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L5- Humoral Memory- Effector Mechanisms Flashcards

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1
Q

Antibodies exist in two forms. What are they?

A
  1. Membrane-bound antibodies on the surface of B lymphocytes as antigen receptors
  2. Secreted antibodies neutralise toxins, prevent the entry and spread of pathogens and eliminate microbes.
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2
Q

What parts of the IG form the antigen binding site?

What parts create an antigen binding surface?

A
  • The V region of one heavy chain (VH ) and the adjoining V region of one light chain (VL ) form an antigen-binding site
  • Three hypervariable regions of a V L domain and the three hypervariable regions of a V H domain are brought together to create an antigen-binding surface
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3
Q

The three hypervariable loops determine antigen specificity by forming a surface complementary to the antigen, and are more commonly termed The…

A

complementarity-determining regions, or CDRs (CDR1, CDR2, and CDR3)

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4
Q

Amino acid residues of the hypervariable regions form multiple contacts with bound antigen. The most extensive contact is…

A

With the third hypervariable region (CDR3), which is also the most variable of the three CDRs

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5
Q

What produces the Ig-mediated signal?

A

B cell receptor (BCR) complex

Ig-mediated signals are transduced by two other molecules called Igα and Igβ that are disulfide linked to one another and are expressed in B cells, non-covalently associated with membrane Ig

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6
Q

Activation of B cells is enhanced by signals by co-receptors. Explain briefly.

A

Co-receptors Amplify or Suppress Antigen Signaling CD21, CD19, and CD81 form the B-cell co-receptor complex.

CD21, also known as complement receptor 2 (CR2), binds C3d. C3d is a degradation product of C3b, which accumulates on the surface of pathogens when complement is activated.

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7
Q

The recognition of antigen by antibody involves covalent, reversible binding. T or F?

A

False.

Non-covalent, reversible binding

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8
Q

Describe affinity of the antibody.

A

The strength of the binding between a single combining site of an antibody and an epitope of an antigen is called the affinity of the antibody, represented by a dissociation constant (Kd )

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9
Q

What indicated a stronger or higher affinity interaction?

A

Smaller K dindicates a stronger or higher affinity interaction because a lower concentration of antigen and of antibody is required for complex formation

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10
Q

K d of antibodies produced in typical humoral immune responses usually varies from…

A

10 −7 M to 10 −11 M

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11
Q

What does avidity strength of the antibody mean?

A

Strength of attachment of the antibody to the antigen must take into account binding of all the sites to all the available epitopes. This overall strength of attachment is called the avidity and is much greater than the affinity of any one antigen-binding site

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12
Q

Where do antibodies come from?

A

Class-switched, high-affinity antibodysecreting plasma cells, which are produced in germinal centres during Tdependent responses to protein antigens, migrate to the bone marrow and persist at this site, where they continue to produce antibodies for years after the antigen is eliminated.

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13
Q

What is the main function of antibodies?

A

To neutralise and eliminate infectious microbes and microbial toxins

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14
Q

List 7 effector functions of antibodies

A
  1. Neutralisation of microbes and toxins
  2. Opsonization and phagocytosis of microbes
  3. Antibody-dependent cellular cytotoxicity
  4. Phagocytosis of microbes opsonised with complement fragments (e.g. C3b)
  5. Inflammation
  6. Lysis of microbes
  7. Complement activation
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15
Q

Antigens are trapped in immune complexes that bind to the surface of follicular dendritic cells called what?

A

Iccosomes

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16
Q

Describe the antigen response response in lymphoid tissue

A
  1. Opsonised antigens entering lymph nodes from afferent lymphatics lymphatics bind to the complement receptors on the surface of macrophages present in the subcapsular sinus
  2. The low endocytic and degradative activity of subcapsular macrophages preserves the antigens trapped on their surfaces, allowing B cells to encounter them
  3. Antigen preservation by subcapsular macrophages also allows antigen to be transported into the follicle to become localised on the surface of follicular dendritic cells
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17
Q

Opsonised antigens are captured and preserved by what cells?

A

Subcapsular macrophages

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18
Q

Activated B cells undergo rounds of mutation and selection for higher-affinity mutants in the germinal centre, resulting in ______

A

high affinity antibody-secreting plasma cells and high-affinity memory B cells

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19
Q

Antibody isotypes have different half-lives in circulation.

What is the short half-life of IgE?

A

IgE has a very short half-life of about 2 days in the circulation (although cell-bound IgE associated with the high-affinity IgE receptor on mast cells has a very long half-life

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20
Q

Antibody isotypes have different half-lives in circulation.

What is the short half-life of IgA?

A

Circulating IgA has a half-life of about 3 days

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21
Q

Antibody isotypes have different half-lives in circulation.

What is the short half-life of IgM?

A

Circulating IgM has a half-life of about 4 days

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22
Q

Antibody isotypes have different half-lives in circulation.

What is the short half-life of IgG?

A

Circulating IgG molecules have a half-life of about 21 to 28 days.

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23
Q

B cell proliferation and differentiation leads to what 4 things?

A
  1. Antibody secretion
  2. Isotope switching
  3. Affinity maturation
  4. Memory B cells
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24
Q

Antibodies of different classes operate in distinct places and have distinct effector functions. T or F?

A

True

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25
Transport proteins that bind to the Fc regions of antibodies carry particular isotypes across epithelial barriers. Provide an example of a transport protein.
ABC transporter
26
Which antibodies are called virus-neutralizing antibodies?
High-affinity IgG and IgA antibodies can neutralize bacterial toxins High-affinity IgG and IgA antibodies can inhibit the infectivity of viruses by directly blocking viral binding to surface receptors
27
Antibody:antigen complexes activate the classical pathway of complement by binding to what?
C1q
28
What important role does complement receptors play?
Removal of immune complexes from the circulation.
29
What is the isotype-specific effector function of; IgG?
1. Opsonization of antigens for phagocytosis by macrophages and neutrophils 2. Activation of the classical pathway of complement 3. Antibody-dependent cell-mediated cytotoxicity mediated by NK cells 4. Neonatal immunity: transfer of material antibody across the placenta and gut 5. Feedback inhibition of B cell activation
30
What is the isotype-specific effector function of; IgM?
1. Activation of the classical pathway of complement | 2. Antigen receptor of naive B lymphocytes
31
What is the isotype-specific effector function of; IgA?
Mucosal immunity: secretion of IgA into the lumens of the gastrointestinal and respiratory tracts
32
What is the isotype-specific effector function of; IgE?
Mast cell degranulation (immediate hypersensitivity reactions)
33
What is the isotype-specific effector function of; IgD?
Antigen receptor of naive B lymphocytes
34
Explain and be able to draw the process of IgA in the lumen of the gut.
1. IgA is synthesized by plasma cells in the lamina propria in the form of a dimer that is held together by a J chain. 2. From the lamina propria, the dimeric IgA is transported into the lumen of the gut through epithelial cells at the base of the crypts by the poly-Ig receptor. 3. Dimeric IgA binds to the layer of mucus overlying the gut epithelium. 4. IgA in the gut neutralises pathogens and their toxins
35
What is the role of the Poly-Ig receptor?
Transport of IgA across epithelial surfaces
36
How does Poly-Ig receptor help IgM?
IgM produced by lamina propria plasma cells is also a polymer (pentamer) associated covalently with the J chain, and the poly-Ig receptor also transports IgM into intestinal secretions
37
What is the dominance of IgA production by intestinal plasma cells due to?
In part to selection induction of IgA isotope switching in B cells in GALT and mesenteric lymph nodes
38
Among IgG antibodies which antibodies are more efficient activators of complement than are other subclasses?
IGg3 and IgG1
39
Antibodies of the IgG isotype coat (opsonize) microbes and promote their phagocytosis by binding to....
Fc receptors on phagocytes
40
The process of coating particles to promote phagocytosis is called _______ substances that perform this function, including antibodies and complement proteins, are called _______?
opsonization Opsonins
41
Free immunoglobulin does not cross-link Fc receptors because?
Aggregation of immunoglobulin on bacterial surface allows cross-linking of Fc receptors which then leads to activation of macrophages and the destruction of bacterium by phagocytosis
42
Explain in detail the process how antibodies of the IgG isotope coat microbes leading to phagocytosis by macrophages
1. Bacterium is coated with complement and IgG antibody, 2. When C3b binds to CR1 and antibody binds to Fc receptor, bacteria are phagocytosed 3. Macrophage membrane fuse creating a membrane-enclosed vehicle, the phagosome 4. Lysosomes fuse with these vesicles which becomes a phago-lysosome delivering enzymes that degrade the bacteria.
43
What is the role of the neonatal Fc receptor?
Involved in the transport of IgG from the maternal circulation across the placental barrier as well as the transfer of maternal IgG across the intestine in neonates
44
Why does IgG have a quite long half-life?
* FcRn does not target bound IgG to lysosomes but recycles to the cell surface and releases it at neutral pH, returning the IgG to the circulation * This intracellular sequestration of IgG away from lysosomes prevents it from being degraded as rapidly as most other serum proteins, including other antibody isotypes, and as a result, IgG has a relatively long half-life.
45
How are neonatal mammals are protected from infection?
By maternally produced antibodies transported across the placenta into the foetal circulation and by antibodies in ingested milk transported across the gut epithelium of newborns For several months after birth, their major defence against infection is passive immunity provided by maternal antibodies Maternal IgG is transported across the placenta, and maternal IgA and IgG in breast milk are ingested by the nursing infant Transepithelial transport of maternal IgA into breast milk depends on the poly-Ig receptor
46
How are mast cells activated?
Mast cells are activated by cross-linking of Fc ε RI molecules, which occurs by binding of multivalent antigens to the IgE molecules that are attached to the Fc receptors
47
How quickly can the contents of the mast cell granules are released into the extracellular environment?
This process can occur within seconds of FcεRI cross-linking, and can be visualized morphologically by loss of the dense granules of mast cells
48
What is antibody-dependent cellular cytotoxicity (ADCC)?
It is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies.
49
How does Natural killer (NK) cells and other leukocytes bind to antibody-coated cells by Fc receptors and destroy these cells by ADCC?
* Antibody binds antigen on the surface of target cells. * NK cells use their Fc receptor, FcγRIIIA, to bind to antibody-coated cells. * Cross linking of Fc receptors signals the NK cell to kill the target cell (ADCC occurs only when the target cell is coated with antibody molecules)
50
What is FcγRIIIA (CD16)?
• FcγRIIIA (CD16) is a low-affinity receptor that binds clustered IgG molecules displayed on cell surfaces but does not bind circulating monomeric IgG.
51
What is Erythrocyte CR1 important for?
Erythrocyte CR1 helps to clear immune complexes from the circulation Immune complexes bind to CR1 on RBC, which transport them to the liver and spleen, where they are removed by macrophages expressing receptors for both Fc and bound C’
52
Describe different features between primary and secondary immune response
Peak response: P: smaller S: larger Antibody isotope: P: usually IgM > IgG S: relative increase in IgG; and under certain situations IgA and IgE Antibody affinity: P: lower average affinity, more variable S: higher average affinity (affinity maturation) Induced by: P: all immunogens S: mainly protein antigens
53
Both the affinity and the amount of antibody increase with repeated immunization – this is referred to as an.........
anamnestic response
54
What is the frequency of antigen-specific B cells that are distinct from primary and secondary response upon immunisation?
Unimmunized primary response: 1:10^4 - 1:10^5 Immunised second response: 1:10^2 - 1:10^3
55
The generation of secondary antibody responses from memory is distinct from the generation of the primary antibody response leads to 4 things... Lower frequency of antigen-specific B cells? Isotype of antibody produced? Affinity of antibody? Somatic hypermutation?
Lower frequency of antigen-specific B cells? From (1:10^4 - 1:10^5) to (1:10^2 - 1:10^3) Isotype of antibody produced? (IgM> IgG) to (IgG, IgA) Affinity of antibody? From low to high Somatic hypermutation? From low to high
56
What is Original Antigenic Sin?
When individuals who have been infected with one variant of influenza virus are infected with a second or third variant, they make antibodies only against epitopes that were present on the original virus Why? Naïve B cells are only able to respond to antigens to which there are no pre-existing antibodies
57
What are thymus independent or T independent cells?
Many non-protein antigens, such as polysaccharides and lipids, stimulate antibody production in the absence of helper T cells, and these antigens
58
What can T independent cells do?
* T-independent antigens are capable of stimulating B cell proliferation and differentiation in the absence of T cell help * Do not stimulate an anamnestic response – no memory
59
What can T independent cells do?
* T-independent antigens are capable of stimulating B cell proliferation and differentiation in the absence of T cell help * Do not stimulate an anamnestic response – no memory or affinity maturation
60
The most important TI antigens are...
Polymeric antigens especially polysaccharides, glycolipids, and nucleic acids
61
Most TI antigens are multivalent, being composed of repeated identical antigenic epitopes. What is the immune response?
Such multivalent antigens may induce maximal cross-linking of the BCR complex on specific B cells, leading to activation
62
Thymus-independent (TI) antigens fall into 2 classes – which activate B cells by different mechanisms....
TI-1 antigen, which has an activity that can directly activate B cells and TI-2 antigen, which has highly repetitive structure and causes simultaneous cross-linking of specific B cell receptors (BCR) on B lymphocyte.
63
What are mitogens?
TI-I antigens cause proliferation of B cells regardless of their specificity – by activating TLRs or other molecules. They are known as mitogens
64
TI-2 antigens are molecules such as bacterial capsular polysaccharides; they stimulate...
B1 cells to produce IgM antibody
65
What is the basis of the successful conjugate vaccines against bacterial pathogens
TD antibody responses to polysaccharide antigens may be induced by coupling antigens to carrier proteins for processing and presentation to carrier proteinspecific memory T cells. The carrier protein is typically an antigen to which the child has been vaccinated previously, eg. Tetanus toxoid

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