purpose of cell death death and digestion

apoptosis

the ADAPTIVE removal of cells such as immune cells that have completed their function and best serve the body by dying and getting out of the way

necrotic cell death

MALADAPTIVE and can induced by infection. bursts cells open, potentially releasing infective virions, and it stokes the fire of inflammation

ATP

membrane integrity

Necrosis can ensue when there is a release of 2 critical factors:

-normal cell

-cell swells up

-cell bursts open

-enzymatic digestion and leakage of cellular components

-causes inflammation

what are the steps of necrosis?

-normal cell

-atrophy

-apoptotic body forms in blebs

-phagocytosis of apoptotic cells and fragments

**no inflammation

what are the steps of apoptosis?

-removal of infected or malignant cells

-normal development

-cell turnover

what is apoptosis essential for?

B cells and T cells

what cells get killed by apoptosis to prevent autoimmune diseases?

Bcl2 and Bcl XL

what are the inhibitors that block BAX and BAK?

TNF-alpha

ROS

Fas ligand

what pro-inflammatory signals induce apoptosis?

p53

what activates BAX and BAK

P53

the stress sensor protein that is known as the guardian of the genome

BAK and BAX

pro-apoptotic proteins that insert themselves into the mitochondrial membranes to form channels for cytochrome c to escape

initiators and executioners

what two enzymes work in the proteolytic caspase cascade to kill the cell?

Fas ligand

TNF-alpha

soluble TNFR ligands that are secreted by NK cells and Cytotoxic T lymphocytes (CTLs) to induce extrinsic apoptosis

perforins

secreted by CD8 and CTLs that creates holes in target cells

phosphatidylerserin

a phospholipid in the inner leaflet of healthy cellular membranes but is flipped/exposed in outer leaflet to mark apoptotic bodies for removal by phagocytes

-pathological

-host inflammatory response

-energy independent

-cell swelling and lysis

-membrane integrity lost

-caspases not activated

-leakage of lysosomal enzymes

-no DNA cleanage

characteristics of necrosis:

-physiological or pathological

-anti-inflammatory response

-energy dependent

-cell atrophy without lysis

-membrane integrity maintained

-caspases activated

-no lysosomal enzyme leakage

-DNA cleavage

characteristics of apoptosis:

eat-me signals or non-self molecular patterns (PAMPs)

what signals are secreted by cells targeted for cell death by phagocytosis?

degradation

acidification

oxidation

what 3 processes occur in the target cells once engulfed by the phagocyte?

ATPase

what enzyme completes acidification?

NADPh oxidase

what enzyme completes oxidation?

proteases

what enzyme completes degradation?

microautophagy

macroautophagy

chaperone-mediated autophagy

what are the 3 types of authophagy?

microautophagy

the lysosome fold inwards and engulfs debris. next the debris is degraded by lysosomal acid hydrolases that catalyze bond cleavages by rxn with water at low pH

macroautophagy

bulk enclosure of debris/pathogens in vesicles called autophagosomes. autophagosomes then fuse with lysosomes to form autophagolysosomes for debris removal

chaperone-mediated autophagy

proteins are shuttled to lysosome by chaperone proteins. next, the proteins are unfolded and translocated across the lysosomal membrane into the lysosome for degradation by proteases

-remove dysfunctional cells

-remove dysfunctional organelles

-clear damaged proteins

-digesting and clearing pathogens

what are the purposes of autophagy?

true

TRUE OR FALSE: all 3 forms of autophagy are ATP dependent

small debris (carbs, lipids, proteins)

what does microautophagy digest?

big debris (carbs, proteins, lipids)

what does macroautophagy digest?

proteins

what does chaperone-mediated autophagy digest?

pathogen degradation

intracellular pathogens (bacteria, parasites, and viruses) that are either free inside the cytosol, inside phagosomes or inside pathogen containing vacuoles are surrounded by isolation membranes. engulfed into autophagosomes, which fuse with lysosomes, and then degraded inside autolysosomes

viral recognition

viral nucleic acids are transferred by autophagy from the cytoplasm to intracellular compartments containing Toll-like receptor 7 (TLR7) which signals the induction of type 1 interferon (IFN) production

antigen presentation

viral antigens (and potentially other endogenously synthesized microbial antigens and self antigens) are engulfed into authophagosomes that fuse with MHC-class-2-containing late endosomes (MIICs) and then loaded onto MHC class2 molecules for presentation to CD4+ T cells. cytosolic antigens that ocntain a KFERQ recognition motif may also be directly imported into M2Cs by chaperon-mediated autophagy. CLIP, class 2 associated invariant chain peptide