3 - Antigens and antibodies Flashcards
(93 cards)
1
Q
What is important to remember about this section?
A
It consists of features and properties of the ADAPTIVE IMMUNE RESPONSE, not the innate immune response
2
Q
Case study - What occurs in a B lymphocyte immunodeficiency?
A
B lymphocyte immunodeficiency
- Prevents production of antibodies
- Antibodies can be measured in the blood by IgG antibody titers
3
Q
What is the treatment for a B lymphocyte immunodeficiency?
A
Treatment
- Monthly prophylactic doses of intravenous immunoglobulin (IVIG)
- This is a polyclonal immunoglobin obtained from a batch of “pooled plasma samples”
- 50,000 plasma donors contribute to the polyclonal immunoglobin
- This provides a wide array of antibodies in the immune system
4
Q
How effective is the treatment for a B lymphocyte immunodeficiency?
A
The patient’s IgG antibody titers against a common bacterial pathogen were measured before and after treatment…
- Before treatment = 32 antibodies
- After treatment = 8,192 antibodies
5
Q
In the adaptive immune response, are antibodies made for one specific antigen or can they bind to many different antigens?
A
Adaptive immune responses are exquisitely specific
- Antibodies are very specific and can only detect one antigen
- This specificity is very important in the immune response
6
Q
What causes the specificity of the adaptive immune response?
A
Specificity is due to lymphocytes having membrane receptors
- Each lymphocyte has just one receptor
- A lymphocyte is a type of agranule white blood cell (leukocyte)
7
Q
What is a lymphocyte?
A
A lymphocyte is any of 3 types of white blood cell in the immune system - all 3 are agranulocytes
- Natural killer cells (NK cells): function in cell-mediated, cytotoxic innate immunity
- T cells: for cell-mediated, cytotoxic adaptive immunity
- B cells: for humoral, antibody-driven adaptive immunity
Lymphocytes are the main type of cell found in lymph, which prompted the name lymphocyte
8
Q
What is an epitope/determinant?
A
Epitope/determinate
- The part of an antigen that is recognized by the immune system, specifically by antibodies (B cells or T cells)
- It is the specific piece of the antigen that an antibody binds to
9
Q
Is the immune response faster and more vigorous on the first exposure to an antigen or upon re-exposure?
A
Re-exposure
10
Q
Why will numerous exposures to an antigen allow for a faster and more vigorous immune response?
A
Due to the presence of memory cells
- Memory cells allow the immune system to be more sensitive to stimulation by antigens than antigen-naive lymphocytes would be
- This is called immunologic memory
11
Q
What does immune system diversity mean?
A
The immune system has a very high diversity
- The body has pre-existing antigen-specific lymphocytes that are capable of reacting to 1x109 antigens
12
Q
What accounts for the great diversity of the immune system?
A
The great diversity of the immune system is due to…
- The expression of cell surface receptors that can react with a diverse number of antigens
13
Q
Describe the process of lymphocyte maturation and its contribution to diversity
A
Process
- Lymphocyte clones mature in generative lymphoid organs in the absence of antigens
- Clones of mature lymphocytes that are specific for a diverse population of antigens enter the lymphoid tissues
- At this point, the lymphocyte can respond to many different antigens due to different, specific receptors on its surface
- Antigen specific clones are exposed to an antigen and are then activated or “selected” for that antigen
- An antigen-specific immune response will occur
14
Q
What are the 3 reasons that immune responses become less intense over time?
A
Decreased intensity due to…
- Removal of antigen, therefore no further immunologic stimulation
- Activated lymphocytes dying within a short period of time by apoptosis
- Regulatory immune mechanisms
15
Q
What is important about the self-regulating property of the adaptive immune system?
A
Self-regulation
- The immune system needs to be very tightly regulated
- Rise up, take care of the problem, go back to “sleep” until we need you again
- Self vs. Non-self: the immune system is “educated” to know this
16
Q
How does the immune system discriminate between “self” and “non-self”?
A
Self vs. non-self
- Adaptive immune responses are directed normally against foreign antigens, not self-antigens
- The immune cells specific for “self” are usually destroyed or regulated
- Autoimmune diseases occur when discrimination is lost
17
Q
A
18
Q
What does immunogenicity mean?
A
Properties that promote an immune response
19
Q
What does adjuvant mean?
A
Immunogenicity is high
- This prolongs retention so that a more vigorous immune response is able to occur
20
Q
What are some common adjuvants?
A
- Alum
- Mineral oil
- Lipids
21
Q
What does antigen mean?
A
Antibody generating substance = antigen
- Note that an immunogen is technically different than an antigen, but they are ususally used interchangeably
22
Q
What does antigenicity mean?
A
Properties that allow a substance to react with an antibody
- This is loosely used to desribe an immunogen
23
Q
What is a hapten?
A
Haptens
- Small molecules that cannot induce antibody formation, but canreact with an antibody that is specific for it
- Haptens mus be coupled to a carrier molecule to induce antibodies
- Therefore, a hapten is an antigen, but not an immunogen
- Antibody response = immunogenic
- No antibody response = not immunogenic
24
Q
What is the size range for the best immunogens?
A
25
What does the complexity of an immunogen relate to?
Internal complexity of immunogens
* More complex means more immunogenic
26
What must occur for an immunogen to degrade?
Degradability
* Immunogen processing must occur before an immunogen can degrade
27
How do immunogens display the property of foreignness?
Foreignness
* Tolerance to self-antigens
* An object must be foreign for the immune system to mount an attack against it
28
Where are immunogens found?
Immunogens are accessible
* Found in easy-to-reach areas called immunodominant areas
* NOT burried, but rather easily accessible
* More likely to induce an immune response this way
29
What is an epitope again? AKA determinant
* The part of an **antigen** that is recognized by the immune system, specifically by antibodies (B cells or T cells)
* It is the specific piece of the antigen that an antibody binds to
30
What is a conformational determinant or conformational epitope? (two names for the same thing)
Conformational determinants/epitopes
* This exists when the part of the antigen that binds to the antibody is formed by an amino acid residues from *different* *parts* of the protein (brought together in 3D space on the antigen)
31
What is a linear determinant or a linear epitope?(two names for the same thing)
This exists when the part of an antigen that recognizes and binds to an antibody (epitope/determinant) is formed by adjacent amino acids on the protein (the antigen)
32
What is a neoantigen?
"New antigens" formed by proteolysis, phosphorylation, etc.
* Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids
33
T lymphocytes can _only_ recognize a certain type of determinant on an antigen. Which type is it?
_Linear_ determinants
34
What type of antigens are detected by antibodies that are generated against intact proteins?
* **Most** antibodies that are generated against _intact proteins_ will recognize _conformational determinants_
* But **some** of the antibodies might recognize a _linear peptide_ fragment of the _original protein_
35
What is the source of _protein_ antigens?
Proteins from the serum, microbes
36
What is the source of _lipoprotein_ antigens?
Cell membranes
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What is the source of _polysaccharide_ antigens?
Bacterial capsules
38
What is the source of _nucleic acid_ antigens?
Cells, microbes
39
What is the most common type of antigen that the body is exposed to?
A _protein_ antigen
40
Which type of antigen is the most immunogenic?
_Protein_ antigens
41
What is some general information regarding antibodies/immunoglobulins?
Antibodies/immunoglobulins:
* Terms are used _interchangeably_
* They are present in the body in "humors"
* The specificity of antibodies/immunoglobulins is similar to that of enzymes and their substrates
* They do _NOT_ present until stimulated by an antigen
42
What is the role of glycoproteins in antibodies/immunoglobulins?
Glycoproteins mediate the biological effects of antibodies/immunoglobulins by _binding to antigens_ in a very specific manner
43
Where do we find antibodies?
Locations:
* Surface of _B lymphocytes_ (antigen receptors)
* Each B lymphocyte expresses **ONE** specificity
* Antigen-naive B lymphocytes have both IgM and IgD
* _Blood plasma_ and _tissue fluids_ contain large amounts of antibody
* Surface of _mast cells/basophils_ contain receptors for IgE antibodies
* _Secretory fluids_ (mucus and milk)
44
What is "anti-serum"?
Antibody-containing serum
* Serum is the fluid portion of the blood after the cellular elements have clotted
* Polyclonal antiserum refers to the _population_ of antibodies
45
What is polyclonal antiserum?
Polyclonal antiserum refers to the _population_ of antibodies which collectively can bind to more than one particular antigen
46
What is an "antibody titer"?
Antibody titer
* Reciprocal of the last dilution of antiserum that still yields a demonstrable antibody binding reaction
47
What is an example of an antibody titer?
Antibody titer problem example
* An assay which measures antibody binding to an antigen gives a demonstrable reaction at an antibody dilution less than or equal to 1:32, but not a dilution of 1:64.
* What is the titer of the antibody? **1:32**
48
How will electrophoretically separated proteins migrate?
These proteins will migrate _within bands_
* *Most* antibodies are found in the gamma fraction
* These are called "_gamma globulins_"
* *Some* antibodies are found in other bands, so "immunoglobulin" is a more accurate term
* "_Immunoglobulin_" is synonymous with "_antibody_"
49
What is the basic structure of an antibody?
Structure
* All antibodies have 2 identical heavy chains and two identical light chains
* Heavy chains are connected together by covalent disulfide bonds
* Light chains are connected to heavy chains by disulfide bonds to form the _antigen binding site_
50
What are constant and variable (V) regions of antibodies?
Heavy and light chains are composed of constant and variable (V) regions
* This alters the amino acid sequence in V region for different antigen specificities
* Heavy and light chain variable regions form the antigen-binding site, which is specific to one antigen
51
What are the two regions that an antibody is divided to?
Two regions
* Hypervariable region
* Framework region
52
What is the hypervariable region of an antibody?
Hypervariable region
* The regions on each chain that form the binding surface
* There are variable amino acids in the hypervariable region that allow for different antigen specificities
* You can think of an antibody as a hand holding up three fingers... The hypervariable region would be the finger tips that will actually touch (bind) to things
53
What is the framework region of an antibody?
Framework region
* The framework region of an antibody supports the hypervariable region
* You can think of the framework region as the fingers of an antibody that support the finger tips (hypervariable region)
54
What is a "hinge region"? What type of antibodies have this region?
IgG, IgA and IgD (all different isotypes of antibodies)
* These three isotypes have hinge regions
* A hinge region is the flexibility of the antibody arms
55
The antibody isotypes are able to express themselves in two forms... What are they?
Two forms
1. Secretory form
2. Membrane form
Note that the _IgD ONLY has a membrane-bound form_
56
What is a J chain? What types of antibodies have this?
J-chain
* Secretory forms of _IgM_ and _IgA_ have a J chain
* This allows for the formation of _pentamers of IgM_ and dimers or _trimers of IgA_
57
What is isotype switching?
Isotype switching
* Allows a single antigen specificity to be used for different biological functions
* A biological mechanism that changes a B cell's production of immunoglobulin (antibodies) from one class to another, such as from the isotype IgM to the isotype IgG
58
Describe the proteolysis of antibodies in **pepsin** digestion and **papain** digestion
59
How do we classify antibodies?
Antibody classification
* Antibodies can be divided into classes or isotypes based on differences in the _amino acid sequence of their heavy chains_
60
What isotypes of antibodies exist?
Isotypes
* Isotypes or classes of antibodies include:
* Immunoglobulin G (IgG)
* Immunoglobulin M (IgM)
* Immunoglobulin A (IgA)
* Immunoglobulin D (IgD)
* Immunoglobulin E (IgE)
* Each type of antibody mediates a **different biological effect**
* Each heavy chain is denoted by the Greek letter of its class (gamma, mu, alpha, delta, elipson)
61
Certain classes of antibodies are divided into subclasses... What are they?
IgG
* IgG1
* IgG2
* IgG3
* IgG4
IgA
* IgA1
* IgA2
62
Which antibody isoform is the most abundant?
* IgG is the most abundant immunoglobulin in normal serum because they have a _longer half-life_
63
What is the secretory form of IgG
64
How does IgG activate complement?
IgG activates complement by the classical pathway
* Recall that the complement system is a part of the immune system that helps or "complements" the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system
65
Which subforms of IgG can opsonize to enhance phagocytosis?
IgG1 and IgG3
* Opsonize
66
How does IgG facilitate antibody-dependent cell-mediated cytotoxicity (ADCC)
IgG can coat tumor cells or virus-infected cells to facilitate antibody-dependent cell-mediated cytotoxicity (ADCC)
67
How does IgG convey protective immunity to the fetus?
IgG has the ability to cross the placenta in order to convey protective immunity to the fetus
68
How abundant is IgM?
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What is the secretory form of IgM?
Pentamer
70
Which is a better activator of complement, IgM or IgG?
IgM
71
Which antibody isoform is the predominate form produced in a primary immune response?
IgM
72
Which antibody isoform is the predominant antibody produced in a secondary immune response?
IgG
73
How abundant is IgA?
IgA accounts for 15% of the total serum immunoglobulins
74
Which antibody is the "mediator" of mucosal immunity?
IgA
75
Where is IgA found?
Tears, saliva, colostrum and milk
76
What is the chemical form of IgA?
IgA is found as a _monomer in serum_ and as a _dimer in secretions_
77
How is the IgA dimer held together?
By a J-chain (similar to IgM)
78
What type of response will IgA partake in during a parasitic infection?
IgA partakes in an eosinophil-mediated ADCC of certain parasitic infections such as helminths (i.e. worms)
79
How is IgA transported?
IgA is transported through mucosal cells
80
How is IgA protected from proteolytic enzymes?
IgA is coupled to "secretory piece" to protect IgA from proteolytic enzymes and act as a "glue" to bind it to the mucus
81
What is "secretory piece" derived from?
"Secretory piece" is derived from the epithelial cell Fc receptor that binds to IgA
82
How abundant is IgE?
Less than 2% of the total serum immunoglobulins are in the isoform of IgE
83
What chemical form is IgE secreted as?
IgE is secreted as a monomer
84
How does IgE partake in a parasitic immune response?
IgE partakes in the eosinophil-mediated ADCC of certain parasites (e.g. worms)
85
How does IgE
86
How abundant is IgD?
IgD is found in very low concentrations in the serum
87
On which lymphocyte is IgD primarily found?
IgD is primarily found on the surface of antigen-naive B lymphocytes along with IgM
88
What is IgD important for?
IgD is important for the transduction of signals across the plasma membrane
89
What does affinity mean?
Affinity
* The strength of binding for antigen of _one_ antigen combining site, i.e. one arm of an antibody
* IgG has great affinity than IgM
90
What is an affinity maturation?
Affinity maturation
* The average affinity for a population of antibodies will increase with repeated immunization with an antigen
91
What does avidity mean?
Avidity
* The overall strength of attachment which takes into account how many antigen combining sites the antibody has bound to
* IgM has greater affinity than IgG
92
What is an allotype?
Allotype
* Differences in the constant regions of antibodies (of the **same isotype**) between individuals due to the presence of multiple alleles of the constant region genes in the human population
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What is an idiotype?
Idiotype
* Collection of hypervariable regions contributed by heavy and light chains that form the antigen-binding site
