Chapter 46
Adjuvants
Sam Sanderson
Questions
1.
The majority of adjuvants in experimental use today are composed of various bacterial components.
Briefly explain the rationale for the use of such bacterial components in adjuvants.
2.
Briefly describe the two major biological functions of the complement system.
3.
The complement-derived anaphylatoxin C5a has many prominent immune stimulatory properties and,
consequently, is a good candidate for use as a molecular adjuvant. However, its use as such would be
severely limited. Describe the major limitation(s) for the use of natural C5a as a molecular adjuvant.
4.
Antigen presenting cells (APC) represent an important class of immune cells essential for generating an
antigen-specific immune response. Briefly describe the basic cellular mechanism by which APCs
contribute to this antigen-specific immune outcome.
5.
Conventional vaccines in use today typically require the use of added adjuvants to initiate and potentiate
an antigen-specific immune response. In contrast, vaccines that incorporate the conformationally-biased
agonists of C5a as molecular adjuvants described in this chapter require no added adjuvants –
vaccinations are accomplished with just water/saline as the vehicle. Describe why this is possible.
6.
In addition to the ability to target antigens to C5a receptor-bearing APCs, the conformationally-biased
C5a agonists/molecular adjuvants induce C5a-like responses at the C5a receptor on the APC. Describe
these C5a-like responses.
7.
Describe why the conformationally-biased C5a agonists/molecular adjuvants invoke their effects at the
C5a receptor expressed on APCs, but not C5a receptors expressed on inflammatory neutrophils.
8.
Bacteria and various components of bacteria are used as adjuvants in order to provide the bacterial
signals that activate principally
a. antibody synthesis
b. the innate arm of immunity
c. clonal expansion of B cells
d. oxidative phosphorylation
9.
Adjuvants typically fall into two major categories, which are
a. vesicles and nanoparticles
b. proteins and DNA
c. live and attenuated
d. vehicles and immunomodulators
10. The two principal biological effects of complement component C5a are
a. intercalation of DNA and de novo protein synthesis
b. inflammation and immune stimulation
c. neo-vascularization and spleen development
d. protease activation and carbohydrate clearance
11. The C-terminal region of complement-derived C5a (C5a65-74) represents
a. the biologically active region of C5a
b. a post-translational signal sequence
c. a site for phosphorylation by kinases
d. a immunogenic site recognized by T lymphocytes
45. Adjuvants
Sam Sanderson
12. A molecular adjuvant can be defined by all of the following except:
a. targets antigens to dendritic cells
b. is a single molecular entity
c. down regulates costimulatory factors
d. activates specific pathways of antigen presentation
2
45. Adjuvants
Sam Sanderson
3
Answers
1.
The majority of adjuvants in experimental use today are composed of various bacterial components.
Briefly explain the rationale for the use of such bacterial components in adjuvants.
Bacterial components in adjuvants provide the bacterial signals that activate the innate arm of the immune
system.
2.
Briefly describe the two major biological functions of the complement system.
a) Generation of the MAC (membrane attack complex) for the lysis of foreign cell membranes, b) activation and
orchestration of the humoral and cell-mediated activities within the innate and acquired arms of the immune
system.
3.
The complement-derived anaphylatoxin C5a has many prominent immune stimulatory properties and,
consequently, is a good candidate for use as a molecular adjuvant. However, its use as such would be
severely limited. Describe the major limitation(s) for the use of natural C5a as a molecular adjuvant.
a) C5a is the principal mediator of local and systemic inflammatory responses, b) C5a is susceptible to
proteolysis (especially the C-terminal Arg residue) to serum carboxypeptidases.
4.
Antigen presenting cells (APC) represent an important class of immune cells essential for generating an
antigen-specific immune response. Briefly describe the basic cellular mechanism by which APCs
contribute to this antigen-specific immune outcome.
APCs take up (internalize) the antigen. The antigen is processed (proteolytically cleaved) via intracellular
antigen processing pathways. The resulting cleaved components then associate with MHC/HLA determinates,
which are subsequently expressed on the APC surface. It is only in the context of MHC/HLA on the APC
surface that an antigen can be recognized by complementary immune cells for the antigen-specific immune
response.
5.
Conventional vaccines in use today typically require the use of added adjuvants to initiate and potentiate
an antigen-specific immune response. In contrast, vaccines that incorporate the conformationally-biased
agonists of C5a as molecular adjuvants described in this chapter require no added adjuvants –
vaccinations are accomplished with just water/saline as the vehicle. Describe why this is possible.
The conformationally-biased C5a agonist/molecular adjuvant specifically targets an attached antigen to and
simultaneously activates C5a receptor-bearing APCs. Thus, no added adjuvants are needed to enhance the
antigen processing and presentation capacity of the APC.
6.
In addition to the ability to target antigens to C5a receptor-bearing APCs, the conformationally-biased
C5a agonists/molecular adjuvants induce C5a-like responses at the C5a receptor on the APC. Describe
these C5a-like responses.
a) Synthesis/release of Th1 and Th2 cytokines, b) potential upregulation of costimulatory factors on the APC
surface, c) internalization of the C5a receptor.
7.
Describe why the conformationally-biased C5a agonists/molecular adjuvants invoke their effects at the
C5a receptor expressed on APCs, but not C5a receptors expressed on inflammatory neutrophils.
The unique three-dimensional structure/conformation is well accommodated by C5a receptors expressed on
APCs, but much less so by C5a receptors expressed on neutrophils.
8.
b
9.
d
10. b
11. a
12. c