Jan. 27th (Exam 1) Flashcards
Where can we find macrophages?
What are they called in the liver?
- Connective Tissues
- GI tract
- Respiratory Tract
- Lungs
- Liver
In the liver they are called Kupffer cells.
What type(s) of immune response are macrophages involved?
What kind of cell surface receptors do macrophages have?
Innate and Adaptive
They have CR1
Additionally CR3 and CR4
What does CR stand for?
What is important about CR1?
Complement Receptor
It binds C3b on bacterial cell surfaces!
Complement activation has begun and macrophages are resident in the tissue infected.
Explain how a macrophage engulfs the pathogens present.
Complement activation causes a massive deposition of C3b on the cell surfaces of bacterium - opsonization.
Nearby macrophages bind the C3bs present via their CR1s.
This facilitates receptor-mediated endocytosis of the bacterium, whose cell membrane fuses with the macrophage.
The phagosome present in the macrophage cytoplasm then fuses with lysosomes creating a phagolysosome.
What are the early complement protein(s)?
What are the terminal complement proteins?
Early: C3
Terminal: C5-C9
What is the purpose of Early Complement proteins?
What is the purpose of the Terminal Complement proteins?
C3b: Opsonization
C3a: inflammation/vascular permeability
C5-C9: Form the MAC
(Membrane Attack Complex)
What does the MAC do?
The Membrane Attack Complex will eventually make holes in bacterial and eukaryotic membranes.
Explain how the terminal complement proteins form the MAC.
- Once the C5 protein gets cleaved and C5b fragment is activated, it starts the assembly of the MAC
- C6 will bind to and stabilize C5b, flexing the complex, creating a binding spot for C7
- C7 binds to C5b6, exposing a hydrophobic region that will facilitate the attachment to the cell membrane
- C8 will then bind to C5b67, exposing a hydrophobic region that inserts itself into the cell membrane.
- C9 will polymerize on the C5b678 complex, forming a membrane spanning channel that disrupts the integrity of the cell and can result in cell death.
How do we get C5b?
What is the structure of the enzyme that cleaves C5?
An enzyme called Alternative C5 convertase.
The enzyme is C3b2Bb, which we saw acting at the end of the alternative C3 convertase.
(the enzyme basically looks like the C3bBb alternative convertase as it is working to cleave more C3.
Check for Understanding:
What is the role of C5b?
Initiating the Membrane Attack Complex.
What prevents the C5b678 complex from getting polymerized by C9 and perforating the cell membrane of human cells like that of bacterial cells?
Only on human cells, a protein called CD59 will bind to the complex and prevents the recruitment of C9 which will form the pores.
What are C3a and C5a examples of?
What types of cells do they bind to?
They are anaphylatoxins
They bind to the cell surface receptors of:
- phagocytes
- endothelial cells
- mast cells
What do anaphylatoxins do?
They induce inflammation by:
- Vasodilation
- Degranulation of immune cells
- Direct migration of other cells to infection site.
What happens if pathogens damage blood vessels?
What happens?
The coagulation system is activated.
How does the coagulation system activation happen (vaguely)?
What do clots accomplish?
A cascade of enzyme activation will lead to blood clotting.
Clots immobilize the pathogen.
What is the role of platlets?
They release chemicals that stimulate other cells types which work in defense and healing.
What are Antimicrobial peptides?
They are soluble effector molecules that kill pathogens.
What are defensins?
How do they penetrate the microbial surfaces?
Where are they made?
These are antimicrobial peptides that can penetrate microbial surfaces.
The electrostatic attraction between the positively charged defensin and the negatively charged electric field of the membrane bring the protein into the membrane forming pores.
They are constantly secreted by mucosal surfaces.
They are also made by neutrophils
What are the two classes of Defensins?
- Alpha (6)
- Beta (4)
What are Pentraxins?
What is their role in immediate response?
Where are we going to find them?
These are opsonins, which are molecules that enhance inflammation.
They do this by acting like a bridge to bind the pathogen and human cell surface receptors on phagocytes.
We will find them circulating in the blood and lymph.
