HUMORAL RESPONSES (Immunogens, Antibodies, B cells) Flashcards
1
Q
Foreign substances that trigger the activation of the immune system
A
Antigens
2
Q
It was proposed that the term antigen be replaced by the term?
A
Immunogens
3
Q
Effectiveness of molecules to activate cells of adaptive immunity
A
Antigenicity or immunogenicity (interchangeable)
4
Q
The _________ of B cells and T cells only recognize specific regions of the antigen.
A
antigen receptors
5
Q
Specific regions are referred to as antigenic determinants or?
A
Epitopes
5
Q
What is the prerequiste of immunogenicity?
A
Antigens should have commnon properties that make them immunogenic
6
Q
Highly immunogenic substances are:
A
- Foreign
- Chemically complex
- High molecular weight
7
Q
Molecules that are synthesized in the laboratory may also function as antigen
A
synthetic antigens or recombinant proteins
7
Q
Foreign molecules are those that are
A
non-self
7
Q
In some disease states, the immune system responds to a particular protein in the body as if it were foreign. That is, these proteins are immunogenic even though they are not really foreign.
An example of this is?
A
autoimmunity
7
Q
Refers to the heterogeneity in building blocks that comprise the antigen.
A
Chemically complex
7
Q
These are weakly immunogenic even though they are of high molecular weight and foreign
A
Polysaccharides
7
Q
Has twenty building blocks, highly immunogenic
A
Proteins
8
Q
Most potent antigens are of?
A
High molecular weight
9
Q
This number of KD is considered nonimmunogenic
A
Less than 1 KD
10
Q
This number of KD is considered weakly imunnogenic
A
Greater than 1 KD but less than 6 KD
10
Q
Small molecules that are not immunogenic can become immunogenic when coupled to a high molecular weight protein
A
Hapten-carrier complex
10
Q
Small molecules are referred to as ______, and the high molecular weight substance is referred to as a ________
A
haptens; carrier
11
Q
Proteins have many antigenic determinants and so are called?
A
multideterminant proteins
11
Q
Complex macromolecules whose building blocks are amino acids
A
Proteins
12
Q
Macromolecules whose building blocks are repeating monosaccharide units
A
Polysaccharides
13
Q
Under some conditions, __________ are immunogenic in that they are very large and foreign.
A
polysaccharides
13
Q
Because building blocks are primarily __________ units, polysaccharides are not complex
A
repeating
14
Q
Polysaccharides of ABO antigen blood groups expressed on red blood cell surfaces are?
A
immunogenic
15
Nucleic acids in the form of ______________ and ____________are not usually immunogenic unless they are coupled to a protein
deoxyribonucleic acid (DNA); ribonucleic acid (RNA)
16
Nucleic acids are immunogenic and anti-double stranded DNA antibodies can be isolated from the patient.
Systemic Lupus Erythematosus (SLE)
16
17
Group of organic molecules that include fats and triglycerides and are components of living cells.
Lipids
18
These are molecules that are generally non-immunogenic unless they are coupled to proteins
Polysaccharides, Nucleic acids, and Lipids
19
Ranking of the Relative Immunicity of Different Types of Molecules (strongest to weakest)
1. Proteins (++++)
2. Polysacharides (++)
3. Lipids (+)
4. Nucleic Acids (+)
20
Molecules that enhance immunogenicity
- Immunization
- Adjuvant
- Alum precipitate
- Squaline
- Freud's complete adjuvant
20
A method of generating protection against infectious disease by administeringan antigen (e.g., inactivated poliovirus, hepatitis B protein).
Immunization
21
Substances that enhance the immune response to an antigen. Enhancing the action of these compounds is that it surrounds the antigen so that it is more dificult to destroy and stays in the system for a longer period of time
Adjuvant
22
Aluminum hydroxide antigen, adjuvant in human vaccines
Alum precipitate
23
A long hydrocarbon molecule present in human sebaceous gland secretions and in sharkliver oil, is a component of MF-59, an eective adjuvant used in human vaccine
Squaline
24
Water in oil emulsion and killed Mycobacterium tuberculosis, enhances immunogenicity
Freud's complete adjuvant
24
Activators of Lymphocyte
- Antigens
- Superantigens
- Mitogens
24
Adaptive immune responses to these are very specific, as are the conditions for inducing responses. These are monoclonal activators
Antigens
24
These are molecules that are typically derived from bacteria and activate subsets of T cells that have a particular common feature in the antigen receptor.
Superantigens
24
Activate a subset of T cells, but not all T cells, a few (oligo) different clones will be present in the population of activated cells, and said to be an oligoclonal activator
Superantigens
24
Polyclonal activators. Typically plant proteins that bind to molecules present on virtually all T cellsand/or B cells.
Mitogens
24
Why are Mitogens termed as polyclonal activator?
because whole populations of cells are activated and many (poly) clones are generated
24
Plant glycoproteins that activate T cells:
● Phytohemagglutinin (PHA)
● Concanavalin A (Con A)
24
Polyclonal activates both T cell and b cell
Pokeweed mitogen (PWM)
24
Has high concentrations of polyclonal activate 3 cells
Lipopolysaccharides (LPS)
24
Recap!
ACTIVATORS OF LYMPHOCYTE
- Antigens (monoclonal)
- Superantigens (oligoclonal)
- Mitogens (polyclonal)
25
These cells have antigen recognizing receptors that bind antigen but interact only withthe epitope.
T cells and B cells
25
Recognize epitopes on an intact antigen. These antigen receptors are membrane bound antibodies, more commonly referred to as membrane immunoglobulin. Recognize antigens via receptors present on their cell surface
B cells
25
Only recognize epitopes on antigen fragments bound to major histocompatibility complex
T cells
25
Can act as potent antigens when introduced into another individual
MHC molecules or MHC proteins
26
T cells recognize antigens via
Receptors referred to as T cell receptors
27
Types of MHC proteins:
- Class 1: Cytotoxic T cells
- Class II: Helper T cells
28
These proteins that play a role in immune responses. Surface of B cells or secreted by plasma cells
antibodies or immunoglobulins
28
The antibodies are synthesized without the transmembrane domain, and so they are 1released to the outside of the cell
B cells diferentiated to plasma cells
29
Expression of antibodies on a B cell surface requires the presence of a ____________ that anchors the antibody into the cellmembrane.
transmembrane sequence
30
Structure of Antibodies
- 2 identical light chains
- 2 identical heavy chains
31
These regions of the antibody molecule determine its specificity
variable regions
31
This region of the antibody molecule determine its isotype
heavy chain
31
Type of bound between light and heavy chain
covalent
31
Refers to the fact that an antibody can only recognize a precise segment of one antigen
Specificity
32
Why is antibody considered bifunctional?
Because antibodies have both an **antigen-binding domain and a separate constant region**
33
Each ________ antibody has 2 identical antigen binding site
monomeric
34
Fragment of antigen binding
Fab portion
34
Did not bind the antigen, readily crystallized
Fc portion
35
Has 3 fragments and consist of Fab and Fc portions
Papain
35
Has one major fragment. Two Fab binding sites in a single structure or unit and the Fc portion of the antibody was degraded
Pepsin
36
Subsequent studies demonstrated that the _________ of antibodies is required for antibodies to mediate their biological function but not for antigen binding
Fc portion
36
Different sets of antibodies bind to the same epitope with different binding strength. One antibody will have better goodness of fit
Avidity
37
Antibodies secreted by one plasma cell can bind similar but not identical epitope
Cross reactivity
37
All antibodies secreted by a given plasma cell will have
same specificity
38
Antibodies secreted by one plasma cell have a specificity that is _______ from the specificity of antibodies secreted by another plasma cell
different
39
The binding between antigen and antibody involves a number of different types of attracting forces, including:
- hydrophobic interactions
- electrostatic interactions, and
- van der Waals forces
39
Non-covalent interactions between antigen and antibody must be _______ to one another. This is the basis of antibody specicity.
complementary (Primary interactions)
40
Primary interactions include:
Hydrophobic, hydrophilic, affinity, and avidity
40
Allow non-polar to react. Van der Waals
Hydrophobic interaction
41
The association constant between antibody and a univalent antigen represents the anity of an antigen-binding site for that antigen
Affinity
41
By which polar molecules interact (e.g., ionic bonds, hydrogen bonds)
Hydrophilic interactions
41
A measure of the overall binding between the antigen binding sites and multivalent antigen
Avidity
41
Interactions with a soluble antigen leads to _________. While, interactions with a particulate antigen leads to ___________.
Precipitation; agglutination
42
Occurs when the antigen is multivalent
Secondary interactions
43
When the immune complexes become too large to remain soluble, they _________ out of solution. A correct proportion of ___________is required to induce precipitation.
precipitate; antigen and antibody
44
In precipitation reactions, Divalent antibodies ____ and multivalent antibodies _____ can be cross-linked by multivalent antigens to form immune complexes
IgG; IgM
45
Can occur in solution and semisolid media (agar gels)
Precipitation reactions
45
Multivalent antigen is particulate and is mixed in appropriate proportion of antibodies
Agglutinin reactions
45
Antigen or antibodies are in excess:
no agglutination
46
Identify the Antibody: γ
- General form: Monomer
- Serum concentration (mg/dL): ~1200
- Molecular weight: ~150 KD
- Protein atachments: (-)
- Distribution: vascular (intra and extra)
- Subclasses: 4
- Complement activation (Classical pathway): (+) except ___
IgG; except IgG4
47
Identify the Antibody: ε
- General form: Monomer
- Serum concentration (mg/dL): negligible
- Half-life in serum: ~2 days
- Molecular weight: ~200 KD
- Protein atachments: (-)
- Distribution: FCER on mast cells, basophils
- Subclasses: (-)
- Complement activation (Classical pathway): (-)
IgE
48
Identify the Antibody: µ
- General form: Pentamer
- Serum concentration (mg/dL): ~150
- Half-life in serum: ~5 days
- Molecular weight: ~900 KD
- Protein atachments: J chain
- Distribution: vascular (intra)
- Subclasses: (-)
- Complement activation (Classical pathway): (+++)
IgM
49
Identify the Antibody: α
- General form: Monomer, Dimer
- Serum concentration (mg/dL): ~100
- Half-life in serum: ~5.5 days
- Molecular weight: ~160 KD (monomer)
- Protein atachments: J chain secretory piece on mucosal ____
- Distribution: vascular (intra) + mucosa
- Subclasses: 2
- Complement activation (Classical pathway): (-)
IgA
50
Identify the Antibody: δ
- General form: Monomer
- Serum concentration (mg/dL): Neglible
- Half-life in serum: N/A
- Molecular weight: ~180 KD (monomer)
- Protein atachments: (-)
- Distribution: membrane (naïve B cells)
- Subclasses: (-)
- Complement activation (Classical pathway): (-)
IgD
51
What are the antibodies present in breast milk/colostrum?
IgG (+) and IgA (+++)
51
The only antibody that can cross placenta
IgG (++)
51
What are the subclasses of IgG and their half-lives
- IgG 1, 2, 4: 21 days
- IgG3: 7 days
52
What are the antibodies that can activate complement (classical pathway)
IgM and IgG
53
These antibodies are present, in their monomeric form, on the surface of naive B cells (B cells that have never been activated)
IgM and IgD
54
Light chains of an antibody
Lambda & Kappa
55
Types of heavy chains isotype in an antibody
- IgM
- IgG
- IgA
- IgE
- IgD
55
Referred to as natural isohemagglutinins
IgM antibodies
56
What cells secrete the pentameric form of IgM?
Antibody secreting plasma cells
(from naive B cells activated by antigens)
57
One of the principal biological functions of IgM is the?
activation of the classical pathway of complement
57
Antibodies to the blood group antigens, ABO, are of the
IgM isotype
58
The first antibody produced in an infection, and plays an important role in host defense
IgM
58
Complement Activation by _____, bound to antigen is the most efficient activator of complement through its interactions with Cl.
The efficacy of IgM as an activator of complement resides in its _________, which allows a single IgM to bind Cl
IgM; pentameric structure
59
AB incompatibility is not a problem for mother-fetus interactions because?
IgM antibodies do not cross the placenta
60
T/F:
Antibodies to the bacterial antigens cross react withblood cells
TRUE
61
These antibodies are found primarily in mucosal secretions, including mucus, tears, saliva, and colostrum nursing mothers
IgA
62
**Small amounts** of these are found in serum. Some of these antibodies are released into the circulation by entering different lymphatics, while others migrate to the basolateral side of the epithelial cells that line mucosal tissues
IgA
63
Activation of B cells leading to IgA production (monomeric or dimeric) occurs primarily in the?
mucosa-associated lymphoid tissues (MALT)
64
Its iaggregated form can activate the alternative pathway of complement
IgA
64
Because a piece of secretory component remains attached to the IgA, the antibody, it is referred to as?
secretory IgA
64
At the mucosal surface, the secretory component is cleaved such that a small piece remains attached to the _________when the antibody is released into the lumen
dimeric IgA
65
Targets organisms for Natural Killer Cells and serves a protective role by **neutralizing the virus**
IgG
65
Its three major roles in host immunity include:
1) Activation of the classical pathway of complement
2) Opsonization: targeting of microorganisms for phagocytosis by neutrophils and macrophages by acting as an opsonin
3) Targeting virally infected cells for destruction by antibody-dependentcell mediated cytotoxicity (ADCC)
IgG
65
Crucial for fetal immunity because these antibodies cross the placenta
IgG
65
Serves as a neutralizing antibody because it binds to microbes in the lumen and prevents their attachment to their cell target
Secretory IgA
65
Its serum concentration is higher than that of any other antibody isotype
IgG
65
Negligible in serum (decrease amount). These antibodies are particularly important for effective immune responses to some parasites, particularly helminth infections in the gastrointestinal tract
IgE
65
The placental transfer of antibodies confers protection to the newborn for about○ six months because the half-life of most IgG subclasses is about?
three weeks (IgG3 half-life is only 7 days, while IgG1,IgG2, IgG4 are 21 days)
65
This triggers the complement system, which leads to the destruction of fetal red blood cells. Severe hemolytic anemia can occur
Ability of IgG to cross the placenta
66
Subclass of IgG that does not activate the complement
IgG4
66
When the _________ binds to the FceR on eosinophils, the eosinophil releases major basic protein, a protein that is cytotoxic for helminths
parasite/IgE complex
66
IgE antibodies bind to cells that express _____, including ________, ________, and ________
FceR; eosinophils, mastcells, and basophils
66
Induced by **mast cell** and **basophil degradation** following cross-linking of IgE by helminths
Histamine release
67
The release of this causes local muscle spasm, which is felt to be important in the expulsion of the infectious organisms from the body
Histamine
68
Previously known as the **reaginic antibody**
IgE
68
The antibody responsible for allergies and anaphylactic shock
IgE
68
The only antibody isotype in which its role remains **elusive**
IgD
68
Trace amounts of IgD found in serum likely represent IgD that has been released from _______, and not IgD secreted from _________
dying cells; plasma cells
68
Unique differences within the constant region of the y and a heavy chains, and kappa light chains present in different individuals
Allotypes
