Inflammation, Apoptosis, And Response To Danger Signals

Question 1

What type of stimulus might activate the intrinsic apoptotic pathway?

Answer 1

Abnormalities in DNA
Lack of O2
Lack of nutrients
Lack of survival signals (mitochondrial dysfunction)

Question 2

What type of stimuli might activate the extrinsic apoptotic pathway?

Answer 2

Removal of survival factors

Proteins of TNF family

Question 3

The intrinsic pathway is __________-dependent, and occurs in response to injury

Answer 3

Mitochondrial

Question 4

Which apoptotic pathway is mitochondria-independent?

Answer 4

Extrinsic pathway

Question 5

Caspases are first synthesized as an inactive precursor called ________, which must be activated by ________ cleavage at specific sites

Answer 5

Procaspases

Protease

Question 6

Describe the general structure of a caspase after protease cleavage

Answer 6

Form a large and small subunit –> form a heterodimer

Question 7

What are the initiator caspases?

Answer 7

Caspase 8

Caspase 9

Question 8

What is the executioner caspase?

Answer 8

Caspase 3

Question 9

Generation of many molecules of executioner caspases in the caspase cascade result in cleavage of _______ protein and nuclear _______

Answer 9

Cytosolic; lamin

Question 10

The extrinsic pathway of apoptosis involves what two membrane receptor-ligand pairs?

Answer 10

FADD:Fas receptor binds Fas Ligand

TRADD:TNF-alpha receptor binds TNF-alpha

[occurs in CD8+ T cells only]

Question 11

What is the first caspase made by the extrinsic pathway of apoptosis?

Answer 11

Caspase 8 (which then combines with caspases 3, 6, and 7)

Question 12

CD8+ mediated death occurs in part because its expression of ____ increases upon antigenic activation as an anti-inflammatory response

Answer 12

FasL

Question 13

Apoptosis of which cell type carries the risk of bystander damage?

Answer 13

CD8+ mediated cell death, due to perforin and granzyme release, even though these are directed at target cell by adhesion molecule binding

Question 14

What is the difference between inflammation due to microbial attack vs. sterile attack?

Answer 14

Microbial attack due to PAMPs

Sterile attack due to DAMPs

Question 15

Which type of inflammation leads to collateral damage?

Answer 15

Chronic inflammation

Question 16

What are the cardinal signs of acute inflammation?

Answer 16

Pallor/Dolor (pain)
Calor (heat)
Rubor (redness)
Tumor (swelling)
Loss of function

Question 17

Describe the onset, duration, and specificity of acute vs. chronic inflammation

Answer 17

Acute: rapid onset, short duration, non-specific

Chronic: insidious/delayed onset, long duration, specific (involves acquired immunity)

Question 18

What are the cardinal signs of chronic inflammation?

Answer 18

Cardinal signs are absent in chronic inflammation

Question 19

What are the causative agents of acute inflammation?

Answer 19

Physical and chemical damage

Pathogen invasion

Tissue necrosis

Immune response

Question 20

What are the causative agents of chronic inflammation?

Answer 20

Persistent infection

Presence of foreign bodies

Autoimmunity

Question 21

What are the fundamental cells involved in acute inflammation?

Answer 21

Neutrophils

Mast cells

Platelets

Basophils

[in addition to all their soluble mediators]

Question 22

What are the fundamental cells involved with chronic inflammation?

Answer 22

B and T lymphocytes
Macrophages
Plasma cells
Antibodies

Question 23

Inflammation is resolved by ___________, which clean up cellular debris utilizing a special type of PRR called _________ receptors.

Specialized anti-inflammatory cytokines include IL-10 and TGF-beta

Answer 23

M2 macrophages

Scavenger

Question 24

How does necrosis compare to apoptosis in terms of cellular size and # of cells affected?

Answer 24

Necrosis: cell swelling, many cells affected

Apoptosis: cell shrinkage, one cell affected

Question 25

How does necrosis compare to apoptosis in terms of cellular content uptake and inflammation?

Answer 25

Necrosis: cell contents ingested by macrophages, significant inflammation Apoptosis: cell contents ingested by neighboring cells, no inflammation

Question 26

How does necrosis compare to apoptosis in terms of membrane integrity?

Answer 26

Necrosis: loss of membrane integrity, cell lysis occurs Apoptosis: membrane blebbing, but integrity maintained, apoptotic bodies form

Question 27

How does necrosis compare to apoptosis in terms of organelles?

Answer 27

Necrosis: organelle swelling and lysosomal leakage, random degradation of DNA Apoptosis: mitochondrial release of pro-apoptotic proteins, chromatin condensation and non-random DNA degradation

Question 28

_________ are molecules released by stressed cells undergoing nerosis that act as endogenous danger signals to promote and exacerbate the inflammatory response

Answer 28

DAMPs

Question 29

DAMPs are also called _______

Answer 29

Alarmins

Question 30

Binding of DAMP ligands to _____ induces intracellular signaling in the phagocytes leading to their activation

Answer 30

PRRs

Question 31

What are some examples of DAMPs due to cell necrosis?

Answer 31

``` dsRNA CpG Uric acid HMGB1 ATP HSP IL-1alpha ```

Question 32

What are some DAMPs associated with ECM degradation?

Answer 32

Hyaluronan | Heparan sulphate

Question 33

______ is a significant alarmin responsible for activating a cell by binding its receptor HMGB1 (high mobility box 1)

Answer 33

RAGE

Question 34

True or false: DAMPs are non-infectious, associated with cell damage or necrosis, and may occur due to radiation, surgery, burns, UV light, etc.

Answer 34

True

Question 35

The signaling system for detection of pathogens and stressors involves the assembly of a ________ sensor and adaptor, and the inactive caspase into the ________________ - which activates the caspase which in turn results in expression of IL-1

Answer 35

NLRP-3 | Inflammasome

Question 36

The inflammosome results in the production of what 2 potent inflammatory cytokines?

Answer 36

IL-1 | IL-18

Question 37

What is SIRS?

Answer 37

Systemic inflammatory response syndrome = pathogenic overstimulation of the immune response

Question 38

What is the effect of non-infectious SIRS?

Answer 38

Caused by DAMPs, leads to shock

Question 39

What is the effect of infectious SIRS?

Answer 39

Sepsis --> septic shock

Question 40

What are the symptoms associated with systemic SIRS and sepsis?

Answer 40

Fever Tachycardia Tachypnea Leukocytosis

Question 41

What symptom is characteristic of severe SIRS or severe sepsis?

Answer 41

Organ failure (due to lack of perfusion)

Question 42

What symptom is characteristic of shock or septic shock?

Answer 42

Hypotension

Question 43

What is the typical cytokine profile of SIRS?

Answer 43

IL-1 IL-6 TNF-alpha [these are the acute phase cytokines, which stimulate the liver to make more APPs including CRP and C' --> cytokine storm]

Question 44

Symptoms of SIRS appear during the hyper-inflammatory phase. The patient's immune system will try to provide a ______ During this period, the patient is significantly _________ The immune system will rebound again with a hyperinflammatory reaction, leading to another compensatory response. Each one becomes less severe until _______ is reached

Answer 44

CARS (compensatory anti-inflammatory response) Immunosuppressed Homeostasis

Question 45

______ is an inherited disorder of abnormal lymphocyte survival caused by dysregulation of the Fas apoptotic pathway

Answer 45

ALPS (autoimmune lymphoproliferative syndrome)

Question 46

ALPs leads to an excess of what cell types?

Answer 46

TCR alpha/beta CD3+CD4-CD8- (double negative T cells) These will accumulate in the LNs, spleen, and peripheral blood - results in lymphoproliferation, autoimmune disease, and malignancy