Innate Immune System -
- existing from ___
- ___ present
- ___ phase of the immune response
- birth (inborn)
- naturally
- first
PRRs -
- Stands for ?
- What are they?
- ___ number of receptors
- examples (4)
- Pattern recognition receptors
- receptors of the innate immune system that recognize common molecular patters on pathogen surface
- limited
- toll like receptors, LPS (CD14), scavenger receptor, glucan receptor
PAMPs -
- stands for?
- molecules specifically associated with groups of ____ (not shared by ___) that are recognized by cells of the innate immune system
- pathogen associated molecular patterns
2. pathogens, host cells
The innate immune system is comprised of what four important factors?
- complement proteins
- professional phagocytes (macrophages and neutrophils)
- natural killer cells
- dendritic cells (also associated with adaptive immune response
Complement System -
- “____”, mark ___ to get eaten by phagocytes (___)
- act as ____ to attract phagocytes
- make ___, ____ cell membrane
- complements the ___ of antibodies
- targets pathogen for both (2) by ___ such as (2) ?
- poor mans antibodies, bad guys, opsonization
- chemical signals
- membrane attach complexes (MACs), lyse bacterial
- activities
- lysis and phagocytosis, effector cells such as macrophages and neutrophils
Complement System -
- roughly # proteins
- ___ is the primary source that makes the proteins, ___ can also make several complement proteins (list the four)
- proteins highly concentrated in (2)
- Require activation through what three pathways? which is antibody dependent?
- 20
- liver, activated macrophages, C1, C3, factor B and D
- blood and tissues
- alternative, lectin, and classical (antibody dependent)
Main functions of compliment proteins -
- list three
- Opsonization ( ____ antibodies): explain
- enhances bactericidal actions of phagocytes: explain
- kills pathogens (___ antibodies): explain
- opsoniazation, enhances bactericidal actions of phagocytes, kills pathogens
- like, coats pathogen surface enabling phagocytes to engulf and destroy pathogen
- “compliments” the activities of antibodies
- pokes holes in cells by forming membrane attack complexes (MACs)
Alternate Pathway -
- ___ is showering the body with the production of ___
- certain complement proteins ____ and attach to surfaces
- ___ are NOT needed
- this type of activation of the complement system is an ?
- liver, complement proteins
- “spontaneously” activate
- antibodies
- “alternative” to using antibodies
Alternate Pathway -
- __ floats around, but will spontaneously split into # parts
- list them
- C3b with either (2)
- C3b binds to either (2) groups which are very common
- The default option in this system is ___: any surface not protected against binding by complement fragments will be targeted for destruction
- C3,2
- C3a and C3b
- get neutralized by water within 60 microseconds OR bind to a bad guy’s (bacteria) surface
- amino or hydroxyl
- death
Alternative Pathway -
1. the most abundant complement protein ___ is constantly being divided into ___
- C3, C3a and C3b
Alternate Pathway -
- another complement protein ___ attaches to ___
- C3 becomes ___
- another complement protein __ comes along and changes C3Bb to ___, which does what?
- __ + ___ = ___
- ____ can split more C3 and C5
- B, C3b
- C3Bb
- D, C3bBb, acts as a buzz saw, splitting both C3 and C5
- C3Bb + D = C3bBb
- C3bBb (convertase)
Alternate Pathway -
- ___ causes ___ to split
- this results in more ___ coat the invader
- C3bBb, other C3 complement proteins
2. C3bBb complement proteins to
Alternate Pathway -
- C3bBb interacts with ___
- ___ activates it by splitting it into __ and __
- The new ___ with combine with other complement proteins (4)
- The result is a ____
- What to those do?
- C5
- convertase, C5a and C5b
- C5b, C6, C7, C8, C9
- Membrane attack complex (MAC)
- they drill a hole in the bacteria’s membrane = dead bacteria
Chemoattractants -
- consist of (2)
- attract and activate (2)
- C3a and C5a
2. macrophages and neutrophils
Human Protection -
1. What are the three protections proteins?
- MCP
- Protein DAF
- Protectin
Protection Proteins - MCP
- Stands for?
- code
- present on ___ cells
- what does it do?
- membrane cofactor of proteolysis
- CD 46
- human
- cleves both C3b and C4b into an inactive form
Protection Proteins - Protein DAF
- Stands for?
- on the surface of ___
- what does it do?
- decay accelerating factor
- our cells
- accelerates the destruction of convertase (C3bBb)
Protection Proteins - Protectin
- code
- a ___ protein
- what does it do?
- CD59
- cell surface
- removes MACs before they drill holes
Lectin Activation Pathway -
- What is MBL?
- produced primarily in the ___
- present in moderate amounts in (2)
- Lectin is a protein that attaches to ____
- MBL binds to ___
- MBL activates the ___ by binding ___ which clips C3 to make ___
- Mannose is a ___ found ___, list 4 examples
- Not found in ____
- Mannose-binding lectin protein
- liver
- blood and tissues
- a carbohydrate molecule
- mannose
- complement system, MASP (MBL associated serine protein), C3b
- monosaccharide, on the surface of many pathogens, yeast, viruses, bacteria, parasites
- in human cells
Classical Pathway -
- ___ dependent
- When an antibody binds to a bacterial surface its ___ provides a platform to activate ___
- once antibodies are produced compliment activation is substantially ___
- both compliment and antibodies do what?
- antibody
- Fc region (tail), C1 (the first protein of the compliment system
- increased
- coat pathogen surface and enables phagocytes to engulf and destroy bacteria phagocytes might otherwise not recognize
Professional Phagocytes -
- What are the two main functions of sentinel phagocytes?
- What does the induction of inflammatory response do?
- What are the two most important professional phagocytes?
- Macrophages roam around in ___
- neutrophils roam around in ___
- engulf and digest invading microorganisms, induction of inflammatory response
- recruits new phagocytic cells and circulating effector molecules to site of infection
- macrophages and neutrophils
- tissue
- blood
Macrophages -
- found all over the place including (3)
- What are the three states of readiness?
- under the skin, lungs, and intestines
2. resting, activated or primed, and hyperactive
Resting Macrophage -
- casually ___
- ___ proliferating
- express very few ___
- live for ___ in ___
- monocytes circulate in ___, exit and differentiate in ___ to macrophages
- give rise to ____
- eating or snacking
- slowly
- Class II MHCs
- months, tissue
- blood, tissues
- dendritic cells
Primed Macrophage -
- converts from resting to primed after receiving ___
- eat ___
- express __ Class II MHCs, function much more as ___, work much more with ___
- ___ can prime a macrophage, example
- can produce ___ (3)
- a signal that there are bad guys in the area
- much more (bigger bites)
- more, antigen presenting cell, helper T cells
- many chemical signals, interferon gamma (IFN-y)
- C3, factor B, factor D
Hyperactive macrophage -
- converts from primed to hyperactive after receiving a ___ from a bad guy, list two examples
- stops ___
- focuses all its attention on ___
- grows ___
- increases ___
- emits ___
- direct signal, LPS and mannose from a bacterial cell wall
- proliferating
- killing
- larger (big enough to eat whole cells)
- rate of eating
- cytokines (TNF)
Hyperactive Macrophage -
- increased number of ___
- increased production of ___
- besides eating bad guys the hyperactive macrophage can ?
- lysosomes
- ROS (reactive oxygen species)
- dump its toxic contents on the bigger bad guys (multicellular parasites)
Macrophages -
- ___ while resting
- ___ when activated
- ___ when hyperactivated
- garbage collector
- antigen presenting cell and killer
- vicious killer
Neutrophils -
- MC content in the ___
- ___ lived
- recently has been shown to present antigen in both (2)
- can exit blood and become activated in about ___
- list three characteristics of neutrophils
- blood
- short (5 days)
- mice and humans
- 30 minutes
- incredible eaters, emit harsh chemistry, and send out powerful signal molecules (TNF)
Neutrophils -
- travel ___ through the blood
- ___ in this state
- must receive some sort of signal that bad guys are present, in must then do what?
- ___ strategy for leaving the blood
- rapidly
- inactive
- slow down and exit the blood
- roll, stop, exit
Adhesion molecules -
1. List four
- SEL
- SLIG
- ICAM
- INT
Adhesion Molecules - SEL
- stands for
- expressed by ___ that line blood vessels after receiving alarm signals
- binds to ___
- selectin
- endothelial cells
- selectin ligand
Adhesion Molecules - SLIG
- stands for
- expressed on the ___
- selectin ligand
2. surface of neutrophils
Adhesion Molecules - ICAM
- stands for
- always expressed on lumen surface of ___
- intercellular adhesion molecule
2. capillary endothelial cells
Adhesion Molecules - INT
- stands for
- __ and ___ transported to the surface of the ___ after being signaled
- strongly binds to ___
- integrin
- pre-made and rapidly, neutrophil
- ICAM
Adhesion Molecules -
1. __ and ___ are NOT a match
- SLIG and ICAM
Neutrophils -
- ___ help
- when macrophages are primed or hyperactivated they express ___, which does what?
- Capillary endothelial cells express ___, stimulated by (2) and takes about ___
- Neutrophil slows enough to sense ___, ___ on capillaries binds to ___ on the neutrophil
- macrophages
- signal molecules (IL-1 and TNF), lets the neutrophil know a bad guy is present, causes a sequence of events to allow the neutrophil to exit the blood
- selectin (SEL), IL-1 and TNF, 6hrs
- inflammation, SEL, SLIG
Neutrophils -
- transports ___ to its surface
- speed?
- integrin binds to ___ and then does what?
- neutrophils exit the blood and enter the tissue, attracted by ?
- all bacterial proteins begin with a special initiator AA called ___. Less than .1% of all human proteins contain this AA. As they ingest bacteria, macrophages burp up f-met peptides.
- integrin ING
- very fast (already made and stored)
- ICAM, stops
- the chemistry of the area (C5a and bacterial fragments)
- formyl methionine (f-met)
Failsafe -
- ___ is on the endothelial capillary cells all the time
- ___ is on the neutrophil all the time
- must have ___ expressed before neutrophils invade
- must have ___ released before neutrophils invade
- ICAM
- SLIG
- SEL
- INT
Neutrophils -
- about 20 billion neutrophils in the ___
- may present ____
- can exit blood and become activated in about ___
- list the three important characteristics
- blood
- antigens (cross presentation)
- 30 minutes
- incredible eaters, emit harsh chemistry, send out powerful signal molecules (TNF)
Natural Killer Cells -
- ___ (with T and B cells)
- ___ lived
- most found in (3)
- ___ strategy for leaving the blood
- ___ rapidly
- Can produce ___ early in an immune response which can stimulate ___
- lymphocytes
- short (one week)
- blood, or liver and spleen
- roll, stop, exit
- proliferate
- IFN y, macrophages
NK cells -
- able to kill certain ___ in vitro without need for specific immunization
- early component of ____
- Can recognize and kill (3) cells
- What are the two roles of NK cells?
- tumor cell
- host response to viral infection (peak 2-3 days)
- virus infected, altered, or stressed cells
- Produces cytokines (like T helper cells), and force infected or cancerous cells to commit suicide (can kill like CTLs) (inject granzyme B or FAS ligand binds with FAS protein)
NK Cells - Perforin/Granzyme B
- perforin does what?
- they inject ___ that cause the cell to die (apoptosis)
- pokes a hole in the membrane
2. enzymes (Granzyme B)
NK Cells - Fas ligand
- fas ligand on ___ binds to fas protein on ___
- interaction triggers ___
- Fas is a ___ protein in the ___ family
- NK cells, invader
- suicide (apoptosis)
- transmembrane, TNF
NK Cells -
- ___ is cleaner than ___
- Necrosis has the cells contents spilling all over the place and increasing ___
- apoptosis has the cells contents ___
- ___ clean these up
- apoptosis, necrosis
- inflammation
- wrapped up in membrane bound vesicles
- macrophages
NK Cells -
- MHC I receptors: ___ signal, recognize ____
- activating receptors (____), bind to (2) on the cell’s surface, ___ signal, recognize molecules being produced by ___, also kill cells not expressing ___
- IgG3 receptors: bind ___ of ___, Ab forms a bridge b/w (2), causes?
- NK cells do NOT have ___
- don’t kill, normal molecules being produced in your cells
- PRRs, unusual carbohydrate or protein, Kill, virus or cancerous cell, MHC molecules
- Fc region, IgG, target and NK cell, NK cell to kill target (antibody dependent cellular cytotoxicity)
- T cell receptors
NK Cells -
- Activation: resting = ____, activated = ____
- Signals that activate NK cells (6)
- interferons are usually given off by ?
- make some cytokines and can kill, make many more cytokines and more effective killers (IFNy prime macrophages, IL-2 is a GF that causes NK cell to proliferate when expressing IL-2 receptors)
- Lack of MHCs, LPS (component of bacterial cell walls, can also stim macrophages), IFNa, IFNb, TNF from hyperactivated macrophages upregulates NK cell IL-2 receptors, IL-12 from primed or hyperactivated macrophages
- by cells under viral attack
Innate Immune System -
- Composed of (3)
- List three professional phagocytes
- what are dendritic cells
- Complement proteins, professional phagocytes, and NK cells
- neutrophils, macrophages, dendritic cells
- liaison b/w innate and adaptive immune system