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Summary Mechanisms of Disease

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Summary of the Mechanisms of Disease course.

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Adult stem cells – examples are; hematopoietic stem cells (blood stem cells, in
bone marrow), mesenchymal stem cells (connective tissue), epidermal stem
cells. These stem cells are tissue specific and can’t change into anything
else. They are multipotent.
Allo-immunity – an immune response against a different organism or individual.
For example, if the mother creates allo-antibodies against the baby.
Angiogenesis – the formation of new blood vessels. It involves the migration,
growth and differentiation of endothelial cells which line the inside wall of blood
vessels. VEGF (vascular endothelial growth factor) is crucial for this process.
Cells that encounter a high level of VEGF will become tip cells and start to
express tip cell genes. Through lateral inhibition (regulated by VEGF and
notch) the cells surrounding this tip cell will have an inhibited VEGF expression
and become stalk cells. Other important angiogenic factors are; bFGF, IL-8 and
TGF-β. The process of sprouting angiogenesis is also regulated by Rab5C,
since it prevents the degradation of the VEGF receptor.
Antigen-presenting cells – there are three types; dendrites, macrophages and
B-cells. Dendrites are considered to be professional cells, because they can
travel and interact with T-cells.
Antigens – there are neoantigens, which are caused by mutations (for example
in cancer cells). They are attached to antigen presenting cells. Tumor cells
can escape through the loss of antigens, so they are not recognised by the
immune system.
Autophagy – the natural, conserved degradation of the cell that removes
unnecessary or dysfunctional components through a lysosome-dependent
regulated mechanism. If a pathogen is removed through autophagy, it is
called xenophagy. It is activated by pattern recognition receptors.
Pathogens can become ubiquitinated and then recognised by the
autophagosome.
Bacterial evasion – strategies that protect against bactericidal mechanisms.
For example; they can neutralize reactive, toxic hydrogen peroxide (reactive
oxygen species). They can alter their cell wall structure so antimicrobial
peptides (or ubiquitin) cannot bind anymore. They can also block NADPH
oxidase. Mycobacterial lipids inhibit phagosome maturation and, in that way,
evade autophagy. These lipids inhibit the recruitment of calcium to PI3K.
Cadherins – transmembrane proteins (so they have an intra- and extracellular
part) that mediate homotypic cell-cell adhesion. So, they differ from
integrins because they don’t interact with the ECM. Their function is
dependent on calcium. VE-cadherin (vascular-endothelial) is the main
cadherin in endothelial cells. They have an extracellular domain with which they
bind to each other. Intracellularly they have cytoplasmic tails which
connect to the cytoskeleton in the cell. Through this mechanism cells can
shape themselves.
Cancer stem cells – a small subpopulation of self-renewing malignant and
oncogenic cells that drive tumor initiation and progression.
Cancer vaccines – can be; cell-based, viral-based, peptide-based and nucleic
acid-based.
CAR T cell – a type of cancer therapy. A T cell with chimeric antigen receptors
(CAR), so there is no T-cell receptor, instead there is an antibody fragment.
It redirects the specificity and function of T lymphocytes and thus depletes the
entire body of the type of cells it is specific for. So, it cannot be used for
cancers in crucial organs. The advantage of this therapy is that antibodies can
recognize cell surface proteins that do not need to undergo activation or
anything like this.

, Cardiac dyad – the site of communication between the sarcoplasmic reticulum
(SR) and infoldings of the sarcolemma, called transverse-tubules. They are
involved in calcium release, leading to hearth contractions.
Cardiomyocytes – a type of heart cells. They are responsible for generating
contractive force in the intact heart. Specialized cardiomyocytes control the
rhythmic beating of the heart. After injury, existing cardiomyocytes in the
border zone will divide and form new cells. This process (wound healing in the
heart of zebrafish) occurs due to signalling of prrx1, lrrc10 (inhibits
proliferation) and nrg1. The cardiomyocytes in the border zone are highly
involved with glycolytic processes, regulation of the cell cycle and stress
response. Remote cardiomyocytes have reduced expression of genes related to
the respiratory chain, mitochondrion and the oxidation-reduction process.
This is interesting because these cells usually use lipid acids to get energy.
Apparently, this type of proliferation is dependent on glycolysis. In humans,
cardiomyocytes do not proliferate and thus the heart cannot regenerate.
Calcium is crucial for contractions of the hearth (levels go up right before
contractions).
CD4+ T cells – a type of helper T cell and lymphocyte. They help coordinate the
immune response by stimulation other immune cells to fight infection. They are
restricted to MHC II antigens.
CD8+ T cells – also known as cytotoxic T lymphocytes. They are very important
for immune defence against intracellular pathogens and tumor
surveillance/killing. They are restricted to class MHC I antigens. This means
that they bind to HLA I receptors and become activated if pathogenic factors
are also bound here. When T-cells are activated, they divide. Because of
this, high levels of proliferation factors can be associated with T-cell activation.
Cell migration – single cell migration can be either mesenchymal and
proteolytic, which is dependent on integrins. It can also be amoeboid and
non-proteolytic, meaning that it can move by itself, without the help of
integrins. There is also collective cell migration which can be seen in
intestinal epithelial migration or the epidermis during wound healing. Leukocytes
have transmigration and interstitial migration. A special form of cell
migration occurs in sprouting angiogenesis (stalk cells and a tip cell).
Cell surface receptor – there are three types; ion-channel-linked receptors, G-
protein-linked receptors and enzyme-linked receptors. The signal molecules
binding to these receptors are usually hydrophilic. G-protein can activate
adenylyl cyclase leading to cyclic AMP and finally protein kinase A, this in turn
influences gene regulatory proteins.
Checkpoint blockade – immune checkpoints are proteins that regulate the
immune response. They can be either stimulatory or inhibitory towards T-cell
activation. By blocking the inhibitory checkpoints, T-cells are activated to kill
the cell. This is a promising type of therapy, especially for cancer. CTLA4
(inhibitory) and CD28 (stimulatory) bind to the same receptors, so there is
competition between these two. PD1 is expressed after activation of a T-cell. This
sends an inhibitory signal to the T-cell, to prevent exhaustion of the cell.
By blocking PD1, the T-cell is revived. The more mutations in cancer, the better
checkpoint blocking works.
Chemotaxis – the directed migration of a cell in response to a chemical
stimulus, such as a growth factor. Usually, the cells move across a chemical
gradient. For example, cancer cells and immune cells use this mechanism.
Clostridioides difficile – a type of gram positive, rod shaped, spore forming
(causing recurrence in patients), anaerobe bacteria. It is a pathogen, since it
secretes toxins. The toxins contain four domains; the N-terminus (catalytic
domain, glucosyl transferase), a protease domain (autocleavage, cytoplasmic
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