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Summary lectures immunopharmacology
- Instelling
- Rijksuniversiteit Groningen (RuG)
Extensive summary of the lectures of immunopharmacology
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IntroductionCase study: rheumatoid arthritis
With this disease your joints are inflamed.
The cartilage keeps the bones from
grinding over eachother. The bone and
cartilage will showly be destructed
because the body thinks they cause the
inflammation. Many inflammatory cells
are present.
The disease is known for pain in the joints,
stiffness, muscle weakness due to the lack
of movement. It will also cause weight loss, fatigue and fever.
The disease is progressive at the starts therefore it needs to be treated hard and fast.
Treatment options are NSAIDs, corticosteroids and biologicals.
Paracetamol is not sufficient, while NSAIDs have a negative influence on the renal function.
Therefore, methotrexate is administered. Adalimumab is an antibody against TNF-alfa.
Vaccination is needed for going to Thailand on holiday. The risk of tuberculosis is increased
because TNF-alfa is absence. And TNF-alfa is needed to fight the tuberculosis. Fever is a
warning sign; the advice is therefore to go to a doctor.
Chapter 1
The immune system consists of two parts: the innate and adaptive immune system. Between
1800 and 1900, there is a 50% chance of surviving the first five years of life. Warning posters
are made to warm the people for different infections with do’s and don’ts. The first process
of vaccination is called variolation. There were two types of smallpox, the minor and major
variant. The people with the minor variant were immune for life, whereas the major variant
was deadly. Therefore, people were encountered with pus from the minor variant of
smallpox to achieve a form of vaccination. Multiple theories were invented to explain the
process of immunity.
,Rudolph Virchow discovered that pathological changes happen to cells. This is against the
germ theory of diseases. He is the first to use forensic analysis of hairs and systemic autopsy.
He was against the theory of Darwin. The Germans isolated and cultured many germs,
improved laboratory methods and discovered mycobacterium. The French invented
microbial fermentation and pasteurization, but also the principle of vaccination and busted
the theory of spontaneous generation. Paul Erlich is founder of the side chain theory, this is
called humoral immunity, which is later evolved to the adaptive immunity. Metchnikoff
came up with the theory that phagocytes protect the body, this is the cellular immunity
which is later evolved into the innate immunity.
The immune system always tries to restore a certain balance in the body (homeostasis).
When that balance is disrupted it needs to be restored as soon as possible. There are
multiple causes of threating that balance. Examples are bacteria, viruses, fungi, parasites
and objects. But sometimes things also need to be removed, you can think of dead cells,
tumors and tumor cells, artificial objects and damaged molecules.
The immune system is the protection of self. You can see the cell as a house with windows
and a lock in a forest. But it needs an alarm to activate the body to fight the intruders.
Epithelial barriers are present to prevent things from entering the body. If the body is
intruded by something that cannot be removed, help is activated from the bone marrow.
The bone marrow produces cells which help
cleaning up tissue damage. When this is not
enough, specialized help is received from
lymphocytes. T-helper cells are problem
solvers and delegate the problem. The
cytotoxic t-cells are the police squad that
actually fight the intruder. B cells and
antibodies are able to spread widely to be able
to protect a large area.
The innate system is needed to act fast!
The adaptive system is needed to be specific!
All leukocytes (white blood cells)
develop from stem cells in bone marrow
OR yolk sac/fetal liver. The stem cell
develops into a progenitor cell that can
differentiate into many types of cells. There are two types of progenitors: myeloid and
lymphoid progenitor. The lymphoid progenitor is responsible for the cells belonging to the
adaptive immune system. But some of them belong to the innate immune system.
,Antigen-presenting cells (APC), such as dendritic cells and macrophages, are phagocytosing
cells. They are strategically located and sample the antigens by fragmenting it into little
pieces. These pieces are then presented on the cell surface, they can be recognized by T
cells. The dendritic cell is the messenger which travels via the lymph nodes from tissue to
tissue to look for more specialized cells (B- and T-cells). APC’s are constantly patrolling the
tissues (mostly the tissues close to the outside world) to look for possible antigens to
present. They encounter each other in the lymphoid structures and communicate there.
To be able to have effective immunity, which is a complicated and delicate balance, there
are certain requirements. The body needs barriers for prevention of intruding, recognition
to be able to detect and identify the foreign substance, communication and organization for
coordination of organize the most optimal tissue response and effector mechanisms to
destruct or suppress the invading pathogen.
The immune system can be seen as a diffuse, body-spanning organ consisting of solid tissues
(organs), fluid tissues (cells) and fluid molecules (plasma). Solid lymphoid tissues are
everywhere. Primary lymphoid tissues are generative lymphoid organs (bone marrow and
thymus). The secondary lymphoid organs are sites for initiation of immune responses
(spleen, lymph nodes and mucosa-associated lymphoid tissue). Where the primary lymphoid
organs take care of development, selection and maturation, the secondary lymphoid tissues
are meeting places for immune cells and antigens. An antigen is any molecule that is
specifically recognized by lymphocytes or antibodies.
Primary lymphoid tissues consist of
bone marrow and the thymus. In
bone marrow, generation of all
immune cells take place. In the
thymus the maturation and
selection of T-cells take place. The
B-lymphocyte is generated in the
bone marrow and stays there,
where it because a naïve B-
lymphocyte. The T-lymphocyte is
generated in the bone marrow and
is then moved to the thymus
where it becomes a naïve T-lymphocyte.
Secondary lymphoid tissues consist mostly of lymph nodes.
They are part of the lymphatic circulation. The lymphatic
circulation drains tissues, collects microbial antigens and
delivers these to lymph nodes. Immune cells in the lymph
nodes sense and intercept pathogens, preventing their
spread through the body. The lymph node consists of the
cortex and the paracortex. B-cells are located in the cortex,
T-cells are located in the paracortex.
, The spleen searches for antigens in the blood. The red pulp consists of macrophages which
can remove damaged red blood cells and invaders. And is a reservoir for monocytes. The
white pulp consists of B- and T-cells for the adaptive response against blood-born antigens.
The tissues connected to the outside world have their own lymphoid structures, they are
called BALT, GALT and MALT, which means Bronchus-, Gut- and Mucosa-associated
lymphoid tissue.
Mucosal immunity in the gut
Inflammatory bowel disease can be caused by an improperly controlled immune response.
The gut is mostly the first point of contact with microbes. Food that is ingested comes in
contact with the gut’s mucosa layer. Most of the microbes are destroyed by the acidic
conditions in the stomach, but hardened microbes can make it to the intestines. The surface
of the gut is covered in villi, whose primary function is the absorption of nutrients. However,
these structures and the underlying tissues also host the largest population of immune cells.
Spread over the gut mucosa dome-like structures called Peyer’s patches are present. They
are primary sites for coordination of immune responses against pathogens whilst providing
tolerance for harmless microbes. The villi contain blood vessels to transport the nutrients
from food to the rest of the body. Lymphatic molecules are drained from the villi and Peyer’s
patches into certain mesenteric lymph nodes. The epithelial layer forms an important barrier
against microbial invasion. In the matrix of the Payer’s patch a mix of immune cells, such as
T-cells, B-cells, macrophages and dendritic cells, is embedded.
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