Laboratory Activity 3a – Basic Concepts of Antigen, Antibody, and Complement Flashcards
1
Q
A substance with the ability to combine with an antibody
A
ANTIGEN
2
Q
• The ability of the antigen to react specifically with the antibodies or cells it provoked
A
Specific Reactivity
3
Q
• The ability to provoke an immune response by stimulating the production of antibodies, proliferation of specific T cells, or both
A
Immunogenicity
4
Q
• Substance that is capable of inducing an immune response
A
Immunogen
5
Q
• No immunogenicity but has reactivity
A
Hapten
6
Q
Two (2) kinds of haptens :
A
o Simple or nonprecipitating
o Complex or precipitating
7
Q
Can combine with antibody; cannot produce precipitates
A
o Simple or nonprecipitating
8
Q
Can combine with the antibody; produces precipitates
A
o Complex or precipitating
9
Q
• Larger molecules attached to haptens that confer new antigenic specificities
A
Carrier/ Schlepper Molecules
10
Q
o Capable of stimulating antibody synthesis in the host and can also react with homologous antibodies
A
Complete antigen
11
Q
o Bacterial cells and proteins
A
Complete antigen
12
Q
o Cannot by themselves stimulate an immune response
A
Hapten/Incomplete Antigen
13
Q
o Can react specifically with homologous antibodies
A
Hapten/Incomplete Antigen
14
Q
• Substance produced in response to antigenic stimulation that is capable of specific interaction with provoking immunogen
A
ANTIBODY or IMMUNOGLOBULIN (Ig)
15
Q
ANTIBODY or IMMUNOGLOBULIN (Ig) General functions:
o Neutralize (?)
o Facilitate (?) and kill microbes
o Combine with antigens on cellular surfaces and cause the destruction of these cells either (?) (outside of the blood vessels within the mononuclear-phagocyte system) or (?) (within the blood vessels through the action of the complement)
A
toxic substances
phagocytosis
extravascularly; intravascularly
16
Q
o A four-chain polypeptide unit that consists of two (2) heavy chains and two (2) light chains held together by disulfide bonds
A
Basic structure
17
Q
4 polypeptide chain:
• 2 heavy chains: each consists of about _____ amino acids
• 2 light chains: each consists of about _____ amino acids
A
450
220
18
Q
are always of the same type
A
The two (2) heavy chains
19
Q
o They determine the immunoglobulin class: α, γ, δ, ε, µ
A
Heavy chains
20
Q
o κ or λ
A
Light chains
21
Q
o Both (?) are found in all classes of immunoglobulins, but only one type is present in a given molecule
A
κ or λ
22
Q
o Holds each light chain to a heavy chain
A
Disulfide bonds
23
Q
o Link the mid-region of the two heavy chains
A
Disulfide bonds
24
Q
o Fragment antigen-binding
A
Fab fragment
25
o Consists of one (1) light chain and one-half (½) of a heavy chain
Fab fragment
26
o The intact immunoglobulin has (?), each representing one (1) antigen binding site
two (2) Fab fragments
27
o Fragment crystalline
Fc fragment
28
halves of the two heavy chains
carboxy-terminal end
29
o This portion of the molecule has no antigen binding ability
Fc fragment
30
o The carboxy-terminal end of the immunoglobulin molecule, where the amino acid sequence is the same for all chains of that type
Constant region
31
o Responsible for the type and antigen-antibody reaction that occurs
Constant region
32
o (?) of heavy chain differs from one antibody class to the other
Constant region
33
o The amino-terminal end of the immunoglobulin molecule, where the amino acid sequence varies
Variable region
34
o This part of the molecule is responsible for the specificity of a particular immunoglobulin
Variable region
35
Variable region is also known as the
ANTIGEN-RECOGNITION UNITS
36
o Different for each antibody molecule
Variable region
37
o Regions within the variable region that actually form the antigen-binding site
Hypervariable region
38
o Through changes in the (?), an immense diversity of antigen-binding sites can be created
Hypervariable region
39
o number of binding sites
Valence
40
o The flexible portion of the heavy chain, located between the first and second constant regions
Hinge region
41
o This allows the molecule to bend to let the two (2) antigen-binding sites operate independently
Hinge region
42
o A glycoprotein that serves to link immunoglobulin monomers together
Joining chain
43
Joining chain is only found in __________ and _________________________
IgM and IgA2
44
• Predominant immunoglobulin in humans comprising approximately 75-80% of the total serum immunoglobulins
IgG
45
• 7S molecule with a molecular weight (MW) of approximately 150,000 Daltons
IgG
46
• Made up of one basic structural unit known as a monomer consisting of two heavy and two light chains, which may be kappa or lambda (but not both)
IgG
47
• Has the longest half-life, approximately 23-25 days
IgG
48
• Functions of IgG:
o Providing (?) for the newborn
o (?) of the complement
o (?)
o (?) of toxins and viruses
o Participation in (?) reactions
immunity
Fixation
Opsonization
Neutralization
agglutination
49
• Most primitive; first to appear in phylogeny and the last to leave in senescence
IgM
50
• First to appear after a primary antigenic stimulus
IgM
51
• Made up of five basic structural units (pentamer) in circular arrangement, 10 heavy chains and 10 heavy light chains
IgM
52
• Possess J chain (MW: approximately 15,000 Daltons)
IgM
53
• 19S molecule with a MW of approximately 900,000 Daltons
IgM
54
IgM Functions:
o Complement fixation .
o Agglutination
o Opsonization
o Neutralization of toxins
55
• In the serum, it primarily appears as a monomer
IgA
56
• is also found as a dimer in body secretions along the respiratory and intestinal mucosa and in milk, saliva, tears and sweat
IgA (IgA2)
57
• The dimer consists of two monomers held together by a J chain
IgA
58
is synthesized in the plasma cells found mainly in mucosal-associated lymphoid tissue (MALT) and it is released in dimeric form
Secretory IgA
59
Secretory component
Secretory IgA
60
is found on the surface of immunocompetent but unstimulated B lymphocytes
IgD
61
• Postulated to be an anti-idiotypic antibody (antibody to antibody) and as such may be involved in the feedback mechanism to switch off B cells
IgD
62
• Function of IgD:
o Immunoregulation
63
• Least abundant immunoglobulin in the serum
IgE
64
• Heat-labile antibody
IgE
65
o Mediates some types of hypersensitivity (allergic reaction), allergies, and anaphylaxis and is generally responsible for an individual’s immunity to invading parasites
IgE
66
o Binds strongly to a receptor on mast cells and basophils and together with antigen, mediates the release of histamine and heparin from these cells
IgE
67
• A defensive system consisting of over 30 proteins produced by the liver and found in circulating blood serum
COMPLEMENT SYSTEM
68
o Serum proteins that interact to enhance the host defense reactions
COMPLEMENT SYSTEM
69
o Most are inactive enzyme precursors that are converted to active enzymes in a precise order
COMPLEMENT SYSTEM
70
• It works as a cascade system: when one reaction triggers another reaction which triggers others and so on; these types of systems can grow exponentially very fast
COMPLEMENT SYSTEM
71
o Following activation, opsonization occurs as complement components coat pathogenic organisms or immune complexes, facilitating the process of phagocytosis
1. Opsonization
72
o Activation of the complement system results in induction of histamine release from mast cells and basophils, and stimulation of inflammatory response
2. Inflammation
73
o In the final stage of the complement cascade membrane attack of target cells (e.g. bacteria and tumor cells) occur, leading to cell death
3. Cytotoxic
74
Nomenclature:
1. ([?] for complement, [?] for the components)
2. The peptide chains
3. Cleaved peptides
4. If further proteolysis results in the loss of fragment activity
5. When a complement protein acquires enzymatic activity
“C”, 1 to 9
Greek letters (e.g. C3-α, C4-β)
lower case Arabic letters (e.g. C3a)
subscript “i”
horizontal bar
75
• Complement components are serum proteins produced by the __________ EXCEPT:
o ____________________________________________________
o ____________________________________________________
76
• Present in HIGHEST concentration in plasma: _____
77
• Key component of the pathways: _____
78
o Involves a more recently evolved mechanism of specific adaptive immunity
Classical Pathway
79
o It is initiated by the presence of antigen-antibody complex (immune complex)
Classical Pathway
80
o Classical pathway normally requires suitable antibodies bound to an antigen, complement components 1, 4, 2 and 3, and calcium (Ca++) and magnesium (Mg++) cations
Classical Pathway
81
Binds to Fc of IgM and IgG
C1q
82
Activates C1s
C1r
83
Cleaves C4 and C2
C1s
84
Part of C3 convertase
C4
85
Binds to C4b
C2
86
Key intermediate in all pathways
C3
87
Initiates membrane attack complex (MAC)
C5
88
Binds C5b in MAC
C6
89
Binds to C5bC6 in MAC
C7
90
Starts pore formation on membrane
C8
91
Polymerizes to cause cell
C9
92
It requires the interaction of all nine (9) major complement components
Classical Pathway
93
• A trimolecular complex (C1q, C1r, and C1s) held together by Ca+2 ions
C1: Recognition Unit
94
• C1q is the largest and consists of 6 globes held on slender shafts that fuse a common base
C1: Recognition Unit
95
o The 6 globes act as the recognition units that bind to the Fc region of IgM and IgG
C1: Recognition Unit
96
• For C1q to initiate the cascade, it must attach to two Fc fragments from IgG and/or IgM
C1: Recognition Unit
97
attaches to the immunoglobulin and initiates complement activation
C1q
98
initiates C1r
C1q binding
99
cleaves C1s
C1r
100
• C4 is a beta globulin originates from a proC4 synthesized by the macrophage
C4: First activation unit
101
• It consists of 3 peptide chains (C4-α, C4-β, C4-γ) joined by disulfide bonds
C4: First activation unit
102
• C4 is cleaved into C4a and C4b by C1s
C4: First activation unit
103
mediates cleavage of C4 into C4a and C4b
C1s
104
is bound to cell membrane while C4a is released into the fluid phase
C4b
105
• C2 is cleaved into C2a and C2b by C1s in the presence of C4b
C2: Second activation unit
106
in the presence of C4b (C14b) cleaves C2 units into C2a and C2b
C1s
107
is bound to the cell-bound C4b while C2b is released in the fluid phase
C2a
108
• It is the most abundant complement component in the serum.
C3: Third activation unit
109
• It is cleaved by C3 convertase into C3a and C3b.
C3: Third activation unit
110
is cleaved by C3 convertase into C3a and C3b
C3
111
remains unbound C3b is bound to the cell bound C4b2a (C4b2a3b: _______________)
C3a
112
• C5 is cleaved by C5 convertase into C5a and C5b
C5: First membrane attack unit
113
is cleaved by C5 convertase into a smaller C5a and a larger C5b
C5
114
is released into the surrounding fluid medium
C5a
115
is the first component of the membrane attack complex. It is the receptor of C6 and C7
C5b
116
binds to C6 forming a stable C5b6 complex
C5b
117
: Second membrane attack unit
C6
118
: Third membrane attack unit
C7
119
binds to C7 forming the stable C5b67 that is bound to the target cell membrane
C5b6
120
: Final membrane attack unit
C8
121
binds to C5b67 complex and leakage of membrane begins.
C8
122
Cell lysis can occur by the C5b678 complex in the absence of
C9
123
: Final membrane attack unit
C9
124
binds to C5b678 complex and accelerates cytolysis by producing circular lesions in the membrane
C9
125
induces the formation of hollow cylinders (tubules) in the bilipid layer of the cell membrane allowing exit of electrolytes and water out of the cell
C5b6789 complex
126
o Provides nonspecific innate immunity
Alternate Pathway
127
o It is considered a primitive defense mechanism, a bypass mechanism that does not require C1, C4 and C2 interaction
Alternate Pathway
128
o An antigen-antibody complex is not required for it to take place
Alternate Pathway
129
Binds C3b to form C3 convertase
Factor B
130
Cleaves Factor B
Factor D
131
Stabilizes C3 convertase
Properdin
132
Begins with the activation of C3 and requires Factors B and D, and magnesium cation (Mg++), all present in normal serum
Alternate Pathway
133
The initial recognition necessary for the alternative pathway is the presence of C3, specifically (?) which is probably continuously generated in small amounts in the circulation
C3b
134
C3 activation: o Non-immunologic
• Lipopolysaccharide (LPS)
• Endotoxin from the cell walls of gram-negative bacteria
• Cell walls of some bacteria
• Cell walls of yeasts (zymosan)
• Cobra venom factor (CVF)
135
C3 activation: o Immunologic
• IgA
• Other antibodies
136
exists in trace amounts in normal serum
C3b
137
interacts with Factor B (C3 proactivator) to form C3bB, which is a magnesium ion-dependent complex
C3b
138
is cleaved by Factor D (C3 proactivator convertase) into 2 fragments, Ba and Bb Ba is released and Bb is bound to C3b forming the C3bBb complex: amplification C3 convertase
C3bB
139
When stabilized by (?), the C3bBb complex becomes the C3 convertase that cleaves C3 into C3a and C3b
Properdin (P)
140
As more (?) is generated, the complex expands (C3bnBb) and becomes a C5 convertase
C3b
141
cleaves C5 into C5a and C5b initiating the membrane attack pathway
C5 convertase
142
Membrane attack complex
(C5b6789)
143
• Involved attachment of mannose-binding lectin to mannose residues on glycoproteins or carbohydrates on surface of microorganisms
Mannose-Binding Lectin (MBL) Pathway
144
Binds to mannose
Mannose Binding Lectin (MBL)
145
Helps cleave C4 and C2
MBL-associated Serine Protease-1 (MASP-1)
146
Cleaves C4 and C2
MBL-associated Serine Protease-2 (MASP-2)
147
Macrophages that digest microbes release chemicals that cause the liver to produce (?): proteins bind to carbohydrates on the microbe surface
lectins
148
is produced by liver in acute phase inflammatory reactions
MBL
149
binds to mannose on many bacterial cells
MBL (mannose-binding lectin)
150
Once MBL binds to target cell, (?) bind to bacterial surface Acts like C1
2 serine proteases (MASP-1, MASP-2)
151
Cleaving of C4 and C2 forming
C3 convertase
152
Cleaving C3 forming
C5 convertase
153
Cleaving of C5 initiates the formation of the
membrane attack complex (C5b6789)
154
are the key elements in a serologic reaction.
Antigens and antibodies
155
The study of the properties and types of antigens and antibodies are essential in the understanding of (?)as well as the (?) of the immune system.
serologic reactions ; responses
156
usually are present in humans as well as in animal serum. They may participate in serologic reactions, although some tests in serology, human complement is often inactivated, and an exogenous complement is used.
complement proteins
157
are activated in a cascade of reactions when these participate in a serologic reaction
complement proteins
158
The pathogens capable of causing infectious diseases in humans include bacteria, viruses, fungi, parasites and infectious proteins. (?) are usually associated with these pathogens.
Antigens
159
The J chain is found only in the following immunoglobulins
160
Activation Sequence: C1q attaches to the immunoglobulin and initiates complement activation ® C1q binding initiates C1r ® C1r cleaves C1s
C1: Recognition Unit
161
Activation Sequence: C1s mediates cleavage of C4 into C4a and C4b ® C4b is bound to cell membrane while C4a is released into the fluid phase
C4: First activation unit
162
Activation sequence: C1s in the presence of C4b (C14b) cleaves C2 units into C2a and
C2b ® C2a is bound to the cell-bound C4b while C2b is released in the fluid phase ® C4b2a complex is now attached on the surface of the cell membrane
C2: Second activation unit
163
Activation sequence: C3 is cleaved by C3 convertase into C3a and C3b ® C3a remains
unbound ® C3b is bound to the cell-bound C4b2a ® C4b2a3b complex is now attached on the surface of the cell membrane
C3: Third activation unit
164
Activation Sequence: C5 is cleaved by C5 convertase into a smaller C5a and a larger
C5b ® C5a is released into the surrounding fluid medium ® C5b is the first component of the membrane attack complex that is bound on the surface of the cell membrane that serves as the receptor of C6 and C7
C5: First membrane attack unit
165
Activation Sequence: C6 binds to cell-bound C5b forming a stable C5b6 complex
C6: Second membrane attack unit
166
Activation Sequence: C7 binds to cell-bound C5b6 forming the stable C5b67 that is bound to the target cell membrane
C7: Third membrane attack unit
167
Activation Sequence: C8 binds to C5b67 complex and leakage of membrane begins ® Cell lysis can occur by the C5b678 complex in the absence of
C8: Final membrane attack unit
168
Activation Sequence: C9 binds to cell-bound C5b678 complex accelerates cytolysis by
producing circular lesions in the membrane ® C5b6789 complex induces the formation of hollow cylinders (tubules) in the bilipid layer of the cell membrane allowing exit of electrolytes and water out of the cell
C9: Final membrane attack unit
169
where C3b that exists in trace amounts in normal serum becomes membrane bound on the surface of target cells
C3 activation
170
The membrane-bound (?) interacts with Factor B (C3 proactivator) to form C3bB, which is a magnesium ion-dependent complex
C3b
171
is cleaved by Factor D (C3 proactivator convertase) into 2 fragments, Ba and Bb
C3bB
172
is released, and Bb is bound to C3b forming the C3bBb complex: amplification C3 convertase
Ba
173
When stabilized by (?), the C3bBb complex becomes the C3 convertase that cleaves C3 into C3a and C3b
Properdin (Factor P)
174
As more (?) is generated, the complex expands (C3bnBb) and becomes a C5 convertase (e.g., C3bBb3b)
C3b
175
MBL acts like (?) of the classical pathway but binds to mannose on many bacterial cells
C1q
176
Once MBL binds to the target cell, (?) bind to the bacterial surface. MASP-1 and MASP-2 act like C1r and C1s of the classical pathway, respectively
two serine proteases (MASP-1, MASP-2)
