Antibodies, Complement, and T Cell Pathogen Recognition Flashcards
1
Q
What are antibodies also known as?
A
Immunoglobulins, Ig
2
Q
What kind of molecules are antibodies?
A
Proteins
3
Q
What is the molecular weight of antibodies?
A
150,000-900,000 kd
4
Q
What are antibodies derived from?
A
The immunoglobulin supergene
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
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
7
Q
What is the crystallisable end of the antibody called?
A
Fc
8
Q
Are Fc domains constant or variable?
A
Constant
9
Q
Are Fab regions constant or variable?
A
Extremely variable between individual Ig’s
10
Q
What is true of the progeny of a single clone of B cells?
A
They are identical
11
Q
What does the basic, monomeric, Ig molecule have?
A
- Two light chains
- Two heavy chains
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
13
Q
How many H chain domains does an IgG molecule have?
A
3
CH1, CH2, and CH3
14
Q
What is found between CH1 and CH2 in an IgG molecule?
A
Many cystine and proline residues
15
Q
What is the region containing the residues between CH1 and CH2 in IgG known as?
A
The hinge region
16
Q
What does the hinge region do?
A
Confers flexibility to the Fab arms
17
Q
Label this diagram of an IgG antibody
A
18
Q
How many classes, or isotypes, of antibodies are there?
A
5
19
Q
What are the classes of antibodies categoried by?
A
Differences exisiting in their H-chain constant regions
20
Q
How many classes of light chains are there?
A
2
21
Q
What are classes of light chains?
A
- Lambda
- Kappa
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
23
Q
What are the classes of Ig?
A
- IgM
- IgG
- IgA
- IgE
- IgD
24
Q
What structure is IgM?
A
Pentameter
25
What is the H chain of IgM have?
µ
26
What is the L chain of IgM have?
λ or κ
27
What are the subclasses of IgM?
None
28
What are the functions of IgM?
* Agglutination
* Complement activation
* Primary response
29
What is the site of IgM?
Blood
30
What is the structure of IgG?
Monomer
31
What is the H chain of IgG?
γ
32
What is the L chain of IgG?
λ or κ
33
What are the subclasses of IgG?
1-4
34
What are the functions of IgG?
* Opsonisation
* Complement activation
* Neutralisation
* ADCC (NK cells)
* Transplacental
* Secondary response
35
What is the site of IgG?
* Blood
* Tissues
36
What is the structure of IgA?
Monomer or dimer
37
What is the H chain of IgA?
α
38
What is the L chain of IgA?
γ or κ
39
What are the subclasses of IgA?
1-2
40
What are the functions of IgA?
* Secretory
* Neutralisation of microbes and toxins
41
What is the site of IgA?
* Mucosa
* Blood
* Breast milk
42
What is the structure of IgE?
Monomer
43
What is the H chain of IgE?
ε
44
What is the L chain of IgE?
γ or κ
45
What are the subclasses of IgE?
None
46
What are the functions of IgE?
* Mast cell degranulation
* ADCC *(Eosinophils)*
47
What is the site of IgE?
* Muscosa
* Tissues
* *Parasites*
48
What is the structure of IgD?
Monomer
49
What is the H chain of IgD?
δ
50
What is the L chain of IgD?
λ or κ
51
What are the subclasses of IgD?
None
52
What is the function of IgD?
B cell antigen receptor
53
What is the site of IgD?
B cell membrane
54
Draw a diagram showing an IgG antibody
* Red - disulphide links*
* Green - light chains*
* Blue - heavy chains*
55
In what form does IgM exist?
Monomeric or pentameric
56
Draw a diagram showing an IgM antibody
* Red - disulphide links*
* Green - light chains*
* Blue - heavy chains*
57
In what form does IgA exist?
Monomeric or dimeric
58
Draw a diagram showing an IgA antibody
* Red - disulphide links*
* Green - light chains*
* Blue - heavy chains*
59
What is the linkage between monomers in IgM and IgA?
Via a J chain
60
Where is IgA the principle Ig?
In secretions, *e.g. GI, respiratory, and genital-urinary mucus*
61
How does IgA protect the organism?
By gaining attachment to mucous membranes, *but is also found in the blood*
62
What happens as the IgA molecule passes into an epithelial cell from the blood stream?
It receives an additional structure termed the secretory component
63
What does the secretory component of IgA do?
Transports the IgA through the cell, and remains attached to it at the mucosal surface.
64
In what ways are antibody specificities determined?
* Combinational diversity
* Junctional diversity
* Somatic hypermutation
65
What happens in each B cell?
## Footnote
*With respect to the gene encoding*
The genes that encode for antibodies are recombined from several alternative segments, giving millions of possible combinations
66
What is the ability of B cell genes to encode for antibodies in different combinations called?
Combinatorial diversity
67
How many possible combinations are there for the variable region of κ light chains?
## Footnote
*Include the number of alternative V and J gene segments*
* 40 alternative V gene segments*
* 5 alternative J gene segments*
40 x 5 = **200 variations**
68
How many possible combinations are there for the variable region of λ light chains?
## Footnote
*Include the number of alternative V and J gene segments*
* 29 alternative V gene segments*
* 4 alternate J gene segments*
29 x 4 = **116 variations**
69
How many possible combinations are there for the variable region of heavy chains?
## Footnote
*Include the number of alternative V, D and J gene segments*
* 51 alternate V gene segments*
* 27 alternate D gene segments*
* 6 alternate J gene segments*
51 x 27 x 6 = **8262 variations**
70
What is the total number of antibody variations?
Since the variable regions of light and heavy chains contribute independantly to specificity;
_(200 + 116) x 8,262 = **2.5** **x 10**_**6**
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
71
How does junctional diversity arise?
In the third hypervariable region, nucleotides are enzymatically inserted, altering the resultant specificity
72
What is the third hypervariable region?
* V-J for light chains
* D-J for heavy chains
73
What happens in somatic hypermutation?
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
What is the consequence of the mutational event in somatic hypermutation?
The antibody specificity may be altered, conferring greater or less affinity
75
What happens if a mutational event in an antibody confers greater affinity?
The cell is more likely to be stimulated to divide
76
What is an increase in affinity due to somatic hypermutation known as?
Affinity maturation
77
What do secreted antibodies bind to?
Circulating antigen
78
What is formed when secreted antibodies bind to circulating antigen?
Immune complexes
79
What do some immune complexes go on to activate?
Complement
80
What happens to immune complexes after formation?
They are trapped by follicular dendritic cells (FDCs) in the germinal centres of lymph nodes
81
What allows FDCs to trap immune complexes?
The cells possess receptors for the Fc of IgG and C3b
82
What may happen to the surface membranes of the FDCs once they have trapped immune complexes?
They may bud off, complete with the attached immune-complex
83
What is the name of the structures formed when surface membranes of FDCs and immune-complexes bud off?
Iccosomes
84
What is the purpose of iccosomes?
To present the original antigen to B cells bearing high affinity surface immunoglobulin
85
What happens to high affinity B cells?
They survive, developing into memory B cells or immunoglobulin secreting plasma cells
86
What is the ability of high affinity B cells to survive conferred by?
Helper T cells (*CD4+)* interacting with the B cell-presented peptide
87
What is the B cell-presented peptide dervied from?
The original antigen
88
How does the Helper T cell help the memory B cells survive?
The CD40 ligand on the T cell interacts with CD40 on the B cell, making Bcl-xL
89
What is Bcl-xL?
A pro-survival protein
90
What happens to low affinity B cells?
They die via apoptosis
91
What happens to the low affinity B cells that have died via apotosis?
They are phagocytosed by macrophages in the germinal centres
92
What are macrophages called once they have phagocytosed low affinity B cells?
Tangible body macrophages
93
What do T lymphocytes play a major role in?
* Defence against intracellular pathogens such as viruses, protozoa, and intracellular bacteria
* Immunity to extracellular pathogens
94
How do T lymphocytes play a major role in immunity to extracellular pathogens?
By providing help for the antibody response
95
What do all T cells express?
The CD3 surface receptor
96
What is the CD3 surface marker specific to?
T lymphocytes
97
What is the CD3 surface marker often used to do?
Characterise T cells
98
What do T and B cells both express?
An antigen specific surface receptor (TcR)
99
How is a huge diversity of TcRs achieved?
*A similar process to that of B-cells,* rearranging TcR genes for V *(variable)*, D *(diversity)*, K *(joining)*, and C *(constant)* gene segments
100
What are individual antigens recognised by?
Clones of T cells
101
What to the antigen-specific receptors of T cells recognise?
Specific epitopes within the antigen
102
What are the forms of TcR?
* γ/δ
* α/ß
103
What % of T cells are of the γ/δ type?
\<10%
104
When do γ/δ T cells become activated?
In infection
105
How important is the role of γ/δ T cells in the immune response?
They are non-essential in most infections
106
What are the main functions of γ/δ T cells?
* Cytokine secretion
* Cytotoxicity
107
What % of T cells are of the α/ß type?
\>90%
108
What do α/ß T cells express?
Either CD4+ *(helper)* or CD8+ *(cytotoxic)* surface makers
109
What do CD4+ helper T cells do?
* Produce cytokines
* Coordinate the immune response
110
What do CD8+ cells do?
Kill cells that are infected with intracellular pathogens
111
What intracellular pathogens can CD8+ cells protect against?
* Viruses
* Some bacteria
* Some intracellular protozoa
112
Give an example of an intracellular bacteria that CD8+ can protect against
Listeria
113
Give an example of an intracellular protozoa that CD8+ cells can protect against
Malaria parasites
114
In what form do TcRs recognise antigens?
Short peptides presented in association with 'self' Major Histocompatibility Complex (MHC) Class I or II molecules
115
How many MHC class I genes are there in humans?
3
116
What are the MHC class I genes in humans?
HLA A, B, and C
117
How many MHC class II genes are there in humans?
3
118
What are the MHC class II genes in humans?
HLA DR, DP, and DQ
119
In general, what do MHC Class I present antigens to?
CD8+ T cells
120
What are MHC Class I expressed on?
Almost all nucleated cells of the body
121
What are the MHC Class I antigens bound for presentation derived from?
The cell's cytosol
122
Where are the MHC Class I antigens usually synthesised?
Endogenously, within the cell
123
What kind of antigens are MHC Class I?
Viral
124
What do MHC Class II present to?
CD4+ T cells
125
Where are MHC Class II expressed?
On professional APCs
126
What cells are professionals APCs?
* B cells
* Macrophages
* Dendritic
127
What are MHC Class II antigens bound for presentation derived from?
Exogenous antigens, *such as soluble proteins or extracellular organisms*
128
What are the stages in the class I MHC pathway of processing of protein antigens?
1. Antigen uptake
2. Antigen processing
3. Transport of peptides to ER and assembly
4. MHC-peptide transport
5. Peptide presentation
129
What are the stages in the class II MHC pathway of processing of protein antigens?
* Antigen uptake
* Antigen processing
* MHC biosynthesis
* MHC-peptide association
* Peptide presentation
130
What do HLA represent, *in addition to their roles as antigen presenting molecules*?
The main antigenic targets in organ graft rejection
131
When is HLA the main antigenic target in organ graft rejection?
Where these are not matched between organ recipient and donor
132
What are some HLA molecules associated with?
Increased susceptibility to specific diseases
133
Give two diseases that are associated with HLA molecules
* HLA-B27
* Ankylosing spondylitis
134
Why are T lymphocytes so named?
Because of the role that the **T**hymus plays in their development
135
Where do pre-T lymphocytes arise from?
Stem cells in the bone marrow
136
Where do pre-T lymphocytes migrate to?
The thymus
137
What happens do once they have migrated to the thymus?
They develop into mature, functional T cells
138
What are mature, functioning T cells capable of doing?
Responding to antigen in the periphery
139
When are T lymphocytes known as Thymocytes?
During their differentiation and migration through the thymus
140
What is negative selection designed to do?
Delete T cells whos antigen receptors recognise self antigens with high affinity
141
Why does negative selection need to delete T cells whose antigen receptors recognise self antigens?
Otherwise they would be autoreactive
142
What does negative selection achieve?
Self tolerance
143
What does positive selection ensure?
That cells capable of recognising foreign antigens survive and diffentiate further
144
Draw a diagram illustrating the process of T cell maturation
145
How long does the antigen-specific immune response take to develop?
A few days
146
Why does the antigen specific immune response take a few days to develop?
Due to the need for clonal selection, differentiation, and expansion of antigen-specific effectors
147
What does the adaptive immune response to infection involve?
Both T and B lymphocytes
148
What is the integrity of the adaptive immune response based on?
* 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
What phases can the adaptive immune response be seperated into?
150
Where does the induction phase of the adaptive immune response occur?
In the lymphoid tissues
151
How do the antigens get to the lymphoid tissue during the induction phase?
They either find their own way there, or, *more commonly,* its transported to lymphoid tissues by migratory Dendritic cells
152
How can an antigen find its own way to the lymphoid tissues for the induction phase?
* Antigen can pass in the circulation through the spleen
* Pass in circulation in afferent lymph entering lymph nodes
153
What is the function of dendritic cells?
They are the main type of professional APCs in the induction of the immune response
154
Where are immature dendritic cells found?
In the periphery
155
What happens to immature DCs after the capture of an antigen in the periphery?
They migrate to regional lymph nodes
156
What happens to immature DC's after they have migrated to regional lymph nodes?
They process the antigen and mature into cells capable of activating naive T cells
157
What is required to stimulate a naive T cell?
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
What are the interactions of surface molecules on the T cell and the APC between?
* CD80 and CD86on the APCs
* CD28 on the T cells
159
What do activated T cells release?
IL-2
160
What does IL-2 play an essential role in?
T cell proliferation and differentiation
161
Draw a diagram illustrating how a co-stimulatory signal and specific signal activates a T cell
162
What expresses the molecules that provide co-stimulatory signals to T cells?
**Only** professional APCs
163
What is the result of professional APCs being the only cells that express the molecules that provide co-stimulatory signals to T cells?
Only professional APCs that are presenting the appropriate antigenic peptide can initiate a T cell response
164
What happens to naive T cells that encounter antigens without receiving a co-stimulatory signal?
They become anergised *(unresponsive)* to further antigen presentation
165
What does the anergisation of naive T cells that encounter antigen without receiving a co-stimulatory signal provide?
A further mechanism of tolerance to self-antigen presentation
166
Why does anergisation achieve a mechanism of tolerance to self-antigen presentation?
As antigen presentation outside of lymphoid tissue usually lacks co-stimulation
167
Draw a diagram illustrating what happens when a naive T cell encounters an antigen alone
168
Draw a diagram illustrating what happens if a T cell recieves a co-stimulatory signal alone
169
What do APCs play a major role in determining?
The type of immune response produced
170
Give an example of how APCs play a major role in the type of immune response produced
By influencing the balance between Th1 and Th2 cells, which biases the outcome towards a cell mediated or humoral response
171
What is a T cell capable of doing once it has been activated by a professional APC?
Recognising the antigen presented by any cell that expresses the same antigen/MHC complex **without** co-stimulation
172
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?
T cells are able to reponsd to antigens presented at distant sites in the body
173
What do T cells undergo following activation?
A process of clonal expansion and differentiation
174
What happens to the T cells produced from clonal expansion and differentiation?
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
How do memory cells differ from naive T lymphocytes?
## Footnote
*In terms of their requirements for activation*
They have less stringent requirements for activation of re-contact with antigen than naive T lymphocytes
176
What is the result of memory cells having less stringent requirements for activation on re-contact with antigens?
On subsequent antigen exposures, a response is developed faster
177
What happens in the effector phase of the adaptive immune response?
Activated cells migrate to the site of infection in order to combat infection within the peripheral tissues
178
What plays a central role in the effector phase of the adaptive immune response?
CD4 cells
179
What is CD4s role in the effector phase?
Co-ordinates the antigen-specific immune response through cytokine release
180
What is the effect of cytokine release in the effector phase of the adaptive immune reponse?
* 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
What happens in the resolution phase of the adaptive immune response?
Non-specific phagocytic cells resolve any damage caused by the infection and promote healing
182
What non-specific phagocytic cells are involved in the resolution phase of the adaptive immune response?
* Macrophages
* Fibroblasts
