Lecture 2 Flashcards
What are the four descriptors of inflammation?
When do they happen?
Rubor - redness Calor - heat Dolor - pain Tumor - swelling happen in the first 4 hours
Describe Complement cascade of proteins
C’
they poke holes in bacteria.
What is the big MAC attack?
Membrane Attack Complex
- there are parts involved in poking holes
- parts of it are released into the blood to mediate inflammation
Where are the following cells located?
Macrophages
Dendritic Cells
Neutrophils
Macrophages and dendritic cells are in the tissues
Neutrophils are hanging out in the blood vessels
Who signals neutrophils to release from blood vessel walls? Where do they go?
Acute phase proteins signal neutrophils that are tethered to the blood vessel wall to let go and head to the infection site
Explain STOP, DROP and ROLL
STOP: neutrophils that travel to the infection site are stopped by adhesion molecules on the surface of the blood vessel wall
DROP: neutrophils squeeze through the blood vessel wall - diapedesis (DROP)
ROLL: neutrophils move to the site of infection
what is the life span of a neutrophil at the infection site?
8 - 24 hours
What is pus?
How is it cleaned up?
dead neutrophils
macrophages eat the pus
What are the different names for macrophages:
- in the blood
- in tissues
- in the brain
in the blood: monocytes
in tissues: macrophages
in the brain: astrocytes
What is the difference between phagocytosis and endocytosis?
Phagocytosis does NOT use a receptor
Endocytosis involves a receptor
What is a TLR?
Toll-like receptor
a piece of a microbe binds and the TLR signals “danger”
Where are TLRs located?
on all sorts of cell types; different cell types have different #s of TLRs
seen on endothelial tissues, cardiac cells/tissue, adipose tissues
astrocytes and microglia
How many TLRs does a macrophage have? A dendritic cell?
1,000 TLRs/macrophage
100 TLRs/dendritic cell
How do TLRs recognize microbes?
- Different TLRs recognize different chemical structures
1. Microbe binds the TLR on the macrophage
2. The TLR tells the macrophage what (broad) type of microbe is there (worm, bacteria, virus, parasite, food, etc)
What is a lysosome and what does it do?
A lysosome digest things with enzymes and acids to destroy it
Describe phagocytosis/endocytosis process.
The pathogen binds to TLR*
the membrane surrounds pathogen and internalizes it (phagosome)
Inside the macrophage, the phagosome fuses with a lysosome (phago-lysosome)
the lysosomal enzymes breaks the bacteria into peptide bits that bind the MHC
In what ways can a pathogen try to avoid the immune response?
- Block uptake (block phagocytosis) - ex. salmonella
- Block phago-lysosome fusion - ex. TB
- Break holes in phagolysosome and escape to cytosol where there are no lysosomal enzyme - ex. listeria
- Live where there is no Major Histo-compatability Complex - malaria
What are the innate immunity cellular products?
Signal - TLR Products: 1. Lipid Mediators 2. Cytokines 3. Chemokines 4. Co-stimulatory Molecules 5. Adhesion Molecules 6. Reactive Oxygen Species (ROS)
What are lipid mediators?
Leukotrienes (LT), Prostaglandins (PG), Platelet Activating Factor (PAF)
What are cytokines?
hormones of the immune system- small proteins that are released in response to a stimuli that can induce responses in other cells
What are interleukins?
They communicate between WBCs
Named “ILs”
What are the two danger signals important for a T cell?
- The T cell receptor binds to the phago-/endo-cytosed antigen pieces that are presented on the surface of the cell “Are you me?”
- The cd86 (macrophage) binds to cd28 (T cell) –> if there is no CD86 on the surface, the macrophage did not bind a microbe or didn’t bind via TLR –> tolerance (we don’t want to attack our self)
What are Reactive Oxygen Species? How are these reactions slowed?
One product of LPS binding to (or ligating) TLR2 is the production of O2-
Rxns are halted by anti-oxidants (Vit E, carotenoids, glutathione)
What are major forms of ROS?
Superoxide = O2-; generated by NADPH oxidases O2- --> H2O2 by superoxide dismutase H2O2 + metal --> OH- O2- + NO --> ONOO- (peroxynitrite) ONOO- + CO2 --> to damage proteins
What are the 4 steps to getting an infection?
- Exposure
- Pathogen causes disease
- stimulate the immune response
What is exposure dependent upon?
Number of infectious particles Route of entry Mode of transmission Location of the infection Host specificity Ability to spread (spores, divide, blood or lymph)
How do pathogens cause disease?
Releasing toxins
Damage host cells or host tissue (esp. viruses)
Immune response to the infectious agent causes the damage (bact. meningitis)
How do you cure infection?
remove all pathogen (intra and extra-cellular)
*some pathogens are hard to get rid of, so once you have them, you have them for life
4 phases of the immune response:
- prevention
- Innate Immunity (0- 4 days)
- Adaptive Immunity (4 - 7 days)
- Memory (20 - 30 years)
Describe Natural Killer Cells (NKs or NKTs)
Kill like CD8 T cells (use perforin to poke holes and gransymes)
express both innate and specific receptors
NKs can contain a ciral infection while cd8s are being made
Describe activating receptors on NK cells
recognize carbohydrates on the surface of cells –> kill them
(when a cell gets infected with a virus, it will change the carbohydrates found on the surface so that NK can recognize the difference)
Describe Inhibiting receptors on NK cells
Recognize MHC class 1 protein - Shut NK cells down
NO MHC = target for NK
What is MHC?
major histocompatibility complex
- these proteins make you, you.
- must be matched for tissue transplant
Describe neutrophils
Found in the blood - tethered to blood vessel walls
Short lived - 8 - 24 hours
Highly phagocytic
Toxic granules
describe macrophages
monocytes in the blood, macrophages in the tissue
long lived
highly phagocytic
need trigger to kill microbes
describe dendritic cells
found in every tissue
highly phagocytic
best as presenting microbes to T cells
carry antigen to lymph nodes
