SSA15 Cancer and the immune system
There are cell specific (apoptosis, negative feedback) and tissue specific (anchorage
dependence) defense mechanisms against cancer. However, the immune system is also a
line of defense beyond this.
15.1 The immune system functions to destroy foreign
invaders and abnormal cells in the body's tissues
Antibodies specifically bind to antigens which are foreign. The antibodies can neutralize the
antigen, but they can also opsonize the target. Opsonization leads to recognition by
phagocytic cells like macrophages, but opsonized cells may also be killed by for example NK
cells. Next to this humoral response, there is also the cellular immune response. Cytotoxic T
cells (CTLs) can specifically recognize foreign HLA:antigen complexes with their TCR.
15.2 The adaptive immune response leads to antibody
production
Adaptive immune response begins when foreign particles are engulfed by phagocytic cells,
macrophages but mainly dendritic cells. In the skin there are special Langerhans cells that do
this. These antigen presenting cells (APCs) then digest this and present the foreign antigen
on MHC class II. This can activate helper T cells. These helper T cells then in turn activate B
cells that will then produce the antibody. The activation leads to maturation into plasma cells.
Antibody coating can neutralize or opsonize the cell, but it can also lead to complement
deposition which can lyse cells via the MAC formation. The immunogenic antigens are not
whole proteins, but oligopeptide fragments.
15.3 Another adaptive immune response leads to the
formation of cytotoxic cells
To activate a CTL response, the antigen needs to be
presented on a MHC class I molecule. Helper T cells can
also contribute to the activation of CTLs. These helper T
cells produce different cytokines than the once eliciting a
B cell response.
Cytotoxic T cells produce toxic proteins like granzymes
which are endocytosed by the target cells. One of this is
perforin which will punch holes in the membrane to lyse
the cell. Another killing mechanism is expression of
FasL. If this binds to the Fas receptor on the target cells,
the extrinsic apoptotic pathway will be activation.
Every cell presents antigens of all of its contents on MHC
class I molecules. Oligopeptide fragments of proteins
degraded by the proteasome are important into the
lumen of the ER via TAP. Here, it is loaded on a MHC
class I molecule via a complex.
15.4 The innate immune response
does not require prior sensitization
It is likely that the initial encounters of the immune system with cancer cells are made by NK
cells. They recognize configurations of cell surface proteins. After an NK cells has initiated
, the innate response, it also produced IFN-gamma to recruit other immune cells like
macrophages. By this, the adaptive response can also be initiated.
15.5 The need to distinguish self from non-self results in
immune tolerance
Self reactive cells are either eliminated via selection or strongly suppressed. There is a
central tolerance (selection) and peripheral tolerance (induction of apoptosis and
suppression). Via induction of tolerance, cancer cells can also evade the immune system.
15.6 Regulatory T cells are able to suppress major
components of the adaptive immune response
Tregs display CD4, CD25 and the transcription factor FOXP3. They also express TCRs
whereby they can specifically block the actions of CTLs with the same TCR. In the lymph
nodes the Tregs can suppress T helper cells and CTLs when they are in close proximity via
the production of TGF-Beta and IL-10. The proliferation is then suppressed.
15.7 The immunosurveillance theory is born and then suffers
major setbacks
Transplantation of a tumor with an active immune system can lead to allograft rejection. This
has nothing to do with the neoplastic nature of the cells, but just the foreign MHC
(histoincompatibility). In syngeneic hosts or in mice with a compromised immune system, this
rejection is not seen.
However, a setback was that nude mice which lack a functioning immune system were no
more susceptible to spontaneous arising of tumors than normal mice. However, although
these mice do not have functioning T cells, they do have a functioning innate immune system
with NK cells.
In an experiment in which certain irradiated cancer cells were injected and after a while the
live version was injected showed that tumor then did not develop. The initial exposure to the
dead cancer cells immunized the mice against the live cancer cells.
Voordelen van het kopen van samenvattingen bij Stuvia op een rij:
Verzekerd van kwaliteit door reviews
Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!
Snel en makkelijk kopen
Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.
Focus op de essentie
Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!
Veelgestelde vragen
Wat krijg ik als ik dit document koop?
Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.
Tevredenheidsgarantie: hoe werkt dat?
Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.
Van wie koop ik deze samenvatting?
Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper lottebambacht. Stuvia faciliteert de betaling aan de verkoper.
Zit ik meteen vast aan een abonnement?
Nee, je koopt alleen deze samenvatting voor €3,49. Je zit daarna nergens aan vast.