lecture 3 Flashcards
(70 cards)
1
Q
first line of defense
A
- innate immune system
- barriers within it
2
Q
barriers
A
- are able to. keep most of the pathogens away
- we might not even realize we were exposed to them
- can keep them away from our tissues and body
3
Q
what happens if pathogens breach the barriers
A
- innate immune cells
4
Q
myeloid origin
A
gives rise to phagocytes:
- dendritic cells
- neutrophils
- macrophages/monocytes
5
Q
lymphoid origin
(these are not all the things it can give rise to, just the ones involved in innate immunity)
A
gives rise to lymphocytes
natural killer cells
6
Q
macrophages
A
- are a differentiatied type of monocyte
(monocytes that have been circulating in the blood that come out of blood become macrophages)
7
Q
phagocytes
A
- kill extracellular pthogens via phagocytois
- first responders to infection
8
Q
lymphocytes
A
- kill intracellular viruses via apoptosis
9
Q
phagocytosis
A
- stretches out membrane,
- “cell eating”
- this forms phagosome (around the extracellular pathogen)
- the phagosome fuses with lysosome that contains the toxic, killing agents that will kill the pathogen
- creates a phagolysosome
- debris from there is expeld from cell
10
Q
phagolysosome
A
- toxins in it are toxic to the cell also, so must be contained
11
Q
phagocytosis steps
A
- fuses with lysosome
- pH drops
- enzymes that were in lysosome get activated
- killing of pathogen in phagolysosome
12
Q
phagosome
A
- ## not toxic at first, bacteria allow the pathogen to live here by blocking following steps
13
Q
macrophages
A
- can “eat up” a huge amount of cells at a time
14
Q
lyssoome
A
- contains acid
- enzymes
- antimicrobials
15
Q
low pH
A
- this can be detrimental to the cells that want to survive in there
16
Q
NADPH oxidase
A
- makes reactive oxygen species that are toxic to the cell
17
Q
myelopersoxidase
A
- makes bleach that is toxic to the pathogen
18
Q
lactoferrin
A
- enzyme that captures iron (Fe2+) that is essential for bacterial growth,
- process called nutritional immunity, way that cells try to sequester essential nutrients from the pathogens
19
Q
defensins
A
- also found in lysosomes
- create pores on pathogen membrane, then lyse cell
20
Q
lysosome
A
- degrades peptidoglycan to kill bacteria, mainly gram positive
21
Q
nutritional immunity
A
- host cell and pathogen are fighting for nutrients
- keeping nutrients from pathgogen prevents them from gorwing
- e.g. taking way co factor iron prevents it from growing
- lactoferrin binds iron to keep it unavailable from pathogen
- transferrin also sequesters iron
22
Q
trace metals that are typically sequestered from pathogens in nutritional immmunitu?
A
- co factors in metabolic enzymes
- e.g. iron, zinc, managenese
23
Q
consequence of infection
A
- low iron in blod
- making so much of the components that sequester iron, makes it unavailable to ur own bell
- leads to hypoferremia of infection
24
Q
neutrophils
A
- eat the pathogens once they catch up with them
0 very abundant - replicate quickly
- about 50-70 percent of blood circulating leukocytes
- swarm in large numbers to site of infection
- main component of pus
- can be used as a measure of infection
- have a life span of only a few days
- will replicate as long as the infection signals are there
- exit blood and rapidly enter infected tissues
25
Multi-lobed nucleus
have packaged their genetic material (DNA) in multiple spheres instead of one big sphere like in most other cell types. These types of nuclei are called lobular nuclei
26
components of neutrophils
- multi lobed nucleus
- granules
- phagosome
27
NETosis
Neutrophil Extracellular Traps
- release chromatin from chromosomes associated with the enzymes and antimicrobial proteins
- produces nets that capture the pathogens
- the nets are decorated with antimicrobial proteins
- ensnares extracellular pathogens
- the associated antimicrobial proteins intoxicate microbes
28
what antimciorbial proteins are used by NETs to intoxicate microbes
- antimicrobial peptides, MPO, elastase
29
sign of infection
- neutrophils are used in clinical settings to measure for infection
- in blood results, if the majority of WBC are neutrophils, signals that person has an infection
30
neutropenia
- people that are unable to produce high numbers of neutrophils ( or none at all)
- patients are highly susceptible to a wide range of pathogens
- innate immune system is highly comprosied
31
how to combat neutropenia
- restore neutrophil levels through blood transufsion
- transfusion of Buffy coat
- must be done quite frequently especially during infection, because neutrophils die quite quickly.
32
neutropenic sespsi
- septic shock
- life threatening needs immediate attention
- infections in neutropenic patients
- if the infection is not controlled
33
macrophages
- professional phagocytes
- good at ingesting pathogens and killing them
- have pseudopods.
- also have a role in adaptive immunity
- last for a long time (months to years)
- differentiate from monocytes that circulate in the blood and enter tissues
34
resident macrophages
- there ar e professional macrophages that are tissue specific, that survey the area for the pathogens
(resident macrophages)
- have specialized functions depending on location
35
tissue-specific macrophaes
- eyes
- digestive and resp tract
- brain
36
dendritic cells
- immature dendritic cells circulate in blood and reside in lymphoid organs and peripheral tissue
- have phagososomes, processes, lysosomes
- important role in adaptive immunity
- bridge between the two
37
immature dendritic cells
- good phagoycytes
38
mature dendritic cells
- role in adaptive immunity
- antigen presenting cells
39
Natural killer cells
- lymphocytes
- not phagocytose
- kill intracellular viruses
- by targetting the virus infected cells via apoptosis
- cytotoxic granules
- circulate the blood
- important role in virus infected cells, and in killing cancer cellsc
40
cytoplasmic granules
- contain perforin and granzyme that trigger apoptosis
- recognize that the cell is infected, release the two enxymes
41
how do NK cells work
- recognize that the cell Is infected
- reaches target cell that has infection signals on sruface
- granules converge and reroute themselves to an areas of contact between the two cells
- contents of the granules are expelled
- cell death
- happens quickly
42
perforin
- released from granule
- forms a pore in the cell membrane which helps deliver granzyme to the inside of cell
43
granzyme
- turns on apoptosis in cell
44
apoptosis
- general process by which a cell dies
- usually done at the end of cell's lifetime
- Genzyme speeds up this process
- pro caspase: turns on the caspaces which turns on the apoptosis process, leads to degradation of the genetic material of the cell
- degrades also the viral nucleic acidswh
45
why does granzyme also kill viral nucleic acids?
- to ensure that the virus does not escape and infect other cells
- prevents viral replication
46
When are NK cells released
- NK cell mediated killing is the second wave of cells
- comes after signalling molecules called inteferons
- can control viral infection usually
- if innate cannot control, activation of t cells
47
how are pathogens detected
- need signals to get there but also need something to allow them to recognize the ahogen
- done through a sort of signal transduction pathway
- with PRRs
48
Pathogen recognition and detection
- PRR recognizes characteristics of the outside of that extracellular pathogen
- those PRR receptors can also be internal (intracellular pathogen that is inside of the cytosol , there are also receptors inside the cell to catch it)
- triggers phagocytosis
- also triggers the production of cytokines and chemokines to call more cells to battle
49
pattern recognition receptors
- essential receptors of innate immunity
- expressed at surface and within many cell types (WBC, some lymphocytes, and epithelial cells)
- low specificity, can recognize broad characteristics of pathogens
- germ-line encoded
- can also recognize damage signals
50
germ-line encoded
- encoded in genome, passed through progeny, cannot change
-
51
innate immunity (with PRRs)
- specificity inherited in genome
- triggers immediate response (when receptors recognize pathogen, triggers immediate phagocytosis immediately and release of cytokines and chemo)
- recognize broad classes of pathogens.
52
What do PRRs recongize
PAMPS
- pathogen associated molecular patterns
53
PAMPS
- common in many pathogens
- can be on cell wall (on outside of pathogen) e.g. cell wall structure
- oligosaccharides
-pettidoglycans
- lipopolysccahrides
- unmethylated CpG DNA in DNA
54
PAMPS for vacteria
- lipopolysaccharides
- peptidoglycans
- lipoproteins
- flagellin
- lipoteichoic acid (LTA)
- DNA
55
PAMPS for virus
- protein capsid
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PAMPS for parasite
- GPI anchor
57
PAMPS for yeast
- zymosan
58
key properties of MPAMPS
- must be only found in pathogens and not in bodies
- very conserved for pathogens (low mutation rate, stays the same)
- usually critical for survival or pathogenesis of pathogen
- makes this an excellen target for reoconition
- used in clinical settings to distunigh between types of pathogens
- detections of PAMPS is critical to the initiation of immune responses
59
examples of PAMPS
- Exposed glycolipids on gram positive bacteria
or peptidoglycan(conserved and exposed)
- LPS on gram negative bacteria
60
look for other examples of PAMPS in lecture notes
61
requirements to be a PAMP
- must be conserved
- must be broadly found in groups of pathogens
62
PRRS in humans
- we have few receptors but they recognize a broad range of characteoriesitcs
63
surface prrS
- recognizee components on the outside of pathogens
- recognize exposed structures on extracellular pathogens
- e.g. LPS, peptidoglycan, flagellin
64
Endosomal PRRs
- recognize components released during degradatoion
- regonzie intracellular pathogenic PAMPS in endosomes and vacuoles
65
Candida albicans PAMPS
-
66
first step of phagocytosis process
- binding of PRRs to PAMPS
- Pseudopods engulf pathogen
- phagosome formation
- fusing with lyosome
67
strategies for bacteria in immane evasion
- producing capsular polysaccharides that cover their PAMPS to become unrecognizable, e.f. K. pneuomniae
- or PAMP variation e.g. N. gonnorahe changes its flagellin structure to prevent immune cell recognition, some bacteria remove their flagella to accomplish this
68
innate cells summary
- phagocytes in tissues are waiting for a breach of barriers
- breach
- bacteria and viruses with extraceullar PAMPS are "eaten" by phagocytes
- signal molecules are produced to call more cells
- if the cells get infected by virus, make signals that the infection is happening, the virus-infected cells will be killed via apoptosis.
-
69
how can intracellular bacteria survive phagocytosis?
- inhibit fusion of phagosome wit lysosome, and survive there (e.g. tuberculosis)
- may have enzymes that prevent the killing by the toxic lysosome enzymes, so they can survive in that enviornment
- the bacteria can also escape the phagolysosome
(e.g. listeria)
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