Lecture 19-23: Proteins of the Immune System Flashcards
(127 cards)
1
Q
What are the five types of human antibody ?
A
- IgA
- IgD
- IgE
- IgG
- IgM
2
Q
How many types is there of IgA ?
A
2
3
Q
How many types is there of IgD?
A
1
4
Q
How many types is there of IgE ?
A
1
5
Q
How many types is there of IgG ?
A
4
6
Q
How many types is there of IgM ?
A
1
7
Q
Where is IgA found ?
A
Mucosal areas such as the gut, respiratory tract, and urogenital tract. Also saliva, tears and breast milk
8
Q
What do IgA antibodies form ?
A
Complexes that bind to multiple antigen molecules
9
Q
What does IgD function as ?
A
An antigen receptor on B that have not been exposed to antigens
10
Q
What does IgD activate ?
A
Basophils and mast cells
11
Q
What does IgD’s activation of basophils and mast cells produce ?
A
Antimicrobial factors
12
Q
What is the function of IgE ?
A
Binds to allergens and triggers histamine release from mast cells and basophils, protects against parasitic worms
13
Q
What is the function of IgG ?
A
Provides the majority of antibody-based immunity against invading pathogens
14
Q
What is the special function of IgG ?
A
The only antibody capable of crossing the placenta to give passive immunity to fetus
15
Q
Where is IgM expressed ?
A
On the surface of B cells in a monomer form and in a secreted form (pentamer) with high avidity
16
Q
What is the function of IgM ?
A
Eliminates pathogens in the early stages of B-cell mediated immunity before there is sufficient IgG
17
Q
What are the outcomes of antibody production ?
A
- Antibody secretion
- Isotype switching
- Affinity maturation
- Memory B cell
18
Q
What is the steps in antibody production by B-cells and plasma cells (T-cell dependent) ?
A
- Immunoglobulin receptors on B-cell surface recognise and attach to antigen which is then internalised and processed
- A fragment of the antigen combines with HLA class II -displayed on the B-cell surface
- Receptor on the T helper cell recognises complex of HLA class II and antigen fragment and is activated producing cytokines, which activate B-cell
- B cell is activated by cytokines and begins clonal expansion- some of the progeny become antibody producing plasma cells
19
Q
What is the structure of an immunoglobulin ?
A
- Two fab regions
- Hinge region
- Fc region
20
Q
What type of molecules are antibodies ?
A
Dynamic and flexible
21
Q
How was the importance and fragility of the flexible hinge discovered ?
A
Cryo-electron tomography and particle electron tomography
22
Q
How many immuglobulin regions does a light chain consist of ?
A
2
23
Q
How many immunoglobulin domains does a heavy chain consist of ?
A
4
24
Q
What type of cleavage site does an immunoglobulin have ?
A
Papain
25
What is the structure of immunoglobulin domains ?
1. Two beta antiparallel sheets that surrounds a hydrophobic core
2. One disulphide bond bridges the sheets
3. Three loops present at one end of the structure form a potential binding surface
26
What provides the vast repertoire of immunoglobulin domains ?
Variations of the amino acid sequences of these loops
27
What binds to the complementarity determining regions or loops ?
Antibodies
28
How is a binding surface formed ?
Six complementarity determining regions come together
29
What are the characteristics of the immunoglobulin fold of the light chain constant region ?
3 plus 4 strands
30
What are the characteristics of the immunoglobulin fold of the variable region ?
4 plus 5 strands
31
What has a diversity region ?
Heavy chain
32
What are the two types of light chains ?
1. Kappa
2. Lambda
33
What are the first antibodies expressed ?
IgM and IgD
34
Where are nucleases only expressed ?
B-cells
35
Where are membrane bound and secreted forms of IgM expressed from ?
The same heavy chain locus
36
Where is the lambda light chain locus ?
Chromosome 22
37
Where is the kappa light chain locus ?
Chromosome 2
38
Where is the heavy chain locus ?
Chromosome 14
39
What is the organisation of heavy an light gene loci mediated by ?
VDJ recombinase enzyme, RAG1 and Rag 1 and other enzymes
40
What are variable gene regions constructed from ?
Gene regions
41
What is rearrangement/recombination of variable gene segments guided by ?
Flanking DNA/Signal sequences
42
How long are Ig domains in antibodies ?
70-110 amino acids
43
What are the steps in genetic recombination (VDJ) ?
1. D to J recombination
2. V to DJ recombination
3. Transcription and splicing
4. Translation and assembly
44
Where does genetic recombination in immunoglobulins occur ?
Developing lymphocytes including B and T cells
45
What does genetic recombination involve ?
Somatic hypermutation/recombination
46
What is each immunoglobulin composed of ?
Heavy and light chain
47
What does every heavy and light chain contain ?
Multiple copies of each gene segment (constant, variable, diversity and joining)
48
What does the light segment not contain ?
Diversity segment
49
What are the key enzymes in genetic recombination in immunoglobulins ?
Recombination activating genes 1 and 2 (Rag 1 and 2), terminal deoxynucleotidyl transferasae and a nuclease (artemis nuclease)
50
How does class switching occur ?
Changing constant regions
51
What do antibodies induce following oponisation ?
Effector responses
52
What is communication with immune system mediated by ?
Fc region
53
What is the function of Fab region ?
Antigen binding
54
What is the function of Fc region ?
1. Phagocytosis
2. ADCC activation
3. CDC activation
4. Humoral tolerance
5. IgG transport
55
What does binding of IgG to an antigen do ?
1. Immune complex formation
2. Opsonisation by antibodies
56
How do antibodies bind ?
Induced fit
57
What is antibody analysis ?
Analysing antibody sequence, structure and posttranslational modifications
58
What are the techniques used for antibody structure characterisation ?
1. Gel electrophoresis
2. Isoelectric focusing
3. Ion exchange chromatography
4. Size exclusion chromatography
5. 2D electrophoresis
59
What is the principle of X-ray crystallography ?
Scattering of xrays by electrons
60
What is a crystal ?
An arrangement of protein units which are periodic in three dimensions
61
What are some examples of protein misfolding ?
1. Alzheimers
2. Ameloidosis
62
What is the molecular make up of ameloidosis ?
Clonal plasma cells secrete light chains which then form fibrils
63
What is the most effective treament of ameloidosis ?
Melephalan and stem cell transplantation
64
What are some antibody functions ?
1. Activation of complement
2. Antibody mediated cell cytotoxicity
3. Phagocytosis
4. Opsonisation
5. Virus neutralisation
6. Receptor internalisation
7. Crosstalk with receptor signaling
65
What is the function of neonatal receptors ?
Recycle antibodies
66
What is the neonatal receptor ?
FcRn
67
What is the Fcy receptor ?
1. FcyRIa
2. FcyRIIa
3. FcyRIIIB
4. FcyRIIb
5. FvyRIIIa
68
What are the complement receptors ?
1. C1q
2. MBL
69
What receptor bins IgA and controls its activity ?
Fcalpha
70
What receptor binds IgE ?
Fcepsilon
71
What molecules are involved in binding IgA ?
Neutrophils, monocytes, macrophages, eosinophils
72
What are the processes involved in IgA binding with its receptor ?
1. Endocytosis
2. Phagocytosis
3. Microbe killing
73
What are the molecules involved in IgE binding ?
B-cells, basophils, mast cells, eosinophils
74
What are the processes controlled by receptor binding IgE ?
1. Phagocytosis
2. Microbe killing
3. Hypersensitivity
75
What does Fcy receptor bind ?
IgG
76
What are the five types of Fcy receptor ?
Inhibitory:
FcyRIIb
Activatory:
FcyRI
FcyRIIa
FcyRIIIa
FcyRIIIb
77
What cells does IgG receptor binding promote ?
1. Neutrophils
2. Monocytes
3. Macrophages
4. Eosinophils
5. Dendritic cells
6. NK cells
7. Microglia
8. Astrocytes
9. Neurons
78
What are the processes involved in IgG receptor binding ?
1. Endocytosis
2. Phagocytosis
3. Microbe killing
4. ADCC
79
What controls the activity of IgG antibodies ?
Fc gamma receptors
80
Where are type I transmembrane proteins found on ?
A wide range of immune cells and non-immune cells
81
What influences the antibody affinity and binding kinetics ?
Complex glycoproteins
82
What mediates the effector activities of IgG ?
Fc gamma receptors
83
What happens following cell activation/inhibition ?
Activation of signalling cascades leading to effector or inhibitory responses involving immuno-tyrosine activation or inhibitory motifs
84
Where is the neonatal receptor found ?
Endothelial cell, epithelial cells and antigen presenting cells
85
Where is the neonatal receptor found ?
Placenta for transport of IgG form mothers milk to the foetus
86
What is the neonatal receptor found in ?
Involved in recycling IgG and increasing serum concentration, increases half life, maintains high levels of IgG to fight infection
87
What is the complement system ?
System of plasma proteins that recognise and interact with pathogens to mark them for destruction by phagocytosis
88
What does amplification of cascade lead to ?
Activation of membrane attack complex
89
What are the main steps in complement ?
1. Oposonisation
2. Chemotaxis
3. Cell lysis
4. Agglutination
90
What are the three pathways of complement ?
1. Classical
2. MBL lectin
3. Alternative
91
How is complement activated ?
IgG binds to complement receptor C1q
92
What influences antibody mediated activation of the complement cascade ?
Glycans
93
Why can IgG-G0 react with MBL ?
No galactose
94
What do all cells need ?
1. Nucleic acids
2. Glycans
3. Proteins
4. Lipids
95
What do glycans play a primary role in ?
Immune recognition and immune evasion
96
What are some roles glycans play in biological systems ?
1. Differentiation
2. Bacterial infection
3. Ligand-receptor binding
4. Viral attachment
5. Viral entry/infection
6. Cell growth and cytokinesis
7. Cell-cell adhesion
8. Metastasis
9
97
What is glycomics ?
The systemic study of all glycan structures of a given cell type or organism
98
What is protein glycosylation ?
The post translational modification/attachment of sugars to proteins
99
What is the most abundant postranslational modification ?
Protein glycosylation
100
What are N-glycans attached to ?
Asparagines
101
What are O-glycans attached to ?
Serines and threonines
102
Where does glycosylation occur ?
ER and golgi
103
How does glycosylation work ?
Large linked lipid precursor molecule is added to polypeptide chain on asparagine residue in the sequence on Asn-X-Ser where X is any amino acid except proline
104
Where are N-glycans processed ?
In golgi and glcoproteins secreted in vesicles
105
How is quality controlled in endoplasmic reticulum ?
Calnexin and calreticulin
106
How is glucose removed from nascent polypeptide ?
Glucosiadases in ER
107
What do incorrectledly folded proteins interact with ?
UDP-glucose
108
How does immune evasion occur?
Sugars
109
How do viruses enter cells ?
Carbohydrate binding proteins
110
How do viruses bind to host cell lectins ?
Sugrads
111
What is used to treat Influenza A and B ?
Tamiflu
112
What is tamiflu ?
Neuraminidase
113
How does neuramindase work ?
Enzyme which removes sialic acids from host cell glycoproteins which new virions need to exit the cell
114
Where are glycans located ?
Fc and Fab regions
115
What are glycans critical for?
Function of the antibody
116
What does IgG0 interact with ?
MBL to activate complement
117
What does desialylation of IVIg do ?
Abrogates anti-inflammatory properites
118
What does loss of core alpha (1,6) fucose on IgG result in ?
Enhanced ADCC activity
119
What are c-type lectin receptors used for ?
Detection and activation through carbohydrate recognition
120
Where are c-type lectin receptors present ?
Dendritic cells
121
What are lectins ?
Sugar binding proteins
122
What are lectin depedent on ?
Ca +2
123
What do lectins contain ?
Carbohydrate recognition domain
124
What is the stucture of defensins ?
Have disulphide bonds which create secondary structures
125
What can anti-TNF therapies be used for ?
Autoimmune disease for example rheumatoid arthiritis
126
What is rituximab therapy for ?
Non-Hodgkins lymphoma
127
What is herceptin therapy used for ?
Her2 positive metastatic breast cancer
