Cellular basis of the disease Bianchi Flashcards
a pathologic event not controlled or modified by the cells
Passive necrosis, - It is caused by a severe exogenous/endogenous injury
What is necrosis usually characterized by?
- massive protein denaturation (e.g. excessive lowering of pH)
- ATP depletion
- cell and organelle swelling
- increased membrane permeability
- usually involves a group of cells
- inflammation
Types of necrosis?
Coagulative, fat, liqufactive, caseous.
Coagulative necrosis is characterized by?
Protein denaturation
Coagulative necrosis is a type of accidental cell death typically caused by ischemia or infarction. In coagulative necrosis, the architectures of dead tissue are preserved for at least a couple of days.[1] It is believed that the injury denatures structural proteins as well as lysosomal enzymes, thus blocking the proteolysis of the damaged cells. The lack of lysosomal enzymes allows it to maintain a “coagulated” morphology for some time. Like most types of necrosis, if enough viable cells are present around the affected area, regeneration will usually occur. Coagulative necrosis occurs in most bodily organs, excluding the brain.[2] Different diseases are associated with coagulative necrosis, including acute tubular necrosis and acute myocardial infarction.
Liquefactive necrosis is characterized by?
Liquefactive necrosis (or colliquative necrosis) is a type of necrosis which results in a transformation of the tissue into a liquid viscous mass. Often it is associated with focal bacterial or fungal infections, and can also manifest as one of the symptoms of an internal chemical burn
Fat necrosis is characterized by?
Adipose tissue destruction, triglyceride hydrolysis, Free fatty acids combine with Ca2+ and settle as chalky areas
Caseous necrosis is characterized by?
Caseous necrosis or caseous degeneration is a unique form of cell death in which the tissue maintains a cheese-like appearance. Unlike with coagulative necrosis, tissue structure is destroyed. Caseous necrosis is enclosed within a granuloma. Caseous necrosis is most notably associated with tuberculoma
whats apoptosis?
“Apoptosis is a type of cell death that is induced
by a tightly regulated suicide program in which cells destined to die
activate intrinsic enzymes that degrade the cells’ genomic DNA and
nuclear and cytoplasmic proteins…..”
apoptosis is characterized by?
*Reduction of cell volume (cell shrinkage)
*Chromatin condensation
Chromatin aggregates beside the peripheral region of cell nuclei forming well
defined aggregate
* Formation of cytoplasmic extrusion and apoptotic bodies
*Phagocytosis of dying cells and apoptotic bodies (efferocytosis)
Apoptotic signalling pathways:
EXTRINSIC pathway:
Activated by the interaction of some extracellular membrane receptors
there with specific ligands (e.g. interaction of R-Fas with FasL, TNF-α with
its receptor )
INTRINSIC pathway:
Also recognized as a mitochondrial pathway, it is activated by several
intracellular stress signals
APOPTOSIS: phases of the process?
- Initiating signalling
- Control and integration
- Common executive phase
- Removal of dead cells (also apoptotic bodies)
extrinsic death signals?
– FAS (FasL, vir. Inf. cells)
– TNFR
– TRAIL receptors (TR1-4)
All of them have a Death Domain
Intrinsic death signals?
– ER stress (unfolded proteins)
– nucleus (DNA damage)
– cytosolic (ROS)
Fas expressing cells are the main target of those cells that carry?
FasL, If these cells interact, Fas expressing cells are killed
Which protein family regulates apoptosis?
- Proteins of the Bcl family regulate
apoptosis
Anti-apoptotic: Bcl-2, Bcl-x
Pro-apoptotic: Bax, Bak
which damage sensors activate the Bax and Bak?
Bim, Bid and Bad of
Bcl fam.
what is the point of convergence between the extrinsic and intrinsic pathways of apoptosis?
Bid
hybrid of necrosis and apoptosis?
necroptosis
The process of necroptosis starts in a manner similar
to that of the ________ form of apoptosis
extrinsic
Does necroptosis require the activation of the caspases?
No, it is a caspase-independent mechanism
Which two kinases does necroptosis involve?
kinase 1 and 3” (RIPK1 and RIPK3)
steps of autophagy?
- Nucleation and formation of the isolation membrane (phagophore)
- Formation of a vesicle called autophagosome, from the isolation membrane,
in which intracellular organelles and cytosolic structures are sequestered - Maturation of the autophagosome by fusion with lysosomes, to deliver
digestive enzymes that degrade the contents of the autophagosome
- Maturation of the autophagosome by fusion with lysosomes, to deliver
if the apoptotic process fails, the cell might launch?
autophagy
Caspase-1-dependent cell death?
Pyroptosis
Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response
Entosis?
the invasion of a living cell into another cell’s cytoplasm
Parthanatos?
is a form of programmed cell death that is distinct from other cell death processes such as necrosis and apoptosis. While necrosis is caused by acute cell injury resulting in traumatic cell death and apoptosis is a highly controlled process signalled by apoptotic intracellular signals, parthanatos is caused by the accumulation of Poly(ADP ribose) (PAR) and the nuclear translocation of apoptosis-inducing factor (AIF) from mitochondria.[1] Parthanatos is also known as PARP-1 dependent cell death. PARP-1 mediates parthanatos when it is over-activated in response to extreme genomic stress and synthesizes PAR which causes nuclear translocation of AIFcell death instances should be considered as parthanatic when they depend on
early PARP1 activation
it continues the caspase independent cell death pathway
Netosis?
NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Various pathogens, antibodies and immune complexes, cytokines, microcrystals, and other physiological stimuli can cause NETosis. Induction of NETosis depends on reactive oxygen species (ROS), the main source of which is NADPH oxidase. Activation of NADPH oxidase depends on increase in the concentration of Ca2+ in the cytoplasm and in some cases on the generation of ROS in mitochondria. NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane.
