Week 5: Adaptive Immunity - Antibodies Flashcards
1
Q
What is the Ig generator?
A
An atigen
2
Q
How many antibodies can the human body produce?
A
Limitless
3
Q
What are the functions of an antibody?
A
Helps to clear the body of extracellular pathogens and toxins and infected or transformed
Are specific and only bind to one epitope on an antigen
4
Q
What do TD antigens generate?
A
- Low affinity IgM antibodies (early)
- High affinity, isotope switched antibodies (late)
- Long lived plasma cells
- Memory cells
5
Q
What do TI antigens generate?
A
- Short lived plasma cells
- Low affinity IgM antibodies
6
Q
Describe the regions of an antibody?
A
- Region that interacts with the antigen (variable)
- Region that interacts with the components of the immune system
7
Q
What are antibodies?
A
Recognize and bind antigen and deliver the bound antigen to other components of the immune system where it is eliminated
8
Q
What are the 5 isotopes of antibodies?
A
IgG, IgM, IgD, IgA, IgE
9
Q
What are the components of an antibody?
A
- Glycoproteins
- Polypeptide chains
10
Q
What is an antibody arm comprised of?
A
Each arm of the chain is made of a complex light chain paired covalently linked with the amino terminal part of a heavy chain by a disulfide bond
11
Q
What is an antibody stem comprised of?
A
2 carboxyl terminal portions of the heavy chains linked together by disulfide bonds
12
Q
What are types of antibody polypeptide chains?
A
- 2 indexical heavy chains
- 2 identical light chains
13
Q
What provides the diversity of antibodies?
A
Variable region
14
Q
What are the components of the antigen binding site?
A
1 heavy and 1 light chain variable region
15
Q
How many antigen binding sites are of an antibody?
A
2 identical sites shaped in a Y
16
Q
What has limited variation in the aa sequence between antibodies?
A
Constant region
17
Q
What is the difference between constant and variable region?
A
C: Meditate the effector functions of the antibody and this region differs between antibody claseses
V: provides diversity of antibodies
18
Q
Describe the fragments of an antibody?
A
- Hinge region is cleaved by protesases, provides flexibility for both arms to bind to antigen
- 2 indexical Fab fragments
- Stem fragment Fc protion
19
Q
What do Fab fragments bind to?
A
Antigen-fab
20
Q
What makes isotopes different from one another?
A
variable domains and Ch chains are unique
N-linked carb groups
21
Q
What is the purpose for Class switch recombination/isotype switching?
A
mediated by cytokines and Replacing the heavy chain constant regions
22
Q
What are the light chain isotopes?
A
kappa and lambda
23
Q
How are light chains generated?
A
During pre-B cell stage of development than can be edited during immature stages of B cell development
24
Q
What is the difference and ratio between kappa and lambda?
A
No differnece
60:40 respectively
25
Describe the components of IgG?
1. Fab=Vh and Fab=VH and CH1 and VL and CL domains
2. Each Fab can bind 1 molecule of antigen
3. The effector functions of antibodies depend on the structures of their CH domains in the Fc fragment.
4. The Fc fragment has 2 disulfide linked heavy chains (CH2 and CH3).
26
What is the purpose of Fc region of IgG?
mediates the opsonization activity of IgG antibodies by binding them to Fc receptors on phagocytic cells
27
How do Ch3 and Ch4 differ between membrane-bound and secreted forms?
1. Region that binds to the Fc receptor on other cells
2. Ch4 is present of IgM and IgE
28
Where are hypervariable regions found?
V domain
29
What forms the antigen binding site?
The pairing of a heavy and light chain in the variable region brings together these hypervariable regions
30
How do the 3 HV regions differ from one another?
Creates the specificity and diversity of the antigen binding sites
31
What is another name for the 3 HV loops?
complementarity-determining regions (CDR1, CDR2, and CDR3) since they provide a binding surface complementary to the antigen
32
What type of binding is receptor ligand?
Noncovalent
33
Describe antigen and antibody interactions?
1. Each individual bond may be weak but in total deliver a strong binding affinity
2. Antigen-binding sites have increased amounts of aromatic amino acids that interact through VDW and hydrophobic interactions with the antigen
34
What is affinity?
The binding strength of the antibody to its epitope
35
What make antibodies most effective?
High affinity to their antigens
36
What are the antibody mediated effector functions?
1. Neutralization of pathogens and toxins
2. Aggrulination of particle antigens
3. Opsonization
4. Complement activation
5. Antibody- dependent cell mediated cytotoxicity
6. Degradation
37
What is the neutralization of antibodies?
Protects against viral or bacteria infections or the damaging effects of toxins generated by pathogens
38
How are neutralization antibodies preform?
1. Formed against medications limiting efficacy
2. Bind to antigens on pathogen that are used to bind to human cells to gain entry
3. Rapidly dividing microbes and genetic variants of pathogens may evade neutralizing antibodies
4. Antibodies bind to pathogens or toxins and prevent the pathogen from infecting or harming cells
39
What is capable of neutralization?
All Ig
40
How is influenza neutralized?
Antibocy would bind to hemagglutinin preventing binding to glycoproteins on epithelial cells
Influenza virus has many variants that limit the neutralizing antibody response
41
What can neutralize microbial toxins and animal venoms?
High affinity IgG and IgA
42
Many diseases are caused by what?
Bacterial toxins
43
Describe the process of agglutination?
1. Enhances neutralization and more efficient clearance of pathogens from the body
2. Antibodies have at least 2 antigen binding sites that can bind and crosslink multiple pathogens causing them to clump together
3. Enhances clearance by phagocytosis or physiological methods
44
What is agglutination used for?
Laboratory testing-combs test for ABO blood typing
45
Describe the process of opsonization?
1. To make tasty
2. Antibodies act as opsonin and flag the pathogen to promote engulfment by phagocytes
3. Fc receptors on macrophages or neutrophils bind to the Fc portion of antibody and cause phagocytosis
46
What is the difference between FcaR and FcyRs?
FcaR: recognize Fc of IgA bound to antigen
FcyRs: recognize of IgG bound to antigen
47
Describe complement dependent cytotoxicity?
1. Pentameric IgM or 2 IgG bound to antigen is necessary to activate the classical complement cascade
2. Pathogen marked by antibody is eliminated by the MAC by creating pores in the pathogen and causing lysis
3. Pathogen can also be marked by C3b for opsonization
48
Describe the complement function of antibody effectors?
1. Immune complexes can form between antibodies bound to soluble antigen
2. ICs can cause local inflammation and must be cleared
3. Activation of complement can assist with removal by the deposition of C3b
49
What is CR1 on erythrocytes do?
Contribute to the removal of these ICs from circulation by binding C3b and then transporting the IC to the spleen or liver for removal
50
What are the functions of Fc receptors on liver and spleen macrophages?
Bind to Fc portion of the antibody within the IC and degrade the IC without destroying the erythrocyte
51
Describe the function of antibody dependent cellular cytotoxicity (ADCC)?
The Fc portion of an IgG antibody bound to the surface of a cell/pathogen interacts with Fc receptor on immune cells such as macrophages, NK cells, and neutrophils triggering the immune cell to target the antibody coated cell for lysis
52
What is ADDC commonly seen in?
Monoclonal antibodies
53
What are the requirements of ADCC?
1. Cell to cell contact
2. FcgRIII is an Fc receptor on NK cells that recognizes IgG
3. Lytic granules contain perforin and granzyme
54
What is perforin?
Pore forming protein that allows entry of granzyme
55
What is granzymes?
Serine proteases that cause mitochondrial and DNA damage that results in apoptosis of the target cell
56
Describe the process of degranulation?
1. Mediated by Fc receptor on granulocytes binding to Fc portion of antibody
2. FcεRI is expressed on mast cell/basophils and eosinophils
3. Mediated by IgE antibodies
4. Triggers signaling that causes degranulation releasing histamines, proteases, and other inflammatory mediators
57
Where is degranulation found in?
Type 1 hypersensitivity reactions and in response to parasitic infections
58
What are the forms of Ig?
1. Membrane bound
2. Secreted as soluble antibody
59
What is the difference between membrane bound and secreted as soluble antibody?
M: serves as an antigen receptor on naive B cells
S: heavy chain carboxyl terminus of heavy chain undergoes RNA splicing to remove hydrophobic anchor
60
What is different about the 1st Ig produced during primary immune response?
Tend to be low affinity antibodies
61
What produces IgM?
B2 and 1 cells
62
What produces IgM?
B2 and 1 cells
63
What is the largest Ig?
IgM
64
Describe the structure of IgM?
1. 4 Ch domains
2. No hinge region
65
What is the structure of surface IgM?
Monomeric
66
What is the structure of secreted IgM?
Pentamer
1. Held together by J chain and intersubunity disulfide bods
2. Contains the 10 antigen binding sites
3, Half-life of 10 days
67
What is the function of IgM?
1. Activates classical complement cascade (opsonization and lysis by mac)
2. Clear circulating antigen by neutralization and agglutination
68
Describe the characteristics of IgD?
1. 3 Ch3 domains
2. Little found in serum
3. Half-life of 3 days
69
Where is IgD found?
Secretions of the upper respiratory tract
70
What is the function of IgD?
1. Serves as an antigen receptor on mature B cells
2. Binds to antigen then to basophils and mast cells resulting in the release of antimicrobial peptides to attack pathogen
71
Describe the characteristics of IgG?
1. Longest serum half-life (21 days)
2. Can cross the placenta and protect fetus
3. Pass through endothelium and protect tissues
4. Bind to the Fc receptors n phagocytes and NK cells (ADCC and opsonization)
72
What is the function of IgG?
1. Serve as an opsin
2. Activate classical complement cascade
3. Clear circulating soluble antigen (neutralization)
4. Provide host defense at mucosal surfaces
73
What is the most abundant Ig in the serum?
IgG
74
How do IgG subclasses differ?
1. Size of hinge region and the number and position of interchain disulfide bonds
75
What is the purpose for a flexible hinge on the IgG?
Allows Ig to bind both arms to different antigen arrangements on pathogen surfaces and alter proteolytic cleavage susceptibility
76
What are the seecreted IgA forms?
Monomers: serum IgA1
Dimers: secretions-IgA2
77
What stabilizes IgA dimers?
J chain with intersubunit disulfide bonds
78
What are the characteristics of IgA?
1. 3 Ch domains
2. 6 day half-life
3. Can be transported across the epithelium
4. Highly gycosylated: allowing them to associate with mucous layer
79
What is the function of IgA?
1. Provide host defense at mucosal surfaces (neutralization, opsonization, agglutination)
2. Provides protection from organisms that target these mucosal areas by binding to them and preventing their attachment to cells
3. Facilitate pathogen expulsion in feces, sputum, tears, and other secretions
80
What are the characteristics of IgE?
1. 4 Ch domains
2. No hinge
3. Half life of 2 days
4. Only works as a cell-surface receptor
81
What is the function of IgE?
1. Provides a mechanism for rapid ejection of parasites and other pathogens from the body
2. pathogen binds to 2 or more IgE on mast cells/basophil/eosinophil, this leads to secretion of mediators that act on smooth muscle to cause sneezing, vomiting, coughing, and diarrhea to eject the pathogen.
3. Mediate allergic reaction by promoting mast cell and basophil degranulation
82
What Ig is secreted by plasma cells and quickly binds to the Fc receptor (FCeRI)? What receptors?
1. IgE
Mastcells (connective tissue), basophils (blood), activated eosinophils (mucosal surfaces)
83
What is the Primary antibody found in secretions such as saliva, mucus, sweat, colostrum, milk, gastric fluid, and tears?
IgA
84
What is the first class of antibodies made by B cells?
IgM
85
What are the limitations of IgM?
It is a bulky pentameric
86
What is isotope class switching?
The change from the expression of IgM and IgD to the expression of one of the other types of Ig isotopes and only occurs during an active immune response
87
What changes in isotope switching?
Ch region of the heavy chain
88
What stays the same in isotope switching?
1. L chain
2. Vh and Vl regions of the Ig (determine specificity)
3. antibodies will all have the same specificity for the same antigen
89
Is class switching reversible?
Irreversible
90
What is the order of class switching?
IgM -> IgG -> IgE
91
How can a Mother provide protective antibodies to their young before and after birth?
Before: IgG can cross through placenta to fetus
After: Dimeric IgA is found in secretion (breast milk)
92
What antibody does a fetus make before birth?
IgM
93
How long can infants produce IgG postnatal?
3-4 months
94
What is the half-life of IgG?
3 weeks
95
When will material IgG be catabolized?
21 weeks (5 months)
96
What happens to the infant if the mother is cleared of antibodies?
Infant is able to make its own Igs
97
Compare the amount of IgG in an adult and infant
Equivalent amount
