Cellular Immune Response 1: Dendritic Cells, Macrophages And Lymphocytes Flashcards
(218 cards)
1
Q
What are cytokines
A
Small , soluble peptides used extensively by the immune system to communicate and influence cell growth, differentiation and function
2
Q
Features of cytokines
A
Pleitropy, autocrine function, paracrine function, endocrine effects, synergism
3
Q
Cytokines require specific cell surface ____ through which to mediate their range of actions on different cells
A
Receptors
4
Q
Cytokines typically __ their cel receptor and own ___
A
Upregulate
Secretion
5
Q
Class I cytokine receptors
A
Interferon
6
Q
Class II cytokine receptors
A
I’ll-2, 3
7
Q
TNF receptor family
A
For cheomkines
8
Q
What are two methods of control cytokines
A
Receptors released as soluble forms and also cytokine binding proteins to neutralize the effects
9
Q
Current definition of dendritic cells. What do they dooo and what to the poses
A
- Dendritic morphology
- Machinery for sensing pathogens
- Ability to process and present antigens to CD4 and CD8 T cells
- Can activate T cells from naive state
- Dictate T cell future function and action
10
Q
Common subtypes of DC
A
MDC, PDC, specialized DC, like LANGERHANS
11
Q
MDC
A
MYELIOID
12
Q
PDC
A
Plasmacytoid
13
Q
Langerhans-a specialized DC
A
In skin
14
Q
What is a marker for mature myeloid DC
A
CD1c
CD80, 86
HLA class I
HLA class II
15
Q
Marker for mature plasmacytoid DC
A
CD123 (il-3 receptor)
CD80, 86
Class I for antigen presentation to CD8
Class II for presentation to CD4
16
Q
What is the first function of DC
A
Pathogen sensing
17
Q
How do dc sense pathogens
A
Pattern recognition receptors , which bind to structures common to pathogens
18
Q
What do PRR bind to
A
Common molecular patterns-PAMPS
19
Q
What are the PRRs that have been conserved through evolution
A
TLR
20
Q
In sensing can the DC tell the difference between staph and strep
A
No
21
Q
Do MDC and PDC have the same PRR
A
No
22
Q
MDC is more specialized for _ response and PDC is more specialized for _ response
A
Antibacterial
Antiviral
23
Q
What TLR are on mDC
A
TLR2, 3, 4, 5
24
Q
TLR2
A
Senses peptidoglycan on gram positive bacteria
25
TLR3
Senses ds RNA from viruses
26
TLR4
Senses lipopolysaccharide on gram negative bacteria
27
TLR5
Senses flagellin on bacteria
28
What TLR are on pDC
TLR7, 8
29
TLR 7
Senses single stranded RNA on viruses
30
TLR9
Senses double stranded DNA on viruses
31
What is the mDC response to TLR binding
Activation and production of it-12
32
What is the outcome of TLR2, 4, 5 and is-12
Strong inflammatory T cell response against bacteria
33
What are TLR2, 4, 5, . Where are they
Cell membrane
34
Where are tlr3, 7, and 9
Internal phagosome
35
What happens when virus stimulates pDC through pamps
TLR3, 7, 9
36
What does TLR4 cause
Activation of il12 and ifn-a
37
What do TLR7 and 9 do
Activation and production of IFN-1
38
Outcome of viral stimulation through pamps of TLR3, 7, 9
Strong inflammatory T cell response against viruses
39
What happens when immature mDC becomes mature
Pinocytotic->not pinocytotic
Low expression of molecules to T cell activation->upregulate CD80, 86, and HLA molecules
Low expression of machinery required to process and present antigen->begins to process microbial antigens in readiness to present them
Localized and sedentary->active migration to local lymph node
Minimal secretion of cytokines->active section of cytokines, especially il12
40
Changes in pDC when becomes active
Small and round->enlarge and become dendritic shape
| Upregulate molecules for T cell activation and secrete interferon a which potent antiviral and pro inflammatory effects
41
Type I interferons
Antiviral
| 2 forms a and b
42
IFN-a
Made by lots of cells but especially pDCwhich
43
IFN-b
Mainly from stromal cells such as fibroblasts
44
Receptor for interferon 1 and 2
Both type I IFN receptor
45
IFN are ___
Paracrine
46
Interferons for virus or bacteria
Virus
47
What else do IFN do
NK
Potentiate mDC
Enhance MHCI expression
Increase MHCII too
48
Who would we treat with recombinant IFN
Chronic carriers of virus such as hepatitis
49
Net result of activating DC
Can activate naive T cell
50
Where does the DC activate the naive T cell
Lymph node
51
The mature DC has 3 signals. What is signal 1
Presentation fo peptide antigen from a pathogen bound to surface MHC
52
DC signal 2
Co stimulation, typically throughCD80 and 86
53
DC signal 3
Cytokines, mainly il12 from mDC
54
What APC is the strongest T cell activator
DC
55
Overall DC picture
Immature-waiting for activation
Pinocytosis/phagocytosis or viral infection-activated
Activated-migrate and change function to activate naive T cells in lymph nodes
Break down proteins into bite size peptides they can present
56
How do DC get to lymph nodes? What chemokine is important
Lymphatics
| Lymph nodes upregulate CCR7, a homing chemokine
57
What is a mononuclear phagocyte
Monocytes and macrophages
58
What do MNP do
Phagocytes
59
Monocytes are in _ and macrophages are in _
Blood tissue
60
Monocytes spend onyl a matter of days int he circulation before seeding to tissues where they differentiate to form what
Macrophages and dendritic cells
| *espciailly during inflammation
61
What is CFU-GM
Colony forming unit for granulocytes and monocytes
62
What do CFU-GM become in the bone marrow over 6 days
CFU-GM->monoblast->promonocyte
63
What does a promonocyte become and where is it found
Monocytes in the blood for 3 days
64
What do. Monocytes become in tissues and how long are they there
Macrophages months
65
Lung macrophag
Alveolar macrophage
66
Bone macrophage
Osteoblast
67
Brain macrophage
Microglia
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Blood monocytes are divided into two categories: those expressing ____ (like TLR4) and those expressing _ and _(the FcyRIII)
Cd14
| Cd14 and cd16
69
Alveolar macrophages are specialized for removing what.
Microorganisms and debris in the air
70
Macrophages in the gut lamina are specialized for what
Bacteria
71
What are osteoclasts
Multinucleated giant cells that resort bone
72
What are 3 important properties of MNP
Process and present antigens to T cells
Release soluble factors(cytokines)
Killing, especially engulfed organisms
73
What are the surface markers found on MNP
```
CD16, 14
Cd35
CD11b/CD18
Cd4
Cd64
MHCII
```
74
What is cd35
Complement receptor 1(CR-1) for C3b
75
CD11b/CD18
Leukocyte function associated antigen 1 (LFA-1)
76
Cd64
FcyRI
77
What do monocytes do when there is inflammation
Upregulate migration to tissue and differentiation to macrophages
78
Under inflammation (LPS) what do macrophages fo
Pro inflammatory and microbicidal phenotype
Upregulation of HLA and antigen presenting machinery
Secrete TNFa, IL-1 and IFN-y
79
Macrophages can ingest and kill ___ ___, such as ___ ___
Intracellular microorganisms, mycobacterium tuberculosis
80
Tissue macrophages involved in chronic inflammatory foci(Tb) may undergo terminal differentiation into ___ ___ ___
Multinucleated giant cells
81
Where are multinucleated giant cells typically found
Granulomata..characteristic of tb
82
Il-1 is a cytokine mainly produced by ____ and ______
Dendritic cells
| Monocytes/macrophages
83
What is il-1 secretion a response to
Stimuli like bacterial lipopolysaccharide
84
What does it-1 do
Pro inflammatory effects
Promotes coagulation and increases endothelial expression of adhesion molecules
Promotes release of il6
Has endocrine effects, inducing fever and synthesis of acute phase proteins in the liver
85
When it TNF produced
Response to gram negative bacteria
86
What secretes TNG
Monocytes/macrophages, dendritic cells, and T cells
87
Tnfb
Lymphotoxin
88
What does local release of TNF cause
```
Killing or target cells
Upregulation of adhesion molecules to enhance migration
Activation of neutrophils and macrophages to kill microbes
Stimulate il-1, 6, and more tnf
Increase expression of mhcI
And MHCII
Enhance presentation
Bacteria and viruses
```
89
Systemic release of TNF
Fever inducing and acute phase properties as in-1
Contribute to shock though
Low blood pressure, reduced heart muscle contractility, intravascular thrombosis
Shock associated itch gram negative sepsis , malaria, and meningococcal
90
What infections may increase systemic tnf and bring about shock
Gram negative bacterial sepsis
Malaria
Meningococcal infections
91
TNF antibody treatment
RA
92
Where are dendritic cells present
Blood and lymph
93
After the 12th-16th week of fetal life B cells are made in the bone marrow. Where are they made before this
Liver
94
Describe the production of B cells
1. Rearrangement of immunoglobulin genes
2. Somatic mutations in rearranged immunoglobulin genes
3. Change in heavy chain constant region used by antibody, refining its effector functions
95
Where are B lymphocytes found
In the middle of germinal centers in lymphoid follicles in ;lymph nodes, MALT, spleen
96
B cells traffick through the blood. They constitute _-_% of lymphocytes
5-15
97
B lymphocytes may undergo end stage diffferentiation int what
Plasma cells
98
Where are plasma cells
Non circulating
| In bone marrow, lymph node medulla and gut
99
Appearance of plasma cell
Eccentric nucleus with a clock face
| Cytoplasmic contents:immunoglobulin heavy and light chains
100
Can you distinguish B and T cells by light or electron microscopy
No
101
What surface proteins are on B cell
BCR, which is a membrane bound or surface immunoglobulin sIg
102
CD79a(Iga) and CD79b(IgB)
Transducer activation signals after antigen binding
| Specific for B cells
103
CD19 and 21
Promote transduction of activation signals after antigen binding
Specific for B cells
104
Cd21 is ___
CR-2 a complement receptor which binds C3d-tagged antigens to enhance signalling
105
Cd20
Capable of signal transduction
| Specific for B cells
106
Cd is the target for ___, a monoclonal antibody used to deplete B cells for therapeutic processes
Rituximab
107
Cd22
Promotes adhesion to interacting cells to enhance signaling
| Specific for B cells
108
Cd23
Regulation of IgE production
Has low affinity for IgE (FceRII)
Not specific to B cells but on it
109
Cd40
Essential coreceptor for T cell dependent antibody responses
110
Cd40L/Cd154
Expressed on T cells
111
CD40L defect
Severe antibody defiency
112
MHCII
Constitutively expressed by B cells
| Also on APC
113
CD80 and 86
Co stimulation of T cells
| On APC
114
Major role of b lymphocytes
1. ensure antibody production against appropriate target antigens with the help of T cells
2. Present antigen to T cells and provide signals for t lymphocyte activation
115
Cognate interaction
T and B cell
B cell. Present antigen to T cell and receives positive signal for antibody production in return while T cell receives a further stimulus to maintain its activated state
116
Where are pre B cells
Bone marrow do not have fully rearranged antigen receptors
117
Immature B cells
In bone marrow are not ready to respond to antigen
118
Virgin B cell
In lymph node and spleen
| Have fully rearranged immunoglobulin genesbut have not encountered antigen
119
Mature B cells
In lymph node and spleen
| Have encountered antigen and possess antigen specificity
120
Memory B cells
Maintain memory of the encounter with antigen and reside in lymphoid system
121
Phase 1 B cell
Pro b cells(progenitor) migrate from periosteal region to the center of the bone marrow, acquiring markers for maturation and differentiation and rearranging immmunoglobulin genes
6 mitosis cycles giving 64 progeny
122
Maturation is supported by ___ __ __, with secretion of il-7
Marrow stromal cells
123
What defines pre B cell
```
Appearance of cytoplasmic heavy chains of IgM class
Mu heavy chain associates with a surrogate light chain CD79a and CD79b to form pre-BCR
```
75% killed
124
How are pre B cells killed in marrow
Positive and negative selection
125
Positive selection
Selection of cell for its attributes
126
Negative selection
Removal of cell with undesirable attributes
127
Pro->pre(cytoplasmic mu)...what happens to pre B cell
It gene rearrangements and selection in the bone marrow
128
Who do we treat with G-CSF and GM-CSF
Patients whose white blood cells have been abated temporarily as part of another treatment
129
GM-CSF is made by what
Cd4 T cells, monocyte/macrophages and endothelium
130
What does GM-csf do
Promote growth of bone marrow cells already committed to the granulocyte and monocyte lineage
131
What makes G-CSF
Similar to GM-CSF
132
What does G-CSF do
Preferential act on cells committed to the granulocyte phenotype
133
What makes M-CSF
Monocyte and macrophages and endothelial cells
134
What does M-CSF do
Mainly made in bone marrow to promote development of these cells types
135
Second phase of B cell development
Virgin B cells leave the marrow to join peripheral B cell pool
May last an hour before going to splanchnic and lymph nodes , at this stage expressing surface IgM and IgD
136
Do allot he virgin B cells survive
No negative selection of autoreactive B cells happens
137
The majority of the peripheral B cell pool comprises virgin B cells while some are __ cells
Memory
138
In the spleen and lymph node what do B cells present
SIg composed of mu and delta heavy chains IgM and IgD
139
Up until this point B cell development is antigen ____
Independent
140
The B cell is ready to encounter antigens in spleen and nodes . At this point what is diversity generation restricted to
```
Somatic hypermutation -NO FURTHER REARRANGEMENT OF GENES contributing to variable segments
Have class switching -alternative heavy chain genes selected
```
141
The optimum immune response will require selection of the B cells with the highest affinity for antigen. How is this done
Competition for antigen
| AFFINITY MATURATION
142
What is affinity maturation
B cells that best bind and internalize antigen will be able to present the antigen to T cells and receive in return the positive signal for expansion
143
Pre B cells has
Cytoplasmic mu
144
Immature B cell has
IgM
145
Virgin B cell has
SIgM and sIgD
146
Mature B cell has
IgM, or IgG, or IgE, or IgA
147
What do mature B cells become
Plasma cells, memory cells,
148
Colonial expansion
High affinity of B cell to antigen presents to T cell which signals its growth and expansion
149
What are the effector B cells
Memory and plasma
150
Effectors are constantly replenished. When are they lost
When not receiving appropriate signals within the node germinal center
151
Pre-b cells identified by cytoplasmic mu chains but no light chains. How are light chains brought about
V-J recombination which give rise to unique immunoglobulin genes and a unique antibody structure....basis for antibody specificity
152
Does antibody specificity arise after it encounters antigen
No before
153
___ antigen binding specifity of immmunoglobulin is produced per b lymphocytes composed of variable regions of light and heavy chains
One
154
The variable region will be constant except for somatic hypermutation. Does the constant region change
Yea it will determine class G, A, E, D, M of antibody
155
Why does an immature B cell have sIgM and IgD. What does IgD do
For the receipt and transduction of activation signals and signified a virgin B lymphocyte(one that hasn’t encountered its antigen)
156
When is sIgD lost
After antigenic stimulation
157
What cytokines do T cells secrete for B cells to mature
IL-4, 6, 10
158
What cytokines stimulat colonial expansion
IL-2, 5
159
Do plasma cells have surface immunoglobulins
No
160
What do plasma cells fo
Produce and secrete a single antibody with a single light chain and heavy chain
161
__ is secreted across mucosa
IgA
162
In secondary follicles, activated B cells form the germinal center. Is this dependent on antigenic stimulation
Yes
163
What is a secondary follicle
Consist of mantle of packed resting small B cells (sIgM, sIgD) or the peripheral blood
The germinal center has a collection of activated B and T lymphocytes
164
Where does B cell activation and maturation take place
Int he germinal center
165
Virgin B cells enter the lymph node. What happens in the lymph node
Follicular dendritic cells have antigens that they present to B cells ....proliferation’s, somatic hypermutation and class switching
166
What are the three functions of follicular dendritic cells
1% of follicle
Present antigen to B cell
Can retain antigen in this form for long periods of time, so B cell with best fit are selected
Additional signals to activate B cells , inc
167
What signal from the follicular dendritic cell activates B cells
TNF family (BAFF), Il-15 and adhesion molecules such as ICAM-1
168
If presented with an antigen that fits the sIg, follicular dendritic cells induce B cell proliferation and the germinal center develops. What are these blasts called
Centroblasts
169
In centroblasts, if the B cells are losing sIg where do they do
Localize at one pole of the follicle
170
Centrocytes
Progeny that centroblasts begin to generate that express sIg and micrate towards the outer zone of the follicle
171
During the generation of centroblasts and centrocytes, what leads to selection of heavy chains
Somatic hypermutation and class switching
172
If encounter T cell in centroblast you get
Memory cells
173
If encounter Il-2 or cd23 and is-1 get what
| In centroblast
Plasmablast and then plasma cell
174
If binding in the centroblast by the centrocytes is strong what do you get. There are three routes
Centrocytes can interact with CD4t cell(CD40/CD40L) and you willl get memory B cell
Exposure to cd23 and il-1a, inducting plasmablast differentiation (then migration to lymph node medullary costs and out into gut Lamina propria , bone marrow, and spleen where they live
Or
Il2-induce plasmablast
Or
If don’t interact undergo apoptosis
175
X linked hyper IgM syndrome
Males
High IgM antibodies but no mature B lymphocytes producing other immunoglobulins
The IgM is ineffective at protecting against bacterial infections
176
Genetic basis for hyper IgM syndrome
CD40L gene, which is present on the X chromosome problem
So some developing B cells are not rescued from apoptosis
While some remain don’t don’t get the maturation signals
May escape death but int he absence of T cell cant only make IgM
177
Thymus dependent B cell activation
T cell dependent
178
Thymus I depended B cell activation
Doesn’t need T cell
179
Remove thymus in mouse
Lose t but also some b function
180
Thymus independent pathway I
LPS activated sIg
181
Thymus independent II
Repeating antigen cross links sIg and activated B cell
182
Thymus dependent pathway
MHCII with antigen binds TCR which gives signals to B cell
183
What is the dominant pathway for B cell activation
T cell dependent
184
Direct activation T cell independent
Polyclonal activation
185
What kind of b celll is usually activated T cell independent
IgM little memory or affinity maturation
186
Why is thymus dependent pathway most important
High affinity
Class switch
Specific antibodies
Memory
187
Describe Thymus dependent pathway of B cell maturation
B cell use sIg as receptor for antigen, which is internalized. Inside B cell a combination of enzymes and physical effects(pH) degrease the antigen(antigen processing) and a small peptide attaches to MHCII and is exported to the surface for antigen presentation . T lymphocytes see MHCII and activated B cell
188
What does thymus dependent pathway ensure
1. B and t lymphocytes specific for the same antigen are given the activation signal
1. Only antigens against which the immune system is fully committed (having both T and B cell recognition) invoke a response
189
What entails the B cell receptor complex and what does it do
SIg and CD79a/b
| Provides signal in B cell activation and transmits te message that there is antigen
190
How is the signal transduce by CD79
ITAMS
| Immunoreceptor tyrosine based activation motifs
191
What do ITAMs do
Intracellular activation cascade is initiated, triggering tyrosine kinase activation and calcium signallling leading to changes in gene expression profiles
192
What on B cells interact with Ligands on T cells
Cd40 and cd80/86
193
What interleukins from T cell are important for B cell activation, growth and colonial expansion
IL-4 activates B cell
I’ll-5, Il-2 for colonial expansion
I’ll-6 growth factor enhances switch to IgG production
194
Results of B cell activation
Colonial expansion , memory, plasma
195
After exposure to antige, when do we see IgM
5-20 days
196
How many days after IgM do we see IgG
2-3
197
What is the IgM and IgG production called when we first see an antigen
Primary response
198
Secondary response
Activation of primed cells in 3-5 days, IgG produced early and in greater quantities
199
X linked agammaglobulinaemia
No circulating B cells, although pre B cells can be identified in bone marrow
No antibodies
Repeated life threatening infection
200
Vaccinations stimulate __ response so that when the real pathogen is met there is pre existing immunity
Primary
201
What is class switching
Selection of different IGH genes
202
Il-4 class switch
IgE
203
IFN-y class switch
IgG
204
What is on virgin cell
IgM and IgD
205
What influences IgA class switch
Site of production-mucosa
| T cells help
206
What do integrins and selectins do for T and B cells
Directed adherence to endothelium and migration into tissue
207
LFA-1(b2 integrins)
On all mature resting and activated T and B cells
208
What is the ligand for LFA-1
ICAM-1
209
What is ICAM-1 on
ON OTHER IMMUNE CELLS AND ENDOTHELIUM
210
When lymphocytes make contact with other lymphocytes or APC, ___/___ adhesion can enhance the interaction and the passage of cell cell signal
LFA-1/ICAM-1
211
L selectin
On T and B cells , highest in naive form
212
What does L selectin on naive t and B cells ensure
Naive cells are attracted to lymph nodes
213
CCR7
Chemokine receptors a surface molecules important in lymph node homing
214
What is CCR7 expressed on
T cells for example
215
B1 integrins
CD29
| Also called Very late activation (VLA)
216
VLA-4, 5, 6
Strongly expressed by resting T cells and are highly up regulated on activation
217
VLA-4
Mediates binding of lymphocytes to endothelium at sites of inflammation where its Logan’s, VCAM-1 is typically unregulated
218
What is the ligand for VLA—4
VCAM-1
