Innate Immunity (complete) Flashcards
(205 cards)
1
Q
is innate or adaptive immunity similar in all individuals of a species
A
innate immunity (adaptive immunity varies from individual to individual)
2
Q
is innate or adaptive immunity generally enhanced by repeated exposure
A
adaptive immunity
3
Q
does innate or adaptive immunity have some sort of “memory”
A
adaptive immunity
4
Q
does innate or adaptive immunity use nonspecific mechanisms to identify invaders
A
innate immunity
adaptive immunity is based on the recognition or specific invader
5
Q
are the mechanisms of innate or adaptive immunity mobilized immediately, and work quickly?
A
innate immunity
effector products of adaptive immunity take several days to produce
6
Q
What happens to the adaptive immune response with each additional exposure to an invader
A
the response becomes quicker, more specific, and is at a higher level.
7
Q
what are the 6 types of organisms that can grow in vertebrates
A
- viruses
- bacteria
- fungi
- parasites
- protozoa
- worms
8
Q
What barriers/mechanisms must be overcome by organisms that want to grow in humans
A
- Skin
- mucous membranes
- ciliary escalator in the respiratory tract
9
Q
which immunity works early in the infection process
A
innate immunity
10
Q
T/F the adaptive immune response depends on the innate immune response for activation and for most of its effector functions
A
True
11
Q
why haven’t our bodies adapted and evolved enough over time to already destroy these pathogens
A
because microbes and viruses evolve faster than vertebrates
12
Q
What are PAMPs
A
pathogen associated molecular patterns.
certain structures that are only found on pathogens
13
Q
What are some examples of PAMPs
A
- double stranded RNA
- LPS (lipopolysaccharide)
- Lipoteichoic acid
- peptidoglycan
14
Q
on what type of pathogen do you see the PAMP double stranded RNA
A
viruses
15
Q
on what type of pathogen do you see the PAMP LPS
A
gram negative bacteria
16
Q
on what type of pathogen do you see lipoteichoic acid
A
the cell wall of gram positive bacteria
17
Q
on what type of pathogen do you see peptidoglycan
A
the cell wall of gram positive bacteria
18
Q
what type of immunity focuses on these PAMPs
A
innate immune mechanisms
19
Q
why don’t these organsims evolve and change their PAMPs so they can’t be used to recognize the organism by immune systems
A
they must be crucial to the organisms and therefor hard to change
20
Q
What are the three possible immune response outcomes
A
- normal response (attacks non-self, leaves self)
- immune hyperactivity (allergies, and autoimmunity)
- immune hypoactivity (infections, cancer, immunodeficiency)
21
Q
what are in eyes that are barriers against infection
A
lysozome in tears
washing of the eyes
22
Q
what acts as barriers on the skin against infection
A
- physical barrier
2. antimicrobial secretions
23
Q
what acts as a barrier in the respiratory system against infection
A
- mucus
- cilia
- alveolar macrophages
24
Q
What acts as a barrier in the genitourinary tracts against infection
A
- low pH of urine
- washing of urine
- lysozyme
- vaginal lactic acid
25
what acts as a barrier in the digestive tract against infection
1. stomach acidity
2. normal flora
3. bile
26
what are commensals in our body
bacteria that live in our body, that aren't pathogenic.
27
lysozyme does what, and comes from where?
breaks down peptidoglycan
| comes from tears, saliva, nasal secretions, body fluids, lysosomal granules
28
lactoferrin and transferrin do what, and come from where?
they bind iron, and compete with microorganisms for it
| they come from granules of PMNs
29
Lactoperoxidase does what, and comes from where?
it is inhibitory to many microorganisms
| it comes from milk and saliva
30
B-lysin does what, and comes from where?
effective against gram positive bacteria
| it comes from thrombocytes and normal serum
31
Chemotactic factors do what and come from where
they induce direct migration of PMNs, monocytes, and other cells
they come from bacteria, products of cell injury, denatured proteins, complement, and cytokines
32
properdin does what, and comes from where?
it activates complement in the absence of the antibody-antigen complex
it is found in normal plasma
33
cationic peptides do what and come from where
they disrupt membranes and block cell-transportation
| they come from PMN granules (defensins)
34
What are the three lines of defense of the immune system. and which are non-specific, and which are specific
1. skin, mucus membranes, chemicals
2. phagocytosis, complement, interferon, inflammation, fever
3. lymphocytes and antibodies
1-2 non-specific, 3 - specific
35
What are the roles of phagocytes in an immune response
1. production of cytokines and chemokines
2. Ingulf and destroy the pathogen (with out without antibodies)
3. presentation of antigen fragements to T-cells
36
which types of phagocytes do the presentation of antigen fragments to T-cells
immature dendritic cells, that have been activated by microbial components and cytokines
37
What happens with the T-cells that have had antigen fragments presented to them by immature dendritic cells
they become effector cells, they create an adaptive immune response (present it to B-cells)
38
What do the cytokines and chemokines secreted by phagocytes do
1. increase vascular dilation
2. increase vascular permeability
3. induce production of proteins that recruit more immune cells
= cause inflammation
39
what does increase vascular dilation and permeability do for an immune response
allows more lymphocytes, antibodies, and complement to enter the site of infection
40
What are antigens
molecules that trigger a specific immune response
41
what are epitopes
the portion of the antigen recognized by the antibody or lymphoocyte
42
how do antigens enter the body
1. through breaks in the skin and mucus membranes
2. direct injection (bite or needle)
3. ingestion or inhalation
43
What is the type of cell from which all cells of the immune system are derived
hematopeotic stem cell (HSC)
44
what does a HSC give rise to each time it divides
another HSC and a progenitor cell that is commited to a certain lineage
45
what are the two lineages of immune cells
myeloid (inflammatory cells)
| lymphoid (lymphocytes)
46
which is the only cell that can be formed from both the myeloid and lymphoid lineages
dendritic cells
47
what controls the specific differentiation of progenitor cells
hematopoeitins
48
what cells come through the myeloid lineage
```
RBCs
platelets
basophils
eosinophils
neutrophils
monocytes (dendritic cells/macrophages)
```
49
what cells come through the lymphoid lineage
B-cells
T-cells
NK cells (natural killer)
50
do all cells of myeloid lineage complete differentiation in the same location
nope,
| bone marrow, peripheral tissues, secondary lymphoid tissue
51
What are the three types of formed elements in blood
1. RBCs (erythrocytes)
2. Platelets
3. WBCs (leukocytes)
52
What is the function of RBCs
carry O2 and CO2 in the blood
53
what is the function of platelets
involved in blood clotting and inflammation
54
what are the two classes of leukocytes
granulocytes
| agranulocytes
55
What are the different types of granulocytes
neutrophils
eosinophils
basophils
56
what are the different types of agranulocytes
monocytes
| lymphocytes
57
list the leukocytes from most abundent to least
```
neutrophils
lymphocytes
monocytes
eosinophils
basophils
```
58
what do neutrophils do
they are major phagocytes and cause accute inflammation
59
what do eosinophils do
perform parasite defense and regulate inflammation
60
what do basophils do
secrete histamine, involved in allergies
61
what can high levels of eosinophils in the blood indicate
allergies or a parasitic worm infection
62
what change in white blood cell count does a bacterial infection cause
increase in all leukocytes, but mostly neutrophils
63
what change in white blood cell count does a viral infection cause
increase in lymphocytes
64
what is diapedesis
the passages of White blood cells through intact capillaries
65
what do lymphocytes do
they are the main cells in adaptive immune response
66
what do monocytes do
mature into macrophages
67
what are the phagocytic cells
neutrophils
macrophages
dendritic cells
68
what role do neutrophils play as phagocytes
short lived, but quick destructive phagocytosis
| release of cytokines = acute inflammation
69
what roles do macrophages play as phagocytes
they are found in various tissues, important in their maintenance and repair
long lived = cells of chronic inflammation
release cytokines
70
which phagocytes are activated by T-cells and antibodies
macrophages
71
what is phagocytosis
a receptor-mediated process whereby large particles are engulfed.
72
what can the phagocytic receptors bind
they can bind microbes directly
| they can bind opsonized particles
73
do some pathogens use phagocytosis to their advantage
yes
74
what are two ways that pathogens can use phagocytosis to their advantage
1. they can get phagocytosed, then rupture the phagosome and enter the cytoplasm
2. they can block the fusion of lysosomes with the phagosome so they can't be destroyed
75
what bacteria rupture the phagosome after they have been phagocytosed and enter the cytoplasm
listeria monocytogenes
| burkholderia pseudomallei
76
what bacteria prevent the fusion of the phagosome and lysosome after being phagocytosed
mycobaterium tuberculosis
| salmonella
77
what can overcome the block of fusion of the phagosome and lysosome by salmonella and mycobacterium tuberculosis
IFN-y (T-cell cytokine)
78
what are the receptors of macrophages involved in
1. scavenging tissue debris from apoptotic cells
2. tissue repair and maintenance
3. production of anti-inflammatory responses
79
which cells are the phagocytotic cells in the second line of defense
macrophages
80
where do macrophages come from
when monocytes leave the blood, they become macrophages in the tissues
81
what are some names for macrophages that stay in a certain area of the body
1. microglial cells (CNS)
2. mesangial cells (kidney)
3. marginal zone (spleen)
4. Kupffer cells (liver)
82
are all macrophages fixed to certain tissues
nope, some are wandering
83
are alveolar macrophages fixed, or wandering macrophages
wandering
84
what makes up the MPS (mononuclear phagocytotic system)
monocytes, macrophages attached to endothelial cells
85
how are microbes killed in a phagocyte
they are absorbed and bathed in free radicals, which destroy them
86
what are the different types of dendritic cells
1. immature
2. mature
3. follicular
87
what do immature dendritic cells do
they phagocytize pathogens, then they become mature
88
what do mature dendritic cells do
they present antigens to T-cells
89
what do follicular dendritic cells do
present immune complexes to B-cells
90
where are dendritic cells very numerous
in epithelia and mucosal surfaces
91
what are langerhans cells
specialized dendritic cells in keratinized epidermis that can remain there for months
92
what are dermal or interstitial dendritic cells
dendritic cells that reside in the dermal layer
93
what are the different dendritic cells that function in the epithelium of the small intestines
1. some sample gut contents directly
2. some wait below the epithelial cells to have samples of lumen transported to them
3. some circulate in the blood and wait for viruses
94
what is the function of the dendritic cells that directly sample the lumen of the small intestine
they prevent inflammatory response against the gut commensial bacteria
95
what are the cells that transfer small intestine lumen to lymphoid tissues
M-cells
96
what are the dendritic cells called that circulate with the blood and wait for viruses
plasmacytoid dendritic cells
97
what do plasmacytoid dendritic cells do when they encounter viruses
produce lots of type 1 interferons
98
what are the primary lymphoid organs
the locations where lymphocytes mature
Bone marrow
thymus
99
what are secondary lymphoid organs
```
the locations where antigens are trapped, where an immune response takes place
lymph nodes
spleen
MALT (tonsils)
GALT (peyers patches)
```
100
what are tertiary lymphoid tissues
locations where lymphoid tissues is created at sites of chronic infection
101
what does the spleen do
filters for antigens in the blood
102
where do you find the lymphatic tissue (white pulp) of the spleen
around arterioles
103
where do you find the marginal zone of the spleen
around the white pulp
104
what do you find in the marginal zone of the spleen
metallophilic macrophages
marginal zone macrophages
specialized B cells
105
how do antigens get to the GALT
they are transported there by M cells
106
what is the first type of cell that the antigens sees in GALT
dendritic cells
107
what do sentinal cells do
recognize pathogens and secrete cytokines to initiate an immune response
108
can all epithelial cells tolerate microbes on their surface
nope, some can, but places like alveoli and small intestines don't because they would interfere with their function
109
how do the alveoli and small intestines prevent the build up of microbes on their surfaces
secreting antimicrobial peptides
| defensins and cathelicidins
110
what are defensins
small antimicrobial peptides with a 3 stranded beta-sheet and 3 disulfide bonds
111
what are cathelicidins
they are small antimicrobial peptides, but differ from defensins in structure (a-helical regions)
112
what are the types of defensins
alpha and beta
113
how do alpha and beta defensins differ
both come from neutrophils, but beta can come from epithelia too
both are antimicrobial, but beta are chemotactic, and induce histamine release
114
what are the paneth cells of the small intestine
cells that produces alpha defensins in response to bacteria
115
what do the a-defensins of paneth cells destroy
giardia, but only one of them (cryptdin-3) kills E. coli
116
how do defensins kill microbes
1. they bind to the acidic phospholipids in the membranes of microbes
2. they enter the membranes and create pores
3. this causes the cells to lyse
117
how do some bacteria combat the pore creation in their membranes by defensins
they modify their membrane lipids with lysine = reduction of negative charge = insensitive
118
what are collectins and ficolins
soluble proteins at mucosal surfaces or in blood that recognize carb configurations on microbes.
119
what are the structures of collectins
they are a long chain, with a big carb recognizing head
120
what do collectins do
the head binds to a sugar on the microbe, this increases phagocytosis, and activates complement
121
what is the complement system
a series of about 30 proteins that can be activated in 3 ways
122
what happens in the activation of the 30 proteins in the complement system
proteins are cleaved into two substances
beta - stays
alpha - leaves
123
what are the three pathways in activation of the complement system
lectin pathway
classical pathway
alternative pathway
124
what are the four ends of the complement system
1. lysis of bacteria
2. chemotaxis of phagocytes to the bacteria
3. opsonization of bacteria
4. all of which increase inflammation
125
what are the two main players in the lectin pathway of the complement system
MBL
| ficolins
126
what are the three main players in the classical pathway of the complement system
IgG, IgM, pentraxins
127
what is the main player in the alternative pathway of the complement system
microbial membranes
128
the early events of all three pathways of the complement system all lead to what
the cleavage of C3 by C3 convertase
129
which complements lead to inflammation, chemoattraction
C3a
| C5a
130
which complements lead to induction of phagocytosis
C3b
131
which complements lead to attack on membranes
C5b, C6, C7, C8, C9
132
which complements lead to promotion of antibody production
C3b
133
which complements are the late events
C5-C9
134
how is the classical pathway of the complement system activated
1. C1q/r/s complex couples with pentraxins or antibodies
2. C1s cleaves C4
3. C4b binds to cell surface
4. C2 binds to C4b
5. C1 cleaves C2
6. C4b-C2b = C3 convertase
7. C3 convertase cleaves = C3a, C3b
135
how is the lecthin pathway of the complement system activated
1. MBL or ficolin bind to the microbial surface carbs
2. MASP's bind to MBL/Ficolin
3. MASP2 cleaves C4
4. C4b stays attached
5. C2 binds to C4b
6. C2 is cleaved by MASP-2
7. C4b-C2b = C3 convertase
8. C3 convertase cleaves = C3a, C3b
136
how is the alternative pathway of the complement system activated
1. C3a and C3b bind to the cell surface
2. B binds to C3b
3. D cleaves B
4. C3b-Bb = C3 convertase
5. C3 convertase cleaves = C3b, C3a
137
what happens to C3b that can't find a microbe to bind to
it is bound by factor H, then factor I cleaves the C3b (making it inactive)
138
what does properdin do in the complement pathways
it stabilizes the C3b/Bb complex
139
what happens when C3b attaches to either the C3b/Bb or C4b/C2b complexes
this leads to the cleavage of C5
140
what does C5a do
it is a proinflammatory peptide that acts on endothelial cells and mast cells.
it is a powerful neutrophil chemoattractant
141
what does C5b do
it nucleates the formation of the (MAC) membrane attack complex (this makes large holes in the cell)
142
defects in which components of the complement can cause SLE (systemic lupus erythematosis)
defects in C1 and C4
143
how do defects in C1 and C4 lead to SLE (systemic lupus erythematosis)
they lack the ability to clear apoptotic cell debris and immune complexes
144
the deficiency of which complement component is the most severs
C3
145
what do defects in the late part (C5-C9) cause
severe nisseria infections
146
how do microbes fight against the actions of the complement system
1. make surface proteins that bind factor H (so that it will inactivate C3b)
2. make proteins that bind to C4bp (an inactivator of C4b)
3. take host control proteins with them as they bud
147
what microbes make surface proteins that bind factor H to fight against the complement system
```
HIV
S. Pyogenes
S. Pneumonia
Neisseria
B. Burgdorferi
gonorrhoeae
```
148
which microbes make proteins that bind C4bp to fight against the complement system
gonorrhoeae
| B. pertussis
149
which microbes take host control proteins with them as they Bud
HIV-1
| vaccina
150
which fuse first, primary or secondary granulues
secondary (yep these fuse first)
151
what does NAPDH oxidase create
```
O2
H2O2
HOCl
OH
ONOO (with NO from iNOS)
```
152
what does iNOS create
NO
| ONOO (with O2 from NAPDH oxidase)
153
which attack first, the toxic O2 intermediates or the toxic nitrogen intermediates
the toxic O2 intermediates are used immediately, the toxic nitrogen intermediates are used later, and last longer
154
what happens when you have defects in any subunit of the NADPH oxidase
you will get a chronic granulomatus disease (CGD)
| patients have a hard time clearing infections and get persisting granulomas
155
What are the three types of sentinel immune cells in tissues
1. macrophages
2. Mast cells
3. immature dendritic cells
156
what do sentinel immune cells do
recognize microbial threats and initiate an inflammatory immune response.
157
what do sentinel cells have to differentiate between
apoptotic bodies and microbial threats
158
what allows sentinel cells to distinguish between apoptotic bodies and microbial threats
TLRs (toll like receptors)
159
what are TLRs (toll-like receptors)
a protein with an extracellular portion with lots of leucine (LRRs) a transmembrane domain, and a Toll/IL-1 receptor (TIR) domain
160
what can TLRs bind
Nucleic acids
Proteins
Lipids
polysaccharides
161
are accessory proteins sometimes used to help things bind to TLRs
yes
162
how do sentinel cells recognize LPS
1. LPS is taken from the cell wall by LBP
2. LBP gives the LPS to CD14
3. CD14 give the LPS to TLR/MD-2 complex
4. this sends a signal into the cell
163
what is required for LPS responsiveness of TLR4
MD-2
164
is CD14 required for LPS response
no, but it helps a lot
165
where do you find TLRs that recognize microbial cell wall components
in the plasma memebrane
166
where do you find TLRs that recognize microbial nucleic acids
in the intracellular membranes (phagosomes or endosomes)
167
What does the Activation of TLRs lead to
production of cytokines
TNF
IFN (alpha and beta)
IL (6 and 12)
168
what do NOD1, NOD2 and Cryopyrin do
recognize parts of peptidoglycan, and activate NF-kB (inflammatory cytokine)
169
when TLRS and sentinel cells recognize microbes, what do they do
release cytokines
release chemokines
release lipid mediators
these lead to a coordinated response by vessels and leukocytes = inflammation
170
what are the 4 main functions of inflammation mediators
1. increase vascular permeability
2. change adhesive properties of the epithelium (increased amounts of leukocytes)
3. activate phagocytes
4. activate NK cells
171
what are the two proteolytic cascades triggered by activation of endothelial cells
kinin cascade
| coagulation cascade
172
how does the kinin cascade affect inflammation
increases vas. permeability
173
how does the coagulation cascade affect inflammation
clotting reactions decrease microbial spread
174
Where does TNF come from
macrophages and mast cells
175
what does TNF do
```
increases:
vascular permeability
endothelial cell adhesiveness
activation of phagocytes
cytoxicity of NKcells
```
176
what does IL-1 come from
macrophages, mast cells, KC, EC
177
What does IL-1 do
increases chemokine production and endothelial cell adhesiveness
178
Where does IL-6 come from
macrophages, mast cells, FB
179
what does IL-6 do
recruites monocytes, systemic effects
180
what does IL-12 come from
macrophages
181
what does IL-12 do
increases IFN-y production by NK cells
| increases NK cytoxicity
182
what does IFN-y come from
NK cells
183
what does IFN-y do
enhances phagocytosis and killing by phagocytes
184
what do chemokines come from
macrophages, mast cells, EC
185
what do chemokines do
attract neurtophils. monocytes, effector T-cells
186
what are the antinflammatory cytokines
IL-10 and TGF-Beta
187
how does arachadonic acid turn into inflammatory mediators
1. a stimulus activates PLA2 and COX-2
2. PLA2 pulls arachadonic acid from phospholipids
3. COX-2 breaks arachadonic acid into PGH2
4. PGH2 is broken down into PGI, PGE, PGF, and thromboxane
188
what are luekotrienes involved in
chronic inflammation
189
what are the steps in getting neutrophils out of the blood and into the tissues
rolling
activation
adhesion
diapedesis
190
what cells dominate acute inflammation
neutrophils
191
what cells dominate chronic inflammation
macrophages and Tcells
192
What mediates the shift from acute inflammation to chronic inflammation
IL-6
193
what effects to proinflammatory cytokines systemically
1. TNF uses fat and muscle cells to mobilize energy stores
2. IL-1 and IL-6 sitmulate the liver to produce proteins to help fight infection
3. IL-1 and IL-6 act on the hypothalamus to induce a fever
194
what is the acute phase response
when IL1 and IL6 stimulate the liver to produce proteins that help fight infection
195
what are antiinflammtory actions
1. glucocorticoids
2. IL10 and TGF-b
3. acetylcholine receptors
196
What are the two types of interferons
```
type 1 (IFN -a and IFN-b)
type 2 (IFN-y)
```
197
what is type 1 interferon
IFNa and IFNb
they are produced by infected cells, and by cells sensing viruses through TLR.
they work against virus's
they leave the infected cells and go to nearby cells. they stop the cells from proliferating the virus
198
what is type 2 interferon
they are antiviral and antibacterial (IFN-y)
199
what does type 1 interferon do to cells
1. through PKR they shut off all translation
2. degrade RNA
3. inhibit transcription
200
what does type 2 interferon do to cells
shut off all translation through PKR
201
what cells produce Interferons
macrophages, immature dendritic cells, plasmacytoid dendritic cells
202
which cells produce the most interferons
plasmacytoid dendritic cells
203
what TLR gives rise to IFN-B
TLR 3
204
what TLD gives rise to IFN-a
TLR 7,8,9
205
what is the most potent activator of macrophages
IFN-y
