Ch2: Innate Immunity Flashcards
1
Q
What are the components of innate immunity? 8
A
- Anatomical barriers
- Antimicrobial substances
- Normal flora that competes with pathogens
- Immune cells
- Sensor systems
- Phagocytosis
- Inflammation
- Fever
2
Q
What is the specificity of innate immunity?
A
Structures shared by classes of microbes or damaged cells
3
Q
What is specificity of adaptive immunity?
A
Structural detail of microbial molecules (antigens)
4
Q
Receptors for innate immunity are encoded where?
A
Germline
5
Q
Which has more diverse receptors, innate or adaptive?
A
Adaptive
6
Q
What encodes adaptive immunity receptors?
A
Genes produced by somatic recombination of gene segments
7
Q
How is the distribution of receptors described in innate immunity?
A
Nonclonal: Identical receptors on all cells of same lineage
8
Q
How is the distribution of receptors described in adaptive immunity?
A
Clonal: Clones of lymphocytes with distinct specificities express different receptors
9
Q
Can both adaptive and innate immunity discriminate against self?
A
Yes
10
Q
How long does innate immune response last?
A
From 0-4 hours
11
Q
When does the early induced response occur?
A
4-96 hours
12
Q
When does the adaptive immune response occur?
A
After 96 hours
13
Q
What is the skin’s mechanical, chemical and microbiological barrier to infection?
A
Mechanical: Perspiration and sloughing
Chemical: Sebum and Defensins
Microbiological: Normal flora
14
Q
What is the GI tract’s mechanical, chemical, and microbiological barrier to infection?
A
Mechanical: Flow of fluid/food
Chemical: Acidity, enzymes, defensins
Microbiological: Normal flora
15
Q
What is the respiratory tract’s mechanical, chemical and microbiological barrier to infection?
A
Mechanical: Flow of fluid, mucus, air
Chemical: Lysozyme in nasal secretions & Defensins
Microbiological: Normal flora
16
Q
What is the urogenital tract’s mechanical, chemical and microbiological barrier to infection?
A
Mechanical: Flow of fluid
Chemical: Acidity in vaginal secretions, spermine and zinc in semen, defensins
Microbiological: Normal flora of urogenital tract
17
Q
What are the eyes’ mechanical, chemical and microbiological barrier to infection?
A
Mechanical: Flow of tears
Chemical: Lysozyme in tears, Defensins
Microbiological: Normal flora
18
Q
What is mucin?
A
Host cell derived glycoproteins that coat pathogens and inhibit adherence
19
Q
Acids and bile salts have what effect in stomach?
A
Make is difficult for organisms to move past stomach
20
Q
What do lysozymes degrade?
A
Peptidoglycans
21
Q
Function of lactoferrin?
A
Sequester iron so bacteria don’t have access
22
Q
What are alpha and Beta defensins?
A
Cationic peptides that damage negatively-charged membranes
23
Q
Defensins are comprised of what?
A
35-40 amino acids containin 3 intra-chain disulfide bonds
24
Q
Charge of defensins?
Why is this important?
A
Positively
Can interact with negative charged membranes
25
Are defensins hydrophobic or hydrophilic?
Both: amphipathic
26
Function of defensins?
Disrupt membrane integrity of bacteria, viruses, and fungi
27
Defensins are formed as what first?
Inactive precursors
28
What is the main source of defensins in the intestine?
Paneth cells
29
When a bacteria enters a surface wound, what happens? 3
1. Resident effector cells secrete cytokines
2. Vasodilation and increased vascular permeability
3. Tissue is inflamed
30
3 types of cells created from lymphoid progenitor cell?
B Cell
T Cell
NK Cell
31
B Cells do what?
Produce antibodies
32
What do B cells transform into?
Plasma cell
33
What do plasma cells do?
Secrete antibodies
34
What do natural killer cells do?
Kill cells infected with certain viruses
35
What does a neutrophil do?
Phagocytose microorganisms
36
What does an eosinophil do?
Kills antibody-coated parasites through release of granules
37
What does a basophil do?
Control immune response to parasites
38
What does a dendritic cell do? 2
1. Activates T Cells
| 2. Initiates adaptive immune response
39
What does a mast cell do?
Expulsion of parasites from body through release of granules containing histamine
40
What is a monocyte?
Circulating precursor cell to macrophage
41
What does a macrophage do? 2
1. Phagocytose microorganisms
| 2. Activates T cells --> Initiates immune response
42
What does a megakaryocyte do? 2
1. Platelet formation and 2. wound repair
43
What does an erythrocyte do?
Oxygen transport
44
4 types of white blood cells?
1. Granulocytes
2. Mononuclear phagocytes
3. Dendritic cells
4. Lymphocytes
45
4 types of granulocytes
1. Neutrophils
2. Basophils
3. Eosinophils
4. Mast cells
46
What is the most abundant cell in innate response?
Neutrophil
47
How long relatively is a neutrophils life?
Short
48
What 3 granulocytes are involved in allergic reaction?
1. Basophils
2. Eosinophils
3. Mast Cells
49
What common cell is a member of the mononuclear phagocyte system?
Monocytes
50
What differentiate from monocytes?
Macrophages
51
What are four common macrophages differentiated from blood monocyte?
1. Microglia (CNS)
2. Kupffer cell (Liver)
3. Alveolar macrophage (Lung)
4. Osteoclasts (bone)
52
Dendritic cells are involved in which immune response?
Adaptive
53
Dendritic cells do what?
Finds material in tissue and brings it to adaptive immunity cells
54
Lymphocytes are involved in which immune response?
Adaptive
55
What is main difference of Natural killer cells and T & B cells?
NK Cells don't have specificity
56
What is first thing to happen when first line barriers are breanched?
Tissue-resident macrophages and complement recognize the material
57
Recognition by macrophage and complement leads to what? 4
1. Macrophage cytokine production
2. Cell migration
3. Inflammation
4. Initiation/activation of adaptive response
58
Macrophage cytokine production causes what? 2
1. Host cells to produce cytokines
| 2. Induce expression of cell surface molecules by epithelial cells
59
E and P selectin are examples of what?
| What do they do?
Cell surface molecules
Bind sialyl-Lewis
60
ICAM's are examples of what?
| What do they do?
Cell surface molecules
Bind integrins
61
5 main ways a pathogen is recognized?
1. Mannose-binding lectin
2. Macrophage mannose receptor
3. Scavenger receptor
4. Toll-like receptor
5. Nucleotide-binding oligomerization domain protein
62
Mannose-binding lectin is found where?
Part of what family?
What does it bind?
Free plasma
Collagenous lectin (collectin) protein family
Carbohydrates expressed by pathogens
63
Define a lectin
Any protein that is not an antibody nor from the immune system but binds to carbohydrate-receptors on cell surfaces
64
Macrophage mannose receptor is what type of molecule?
What is it dependent on?
What does it bind to?
Lectin
Calcium
Sugars on pathogens
65
Scavenger receptors recognize what? (2)
1. Anionic polymers
| 2. Acetylated low-density lipoproteins
66
Toll-like receptors recognize what?
PAMP's
67
Nucleotide-binding oligomerization domain (NOD) proteins are similar to what?
TLR's
68
Main effects of triggering receptors on macrophages? 2
1. Increase phagocytosis
| 2. Increase proinflammatory cytokine production
69
Define phagocytes
Cells that engulf and digest microbes and cellular debris
70
Which phagocytes are found even in healthy tissues? (2)
1. Macrophages
| 2. Dendritic cells
71
Which phagocyte only appears when needed?
Neutrophils
72
What bacteriocidal agents does a phagocyte have? 6
1. Acidification
2. Toxic oxygen-derived products
3. Toxic NO
4. Antimicrobial peptides: Defensins & Cationic
5. Enzymes: Lysozyme and Hydrolases
6. Competitors: Lactoferrin & VB12-BP
73
What is respiratory burst?
Rapid, transient release of ROS
74
What are the steps for producing ROS? 3
1. In endocytic vacuole, NADPH oxidase produces superoxide.
2. Superoxide dismutase converts this to peroxide
3A. Peroxidase and iron convert this to hypochlorite and hydroxyl radicals
3B. Catalase converts this to H2O and O2 to increase pH for activation of defensins and lysozymes
75
Nitric oxide production also occurs which is produced by what?
What induces this?
NO Synthase
IFN-Gamma
76
What type of receptor is a Toll-like receptor?
Pathogen recognition receptor
77
What do Toll-like receptors recognize?
PAMP's
78
Toll-like receptors are expressed intracellularly or extracellularly?
Both
79
What do intracellular TLR's usually recognize?
Nucleic acids
80
What TLR's recognize bacterial lipopeptides?
TLR-1:TLR-2
| TLR-2:TLR-6
81
What TLR's recognize bacterial peptidoglycan
TLR-2
82
What TLR's recognize LPS?
TLR-4
83
What TLR's recognize bacterial flagellin?
TLR-4
84
What TLR recognizes dsRNA?
TLR-3
85
What TLR's recognize ssRNA?
TLR-7 and TLR-8
86
What TLR's recognize CpG DNA?
TLR-9
87
What bacteria will be noticed by TLR4?
| Why?
Gram-negative bacteria
| Have LPS
88
What is required for LPS recognition by TLR4? (3)
LPS-binding protein (LBP)
MD2
CD14
89
Steps of TLR activation and the result? 5
1. TLR is engaged by bacteria or virus
2. TIR signaling domain recruits adaptor proteins
3. Activation of transcription factors occurs (NF-KB and IRF's)
4A. NF-KB causes an increase in expression of cytokines, adhesion molecules, costimulators
4B. IRF's cause a production of type 1 interferon (IFN alph/Beta)
5A. Increased expression causes acute inflammation and stimulation of adaptive immunity
5B. Production of IFN causes an antiviral state
90
What do cytokines do?
Bind to surface receptors and regulate cell function
91
What is cytokine redundancy?
Multiple cytokines perform similar functions
92
What does it mean if a cytokine is pleiotropic?
Single cytokine can stimulate multiple functions
93
What is a chemokine?
Cytokine important in chemotaxis
94
What is a colony stimulating factor?
Cytokine important in multiplication and differentiation of leukocytes
95
What is an interferon?
Important cytokine that controls viral infections and inflammatory response
96
What is a interleukin?
Important cytokine that is produced by leukocytes for both innate and adaptive immunity
97
What is tumor necrosis factor?
Cytokine that kills tumor cells and initiates inflammation
98
What are five common pro-inflammatory cytokines?
```
IL-6
TNF-Alpha
IL-1Beta
CXCL8
IL-12
```
99
IL-6 has what effects? 2
1. Fever
| 2. Acute-phase production production by hepatocytese
100
TNF-alpha has what effects? 4
1. Activation of vascular endothelium and increases vascular permeability --> complement and cells leak into tissue
2. Fever
3. Mobilization of metabolites
4. Shock
101
IL-1Beta has what effects?
1. Activates vascular endothelium --> Leaking
2. Activate lymphocytes
3. Local tissue destruction
4. Increase access of effector cells
5. Fever
6. Production of IL-6
102
Function of CXCL8?
1. Chemotaxic factor that recruits neutrophils and basophils to site of infection
103
Function of IL-12?
Activate NK cells
104
Function of IL-1, IL-6, and TNF-alpha in liver?
| Which will cause what?
Activates acute-phase proteins (CRP, MBL)
Activation of complement and opsonization
105
Function of IL-1, IL-6, and TNF-alpha in bone marrow?
| Which will cause what?
Neutrophil mobilization
Phagocytosis
106
Function of IL-1, IL-6, and TNF-alpha in hypothalamus?
| Which will cause what? 3
Increased body temperature
Decrease pathogenic replication
Increased antigen processing
Increased specific immune response
107
Function of IL-1, IL-6, and TNF-alpha in fat and muscle?
| Which will cause what? 3
Protein and energy mobilization --> Increase body temp
Decrease pathogenic replication
Increased antigen processing
Increased specific immune response
108
Function of IL-1, IL-6, and TNF-alpha in dendritic cells?
| Which will cause what?
TNF-alpha stimualtes migration to lymph nodes and maturation.
Initiation of adaptive immune response
109
Acute-phase proteins are produced by what?
Liver
110
4 members of acute-phase proteins?
1. Serum amyloid protein
2. C-reactive protein
3. Fibrinogen
4. Collectin family
111
Members of collectin family include? (3)
1. Mannose-binding lectin
2. SP-A
3. SP-D
112
What does C-reactive protein bind to?
Phosphocholine component of LPS in bacterial and fungal cell walls
113
3 roles of inflammation?
1. Deliver additional effector molecules to site
2. Provide physical barrier of coagulation to prevent pathogen spreading
3. Promote repair of injured tissue
114
Which is bad, local or systemic infection?
SYSTEMIC
115
Explain why local infection leads to survival! 5
1. Macrophage activated to secrete TNF-alpha in the tissue
2. Increased release of plasma proteins, phagocytes, lymphocytes into tissue and platelet adhesion to blood vessel wall
3. Phagocytosis of bacteria with local vessel occlusion cause containment of infection.
4. Antigens drain and taken to lymph node
5. Survival and stimulation of adaptive immune response
116
Explain why systemic infection leads to death? 4
1. Macrophages activated in liver and spleen secrete TNF-alpha into bloodstream
2. Systemic edema causes decreased blood volume which collapses vessels
3. Disseminated intravascular coagulation leads to wasting and multiple organ failure septic shock
4. death
117
4 types of adhesion molecules?
1. Vascular addressin
2. Selectin
3. Integrin
4. Immunoglobulin
118
What do selectins bind?
Carbohydrates
119
What do selectins initiate?
Leukocyte-endothelial interaction
120
P-selectin is found where? What is its ligand?
Activated endothelium and platelets
PSGL-1
Sialyl Lewis
121
E-selectin is found where? What is its ligand?
Activated endothelium
Sialyl Lewis
122
What do integrins bind to? (2)
| Function?
Cell-adhesion molecules and ECM
Strong adhesion
123
What kind of cells contain integrins?
Monocytes, T Cells, macrophages, neutrophils, dendritic cells
124
LFA-1 have what ligand?
ICAM's
125
Mac-1 (CR3) has what ligands? (3)
ICAM-1
iC3b
Fibrinogen
126
CR4 integrin has what ligand?
iC3b
127
VLA-5 has what ligand?
Fibronectin
128
Function of immunoglobulin superfamily?
Various roles in cell adhesion by being ligands for integrins
129
ICAM-1 is found where?
| Ligands? (2)
Activated endothelium
| LFA-1, Mac1
130
ICAM-2 is found where?
| Ligand?
Resting endothelium
Dendritic cells
LFA-1
131
VCAM-1 is found where?
| Ligand?
Activated endothelium
| VLA-4
132
PECAM is found where?
| Ligand?
Activated leukocytes
| Endothelial cell-cell junctions
133
How do cells home to the site of infection?
Follow chemotactic gradient formed by CXCL8:CXCL8 receptor interactions
134
4 steps of leukocyte getting to the site of infection
1. Rolling by weakly binding cell addressin to endothelium selectin.
2. Integrin activation by chemokines interacting with chemokine receptor on cell
3. Integrin binds to endothelial ICAM tightly
4. Migration through endothelium
135
What activates the high affinity state of integrin:ICAM interactions?
Chemokines
136
First cells to arrive at site of infection?
Neutrophils
137
Where are neutrophil reserves stored?
Bone marrow
138
What do neutrophils do upon reaching infection site?
Engulf and kill bacteria
Then die in the tissue and are engulfed and degraded by macrophages
139
Neutrophil receptors recognize what?
| Specifically what?
Pathogens
| PAMP's
140
What receptors allow neutrophils to recognize complement components?
CR3 and CR4
141
Can multiple receptors work at the same time in neutrophils?
Yes
142
Azurophilic granules are filled with what?
Proteins and peptides that disrupt and digest microbes
143
Examples of enzymes that digest microbes?
1. Lysozyme
2. Defensins
3. Myeloperoxidase
4. Neutral proteases (cathepsin G, elastase, proteinases)
5. Bactericidal/permeability increasing protein
144
Function of bactericidal/permeability-increasing protein?
Binds LPS and kills Gram-negative bacteria
145
Effect of triggering receptors on macrophages?
1. Increase phagocytosis
| 2. Increase proinflammatory cytokine production
146
Complement is produced where?
Liver
147
Result of complement activation (3)
Opsonophagocytosis
Inflammation
Lysis
148
How many ways exist for complement to be activated
3
149
Complement protein naturally exist how?
Zymogens
150
What enzyme form are many complement proteins?
Serine proteases (cut proteins where serines exist)
151
First serine protease in classical pathway is what?
C1R
152
What does C1R doing its action represent?
Activating step of classical pathway of complement
153
The C1 complex (contains C1R) binds what? 3
| Via what
1. IgM
2. IgG1
3. IgG3
C1q
154
What are the three best antibody isotypes for capacity to fix complement?
IgM
IgG3
IgG1
155
What are the steps of the classical pathway of complement? 7
1. C1q recognizes antibodies on bacterial surface
2. C1r cleaves itself, two C1s copies, and itself again
3. C1s cleaves C4 into C4a and C4b
4. C4b binds to pathogen surface
5. C4b binds C2
6. C1s cleaves C2 into C2a and C2b
7. C4bC2a forms the classical C3 convertase and cleaves C3 into C3a and C3b
156
How many C3 molecules can the classical C3 convertase cleave?
1000
157
C3a acts how?
Powerful chemoattractant for immune cells
158
C3b acts how?
Powerful opsonin (coats pathogen for receptor recognition)
159
What is the classical C5 convertase?
C4bC2aC3b
160
How are host cells protected by C3b deposition?
The thioester bond on C3b is rapidly hydrolyzed if it does not react with a pathogen so that it cannot bind to human cells.
161
What are the steps of C3b leading to opsonophagocytosis? 5
1. Complement activation leads to C3b binding to bacteria
2. CR1 on macrophages binds C3b
3. Endocytosis of bacterium
4. Phagosome is formed
5. Lysosome fuses with phagosome to form phagolysosome
162
C3a and C5a are both known as what?
Anaphylatoxins
163
What do anaphylatoxins do? (4)
1. Increase vascular permeability
2. Increase cell adhesion molecule expression
3. Cause smooth muscle contraction
4. Release of histamine from mast cells
164
The actions of anaphylatoxins lead to what?
Influx of antibodies, complement proteins, and cells to establish strong chemotactic gradient
165
What are the steps of the formation of membrane attack complex? 2
1. C5 convertase (C4bC2aC3b) cleaves C5 into C5a and c5b
| 2. C5b binds C6 to initiate MAC formation and lyse bacteria
166
Most important part of formation of Membrane Attack Complex?
C9 because it forms membrane pores
167
In absence of IgM or IgG what can initiate the classical complement pathway?
C-reactive protein binding to C1
168
What type of molecule is C-reactive protein?
Acute phase protein made in liver
169
Advantage of CRP binding and activating classical complement pathway?
In absence of antibody, as it typical in early infection, allows for classical pathway to be activated
170
What does the Lectin pathway of complement activation use to initiate? 2
Mannose-binding lectin
| Ficolins
171
What do Mannose-binding lectin and Ficolins bind directly to?
Microbial sugars without needing pathogen specific antibody
172
Mannose-binding lectins and ficolins are structurally similar to what?
C1Q
173
What acts as C1r and C1s in lectin pathway?
Mannose-binding lectin-associated proteases (MASP-1 and MASP-2)
174
Steps of lectin pathway of complement activation? 6
1. MASP-2 cleaves C4 to C4a and C4b
2. C4b binds to microbial surface
3. MASP-2 cleaves C2 to C2a and C2b
4. C2a binds to C4b forming classical C3 convertase
5. C4b2a binds C3 and cleaves it into C3b and C3a.
6. C3b binds to microbial surface
175
Main difference between Lectin pathway and Classical pathway?
C1 is not involved in lectin
176
The alternative pathway lacks what molecule?
C1 or a Mannose-binding lectin
177
Chronological order of the 3 complement activations?
1. Alternative pathway
2. Lectin pathway
3. Classical pathway
178
How is a C3 convertase generated in alternative pathway?
1. C3 made in the liver
2. Tickover (C3 thioester bond hydrolyzed without cleaved forming iC3)
3. iC3 binds Factor B
4. Factor B-iC3 bind Factor D
5. Factor D cleaves Factor B into Ba and Bb
6. Soluble iC3bBb is formed and cleaves C3 into C3a and C3b
7. C3b is deposited into pathogen
8. C3b finds Factor B
9. Factor D cleaves Factor B into Ba and Bb to form C3bBb
179
What is the alternative C3 convertase?
C3bBb
180
What is the alternative C5 convertase?
(C3b)2Bb
181
What does Properdin/Factor P do?
Stabilize C3bBb and extends its life --> increase C3b opsonization
182
What does Factor H do?
Binds C3b and changes its conformation which allows Factor I to cleave it into iC3b (inactive) which will be involved in adaptive immunity
183
What does Decay Accelerating factor (DAF) do?
Removes Bb from C3bBb making the alternative C3 convertase inactive
184
Membrane cofactor protein (MCP) does what?
Removes Bb from C3b and allows Factor I to cleave C3b into iC3b which is inactive
185
Where are DAF and MCP expressed?
| Why?
Surface of healthy host cells
Prevent alternative pathway from acting on self
186
What does C1 inhibitor do?
Inhibits C1r and C1s serine protease activity
187
What does Factor I do?
Cleaves C3b and C4b
188
What does C4-binding protein (C4BP) do?
Causes dissociation of classical pathway C3 convertase by assisting in cleavage of C4b
189
What does CD59 do?
Blocks C9 binding and prevents formation of MAC
190
What does Type 1 complement receptor do? (CR1)
Causes dissociation of C3 convertase subunits (C3b AND C4b)
191
All 3 complement activation pathways converge where?
C3 convertase
192
The C3b that is bound to surface of a cell initiates what?
Opsonization
Inflammation
Cell lysis
193
Initiators of classical pathway include? (3)
IgM
IgG
CRP
194
Initiators of Lectin pathway include? 2
1. Mannose-binding lectins
| 2. Ficolins
195
Initiator of alternative pathway is what?
C3 itself
196
Does alternative pathway need antibody?
No
197
Does alternative pathway need microbial sugar recognition?
No
198
Does alternative pathway need inhibitors to prevent attack on self?
Yes
199
C3b functions as what? (3)
1. Opsonin
2. Part of C3 convertase
3. Part of C5 convertase
200
C3a stimulates what?
Inflammation
201
Factor B is so important for what role?
Active enzyme of C3 and C5 convertases
202
Outome of complement opsonization and phagocytosis?
Phagocytosis and killing of microbe
203
Outcome of complement-mediated cytolysis?
MAC complex allows for osmotic lysis of microbe
204
Outcome of complement stimulation of inflammatory reactions?
Destruction of microbes by recruited leukocytes
205
Initial serine protease in each pathway?
Classical: C1s
Lectin: MASP-2
Alternative: Factor D
206
C3 convertase in each pathway?
Classical: C4b2a
Lectin: C4b2a
Alternative: C3bBb
207
What is chronic granulomatous disease caused by?
Lack of NADPH oxidase --> no respiratory/oxidative burst
208
What happens to bacteria in chronic granulomatous disease?
Taken up by macrophages but can't be destroyed
209
What is leukocyte adhesion deficiency the result of?
Malfunctioning cell adhesion molecules
210
Result of leukocyte adhesion deficiency?
Cells can't enter sites of infection = No recruitment
211
Interleukin Receptor-Associated kinase deficiency is result of what?
Lack of response to TLR and IL-1
212
Result of interleukin receptor-associated kinase deficiency?
Can't initiate inflammatory response
213
Result of disorder with C1q, C1s, C4?
Autoimmune (SLE, glomerulonephritis)
214
Result of disorder with C3, C6, Factor I?
Recurrent bacterial infection
215
Result of disorder with C1r, C2, C5, C7
Recurrent bacterial infections AND autoimmunity
216
Result of disorder with C1INH
Can't turn off C1 binding --> Hereditary angioedema
217
A virus infected cell releases what?
Interferons
218
What are interferons?
Cytokines that interrupt viral replication
219
3 parts of Interferon response?
1. Induce resistance to viral replication in all cells
2. Increase expression of ligands for receptors on NK cells
3. Activate NK cells to kill virus-infected cells
220
What are the Type I interferons?
IFN-alpha
| IFN-beta
221
What is the Type II interferon?
IFN-gamma
222
What is first group of molecules to be produced in response to virus?
IFN-alpha, IFN-Beta, TNF-alpha, IL-12
223
What is second group of molecules to be produced in response to virus?
NK-cells
224
What is third group of molecules to be produced in response to virus?
T-cells
225
NK cells have what two types of receptors on surface?
1. Activating
| 2. Inhibitory
226
Host cells have what type of proteins that will bind to NK cells?
Proteins that bind to inhibitory receptors on NK Cells
227
What is the one activating receptor that can overcome all inhibitory signals on an NK Cell?
NKG2D
228
2 classes of inhibitory and activating receptors on NK cells?
Immunoglobulin-like receptors
| Lectin-like receptors
229
Inhibitory NK cells naturally bind what?
Host MHC and receive negative signal
230
In virus infected cells, what happens to MHC?
| Result
Down-regulation of MHC expression
| NK Cell loses negative signal
231
Virus-infected cells express what protein at their surface?
Which binds to what?
Result?
MIC protein
Binds to activating receptor NKG2D
Positive signal sent to NK cell
232
What is in the granules that NK cell releases?
1. Perforin
2. Granulysin
3. Granzymes
233
Main source of TNF? 2
| Targets (6)
Macrophages and T cells
```
Endothelial cells: Activate
Neutrophils: Activate
Hypothalamus: fever
Liver: Make acute phase proteins
Muscle, fat: Catabolism
Many cells: Apoptosis
```
234
Source of IL-1? (2)
| Targets? 4
Macrophages and endothelial cells
Endothelial cells: Activate
Hypothalamus: Fever
Liver: Acute-phase protein synthesis
T cells: Differentiation
235
Source of chemokines? 6
Target?
1. Macrophages
2. Dendritic cells
3. Endothelial cells
4. cells
5. Fibroblasts
6. Platelets
Leukocytes: Increase integrin affinity, chemotaxis, activation
236
IL-12 source? (2)
| Target? (2)
1. Dendritic cells
2. Macrophages
1. NK Cells: Activation
2. T Cells: Differentiation and activation
237
IFN-gamma source? (2)
| Target (2)
1. NK cells
2. T cells
1. Activate macrophages
2. Stimulate antibody response
238
IFN-alpha source (2)
| Target? (2)
1. Dendritic cells
2. Macrophages
1. All cells: Antiviral state
2. NK cells: activate
239
IFN-beta source?
| Target? (2)
1. Fibroblasts
1. All cells: Antiviral state
2. NK cells: activate
240
IL-10 source? (3)
| Target? (2)
1. Macrophages
2. Dendriticl cells
3. T cells
Macrophages and dendritic cells: Inhibit IL-12
241
IL-6 source? (3)
| Target? 2
1. Macrophages
2. Endothelial cells
1. Liver: Acute phase proteins
2. B cells: Proliferation
3. T cells
242
IL-15 source?
| Target: (2)
Macrophages
1. NK cells: Proliferation
2. T cells: Proliferation
243
IL-18 source?
| Target? (2)
Macrophages
1. NK cells: IFN-gamma synthesis
2. T cells: IFN-gamma synthesis
244
TGF-Beta source?
| Target? (2)
Many cells
1. Inhibition of inflammatin
2. T cells: Differentiation
245
Goal of innate defenses? 2
1. Recognize infection
| 2. Limit and stop spread
246
Initiators of inflammation are?
| How so
Tissue macrophages
| Release cytokines
247
Complement helps clear infections when?
Before and after antibodies are produced
