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Z Old Infection IGNORE > Antibodies, Complement, and T Cell Pathogen Recognition > Flashcards

Antibodies, Complement, and T Cell Pathogen Recognition Flashcards

1
Q

What are antibodies also known as?

A

Immunoglobulins, Ig

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2
Q

What kind of molecules are antibodies?

A

Proteins

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3
Q

What is the molecular weight of antibodies?

A

150,000-900,000 kd

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4
Q

What are antibodies derived from?

A

The immunoglobulin supergene

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5
Q

What do the two ends of the Ig do?

A
  • One end binds to antigens
  • The other end is crystallisable, and is responsible for effector functions
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6
Q

What is the end of the Ig that binds to antigens called?

A

The Fab region

The Fragment of the Molecule that is antigen binding

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7
Q

What is the crystallisable end of the antibody called?

A

Fc

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8
Q

Are Fc domains constant or variable?

A

Constant

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9
Q

Are Fab regions constant or variable?

A

Extremely variable between individual Ig’s

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10
Q

What is true of the progeny of a single clone of B cells?

A

They are identical

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11
Q

What does the basic, monomeric, Ig molecule have?

A
  • Two light chains
  • Two heavy chains
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12
Q

What happens to the heavy and light chains in an Ig molecule?

A

Intrachain S-S links divide H-L chains into domains that are seperately folded

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13
Q

How many H chain domains does an IgG molecule have?

A

3

CH1, CH2, and CH3

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14
Q

What is found between CH1 and CH2 in an IgG molecule?

A

Many cystine and proline residues

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15
Q

What is the region containing the residues between CH1 and CH2 in IgG known as?

A

The hinge region

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16
Q

What does the hinge region do?

A

Confers flexibility to the Fab arms

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17
Q

Label this diagram of an IgG antibody

A
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18
Q

How many classes, or isotypes, of antibodies are there?

A

5

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19
Q

What are the classes of antibodies categoried by?

A

Differences exisiting in their H-chain constant regions

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20
Q

How many classes of light chains are there?

A

2

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21
Q

What are classes of light chains?

A
  1. Lambda
  2. Kappa
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22
Q

What does an individual Ig molecule include?

Referring to light chains

A

Only L chains (both identical) of one class

Though we all possess Ig molecules, which are made of either

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23
Q

What are the classes of Ig?

A
  1. IgM
  2. IgG
  3. IgA
  4. IgE
  5. IgD
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24
Q

What structure is IgM?

A

Pentameter

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25
Q

What is the H chain of IgM have?

A

µ

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26
Q

What is the L chain of IgM have?

A

λ or κ

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27
Q

What are the subclasses of IgM?

A

None

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28
Q

What are the functions of IgM?

A
  • Agglutination
  • Complement activation
  • Primary response
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29
Q

What is the site of IgM?

A

Blood

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30
Q

What is the structure of IgG?

A

Monomer

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31
Q

What is the H chain of IgG?

A

γ

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32
Q

What is the L chain of IgG?

A

λ or κ

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33
Q

What are the subclasses of IgG?

A

1-4

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34
Q

What are the functions of IgG?

A
  • Opsonisation
  • Complement activation
  • Neutralisation
  • ADCC (NK cells)
  • Transplacental
  • Secondary response
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35
Q

What is the site of IgG?

A
  • Blood
  • Tissues
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36
Q

What is the structure of IgA?

A

Monomer or dimer

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37
Q

What is the H chain of IgA?

A

α

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38
Q

What is the L chain of IgA?

A

γ or κ

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39
Q

What are the subclasses of IgA?

A

1-2

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40
Q

What are the functions of IgA?

A
  • Secretory
  • Neutralisation of microbes and toxins
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41
Q

What is the site of IgA?

A
  • Mucosa
  • Blood
  • Breast milk
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42
Q

What is the structure of IgE?

A

Monomer

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43
Q

What is the H chain of IgE?

A

ε

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44
Q

What is the L chain of IgE?

A

γ or κ

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45
Q

What are the subclasses of IgE?

A

None

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46
Q

What are the functions of IgE?

A
  • Mast cell degranulation
  • ADCC (Eosinophils)
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47
Q

What is the site of IgE?

A
  • Muscosa
  • Tissues
  • Parasites
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48
Q

What is the structure of IgD?

A

Monomer

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49
Q

What is the H chain of IgD?

A

δ

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50
Q

What is the L chain of IgD?

A

λ or κ

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51
Q

What are the subclasses of IgD?

A

None

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52
Q

What is the function of IgD?

A

B cell antigen receptor

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53
Q

What is the site of IgD?

A

B cell membrane

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54
Q

Draw a diagram showing an IgG antibody

A
  • Red - disulphide links*
  • Green - light chains*
  • Blue - heavy chains*
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55
Q

In what form does IgM exist?

A

Monomeric or pentameric

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56
Q

Draw a diagram showing an IgM antibody

A
  • Red - disulphide links*
  • Green - light chains*
  • Blue - heavy chains*
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57
Q

In what form does IgA exist?

A

Monomeric or dimeric

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58
Q

Draw a diagram showing an IgA antibody

A
  • Red - disulphide links*
  • Green - light chains*
  • Blue - heavy chains*
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59
Q

What is the linkage between monomers in IgM and IgA?

A

Via a J chain

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60
Q

Where is IgA the principle Ig?

A

In secretions, e.g. GI, respiratory, and genital-urinary mucus

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61
Q

How does IgA protect the organism?

A

By gaining attachment to mucous membranes, but is also found in the blood

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62
Q

What happens as the IgA molecule passes into an epithelial cell from the blood stream?

A

It receives an additional structure termed the secretory component

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63
Q

What does the secretory component of IgA do?

A

Transports the IgA through the cell, and remains attached to it at the mucosal surface.

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64
Q

In what ways are antibody specificities determined?

A
  • Combinational diversity
  • Junctional diversity
  • Somatic hypermutation
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65
Q

What happens in each B cell?

With respect to the gene encoding

A

The genes that encode for antibodies are recombined from several alternative segments, giving millions of possible combinations

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66
Q

What is the ability of B cell genes to encode for antibodies in different combinations called?

A

Combinatorial diversity

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67
Q

How many possible combinations are there for the variable region of κ light chains?

Include the number of alternative V and J gene segments

A
  • 40 alternative V gene segments*
  • 5 alternative J gene segments*

40 x 5 = 200 variations

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68
Q

How many possible combinations are there for the variable region of λ light chains?

Include the number of alternative V and J gene segments

A
  • 29 alternative V gene segments*
  • 4 alternate J gene segments*

29 x 4 = 116 variations

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69
Q

How many possible combinations are there for the variable region of heavy chains?

Include the number of alternative V, D and J gene segments

A
  • 51 alternate V gene segments*
  • 27 alternate D gene segments*
  • 6 alternate J gene segments*

51 x 27 x 6 = 8262 variations

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70
Q

What is the total number of antibody variations?

A

Since the variable regions of light and heavy chains contribute independantly to specificity;

(200 + 116) x 8,262 = 2.5 x 106

<em>In practice, there are fewer than this, since not all V gene segments are utilised with equal frequency, and not all variable heavy and light regions will pair successfully </em>

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71
Q

How does junctional diversity arise?

A

In the third hypervariable region, nucleotides are enzymatically inserted, altering the resultant specificity

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72
Q

What is the third hypervariable region?

A
  • V-J for light chains
  • D-J for heavy chains
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73
Q

What happens in somatic hypermutation?

A

Once B-cells have been stimulated by antigens, they are more likely to undergo a point mutation in the variable regions of rearranged H and L genes. These point mutations result in the appearance of mutant immunoglobulin molecules on the surface of the B cell that are able to interact with antigens

74
Q

What is the consequence of the mutational event in somatic hypermutation?

A

The antibody specificity may be altered, conferring greater or less affinity

75
Q

What happens if a mutational event in an antibody confers greater affinity?

A

The cell is more likely to be stimulated to divide

76
Q

What is an increase in affinity due to somatic hypermutation known as?

A

Affinity maturation

77
Q

What do secreted antibodies bind to?

A

Circulating antigen

78
Q

What is formed when secreted antibodies bind to circulating antigen?

A

Immune complexes

79
Q

What do some immune complexes go on to activate?

A

Complement

80
Q

What happens to immune complexes after formation?

A

They are trapped by follicular dendritic cells (FDCs) in the germinal centres of lymph nodes

81
Q

What allows FDCs to trap immune complexes?

A

The cells possess receptors for the Fc of IgG and C3b

82
Q

What may happen to the surface membranes of the FDCs once they have trapped immune complexes?

A

They may bud off, complete with the attached immune-complex

83
Q

What is the name of the structures formed when surface membranes of FDCs and immune-complexes bud off?

A

Iccosomes

84
Q

What is the purpose of iccosomes?

A

To present the original antigen to B cells bearing high affinity surface immunoglobulin

85
Q

What happens to high affinity B cells?

A

They survive, developing into memory B cells or immunoglobulin secreting plasma cells

86
Q

What is the ability of high affinity B cells to survive conferred by?

A

Helper T cells (CD4+) interacting with the B cell-presented peptide

87
Q

What is the B cell-presented peptide dervied from?

A

The original antigen

88
Q

How does the Helper T cell help the memory B cells survive?

A

The CD40 ligand on the T cell interacts with CD40 on the B cell, making Bcl-xL

89
Q

What is Bcl-xL?

A

A pro-survival protein

90
Q

What happens to low affinity B cells?

A

They die via apoptosis

91
Q

What happens to the low affinity B cells that have died via apotosis?

A

They are phagocytosed by macrophages in the germinal centres

92
Q

What are macrophages called once they have phagocytosed low affinity B cells?

A

Tangible body macrophages

93
Q

What do T lymphocytes play a major role in?

A
  • Defence against intracellular pathogens such as viruses, protozoa, and intracellular bacteria
  • Immunity to extracellular pathogens
94
Q

How do T lymphocytes play a major role in immunity to extracellular pathogens?

A

By providing help for the antibody response

95
Q

What do all T cells express?

A

The CD3 surface receptor

96
Q

What is the CD3 surface marker specific to?

A

T lymphocytes

97
Q

What is the CD3 surface marker often used to do?

A

Characterise T cells

98
Q

What do T and B cells both express?

A

An antigen specific surface receptor (TcR)

99
Q

How is a huge diversity of TcRs achieved?

A

A similar process to that of B-cells, rearranging TcR genes for V (variable), D (diversity), K (joining), and C (constant) gene segments

100
Q

What are individual antigens recognised by?

A

Clones of T cells

101
Q

What to the antigen-specific receptors of T cells recognise?

A

Specific epitopes within the antigen

102
Q

What are the forms of TcR?

A
  • γ/δ
  • α/ß
103
Q

What % of T cells are of the γ/δ type?

A

<10%

104
Q

When do γ/δ T cells become activated?

A

In infection

105
Q

How important is the role of γ/δ T cells in the immune response?

A

They are non-essential in most infections

106
Q

What are the main functions of γ/δ T cells?

A
  • Cytokine secretion
  • Cytotoxicity
107
Q

What % of T cells are of the α/ß type?

A

>90%

108
Q

What do α/ß T cells express?

A

Either CD4+ (helper) or CD8+ (cytotoxic) surface makers

109
Q

What do CD4+ helper T cells do?

A
  • Produce cytokines
  • Coordinate the immune response
110
Q

What do CD8+ cells do?

A

Kill cells that are infected with intracellular pathogens

111
Q

What intracellular pathogens can CD8+ cells protect against?

A
  • Viruses
  • Some bacteria
  • Some intracellular protozoa
112
Q

Give an example of an intracellular bacteria that CD8+ can protect against

A

Listeria

113
Q

Give an example of an intracellular protozoa that CD8+ cells can protect against

A

Malaria parasites

114
Q

In what form do TcRs recognise antigens?

A

Short peptides presented in association with ‘self’ Major Histocompatibility Complex (MHC) Class I or II molecules

115
Q

How many MHC class I genes are there in humans?

A

3

116
Q

What are the MHC class I genes in humans?

A

HLA A, B, and C

117
Q

How many MHC class II genes are there in humans?

A

3

118
Q

What are the MHC class II genes in humans?

A

HLA DR, DP, and DQ

119
Q

In general, what do MHC Class I present antigens to?

A

CD8+ T cells

120
Q

What are MHC Class I expressed on?

A

Almost all nucleated cells of the body

121
Q

What are the MHC Class I antigens bound for presentation derived from?

A

The cell’s cytosol

122
Q

Where are the MHC Class I antigens usually synthesised?

A

Endogenously, within the cell

123
Q

What kind of antigens are MHC Class I?

A

Viral

124
Q

What do MHC Class II present to?

A

CD4+ T cells

125
Q

Where are MHC Class II expressed?

A

On professional APCs

126
Q

What cells are professionals APCs?

A
  • B cells
  • Macrophages
  • Dendritic
127
Q

What are MHC Class II antigens bound for presentation derived from?

A

Exogenous antigens, such as soluble proteins or extracellular organisms

128
Q

What are the stages in the class I MHC pathway of processing of protein antigens?

A
  1. Antigen uptake
  2. Antigen processing
  3. Transport of peptides to ER and assembly
  4. MHC-peptide transport
  5. Peptide presentation
129
Q

What are the stages in the class II MHC pathway of processing of protein antigens?

A
  • Antigen uptake
  • Antigen processing
  • MHC biosynthesis
  • MHC-peptide association
  • Peptide presentation
130
Q

What do HLA represent, in addition to their roles as antigen presenting molecules?

A

The main antigenic targets in organ graft rejection

131
Q

When is HLA the main antigenic target in organ graft rejection?

A

Where these are not matched between organ recipient and donor

132
Q

What are some HLA molecules associated with?

A

Increased susceptibility to specific diseases

133
Q

Give two diseases that are associated with HLA molecules

A
  • HLA-B27
  • Ankylosing spondylitis
134
Q

Why are T lymphocytes so named?

A

Because of the role that the Thymus plays in their development

135
Q

Where do pre-T lymphocytes arise from?

A

Stem cells in the bone marrow

136
Q

Where do pre-T lymphocytes migrate to?

A

The thymus

137
Q

What happens do once they have migrated to the thymus?

A

They develop into mature, functional T cells

138
Q

What are mature, functioning T cells capable of doing?

A

Responding to antigen in the periphery

139
Q

When are T lymphocytes known as Thymocytes?

A

During their differentiation and migration through the thymus

140
Q

What is negative selection designed to do?

A

Delete T cells whos antigen receptors recognise self antigens with high affinity

141
Q

Why does negative selection need to delete T cells whose antigen receptors recognise self antigens?

A

Otherwise they would be autoreactive

142
Q

What does negative selection achieve?

A

Self tolerance

143
Q

What does positive selection ensure?

A

That cells capable of recognising foreign antigens survive and diffentiate further

144
Q

Draw a diagram illustrating the process of T cell maturation

A
145
Q

How long does the antigen-specific immune response take to develop?

A

A few days

146
Q

Why does the antigen specific immune response take a few days to develop?

A

Due to the need for clonal selection, differentiation, and expansion of antigen-specific effectors

147
Q

What does the adaptive immune response to infection involve?

A

Both T and B lymphocytes

148
Q

What is the integrity of the adaptive immune response based on?

A
  • The ability of B and T lymphocytes to recirculate between the blood and lymphoid tissues
  • The ability for activated effort cells to migrate into the somatic tissues at sites of infection
149
Q

What phases can the adaptive immune response be seperated into?

A
150
Q

Where does the induction phase of the adaptive immune response occur?

A

In the lymphoid tissues

151
Q

How do the antigens get to the lymphoid tissue during the induction phase?

A

They either find their own way there, or, more commonly, its transported to lymphoid tissues by migratory Dendritic cells

152
Q

How can an antigen find its own way to the lymphoid tissues for the induction phase?

A
  • Antigen can pass in the circulation through the spleen
  • Pass in circulation in afferent lymph entering lymph nodes
153
Q

What is the function of dendritic cells?

A

They are the main type of professional APCs in the induction of the immune response

154
Q

Where are immature dendritic cells found?

A

In the periphery

155
Q

What happens to immature DCs after the capture of an antigen in the periphery?

A

They migrate to regional lymph nodes

156
Q

What happens to immature DC’s after they have migrated to regional lymph nodes?

A

They process the antigen and mature into cells capable of activating naive T cells

157
Q

What is required to stimulate a naive T cell?

A

Two signals;

  • Recognition of an antigen/MHC complex by the T cell’s TcR
  • Interaction of surface molecules on the T cell and the APC
158
Q

What are the interactions of surface molecules on the T cell and the APC between?

A
  • CD80 and CD86on the APCs
  • CD28 on the T cells
159
Q

What do activated T cells release?

A

IL-2

160
Q

What does IL-2 play an essential role in?

A

T cell proliferation and differentiation

161
Q

Draw a diagram illustrating how a co-stimulatory signal and specific signal activates a T cell

A
162
Q

What expresses the molecules that provide co-stimulatory signals to T cells?

A

Only professional APCs

163
Q

What is the result of professional APCs being the only cells that express the molecules that provide co-stimulatory signals to T cells?

A

Only professional APCs that are presenting the appropriate antigenic peptide can initiate a T cell response

164
Q

What happens to naive T cells that encounter antigens without receiving a co-stimulatory signal?

A

They become anergised (unresponsive) to further antigen presentation

165
Q

What does the anergisation of naive T cells that encounter antigen without receiving a co-stimulatory signal provide?

A

A further mechanism of tolerance to self-antigen presentation

166
Q

Why does anergisation achieve a mechanism of tolerance to self-antigen presentation?

A

As antigen presentation outside of lymphoid tissue usually lacks co-stimulation

167
Q

Draw a diagram illustrating what happens when a naive T cell encounters an antigen alone

A
168
Q

Draw a diagram illustrating what happens if a T cell recieves a co-stimulatory signal alone

A
169
Q

What do APCs play a major role in determining?

A

The type of immune response produced

170
Q

Give an example of how APCs play a major role in the type of immune response produced

A

By influencing the balance between Th1 and Th2 cells, which biases the outcome towards a cell mediated or humoral response

171
Q

What is a T cell capable of doing once it has been activated by a professional APC?

A

Recognising the antigen presented by any cell that expresses the same antigen/MHC complex without co-stimulation

172
Q

What is the result of T cells being able to recognise the antigen presented by any cell that expesses the same antigen/MHC complex without costimulation after it has been activated?

A

T cells are able to reponsd to antigens presented at distant sites in the body

173
Q

What do T cells undergo following activation?

A

A process of clonal expansion and differentiation

174
Q

What happens to the T cells produced from clonal expansion and differentiation?

A

Some of these cells become activated T helper or cytotoxic cells, whilst others remain in a partially-activated state and recirculate as memory cells

175
Q

How do memory cells differ from naive T lymphocytes?

In terms of their requirements for activation

A

They have less stringent requirements for activation of re-contact with antigen than naive T lymphocytes

176
Q

What is the result of memory cells having less stringent requirements for activation on re-contact with antigens?

A

On subsequent antigen exposures, a response is developed faster

177
Q

What happens in the effector phase of the adaptive immune response?

A

Activated cells migrate to the site of infection in order to combat infection within the peripheral tissues

178
Q

What plays a central role in the effector phase of the adaptive immune response?

A

CD4 cells

179
Q

What is CD4s role in the effector phase?

A

Co-ordinates the antigen-specific immune response through cytokine release

180
Q

What is the effect of cytokine release in the effector phase of the adaptive immune reponse?

A
  • B-cell isotype switching
  • Affinity maturating of antibody response
  • CD8 cells in the induction of effector CTL
  • Enhancement of NK cell function
  • Macrophage activation in delayed type hypersensitivity reactions
  • Bacterial and fungal killing
181
Q

What happens in the resolution phase of the adaptive immune response?

A

Non-specific phagocytic cells resolve any damage caused by the infection and promote healing

182
Q

What non-specific phagocytic cells are involved in the resolution phase of the adaptive immune response?

A
  • Macrophages
  • Fibroblasts

Z Old Infection IGNORE (23 decks)

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