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Summary Immunopharmacology lectures
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- Rijksuniversiteit Groningen (RuG)
Summary of all Immunopharmacology lectures
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Immunopharmacology lecturesChapter 1
The immune system consists of innate immunity, this is the immunity that you are born with and the
adaptive immunity, this is the immunity that you develop during your life.
When vaccinations were introduced the amount of deaths by diseases decreased. Variolation was
the first vaccination and was against smallpox. Lady Montague took the practice of infecting with a
minor form of smallpox to England where it was tested on prisoners and children. There were several
theories that would explain the mechanism of how it works. Robert Hooke discovered cells and
Rudolph Virchow found out there were different cells, he described pathological changes to cells. For
the germ theory Robert Koch and Louis Pasteur were important investigators.
The immune system tries to restore balance in the body and thereby keep you healthy. The balance
in the body can be disturbed by bacteria, viruses, fungi, parasites and objects. Also it can be
disturbed by the removal of dead cells, artificial objects, tumors and tumor cells and damaged
molecules.
Cellular alarm systems detect whether there
is something wrong with the cell. Epithelial
barriers are the walls around the cells that
keep unwanted things from entering. Inside of
these cells there are tissue-resident immune
cells that protect the cells and see if all the
cells are healthy. When the tissue-resident
immune cells are not capable of restoring the
balance in the cells the bone marrow comes
to help. There are cells that clean up the mess
made. When these cells cannot handle it, the
specialised help from lymphocytes is required.
These lymphocytes can either be T-helper
cells, navigate other cells, or Cytotoxic T-cells,
kill cells. B cells and lymphocytes produce
antibodies. The innate immune system is very
fast but not flexible and does not have to
develop after birth, it is not specific therefore
it has limited recognition, limited memory and
limited recognition of self. The adaptive
immune system is specific, flexible but is slow,
it is able to recognize millions of antigens and
memorize these, it distinguishes self from
nonself, has fast expansion and needs to develop after birth. Immune cells develop from the bone
marrow or yolk sac/fetal liver. These cells develop into a progenitor cell that can differentiate into
many types of cells.
For effective immunity there are requirements:
- Barriers for prevention
- Recognition, for detection and identification of the foreign substance
- Communication and organization, coordination to mount the most optimal immune response
, - Effector mechanisms, to destruct or suppress the invading pathogen.
The immune system can be seen as a body-spanning organ that consists of solid tissues, fluid tissues
and fluid molecules. Primary lymphoid tissues are the bone marrow and thymus. Secondary
lymphoid tissues are the spleen and lymph nodes. In the primary lymphoid tissues the development
and maturation of the immune cells take place and in the secondary lymphoid organs there is the
meeting place for immune cells and antigen. In the bone marrow the generation of all immune cells
takes place. In the thymus the maturation of T cells takes place and the selection of non-self reactive
T-cells. What happens is that the progenitors from the bone marrow migrate to the thymus to
develop into naïve T-cells.
Naïve T-cells develop into
effector T-cells after
recognition of an antigen. The
B-cells stay in the bone marrow
to develop in naïve B-cells and
these recognise antigen, and
the develop into antibody-
producing plasma cells.
The innate and adaptive immune system is connected by the antigen-presenting cells (APC), these
are dendritic cells or macrophages. These cells are phagocytosing and have a strategic location to
allow for quick recognition of an unwanted substance. The dendritic cell travels from tissues to
lymph nodes to look for help from more specialised cells like the B and T cells. The APC patrols the
tissues, especially the ones that are connected with the outside world. Lymphocytes patrol the body
looking for antigens they recognise. The APC and lymphocytes find each other in lymphoid structures
like the lymphnodes and communicate with each other there. The lymphnodes are part of the
lymphatic circulation. This lymphatic circulation drains all the tissue from antigens and delivers these
to lymphnodes. Immune cells in the lymphnode sense and
intercept pathogens preventing their spread throughout the body
by initiating an immune response.
A lymph node has a cortex, outside, containing B cells and a
paracortex, inside, containing T cells. the T and B cells come in via
the bloodstream, when in the lymph node, they go to their
specialised area. The dendritic cell comes in via an afferent lymph
vessel and leaves the lymph node via the efferent lymph vessel.
Clogged lymph systems will cause you to be unable to get rid of
your fluids causing an oedema.
The spleen protects the blood from antigens and threats that might enter the blood directly. The
spleen also cleans the blood. The red pulp area is where the macrophages are to remove damaged
cells and senses if there are any invaders in the blood. The white pulp contains the B and T cells for
the adaptive response against blood-born antigens. Other tissues that are important to quickly
response to outside world are BALT (lungs), GALT (gut) and MALT (general).
When the body is busy beating an infection the lymphnodes in the body swell which makes them
visible. This happens because the adaptive immune system can expand quickly if necessary but can
also contract again, this is called clonal expansion.
, Chapter 2
Cells recognise dangers in different
ways, the innate immune system has
pattern recognition receptors which are
specific for damaged cells and
microorganisms whereas they have a
small variety. The adaptive immunity
system can recognise millions of
different things through antigen
receptors, their diversity is limitless. The
distribution of the innate immune
system is nonclonal, this means that the
receptors are identical on all cells of the
same lineage. Distribution of receptors
in the adaptive immune system is
clonal, meaning that clones of
lymphocytes with distinct specificities
express different receptors. The innate immune system can discriminate normal self and nonself,
they can see whether it is a healthy cell or a microorganism but that is it. Whilst the adaptive
immune system is selective based on selection against self-reactive lymphocytes.
To recognise microorganisms
characteristics needs to be
distinguished. Innate immune cells
recognise pathogen-associated
molecular patterns (PAMPS). These
cells also recognised damage-
associated molecular patterns
(DAMPS), these are recognised
because the cells start leaking parts
that do normally not leave cells. The
receptors that are able to recognise
these PAMPS and DAMPS are toll-like
receptors, C-type lectin receptors,
NOD-like receptors and RIG-like
receptors. These receptors are present on the outside and the inside of the
cell. The toll-like receptors are either on the outside sensing bacterial
product of the cells or in the endosomes to sense products taken up by the
cell. The C-type lectin receptors are only on the outside of the cell sensing
microbial polysaccharides. NOD-like receptors and RIG-like receptors are
only exist in the cytosol, the NOD-like receptor senses bacterial
peptidoglycans and products of damaged cells and the RIG-like receptor
senses viral RNA.
Toll-like receptors on the outside of the cell sense bacterial product and on
the endosomes are for the sensing of viruses and intracellular bacteria. Once the receptors recognise
a bacterial product, it will activate leading to the activation of transcription factors. After recognition
it will recruit adaptor proteins whereafter it will activate either the NF-kB pathway or the IRFs
(interferon regulatory factors) pathway. When the Toll-like receptor is on the outside of the
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