Cellular Immune Response 1: Dendritic Cells, Macrophages And Lymphocytes Flashcards

1
Q

What are cytokines

A

Small , soluble peptides used extensively by the immune system to communicate and influence cell growth, differentiation and function

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2
Q

Features of cytokines

A

Pleitropy, autocrine function, paracrine function, endocrine effects, synergism

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3
Q

Cytokines require specific cell surface ____ through which to mediate their range of actions on different cells

A

Receptors

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4
Q

Cytokines typically __ their cel receptor and own ___

A

Upregulate

Secretion

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5
Q

Class I cytokine receptors

A

Interferon

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6
Q

Class II cytokine receptors

A

I’ll-2, 3

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7
Q

TNF receptor family

A

For cheomkines

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8
Q

What are two methods of control cytokines

A

Receptors released as soluble forms and also cytokine binding proteins to neutralize the effects

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9
Q

Current definition of dendritic cells. What do they dooo and what to the poses

A
  1. Dendritic morphology
  2. Machinery for sensing pathogens
  3. Ability to process and present antigens to CD4 and CD8 T cells
  4. Can activate T cells from naive state
  5. Dictate T cell future function and action
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10
Q

Common subtypes of DC

A

MDC, PDC, specialized DC, like LANGERHANS

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11
Q

MDC

A

MYELIOID

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12
Q

PDC

A

Plasmacytoid

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13
Q

Langerhans-a specialized DC

A

In skin

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14
Q

What is a marker for mature myeloid DC

A

CD1c
CD80, 86
HLA class I
HLA class II

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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

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16
Q

What is the first function of DC

A

Pathogen sensing

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17
Q

How do dc sense pathogens

A

Pattern recognition receptors , which bind to structures common to pathogens

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18
Q

What do PRR bind to

A

Common molecular patterns-PAMPS

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19
Q

What are the PRRs that have been conserved through evolution

A

TLR

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20
Q

In sensing can the DC tell the difference between staph and strep

A

No

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21
Q

Do MDC and PDC have the same PRR

A

No

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22
Q

MDC is more specialized for _ response and PDC is more specialized for _ response

A

Antibacterial

Antiviral

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23
Q

What TLR are on mDC

A

TLR2, 3, 4, 5

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24
Q

TLR2

A

Senses peptidoglycan on gram positive bacteria

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25
Q

TLR3

A

Senses ds RNA from viruses

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26
Q

TLR4

A

Senses lipopolysaccharide on gram negative bacteria

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27
Q

TLR5

A

Senses flagellin on bacteria

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28
Q

What TLR are on pDC

A

TLR7, 8

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29
Q

TLR 7

A

Senses single stranded RNA on viruses

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30
Q

TLR9

A

Senses double stranded DNA on viruses

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31
Q

What is the mDC response to TLR binding

A

Activation and production of it-12

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32
Q

What is the outcome of TLR2, 4, 5 and is-12

A

Strong inflammatory T cell response against bacteria

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33
Q

What are TLR2, 4, 5, . Where are they

A

Cell membrane

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34
Q

Where are tlr3, 7, and 9

A

Internal phagosome

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35
Q

What happens when virus stimulates pDC through pamps

A

TLR3, 7, 9

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36
Q

What does TLR4 cause

A

Activation of il12 and ifn-a

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37
Q

What do TLR7 and 9 do

A

Activation and production of IFN-1

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38
Q

Outcome of viral stimulation through pamps of TLR3, 7, 9

A

Strong inflammatory T cell response against viruses

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39
Q

What happens when immature mDC becomes mature

A

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

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40
Q

Changes in pDC when becomes active

A

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

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41
Q

Type I interferons

A

Antiviral

2 forms a and b

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42
Q

IFN-a

A

Made by lots of cells but especially pDCwhich

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43
Q

IFN-b

A

Mainly from stromal cells such as fibroblasts

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44
Q

Receptor for interferon 1 and 2

A

Both type I IFN receptor

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45
Q

IFN are ___

A

Paracrine

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46
Q

Interferons for virus or bacteria

A

Virus

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47
Q

What else do IFN do

A

NK
Potentiate mDC
Enhance MHCI expression
Increase MHCII too

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48
Q

Who would we treat with recombinant IFN

A

Chronic carriers of virus such as hepatitis

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49
Q

Net result of activating DC

A

Can activate naive T cell

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50
Q

Where does the DC activate the naive T cell

A

Lymph node

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51
Q

The mature DC has 3 signals. What is signal 1

A

Presentation fo peptide antigen from a pathogen bound to surface MHC

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52
Q

DC signal 2

A

Co stimulation, typically throughCD80 and 86

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53
Q

DC signal 3

A

Cytokines, mainly il12 from mDC

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54
Q

What APC is the strongest T cell activator

A

DC

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55
Q

Overall DC picture

A

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

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56
Q

How do DC get to lymph nodes? What chemokine is important

A

Lymphatics

Lymph nodes upregulate CCR7, a homing chemokine

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57
Q

What is a mononuclear phagocyte

A

Monocytes and macrophages

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58
Q

What do MNP do

A

Phagocytes

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59
Q

Monocytes are in _ and macrophages are in _

A

Blood tissue

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60
Q

Monocytes spend onyl a matter of days int he circulation before seeding to tissues where they differentiate to form what

A

Macrophages and dendritic cells

*espciailly during inflammation

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61
Q

What is CFU-GM

A

Colony forming unit for granulocytes and monocytes

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62
Q

What do CFU-GM become in the bone marrow over 6 days

A

CFU-GM->monoblast->promonocyte

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63
Q

What does a promonocyte become and where is it found

A

Monocytes in the blood for 3 days

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64
Q

What do. Monocytes become in tissues and how long are they there

A

Macrophages months

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65
Q

Lung macrophag

A

Alveolar macrophage

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66
Q

Bone macrophage

A

Osteoblast

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67
Q

Brain macrophage

A

Microglia

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68
Q

Blood monocytes are divided into two categories: those expressing ____ (like TLR4) and those expressing _ and _(the FcyRIII)

A

Cd14

Cd14 and cd16

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69
Q

Alveolar macrophages are specialized for removing what.

A

Microorganisms and debris in the air

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70
Q

Macrophages in the gut lamina are specialized for what

A

Bacteria

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71
Q

What are osteoclasts

A

Multinucleated giant cells that resort bone

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72
Q

What are 3 important properties of MNP

A

Process and present antigens to T cells
Release soluble factors(cytokines)
Killing, especially engulfed organisms

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73
Q

What are the surface markers found on MNP

A
CD16, 14
Cd35
CD11b/CD18
Cd4
Cd64
MHCII
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74
Q

What is cd35

A

Complement receptor 1(CR-1) for C3b

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75
Q

CD11b/CD18

A

Leukocyte function associated antigen 1 (LFA-1)

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76
Q

Cd64

A

FcyRI

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77
Q

What do monocytes do when there is inflammation

A

Upregulate migration to tissue and differentiation to macrophages

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78
Q

Under inflammation (LPS) what do macrophages fo

A

Pro inflammatory and microbicidal phenotype
Upregulation of HLA and antigen presenting machinery
Secrete TNFa, IL-1 and IFN-y

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79
Q

Macrophages can ingest and kill ___ ___, such as ___ ___

A

Intracellular microorganisms, mycobacterium tuberculosis

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80
Q

Tissue macrophages involved in chronic inflammatory foci(Tb) may undergo terminal differentiation into ___ ___ ___

A

Multinucleated giant cells

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81
Q

Where are multinucleated giant cells typically found

A

Granulomata..characteristic of tb

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82
Q

Il-1 is a cytokine mainly produced by ____ and ______

A

Dendritic cells

Monocytes/macrophages

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83
Q

What is il-1 secretion a response to

A

Stimuli like bacterial lipopolysaccharide

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84
Q

What does it-1 do

A

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

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85
Q

When it TNF produced

A

Response to gram negative bacteria

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86
Q

What secretes TNG

A

Monocytes/macrophages, dendritic cells, and T cells

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87
Q

Tnfb

A

Lymphotoxin

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88
Q

What does local release of TNF cause

A
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
Q

Systemic release of TNF

A

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
Q

What infections may increase systemic tnf and bring about shock

A

Gram negative bacterial sepsis
Malaria
Meningococcal infections

91
Q

TNF antibody treatment

A

RA

92
Q

Where are dendritic cells present

A

Blood and lymph

93
Q

After the 12th-16th week of fetal life B cells are made in the bone marrow. Where are they made before this

A

Liver

94
Q

Describe the production of B cells

A
  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
Q

Where are B lymphocytes found

A

In the middle of germinal centers in lymphoid follicles in ;lymph nodes, MALT, spleen

96
Q

B cells traffick through the blood. They constitute -% of lymphocytes

A

5-15

97
Q

B lymphocytes may undergo end stage diffferentiation int what

A

Plasma cells

98
Q

Where are plasma cells

A

Non circulating

In bone marrow, lymph node medulla and gut

99
Q

Appearance of plasma cell

A

Eccentric nucleus with a clock face

Cytoplasmic contents:immunoglobulin heavy and light chains

100
Q

Can you distinguish B and T cells by light or electron microscopy

A

No

101
Q

What surface proteins are on B cell

A

BCR, which is a membrane bound or surface immunoglobulin sIg

102
Q

CD79a(Iga) and CD79b(IgB)

A

Transducer activation signals after antigen binding

Specific for B cells

103
Q

CD19 and 21

A

Promote transduction of activation signals after antigen binding
Specific for B cells

104
Q

Cd21 is ___

A

CR-2 a complement receptor which binds C3d-tagged antigens to enhance signalling

105
Q

Cd20

A

Capable of signal transduction

Specific for B cells

106
Q

Cd is the target for ___, a monoclonal antibody used to deplete B cells for therapeutic processes

A

Rituximab

107
Q

Cd22

A

Promotes adhesion to interacting cells to enhance signaling

Specific for B cells

108
Q

Cd23

A

Regulation of IgE production
Has low affinity for IgE (FceRII)
Not specific to B cells but on it

109
Q

Cd40

A

Essential coreceptor for T cell dependent antibody responses

110
Q

Cd40L/Cd154

A

Expressed on T cells

111
Q

CD40L defect

A

Severe antibody defiency

112
Q

MHCII

A

Constitutively expressed by B cells

Also on APC

113
Q

CD80 and 86

A

Co stimulation of T cells

On APC

114
Q

Major role of b lymphocytes

A
  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
Q

Cognate interaction

A

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
Q

Where are pre B cells

A

Bone marrow do not have fully rearranged antigen receptors

117
Q

Immature B cells

A

In bone marrow are not ready to respond to antigen

118
Q

Virgin B cell

A

In lymph node and spleen

Have fully rearranged immunoglobulin genesbut have not encountered antigen

119
Q

Mature B cells

A

In lymph node and spleen

Have encountered antigen and possess antigen specificity

120
Q

Memory B cells

A

Maintain memory of the encounter with antigen and reside in lymphoid system

121
Q

Phase 1 B cell

A

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
Q

Maturation is supported by ___ __ __, with secretion of il-7

A

Marrow stromal cells

123
Q

What defines pre B cell

A
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
Q

How are pre B cells killed in marrow

A

Positive and negative selection

125
Q

Positive selection

A

Selection of cell for its attributes

126
Q

Negative selection

A

Removal of cell with undesirable attributes

127
Q

Pro->pre(cytoplasmic mu)…what happens to pre B cell

A

It gene rearrangements and selection in the bone marrow

128
Q

Who do we treat with G-CSF and GM-CSF

A

Patients whose white blood cells have been abated temporarily as part of another treatment

129
Q

GM-CSF is made by what

A

Cd4 T cells, monocyte/macrophages and endothelium

130
Q

What does GM-csf do

A

Promote growth of bone marrow cells already committed to the granulocyte and monocyte lineage

131
Q

What makes G-CSF

A

Similar to GM-CSF

132
Q

What does G-CSF do

A

Preferential act on cells committed to the granulocyte phenotype

133
Q

What makes M-CSF

A

Monocyte and macrophages and endothelial cells

134
Q

What does M-CSF do

A

Mainly made in bone marrow to promote development of these cells types

135
Q

Second phase of B cell development

A

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
Q

Do allot he virgin B cells survive

A

No negative selection of autoreactive B cells happens

137
Q

The majority of the peripheral B cell pool comprises virgin B cells while some are __ cells

A

Memory

138
Q

In the spleen and lymph node what do B cells present

A

SIg composed of mu and delta heavy chains IgM and IgD

139
Q

Up until this point B cell development is antigen ____

A

Independent

140
Q

The B cell is ready to encounter antigens in spleen and nodes . At this point what is diversity generation restricted to

A
Somatic hypermutation -NO FURTHER REARRANGEMENT OF GENES contributing to variable segments 
Have class switching -alternative heavy chain genes selected
141
Q

The optimum immune response will require selection of the B cells with the highest affinity for antigen. How is this done

A

Competition for antigen

AFFINITY MATURATION

142
Q

What is affinity maturation

A

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
Q

Pre B cells has

A

Cytoplasmic mu

144
Q

Immature B cell has

A

IgM

145
Q

Virgin B cell has

A

SIgM and sIgD

146
Q

Mature B cell has

A

IgM, or IgG, or IgE, or IgA

147
Q

What do mature B cells become

A

Plasma cells, memory cells,

148
Q

Colonial expansion

A

High affinity of B cell to antigen presents to T cell which signals its growth and expansion

149
Q

What are the effector B cells

A

Memory and plasma

150
Q

Effectors are constantly replenished. When are they lost

A

When not receiving appropriate signals within the node germinal center

151
Q

Pre-b cells identified by cytoplasmic mu chains but no light chains. How are light chains brought about

A

V-J recombination which give rise to unique immunoglobulin genes and a unique antibody structure….basis for antibody specificity

152
Q

Does antibody specificity arise after it encounters antigen

A

No before

153
Q

___ antigen binding specifity of immmunoglobulin is produced per b lymphocytes composed of variable regions of light and heavy chains

A

One

154
Q

The variable region will be constant except for somatic hypermutation. Does the constant region change

A

Yea it will determine class G, A, E, D, M of antibody

155
Q

Why does an immature B cell have sIgM and IgD. What does IgD do

A

For the receipt and transduction of activation signals and signified a virgin B lymphocyte(one that hasn’t encountered its antigen)

156
Q

When is sIgD lost

A

After antigenic stimulation

157
Q

What cytokines do T cells secrete for B cells to mature

A

IL-4, 6, 10

158
Q

What cytokines stimulat colonial expansion

A

IL-2, 5

159
Q

Do plasma cells have surface immunoglobulins

A

No

160
Q

What do plasma cells fo

A

Produce and secrete a single antibody with a single light chain and heavy chain

161
Q

__ is secreted across mucosa

A

IgA

162
Q

In secondary follicles, activated B cells form the germinal center. Is this dependent on antigenic stimulation

A

Yes

163
Q

What is a secondary follicle

A

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
Q

Where does B cell activation and maturation take place

A

Int he germinal center

165
Q

Virgin B cells enter the lymph node. What happens in the lymph node

A

Follicular dendritic cells have antigens that they present to B cells ….proliferation’s, somatic hypermutation and class switching

166
Q

What are the three functions of follicular dendritic cells

A

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
Q

What signal from the follicular dendritic cell activates B cells

A

TNF family (BAFF), Il-15 and adhesion molecules such as ICAM-1

168
Q

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

A

Centroblasts

169
Q

In centroblasts, if the B cells are losing sIg where do they do

A

Localize at one pole of the follicle

170
Q

Centrocytes

A

Progeny that centroblasts begin to generate that express sIg and micrate towards the outer zone of the follicle

171
Q

During the generation of centroblasts and centrocytes, what leads to selection of heavy chains

A

Somatic hypermutation and class switching

172
Q

If encounter T cell in centroblast you get

A

Memory cells

173
Q

If encounter Il-2 or cd23 and is-1 get what

In centroblast

A

Plasmablast and then plasma cell

174
Q

If binding in the centroblast by the centrocytes is strong what do you get. There are three routes

A

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
Q

X linked hyper IgM syndrome

A

Males
High IgM antibodies but no mature B lymphocytes producing other immunoglobulins
The IgM is ineffective at protecting against bacterial infections

176
Q

Genetic basis for hyper IgM syndrome

A

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
Q

Thymus dependent B cell activation

A

T cell dependent

178
Q

Thymus I depended B cell activation

A

Doesn’t need T cell

179
Q

Remove thymus in mouse

A

Lose t but also some b function

180
Q

Thymus independent pathway I

A

LPS activated sIg

181
Q

Thymus independent II

A

Repeating antigen cross links sIg and activated B cell

182
Q

Thymus dependent pathway

A

MHCII with antigen binds TCR which gives signals to B cell

183
Q

What is the dominant pathway for B cell activation

A

T cell dependent

184
Q

Direct activation T cell independent

A

Polyclonal activation

185
Q

What kind of b celll is usually activated T cell independent

A

IgM little memory or affinity maturation

186
Q

Why is thymus dependent pathway most important

A

High affinity
Class switch
Specific antibodies
Memory

187
Q

Describe Thymus dependent pathway of B cell maturation

A

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
Q

What does thymus dependent pathway ensure

A
  1. B and t lymphocytes specific for the same antigen are given the activation signal
  2. Only antigens against which the immune system is fully committed (having both T and B cell recognition) invoke a response
189
Q

What entails the B cell receptor complex and what does it do

A

SIg and CD79a/b

Provides signal in B cell activation and transmits te message that there is antigen

190
Q

How is the signal transduce by CD79

A

ITAMS

Immunoreceptor tyrosine based activation motifs

191
Q

What do ITAMs do

A

Intracellular activation cascade is initiated, triggering tyrosine kinase activation and calcium signallling leading to changes in gene expression profiles

192
Q

What on B cells interact with Ligands on T cells

A

Cd40 and cd80/86

193
Q

What interleukins from T cell are important for B cell activation, growth and colonial expansion

A

IL-4 activates B cell
I’ll-5, Il-2 for colonial expansion
I’ll-6 growth factor enhances switch to IgG production

194
Q

Results of B cell activation

A

Colonial expansion , memory, plasma

195
Q

After exposure to antige, when do we see IgM

A

5-20 days

196
Q

How many days after IgM do we see IgG

A

2-3

197
Q

What is the IgM and IgG production called when we first see an antigen

A

Primary response

198
Q

Secondary response

A

Activation of primed cells in 3-5 days, IgG produced early and in greater quantities

199
Q

X linked agammaglobulinaemia

A

No circulating B cells, although pre B cells can be identified in bone marrow
No antibodies
Repeated life threatening infection

200
Q

Vaccinations stimulate __ response so that when the real pathogen is met there is pre existing immunity

A

Primary

201
Q

What is class switching

A

Selection of different IGH genes

202
Q

Il-4 class switch

A

IgE

203
Q

IFN-y class switch

A

IgG

204
Q

What is on virgin cell

A

IgM and IgD

205
Q

What influences IgA class switch

A

Site of production-mucosa

T cells help

206
Q

What do integrins and selectins do for T and B cells

A

Directed adherence to endothelium and migration into tissue

207
Q

LFA-1(b2 integrins)

A

On all mature resting and activated T and B cells

208
Q

What is the ligand for LFA-1

A

ICAM-1

209
Q

What is ICAM-1 on

A

ON OTHER IMMUNE CELLS AND ENDOTHELIUM

210
Q

When lymphocytes make contact with other lymphocytes or APC, ___/___ adhesion can enhance the interaction and the passage of cell cell signal

A

LFA-1/ICAM-1

211
Q

L selectin

A

On T and B cells , highest in naive form

212
Q

What does L selectin on naive t and B cells ensure

A

Naive cells are attracted to lymph nodes

213
Q

CCR7

A

Chemokine receptors a surface molecules important in lymph node homing

214
Q

What is CCR7 expressed on

A

T cells for example

215
Q

B1 integrins

A

CD29

Also called Very late activation (VLA)

216
Q

VLA-4, 5, 6

A

Strongly expressed by resting T cells and are highly up regulated on activation

217
Q

VLA-4

A

Mediates binding of lymphocytes to endothelium at sites of inflammation where its Logan’s, VCAM-1 is typically unregulated

218
Q

What is the ligand for VLA—4

A

VCAM-1