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Aantekeningen human immunology
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Aantekeningen van de colleges van het vak human immunology, met deze aantekeningen kan je het tentamen halen.
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Lecture 1Chapter 1: an overview
History of immunology
Understanding how our body can evolve to protect itself
Plague: survivors were less likely to be re-infected, most deadly disease
First reference of vaccination is from China. In the 1790s Edward Jenner develops a
protection against small pox (pokken). The 8-year old James Phipps was inoculated with
material from a cowpox.
Main functions immune system
Protect us from infectious bacteria, viruses and fungi
Protect from rogue cells (tumors)
Whilst preventing excessive collaborator against self-damage
The immune system can be divided into the
innate immune system and the adaptive
immune system.
The first line of defense are the physical barriers
are the skin (2 m^2) and the digestive, respiratory
and reproductive tract with the mucous membrane
(400 m^2)
A macrophage (macro = big, phage= to eat) crawls to the
compound that gives away danger molecules, when it
encounters it, it creates a phagosome (vesicle around
compound). This vesicle fuses in the macrophage into a
lysosome. It is destroyed, this process is called phagocytosis.
The innate immunity (2nd level of defence, inspecific) works with pattern recognition
receptors (PRRs). It is pathogen, species or variant specific. And is highly effective.
Myleoid progenitor make the innate immune cells. The innate immunity consists of NK cells,
macrophages and neutrophils.
Monocytes = cells that will mature into
macrophages and exit the bone marrow and
enter the blood.
The monocytes start looking for a crack
where they can leave the blood (and
mature).
The b cell produce antibodies, the helpter t
cell provide assistance and the killer t cell
kill infected cells
Macrophages wait for work that need to be done, if so they give of chemicals which increase
the blood flow (redness), cause endothelial cells to leave some space so fluid can leak out
(swelling) and release chemicals that stimulate the nerves to the brain (pain signals).
These proteins that are produced and secreted are called cytokines (hormone like
messengers), that facilitate communication between immune cells.
,The adaptive immune system (3rd level of defence, specific)
An antibody = soluble B cell receptor. The antibody pool is a complex of proteins, which are
coded by our genome.
Antibodies are produced by plasma B cells when there is an antigen present.
Antibodies
Different type of antibodies relate to different locations in our body
and contain additional features that make it locally especially
effective
Recognise invaders but led others do the dirty work
The Fc region (constant region) is mostly the same, two identical
hands (Fab region) differs
The Fc region determines the class of the antibody
IgD, IgM, IgG, IgE, IgA
Neutralisation
Opsonization
Many different antibodies are required because of
the specific binding to an antigen. This was found by
Susumu Tonegawa (1977).
Mature antibody are made by modular design. In
every B cell, that encode the antibody heavy chain
there are multiple copies of 4 types of DNA
molecules (V, D, J and C) aka gene segments.
Each copie is slightly different. These segments are
mixed and matched resulting in huge diversity. The
DNA for the light chain is also assembled by picking gene segments and pasting them.
This is not yet enough, therefore after gene segments are joined together additional DNA
bases can be added or deleted which is called junctional diversity.
Clonal selection takes place when the immune system is attacked. This means that more B
cells specific for an antibody are made. First, B cell receptors are made and transported to
the surface. They wait for the antigen that fits (cognate antigen). When it fits, the cell is
triggered and doubles in size and divide in two daughter cells, thus proliferation.
Neutralizing antibodies = antibodies that bind a virus outside the cell and keep the virus
from entering the cell or from reproducing (once it has entered).
Antibodies cannot do anything more once the virus is in the cell. Therefore, we have the killer
T cell. They are kind of similar to B cell, both produced in bone marrow, TCRs on surface
and a clonal selection.
T cells
Receptor always remains on the cell surface
Similar in construction as antibody
Requires antigen presentation
Cytotoxic CD8 T cells (CTL) will kill the target (viral infections): potent
weapon that can destroy virus infected cells
CD4 T helper cells (Th) will instruct / educate B and other T cells in their
activity: direct action by secreting cytokines like IL-2 and IFN-y
CD4 regulator T cells (Tregs) can inhibit or limit local immune function
activity: keep immune system from overreacting
, Antigen = a molecule or molecular structure or any foreign particulate matter or a pollen
grain that can bind to a specific antibody or T-cell receptor
Epitope = more specific, the part that is actually recognised by the antibody or t-cell
receptor. One antigen can contain multiple epitopes.
T cell antigen presentation
Class I MHC
Functions as billboards which inform killer T cells what is going on in the cell
Consists of a heavy chain
expressed on all nucleated cells
bound by CD8 T cells
Class II MHC
Consists of a alpha and beta chain
mainly expressed by professional antigen presentation cells (APCs)
display APCs problems that exist outside of the cells, to inform T helper cells
bound by CD4 T cells (2x4=8)
There are different layers of immunity and they all communicate together
B en T cells contain different and less DNA than other cells
The lymphoid system is a highway for your immune system, the immune cells can come
together in secondary lymphoid structures.
The primary structures are bone marrow and thymus.
Memory: the adaptive immune response has memory. If infected first the innate immune
system works, later the primary adaptive immune response is done. When another infection
is taken place the result is a stronger and bigger response of the adaptive immune system.
Lecture 2
Chapter 2: the innate immune system
The innate immune system contains complement proteins, professional phagocytes and
natural killer cells. These cooperate to defense our body and activated the adaptive system
if more complicate invaders enter out body.
The complement system is about 20 proteins that work together. It is produced mainly by
hepatocytes in the liver. It is already developed in the first trimester of foetal development.
Activity lead to production of the membrane attack complex (MAC) and recruitment of
immune cells.
3 pathways of activation
- Classical pathway (antibodies that are produced by the B cell section)
- Alternative pathway (main path)
o C3 falls apart into C3a and C3b (very reactive)
o C3b binds amino or hydroxyl group (end groups of all amino acids, so many
on the surface)
If it doesn’t bind it is neutralized by a water molecule
Our cells can inactivate C3b through an enzyme called MCP (bacteria
do not have this)
o Next a B complement protein binds to it. (C3bB complex formed)
o Complement protein D comes along and cliffs of a part of the B protein, a
C3bBb complex is formed
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