Acquired Immmunity-antigen Receptors Flashcards
(199 cards)
1
Q
Characteristics of the acquired immune system
A
Specificity, memory, variable intensity
2
Q
What elements of the immune system bind and recognize antigens
A
Antibodies
T cell receptors
MHC molecules
3
Q
The part of the antigen with which the antibody interacts is the ___
A
Epitope
4
Q
Why is the epitope the antigeni determinant
A
Determines which antibody will bind
5
Q
What are antibodies
A
Large glycoproteins
6
Q
What is the T cell receptor
A
Large glycoproteins
7
Q
Unlike an antibody that interacts with the whole intact antige, what do T cell receptors interact with
A
Short segment of aa, the peptide epitope, derived from the intact antigen proteolysis
8
Q
Can T cells interact with soluble peptide epitope directly?
A
No peptide must be held and presented by other glycoprotein molecules, MHC
9
Q
What are MHC
A
Glycoprotein
Hold the peptide antigen enclosed within a groove
10
Q
So what is recognized by a T cell receptors
A
MHC and peptide epitope
11
Q
What forces do antigens renter act with antibodies, TCR, and MHC
A
Non covalent
H bond and electrostatic attraction and van deer waals
12
Q
Dissociation constant
A
Strength or affinity of antigen interaction
Concentration allowing half the antibodies to be completed and half to remain in solution
13
Q
The smaller the Kd the ___ the affinity
A
Higher
14
Q
Rank affinity for antigens of antibodies, MHD and T cell
A
Antibodies greater than MHC greater than T cell
15
Q
How many sites does IgM have to bind
A
10, it has five arms
16
Q
How many sites does igG have to bind
A
2, it has 1 arm
17
Q
Avidity
A
Strength of attachment
18
Q
If blood is clotted and removed from he plasma, what is left
A
Serum
19
Q
Antigen binding site of antibody
A
Regions that are highly variable in their aa content in different molecules
20
Q
Heavy chains
A
Antibodies have relatively constant parts, hold different functional properties such as ability to activate complement
21
Q
Describe the basic immunoglobulin
A
Two heavy chains and two light chains connected by inter chain disulphide bonds…within the chains, distinctive motifs are formed by intra chain disulphide bonds
22
Q
Immunoglobulin. Superego need family
A
Many immunological molecules have similar domain structures
23
Q
Different heavy chains give rise to different classes. What are they
A
IgA, IgD, igE, iGG, IgM
24
Q
Formula of an immunoglobulin
A
Heavy2Light2
25
There are two alternative types of light chain. What are they
Kappa and lambda
| Either have two kappa(more common) or two lambda
26
What are the five heavy chain types
Alpha, beta, delta, epsilon, gamma, and mu
| The 2 will be identical
27
Each heavy chain and light chain have a stable segment and a zone that varies a lot . What are they called
C region-constant (effector function such as complement activation
V regions-variable (antigen binding site
28
How may hypervariable of complementarity-determining regions(CDR) are in each heavy and light chain
3
29
To form the full antibody molecule, the two heavy chains are linked together by what
Two interchain disulphide bonds
30
Each heavy chain is attached to a light chain by what
Interchain disulphide bond
31
All immunoglobulin domains contain two layers of B pleated sheet with 3 or 4 strange of anti parallel polypeptide chain
Ok
32
Immunoglobulin supergene family
MHC, T and adhesion molecules have similar domain structure
33
V underscore H
Variable region heavy
34
C underscore L
Constant region light chain
35
Hinge region
Middle of molecule allows freedom to the two arms bearing the antigen binding sites ...flexible
36
Papain
Enzyme cleaves at the hinge region , breaking the two interchain disuphide bonds between the heavy chains in the process, to produce three fragments
37
When cleaved by papain, describe the 3 fragments
2 Identical and retain antigen binding ability
Called Fab fragments (fragment antigen binding)
45kDa each
1 is larger (55kda) and cant bind antigen but retains effector function
It is crystal likable and termed the Fc fragment (bc can bind Fc receptor )
38
Pepsin
Enzyme that leaves the heavy heavy disulphide bond in tact cuts into two fragments
39
Describe the two fragments from pepsin digestion of antibody
F(ab’)2- 2 Fab fragments linked with antigen binding site, but no effector function remaining
40
How do we achieve variation of effector region
H chain
| 5 subtypes but gamma is further gone intoy1-4 and alpha a1-2
41
IgG and igA subclasses
IgG1-4
| IgA1-2
42
What is the most abundant immunoglobulin
IgG
43
IgG2
Capsulitis bacteria
44
IgG1-3
Activators of the classical complement pathway
45
How can we increase the binding of C1q to igG
Bind igG to antigen
46
What domain does C1q interact with
CH2
47
The igG has three constant domains on the heavy chain. What are these called
CH1-3
48
IgG is a monomer and has how many classes
4
49
Half life of igG
23 days
50
Proportion of IgG in circulation
50
51
IgA structural form
Monomer (circulating )
| Diner (secretory)
52
IgA accessory chain
J chain polyimmunoglobulin receptor (secretory chain)
53
IgA subclasses
IgA1, igA2
54
IgA heavy chain
A
55
IgA number of domains in heavy chain
3
56
IgA half life
6 days
57
IgA proportion in circulation
50
58
IgM structure
Pentamer
59
IgM accessory chain
J chain
60
IgM heavy chain
Mu
61
IgM number of domains in heavy chain
4
62
Half life igM
5 days
63
IgM proportion found in circulation
80%
64
IgD structure
Monomer
65
IgD heavy chain
Delta
66
IgD number of domains in heavy chain
3
67
IgD half life
3 days
68
IgD proportion in circulation
75%
69
IgE structure
Monomer
70
IgE heavy chain
Epsilon
71
IgE number of domains in heavy chain
4
72
IgE half life
2.5 days
73
IgE proportion found in circulation
5o
74
IgG adult serum concentration
6-12 g/l
75
IgA adult serum concentration
1-4g/l
76
IgM adult serum concentration
.5-2 g/l
77
IgD adult serum concentration
.04 g/l
78
IgE adult serum concentration
.003 g/l
79
Rank IgG based on proportion
IgG1 more than igG2 more than IgG3 more than IgG4
80
What are the three cellular receptors for the Fc portion of IgG
FcyRI, FcyRII, FcyRIII
81
Strongest igG to tetanus
1 and 4
82
IgG Highest it reaction to bacterial polysaccharides
2
83
FcyRI receptor
1, 2, 4
84
FcyRII igG
1, 3
85
FcRIII igG
1, 3
86
IgG activation of complement
1 mainly. Also 2 and 3
87
Which igG cross placenta
All
88
The Fcy receptors are important for placental transfer
IgG protect newborn
89
FcyRI
CD64 high affinity
| On monocytes, macrophages and activated neutrophils
90
FcRyII
CD32 low affinity on monocytes, neutrophils, eosinophils, and B cells
91
FcyRIII
CD 16 low affinity
| On monocytes, neutrophils, and NK cells
92
Why is IgA distinct
Can be monomer or dimer.
| Major immunoglobulin excreted on external surfaces
93
What is a j chain
Short peptide joins 2 igA
94
The IgA in circulation is ___ the IgA in secretion is ___(saliva, bronchial fluid, gut secretions, gut secretions, tears)
Monomer
| Dimer
95
How is IgA secreted
Attachment of dimeric IgA to a molecule, poly-IgR, which is synthesized by epithelial cells lining mucosal surfaces
96
What happens to the IgA-poly-IgR complex
Endocytosed, transported through the epithelial cell and secreted into the lumen ...then it is cleaved , releasing IgA and a remnant of poly-IgR, termed the secretory chain
97
Selective IgA defiency
Severe, intractable infections of the major mucosal surfaces (GI, upper and lower respiratory tracts) are common
98
As the major secretory immunoglobulin, what does IgA protect against
Bacterial, viral, protozoan infections of mucosa and can activate complement through the alternative pathway as well as having specific receptors FcaR on monocytes and neutrophils
99
IgA receptor
FacR on monocytes and neutrophils
100
How is IgM distinctive
A oentamer of five monomers joined by J chain
101
IgM is the __ antibody synthesized in an antibody response (primary response)
First
102
Does igM activate compllement
Yes very well
103
How many binding sites does IgM have
10
104
IgM can become ____ so that when reacting with repeating epitopes on a cell or bacterial surface
Flexed
105
Why is flexing of igM important
Helpful bc they dont have high affinity like later produced ones..use more binding sites
106
IgD
Low serum concentration
Surface expression of IgD is evident at a relatively immature stage of B cell cycle, and the signaling provided by this receptor on interaction with antigen in a lymphoid follicle is critical part of B lymphocyte activation
107
IgE is the ___ immunoglobulin monomer
Largest
108
How many CH domains does IgE have
4
109
When do IgE levels rise
Allergic reactions and immune responses to parasitic both involving activation of mast cells, which is the main effector of IgE
110
__ cells bear 10^4-10^6 high affinity FcERI receptors for IgE
Mast cells
111
What happens when IgE activates mast cells
Itchy, hypervascular responses
112
What has low affinity FceRII(CD23) receptors for IgE
B cells and eosinophils
113
What happens when FceRII on B cells bind
Regulation of IgE production
114
Isotype
Structural features of a particular immunoglobulin class or heavy or light chain type in a species
115
Allotropes
Other parts of immunoglobulins have genetically determined differences between individuals
116
What do immunoglobulins on B cells do
Bind antigen, internalize, break down, and a portion os presented to T cells to activate their response to the antigen
117
Isotypes
Epiptopes that are present on all molecules of a class or chain type in a species
118
Allotypes
Vary between individuals,
119
Idiotypes
Reflect variation in the antigen binding sites of immunoglobulins
120
Primary immune response
Slow, IgM
121
Repeat exposure
More rapid IgG, higher peak and baseline
122
Each plasma cell produces a __ antibody
Single
123
How do B cells insert into B cell
Short extension of immunoglobulin molecules at the carboxy-terminus during synthesis
124
What antibodies are on B cells
G, A, D
125
What happens when B cells bind antigen through antibody
Internalization and antigen processing and presentation for T cells
126
Primary immune response
Inject
Antibody response 5-10days later IgM
Rises 10-20 days
Declines
127
Secondary antibody response (same antigen again)
```
More rapid
Higher peak level and declines to a higher base level
IgG
Antigen specific response
Displays memory
```
128
Does IgM or IgG have higher affinity
IgG
| Darwin..highest affinity compete and win
129
Hapten
Small molecules too small to elicit immune response. If bind to a larger protein carrier can elicit production of antibodies
DRUGS
130
Monoclonal antibody
Clone of plasma cells, unvarying aa sequence
131
Polyclonal
Many different clones of plasma cells and many different antibody types in a typical antibody response
132
Dominant epitopes
Antibody responses to large macromolecular antigen are not evenly distributed throughout the antigen, some areas are targeted more frequently than others and are termed the dominant
133
What are the two situations where monoclonal antibodies are identifiable in any quantity
1. Tumor of plasma cell origin leads to expansion of a single clone of cells, like myeloma
2. Tumor is fused with a B cell to give an immortalized, antibody producing clone of B lymphocytes
134
What does changing heavy chains do
Modify effector function without altering antigen binding
135
Potential binding capacity exceeds 10^11
Wow
136
Each heavy and light chain is encoded by a gene ___
Complex
137
Each gene complex there are ___ that encode variable regions and constant regions
Segments
138
J genes
Join these two
139
D genes
Generate diversity
140
What is IGKV1
Immunogloblun kappa variable chain gene number 1
141
What chromosome is kappa on (light chain)
2
142
What chromosome is lamba light chain on
22
143
What is the sequence of genes of the light chain from 5’-3’ end
V, J, G
144
Why are there 200 different kappa light chains and 15- different lamda light chains
Kappa-4- IGKV gene segments and 5 IGKJ segments and one IGKC segment
Lambda-30 IGLV, 5IGLC, each C gene accompanied by its own IGLJ
145
What chromosome is the heavy chain on
14
146
What are the differences between light and heavy chain genes
```
Additional diversity is achieved by D segments
The constant region gene segments encoding the heavy chain isotypes (IGHG1-4 for the IgG subclass heavy chains; IGHA1-2 for IgA subclasses;IGHM, IGHD and IGHE for IgM, IgD and IgE ) are located together, downstream from the IGHV, IGHD, and IGHJ segments rather than on separate chromosomes
```
147
How many possibilities are there for heavy chains and how
5.67 million ...combitorial diversity since relies on combinations of different genes
148
What is junctional diversity and how much does it increase immunoglobulin diversity
Deliberate imprecision in the joining together of IGHD and IGHJ, IGHV to the IGHD-IGHJ combination that forms, and also in equalize the V-J segments as they join for the light chain genes
30 million times
149
Combinatorial and junctional diversity focus on changes in ___ regions , which are mainly encoded from the joining regions of the genes ....can make many different shapes in antibody binding region
Hypervariable regions (CDRs)
150
Somatic hypermutation
Parts of the variable regions of different antibodies differ in single aa which is changed after antigenic stimulation
Substitution, deletion or addition of a single nucleotide occurring after gene arrangement
Class switch between primary and secondary immune response
151
When does somatic hypermutation occur
Cell is undertaking the class switch between the primary and secondary responses
152
What does somatic hypermutation do
Introduces additional diversity and is focused around CdR
153
Somatic hypermutation is dependent on what enzyme
Activation induced cytidine deaminase
154
Genetic effects in activation induced cytidine deaminase
Failure of B cells to generate diversity through this process resulting in poor production of high affinity antibodies and a rare immune defiency state called hyper IgM syndrome type 3
155
Heavy chain light chain potential for functional diversity
10^11-12
156
TCRaB potential for diversity
10^16
157
TCR ydelta
10^18
158
Class switch recombination
```
Antigen specificity doesn’t change
IgM class developed.
Then to sIgM to bind antigen
Then class switch
Activation induced cytidine deaminase
```
159
Affinity maturity
IgM low affinity igG high
Darwinian
In limited antigen supply, they bind to highest affinity and lymph nodes only select bound antigens for maturation and differentiation
160
The heavy genes on the chromosome are assembled first. Describe this
IGHD and IGHJ segment combining before IGHV segment is added.
VDJ is produced through this arrangement (allelic exclusion0other chromosome is inhibited from undergoing same process)
Constant heavy chain added to the rearranged IGH VVDJ
Invariable the IGHM is selected
161
The light chain genes rearranges after heavy. Describe this
V and J segments are rearranged and combined with the constant region gene
The IGK gene is selected first(if unsuccessful on both chromosome 2 then IGL is sought note majority are unsuccessful since kappa greater than lambda)
162
Class switching
IgM heavy chain replaced by selection of IGHG, IGHA or IGHE genes
By switch region 5’ to IGH genes
163
The only IGH gene not to have a switch region is IGHD. What does this explain
Few mature b cellls express sIgD and few IgD is made
164
VJD recombinant
| Recombination activation genes (RAG1 and RAG2)
The heptamer and nonamer must be separated by a 12-mer on one side and a 23-mer on the other. This is the 12-23 rule. These two enzymes catalyst this process
Critical for developing B cells and T cells.
165
RAG knockout
Can’t rearrange immunoglobulin genes of T cell receptors and are profoundly immune deficient
166
Downstream from V (of VDJ) is what
Heptamer (7 nucleotide sequence) followed by a random set of nucleotides (12 or 23) and then a further 9 (a nonamer)
167
What is upstream
Nonamer-random 12 or 13-heptamer
| Opposite
168
The two heptamer and nonamer are __
Palandromic
169
What doe this allow
A loop to be made of dsdna
170
TCR is composed of two chains. What are they. Which is more common
A/B (90%) gamma/delta(10%)
171
Are the TCR chains part of the immunoglobulin supergene family.
Yup
172
How do TCR vary in structure
Large pool of gene segments for individual receptor chains; and random imprecision int he joining together of the selected variable, diversity and joining genes
173
Do tCR somaticalaly mutate after gene rearrangement
No
174
What do TCR bind
Antigen and MHC
175
The _TCR appears not he surface of primitive T cell in thymus before _ can be seen
Gamma delta
| Alpha beta
176
Is ab of gamma delta more common
Ab
177
Describe ab TCR
Disulphide bonded heterodimer comprising an a chain and a b chain
Va, Vb, Ca C3b for constant and variable regions
Structure of domains in TCR is analogous with immunoglobulin domains and form part of immunoglobulin supergene family
Have hypervariable regions in variable domain , forming CDR1-3
178
What do CDR 1 and 2 interact with
Two a helices of the a1 and a2 domain of MHC as run along the sides of the antigen binding groove
179
What does CDR3 interact with
Peptide int he groove
180
Gamma delta TCR
```
Gene reagrrangement is an early thymic arrangement
Disulfide linked heterodimer
Or
Non disulfide linked heterodimer
Or
disulfide linked yy homodimer
```
181
Describe formation of a chain
Analogous to heavy and light chain
TRAV, TRAJ, TRAC recombination
Potential diversity is 2500
182
What are the functional segments of b chain
TRBV, TRBD, TRBJ, TRBC
| Potential diversity is 2600
183
What makes TCR genes different from immunoglobulins
1. TRAC and TRBC genes do not encode segments typical of secreted proteins, indicating that secretion of TCD is not an important functional characteristic
2. no somatic hypermutation in the genes encoding a complete ab TCR.
184
Human gamma chain
TRGV, TRGJ, TRGC
| Diversity 120
185
Delta chain
In the middle of the a chin
TRDV, TRDD, TRDJ, TRDC
Diversity is 36
186
Diversity of gamma and delta together
4320
187
How do we bring different gene components of the TCR together
Nonamer heptamer sequence and 12 23 nucleotide sequence
| 12-23 rule
188
What other mechanisms create tcr diversity
Imprecise joining (frameshift mutatiosn and new nucleotide sequences)
189
Heavy chain, light chain, a chain, b chain, gamma chain, delta chain number of variable segments
45, 30-40, 50, 50, 8, 10
190
Heavy chain, light chain, a chain, b , gamma, delta number of D segments
30, 0, 0, 2, 0, 2
191
Which chains allow D segments to be read in all three reading frames
Beta and delta
Rarely heavy
192
Heavy chain, light chain, alpha chain, beta chain, gamma hair, delta chain hunger of joining J segments
12, 4-5, 50, 13, 2, 3,
193
Heavy chain combat oral diversity
3-5x10^6
194
Heavy chain light chain somatic hypermutation
3x10^6
195
Total potential heavy and light chain
10^11-10^12
196
Alpha beta chain combitoral diversity
-2500
197
A b chain total potential diversity
10^16
198
Gamma delta combitorial diversity
80
199
Gamma delta total potential diversity
10^18
