Neutrophils 2 Flashcards
What are the tissue breakdown products that shrink the endothelial cells and make the venules more permeable?
Histamine, thrombin, leukotrienes and bradykinins
What is the difference between selectins and integrins in regards to neutrophils?
Selectins slow down neutrophils
Integrins stop neutrophils
When the venule is more permeable because the endothelial cells have shrunk what happens next?
- Fluids and proteins flow into the tissue
- This reduces the fluid in the vessel
- Oncotic pressure increases in the tissue which causes more fluid to flow out -→ Tissue swells and becomes red and painful (arachidonic acid)
- Flow of blood reduces (stasis)
What are Weible Palade Bodies and what do they contain?
Vesicles in endothelial cells
- P- Selectins
- vWF
- IL-8 (chemotactic factor)
What are Selectins?
Transmembrane glycoproteins that bind to sugar moieties and thus are considered to be a type of lectin
What happens when P-selectins are activated by histamine or thrombine?
It moves from the inside of an endothelial cell to the cell surface
What is the function of a P-selectin?
It functions as a cell adhesion molecule (CAM) on the inner surface of an endothelial cell
What is the function of the L-selectin on the surface of a neutrophil and the P-selectin on the endothelial cell?
The L-selectin binds to the P-selectin and slows the neutrophil down
What selectins show up on the surface of the endothelial cell after it is stimulated with IL-1 and TNF from macrophages?
L-selectins and E-selectins (they slow the neutrophils down)
When integrins are present on neutrophils are they called Cell Adhesion Molecules?
No. When they are attached to endothelial cells they are called CAMs. Same function though.
ICAM-1 is what?
Inter/intra cellular Adhesion Molecule
It’s an integrin
Difference between glycoprotein and proteoglycan
Whichever word comes later is the majority component
- Glycoprotein
- Glyco = small amount
- Protein = large amount
VCAM-1 is what?
Vascular Cell Adhesion Molecule
It’s an integrin
What are the 2 integrins on the surface of the neutrophil?
CD11 and CD18
What is LFA-1 and what is its function?
Leukocyte Function-associated Antigen-1 (LFA-1) is an integrin found on leukocytes. It plays a role in emigration which is when leukocytes leave the bloodstream.
In general, what effect do selectins and integrins have on the neutrophil in the blood stream?
Selectins: Slow neutrophil down
Integrins: Stop Neutrophil
What does CD-31 do to the neutrophil in the bloodstream?
CD-31 on endothelial cells “shakes hands” with CD-31 on neutrophil and begins to move it across the basement membrane toward the tissue (transmigration)
- All endothelium have CD-31
What happens when complement (like C5) lands on a bacteria?
It splits. C5a is chemotactic
What are chemotactic factors for macrophages and neutrophils called?
Chemokines
- Released by the cell
- Chemo = chemotactic
- Kine = cytokine
How does a neutrophil recognize a pathogen and become activated?
It has Pattern Recognition Receptors (PRR) and Toll Like Receptors (TLR): Both have to be engaged for phagocytosis to begin
- CD-14
- TLR2 recognizes gram positive bacteria, fungi and many other pathogens
- TLR4 (recognizes the LPS on surface of gram negative bactera)
What other ways can a neutrophil (or a macrophage) be activated besides TLR4 and CD-14?
It has receptors for opsonins
- Receptor for IgG (the Fc portion called FcgammaIR)
- Receptor for MBL (called C1q)
- Receptor for C3b (called CR1 and 3)
(The pathogens get coated by the IgG, MBL and C3b which makes the bacteria tasty to the neutrophil)
What is the neutrophil receptor for MBL called?
C1q
What are the complement receptors on neutrophils called?
CR1/CR3
(Complement Receptor)
What are the IgG receptors on neutrophils called?
Fc gamma IR
What 2 components does the neutrophil use to directly recognize the pathogen?
TLR 2/4 in conjunction with CD14
What are 3 ways that pathogens are indirectly recognized by the neutrophil
Opsonization (C3b), IgG and MBL
Neutrophils can kill bacteria via what 2 pathways?
- ROS (Reactive Oxygen Species)
- Using O2 (Oxygen dependent)
- Digestive Enzymes
- Without using O2 (Oxygen independent)
Neutrophils have an enzyme called NADPH Oxidase. What does it do?
It uses the Hexose Monophosphate Shunt to turn two O2 molecules into O2- (superoxide) which then attacks bacteria (or anything else in its path)
(This happens in macrophages as well)
Neutrophils have an enzyme called Superoxide Dismutase. What does it do?
It creates Hydrogen Peroxide which digests bacterial components
(O2- + 2H+ → H2O2)
(This process also happens in macrophages)
If a neutrophil has myeloperoxidase and it picks up H2O2 + Cl- (or some other halogenating ion), what will it produce?
HOCl- + H2O
(Hydrogen chloride/hypochloride/bleach)
This is the strongest antibiotic in our body
Macrophages don’t do this (they don’t have myeloperoxidase)
When inegrins are present on endothelial cells, what are they called?
Cell Adhesion Molecules (CAMs)
Neutrophils connect with vascular endothelial cells via what 2 main connections?
- LFA1 and MAC1 connect with ICAM1
- VLA1 connects with VCAM1
What is it called when a neutrophil is connected with an endothelial cell and it crosses from the vascular space into the tissue?
Transmigration aka diapedesis
What is the process where neutrophils project proteins into the extracellular space to kill bacteria?
NETs
- Neutrophilic Extracellular Traps
- Captures and kills bacteria in the extracellular space
What is the most important component of a primary granule in a neutrophil?
Myeloperoxidase
What is the most important component of secondary granules in neutrophils/macrophages?
Lactoferrins
- They take iron (which bacteria love) and pulls them out of bacteria (which are in the phagosome)
- This is why we get anemia of chronic disease. The body perceives that is under constant attack and it stores the iron
What substance is in the tertiary granules of neutrophils?
Cathepsin and gelatinase
What makes up the 3 mechanisms of the “killing factories” of neutrophils which degrades the pathogens?
- Oxygen dependent
- Reactive Oxygen Species (ROS)
- Bleach
- Oxygen independent
- Digestive enzymes
- Neutrophil Extracellular Traps (NET)
- Bacteria are trapped and killed
How does lactoferrin fight bacteria?
It pulls the iron out of the bacteria and it dies