Exam 2 Flashcards
1
Q
How long does the primary response take to clear a pathogen?
A
14 days
2
Q
What cell type is prominent in the primary response?
A
DC
3
Q
How long does it take the secondary response to clear a pathogen?
A
3 days
4
Q
What cell type is prominent in the secondary response?
A
T/B cells
5
Q
What 3 things are special about the secondary response?
A
diversity
memory
specificity
6
Q
What are the 4 steps of the primary response?
A
- antigen—–DC interaction
- DC —— T cell interaction
- antigen —— B cell interaction
- T cell —— B cell interaction
7
Q
What are the 3 functions of DCs?
A
- pathogen recognition
- phagocytosis
- antigen processing
8
Q
How do DCs recognize pathogens?
A
PRR
9
Q
What MHC presents intracellular antigens?
A
MHC I
10
Q
What MHC presents extracellular antigens?
A
MHC II
11
Q
What MHC presents smaller peptides?
A
MHC I
12
Q
What cell recognizes peptides presented on MHC I?
A
CD8+ T cells
13
Q
What cell recognizes peptides presented on MHC II?
A
CD4+ T cells
14
Q
What cells present MHC I?
A
all cells
15
Q
What cells present MHC II?
A
antigen presenting cells
(DC, B cells, macrophages, TECs)
16
Q
What does MHC I look like?
A
asymmetrical (2 alpha subunits as peptide binding groove)
17
Q
What does MHC II look like?
A
symmetrical (alpha and beta subunit as peptide binding groove)
18
Q
What are the steps of DC presenting antigen to T cells?
A
- immature DC encounters pathogen
- DC travels to SLT and phagocytoses pathogen
- B7 is unregulated on DC
- DC presents peptide to T cell on MHC II
19
Q
What is the place for antigen presentation and B/T cell activation?
A
SLT
20
Q
How does a T cell find a presenting DC?
A
T cells cycle through the blood and into the SLT and if it doesn’t find a presenting DC in SLT it will re-enter bloodstream
21
Q
What 3 molecular interactions occur when DCs present to naive T cells?
A
TCR—–MHC
CD4 or CD8
CD28—-B7
22
Q
What cytokine induces T cell proliferation via autocrine signaling?
A
IL-2
23
Q
What causes SHM and class switching in BCR?
A
RNA splicing of heavy chain
24
Q
Memory B cells and naive B cells express _______ Ig
A
membrane bound Ig
25
Naive B cells express membrane bound Ig___ and Ig___
IgM
IgD
26
Where does class switching occur on BCR?
Fc heavy chain
27
Where does SHM occur on BCR?
Fab heavy chain
28
When B and T cells interact, who presents to who?
B cell presents antigen (from DC) to T cell
29
Why is B and T cell interactions important?
required for T cell dependent B cell activation
30
What 3 molecular interactions occur when B and T cells interact?
B cell ------ T cell
1. MHC II -----TCR
2. MHC II ----- CD4
3. CD40 ----- CD40L
31
What is up regulated on B cells when its MHC interacts with TCR?
CD40
32
What are the steps of germinal center formation?
1. DC presents to naive T cell (in T cell zone)
2. T cell activated
3. Naive B cell (in follicle) interacts with follicular DC
4. B cell processes and presents antigen (MHC II)
5. T cell interacts with B cells MHC (in cortex) = conjugate pair
6. T cells differentiate
Memory B cells (IgM secerted)
7. OR... B cell reenters follicle and forms germinal center (class switching and SHM)
8. plasma cells made and secrete different Ig's
33
Do memory B cell's BCR do class switching/SHM?
a little but not much
34
Do long-lived plasma cells do class switching/SHM?
yes
35
What kind of B cells are inactivated in the secondary immune response and why?
naive B cells
- not specific
36
What 3 isotypes are important for T2HSR?
IgG1
IgG3
IgM
37
What do IgG1 and IgG3 do?
opsonization
activate NK cells
activate complement
38
What does IgM do?
complement activation
39
What are the 3 basic functions of T2HSR?
1. apoptosis
2. lysis
3. phagocytosis
40
What is a T2HSR?
IgM/IgG recognizes innocuous cell surface molecules as foreign leading to 3 Ab mediated cell death
41
What are the 3 Ab mediated cell death mechanisms of T2HSR?
1. complement activation (MAC)
2. ADCC (NK cells)
3. opsonization (phagocytosis)
42
What isotype is important for Ab-mediated complement activation?
IgM
43
In Ab-mediated complement activation, what part of IgM binds to pathogen surface?
Fab
44
In Ab-mediated complement activation, complement ______ recognizes Ab Fc region
C1q
45
In Ab-mediated complement activation, C1q binding to Ab Fc region causes activation of...
C1s
C1r
46
In Ab-mediated complement activation, activation of C1r and C1q leads to _________ = MAC = lysis
C5 convertase
47
In Ab-mediated complement activation, when C1q binding site is exposed the IgM pentamer is in the _________ form
staple
48
COMPLEMENT ACTIVATION STEPS
SKIP
SKIP FOR NOW
49
What molecule initiates the MAC formation?
C5b
50
What isotype is used for ADCC?
IgG1
51
How does the receptor involved in ADCC work?
FCGRII binds to Fc of IgG1 (whose Fab is bound to cell surface)
52
What receptor does NK cells express for ADCC?
FcGRII
53
What enzyme is involved in FAS-L / granzymes mechanism?
caspace
54
In Ab-mediated opsonization, what part of Ab binds to cell surface and which part binds with phagocyte?
cell surface: Fab
phagocyte: Fc
55
What are 2 phagocytes?
macrophages and neutrophils
56
In Ab-mediated opsonization, where are the cells degraded?
lysosomes
57
What are the 3 types of T2HSRs?
1. mismatched blood transfusions
2. hemolytic disease in newborns
3. drug induced anemia
58
What isotype does mismatched blood transfusions use?
IgM
59
How does mismatched blood transfusions work?
IgM binds to blood antigens and lysis of blood cells
60
What isotype does hemolytic disease in newborns use?
IgG
61
What is hemolytic disease in newborns?
IgG of mother recognizes RH+ RBC of fetus and binds to fetal RBC and fetal NK cells recognize IgG bound and kills RBC
62
How does drug induced anemia work?
IgM binds to RBC causing RBC lysis
63
What isotype does drug induced anemia use?
IgM
64
What blood type is not affected by hemolytic disease?
type O (lack antigens on surface)
65
What makes blood types special from one another?
glycoproteins of RBC surface
66
What is the backbone antigen on RBC surface?
H antigen
67
Most people possess _______ Ab against blood carb antigens they don't express
IgM
68
Why do people have IgM Ab against other blood types that aren't thier own?
common microbes express similar carb antigens that induce host immune response
69
Why is RBC lysis dangerous?
hemoglobin is released from RBC which metabolizes into toxic billibrubin
70
What are the steps of hemolytic disease in newborns?
1. FIRST PREGNANCY: Rh+ RBC activate mother's B cells to produce anti-Rh IgM (cannot cross placental barrier)
2. SECOND PREGNANCY: On secondary exposure, anti-Rh IgG can cross the placental barrier and attach to Rh+ fetal RBC causes lysis via fetal NK cells
71
How does Rho Gam therapy work?
Anti-Rh antibodies bind and inactivate fetal Rh antigens to prevent mother's cell from recognizing them
72
What 2 mechanisms does Rho Gam use to prevent mothers immune system from recognizing RH+ RBC?
1. FcGRIIB receptor will prevent B cell signaling
2. Anti-D antibodies bind to RH+ RBC causing macrophage to phagocytose RBCs
73
What are DT4 HSRs?
Skin permeable antigens activate CD4+/Th1 cells resulting in sensitization followed by DT4 HSR on second exposure
74
What does the "delayed" come from in DT4 HSR?
required recruitment and activation of macrophages
75
DT4 HSR are Th__ cell-mediated macrophage activation
Th1
76
What cell is important for DT4 HSR?
macrophages
77
What are the polarizing cytokines for DT4 HSR?
(Th1)
IL-12
IFN-g
IL-18
78
What are the effector cytokines of DT4 HSR?
(Th1)
IFN-g
TNF
79
What are the effector mechanisms of DT4 HSR?
(Th1)
cell mediated immunity (barrier protection)
macrophage activation
inflammation
80
What are DT4 HSR antigens?
intracellular antigens
contact antigens
81
What 3 things happen during the sensitization phase of DT4 HSR? (first exposure)
1. antigen processing and presentation by MHC II
2. IL-2mediated differentiation of naive Th0 to Th1 cells
3. development of memory T cells
82
PPD / mycobacterium induces a ......
pure Th1 immune response
83
What are the 3 types of memory T cells in DT4 HSR?
1. central MTC
2. effector MTC
3. resident MTC
84
Where are central MTC located?
circulate blood/SLT
85
What memory T cell is is specific for one antigen?
central MTC
86
Where are effector MTC located?
circulate blood / SLT / tissue
87
Where are resident MTC located?
in tissue (return to site of infection)
88
What does it mean when resident MTC are "bleeding"?
not all resident MTC go to site of infection, some go to other tissues in case there is another infection elsewhere
89
What T cell has CD45RA?
naive T cells
90
What T cells have CD45RO?
all memory T cells
91
What T cells have CCR7?
naive T cells
central MTC
(for trafficking to SLT)
92
What T cell has CD103?
resident MTC
(expressed on epithelial cells)
93
Where are monocytes located?
blood
94
Where are macrophages located?
tissue
95
_________ and _________ come from granulocyte-monocyte progenitors
monocytes
neutrophils
96
macrophages develop from ___________
monocytes
97
Macrophages produces ______ to recruit monocytes from blood which differentiate into macrophages
CCL2
98
What happens in the effector phase of DT4 HSR? (second exposure)
1. APC present to memory Th1 cells
3. memory T cells produce INF-g/TNF
4. INF-g/TNF = recruitment of monocytes/macrophages
99
What are the initiators of the effector phase of DT4 HSR?
Th1 cells
100
What cytokines induce recruitment of macrophages in the effector phase of DT4 HSR?
INF-g/TNF
101
What do macrophages present to in the effector phase of DT4 HSR?
memory Th1 cells
102
_____ induces MHC expression in macrophages for the effector phase of DT4 HSR?
IFN-g
103
What kills a the pathogen in macrophages?
RNS/ROS
104
What secretes INF-g/TNF to activate macrophages in effector phase of DT4 HSR?
TH1 cells
105
The secretion of IFN-g/TNF in the effector phase of DT4 HSR, causes a inflammatory ______
loop
106
Draw out the inflammatory loop in the effector phase of DT4 HSR?
1. IL-12 induces more Th1 cells
2. TNF-g induces macrophage activation and vascular permeability
3. IL-8 neutrophils recruitment
4. CCL2 monocyte recruitment
5. IL-6 and IL-1 induces inflammation/fever
107
What cytokines are in the inflammatory loop in the effector phase of DT4 HSR?
TNF
IL-12
IL-8
IL-6
IL-1
CCL2
108
What does IL-6 and IL-1 induce in the inflammatory loop in the effector phase of DT4 HSR?
inflammation and fever
109
What does IL-12 induce in the inflammatory loop in the effector phase of DT4 HSR?
recruitment of more TH1
110
What does IL-8 in the inflammatory loop in the effector phase of DT4 HSR?
neutrophil recruitment
111
What does chronic macrophage activation due to inability to eliminate pathogen cause?
granuloma formation
112
What are granulomas?
multi-nucleated giant cell of fused immune cells to wall off pathogen from tissue
113
What are foam cells?
macrophages that have ingested large amounts of lipids (in granulomas)
114
What 2 materials can cause granulomas?
silica and sutures
115
What happens if a granuloma cannot be cleared?
it will rupture and release pathogen causing tissue/blood vessel damage
116
What is the root cause of tissue/blood vessel damage when granulomas rupture?
persistent ROS/RNS activation
117
How does TB tests work?
PPD is injected into dermis
118
What are TB test reactions mediated by?
CD4 / Th1 cells
119
What is the lipid for poison oak?
urushiol (covalently binds to proteins)
120
Poison oak can penetrate skin which makes it __________ __________
contact dermatitis
121
Poison oak reactions have multiple T cell subsets compared to TB tests but what is it mainly mediated by?
CD4 / TH17
122
TB skin tests and poison oak are both types of ....
DT4 HSR
123
DT4 HSR are CD___ T cell mediated
CD4 T cells
124
CD8 T cells require stronger activation of _____ due to its cytosolic activity
B7
125
What 2 ways can DC cells activate CD8 T cells since they need a lot more B7?
1. sequential activation
2. cross presentation
126
What is sequential activation of CD8 T cells?
DC ---CD4 T cell interaction increases B7 levels, then DC interacts/activates CD8 T cell
127
What is cross presentation of CD8 T cells?
DC----CD4 T cell interactions, then changes their antigen processing to present on MHC I which can activate CD8 T cells
(present extracellular antigen on MHC I)
128
What is it called in cross presentation when DC switches thier antigen processing to present on MHC I?
cytosolic diversion
129
CD4 T cell engagement help CD8 T cells activate by providing paracrine _____ in cross presentation
IL-2
130
TCRs recognize just the peptide presented?
No, interact with the MHC as well
131
NKT cells recognize ____ presented by ____ on APCs
glycolipids
CD1d
132
NKT cells DO NOT recognize...
MHC---peptide complex
133
What is different about NKT cell's TCRs?
no memory or diversity
134
How do NKT cells kill?
same as NK cells
135
o
o
136
How does CD1a present lipids differently than how MHC presents peptides?
lipid is buried in CD1d and the A' roof is what is recognized
137
Is CD1a activated on LC cells when the A' roof is blocked or unblocked?
unblocked
138
What causes A' roof to be blocked in CD1a?
healthy skin lipid head causes steric hinderance
139
What is the term for the A' roof being blocked and unblocked on CD1a?
interference model
140
In the interference model of CD1a, binding of TCR is soley based on _____ not _____
CD1a not ligand
141
CD1__ is highly expressed on LC DCs
CD1a
142
CD1__ is expressed on NKT cells
CD1d
143
What are LC DCs?
Specialized DCs in epidermis
144
What are fillagrin linkages?
links keratinocytes to build skin layers
145
What linkage in skin is abnormal in atopic dermatitis?
fillagrin linkages
146
What does the corneum/corneocytes provide?
waterproof surface of skin
147
What are corneocytes?
keratinocytes without nucleus
148
Where are regular LC DCs located?
epidermis
149
When LC DCs sample a foreign lipid with its CD1a what T cell subset is produced?
TH17
150
What are 2 different methods does the skin use to sense urushiol?
1. LC DCs sense urushiol lipids
2. Dermal DCs sense peptide--urushiol complex
151
The method of LC DCs sensing urushiol lipids uses CD___ / TH___ activation
CD4/TH17
152
The method of dermal DCs sensing peptide-urushiol complex MAINLY uses CD___/TH___ activation
CD4/TH1
(can use CD8/CTL)
153
How does the skin sense PPD from TB skin test?
injected directly into dermis by passing LC DCs and being sensed by dermal DCs and macrophages
154
What are the 2 most common DT4 HSRs?
1. contact dermatitis (poison oak)
2. TB skin test (mycobacterium)
155
What 4 things are different about the DT4 HSR of a TB test v. urushoil?
1. antigen
2. antigen recognition
3. antigen processing
4. antigen presentation
156
What kind of pregnancy is required for hemolytic disease in babies?
Rho - mother
Rho + fetus
157
Why is the first pregnancy not an issue in hemolytic disease but its an issue in the second?
IgM cannot cross the placental barrier in the 1st but IgG memory Ab are made which can cross the barrier during the 2nd
158
What does the follow do in the inflammatory loop in the effector phase of DT4 HSRs?
1. IL-12
2. TNF-g
3. IL-8
4, CCL7
5. IL-6/IL-1
1. IL-12: recruits more memory T cells
2. TNF-g: recruits macrophages & increase vascular perm
3. IL-8: neutrophil recruitment
4, CCL7: recruits monocytes
5. IL-6/IL-1: inflammatory/fever response
159
What isotype is best for activating complement?
IgM
160
NKT cells use CD1__ and LC DCs use CD1__
NKT: CD1d
LC DC: CD1a
161
Only CD1___ has an A’ roof
CD1a (LC DCs)
162
Why is there no diversity for TCR recognizing CD1a—lipids?
The A’ roof is the same for all receptors
163
What 2 things are special about NKT cells?
1. Invariant TCR (no diversity)
2. Only identified glycolipids
164
INF and TNF are important for what 2 things?
1. Macrophage recruitment
2. Granuloma formation
165
Since dermal DCs dont have CD1a what do they use?
PRR
166
What are the 2 possible fates of B cells once a conjugate pair is formed?
1. Becomes memory B cell (secertes IgM)
2. Becomes plasma cells (isotype switches by returning to germinal center)
167
Th1/CD4 responses involve recruitment of what cell type?
macrophages (DT4HSR)
168
Does the TB skin test elicit an immune response from LC DCs or dermal DCs?
Dermal DCs (injected into dermis directly)
