentation work?
Professional APCs: macrophages and dendritic cells.
The MHC complex is the basis of immunology. There is type 1 and type 2 MHC.
All nucleated cells have MHC class 1 - this is a receptor complex on the surface of cells. The cell will
present small waste products on the surface which immune cells will recognize as self. If something is
wrong in the cell, for example when a virus infects, the MHC will change and be recognized as non-
self and this functions as an alarm to the immune system.
MHC class 2 presentation is done by the immune system itself. This receptor presents things that
have been phagocytosed. MHC-class 2 is recognized by adaptive immune cells.
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