Feb. 3rd (Exam 1) Flashcards
When is NADPH oxidase assembled?
It is assembled after the fusion of the phagosome with the granules.
What is the respiratory burst?
This is the rapid oxygen consumption that produces toxic oxygen species.
What is the initial impact of the NADPH oxidase on pH and the activity of antimicrobial peptides / proteins?
The pH initially goes up and this activates the antimicrobial peptides and proteins.
These will kill the trapped pathogens.
What happens regarding the enzymes of the lysosome (hydrolases) once the phagosome fused with granules eventually fixes itself with a lysosome?
They will become activated once the pH has gone down from the initial burst.
What happens after the phagosome granule fusion fixes itself with a lysosome containing acid hydrolases?
The neutrophil will die because it cannot replenish its granules.
What are the two ways that a neutrophil can die?
- Apoptosis - engulfed by macrophages
- Netosis
What is netosis?
Netosis is the process of death where the nucleus swells and bursts, the chromatin dissolves, leaving cell remnants and antimicrobial proteins like defensins and proteases.
What does netosis form?
What do they do?
Neutrophil Extracellular Traps (NETs)
They trap and kill pathogens even after the death of the neutrophil.
What do the cytokines IL-1beta, TNF-alpha, and IL-6 do to the liver regarding the acute phase response?
They signal for the hepatocytes of the liver to make acute phase proteins like C-reactive protein and Mannose binding lectin protein, which activate the other pathways of complement activation.
What do the cytokines IL-1β, TNF-α, and IL-6 do to the bone marrow epithelium regarding the acute phase response?
They help mobilize the neutrophils that will phagocytize pathogens in the infected tissue.
What do the cytokines IL-1β, TNF-α, and IL-6 do to the hypothalamus regarding the acute phase response?
They increase the body temperature leading to impaired pathogen replication.
What do the cytokines IL-1β, TNF-α, and IL-6 do to the fat and muscle regarding the acute phase response?
They promote degradation of fat and muscle to create energy that increases body temperature leading to impaired pathogen replication.
What are pyrogens?
What are the examples?
These are cytokines that induce the systematic effect of fever (whole body).
IL-1β, TNF-α, and IL-6
What does higher temperatures grant us in the acute phase response?
- Less replication of pathogens
- Adaptive immune system is more potent
- Human cells become less sensitive to the effects of TNF-alpha
- We eat less, feel lethargic, and tired - all thought to preserve energy.
What is the cytokine that is responsible for the changes in proteins made by hepatocytes?
IL-6
What is the acute phase response summed up to be?
It really is the sum of the changes of the 30+ plasma proteins following an infection.
During the acute phase response, by what percent does the production of acute phase proteins increase?
by nearly 25%
What is the most abundant plasma protein?
What happens to its production during the acute phase response?
Albumin
goes way down
What happens to most of the production of the other plasma proteins during the acute phase response?
They go up.
What is the C-reactive protein a family of?
What kind of stuff does it bind to?
It is in the pentraxin family and it binds bacteria, yeast, fungi and parasites.
What is the purpose of the C-reactive protein?
- It opsonizes things and triggers the classical complement pathway
- It binds to phagocytes and bring them pathogens it has bound (remember it acts like a bridge)
What does Serum Amyloid A protein do?
This protein will bind to TLRs and to scavenger receptor (SR) B family, activating cells to produce inflammatory cytokines.
What is MBL?
Mannose Binding Lectin (MBL) is a C-type lectin (utilizes Calcium) that binds mannose containing carbs of the 4 categories of pathogens.
For each “flower” of MBL, how many carb recognition domains are there?
There are three for each flower (6 total flowers)
Do humans have mannose on their cell surface?
Why does MBL not bind?
Yes
The geometry is slightly differenent.
What does MBL circulate with it?
Zymogens that are called MBL-associated serine proteases.
- MASP 1
- MASP 2
What cuts/activates MASP2?
The binding of MBL to mannose.
What will MASP 2 do once it is activated?
- It will cleave C4, which some of the C4b fragment attaches to the cell membrane. (which is similar to C3)
- It will cleave C2 into C2a and C2b, which the former binds to the C4b on the pathogen surface.
What is the Classical C3 convertase?
C4bC2a convertase
Explain the other way of obtaining the classical C4bC2a convertase utilizing C-reactive protein.
C-reactive protein binds to the bacterias surface and interacts with C1
C1 looks just like MBL with MASP 1+2 bound and contains C1q to which C-reactive protein binds.
Upon binding, C1r (two copies) breaks itself and C1s.
C1s, after it has been cleaved will cleave C4 and C2 resulting in the same C4bC2a convertase.
Generally, how are interferons produced when there is detection of viral nucleic acids?
When there is a presence of viral nucleic acids in the cytoplasm, special sensor proteins detect them.
Once they are recognized, they activate signalling pathways that end with some type of transcription factor that triggers the expression of interferon genes.
