Interaction between polyclonal and clonal activators

Synergism

Low doses of polyclonal activators increase responses to stimulatory cytokines or induce production of these stimulatory cytokines. This partly accounts for the effect of adjuvants. Adjuvants augment immune responses by a process of synergism between signals via the antigen receptor and those lymphoid system cell surface components that interact with the many elements that make up adjuvants.

Table 1 Examples of polyclonal activators

Name

Source

Cells activated

Mitogenic lectins - bind polysaccharide of surface structures

Cells required

Phytohemagglutinin (PHA) Concanavalin A (Con A) Pokeweed mitogen (PWM) Streptolysin O (SLO) Nocardia water-soluble mitogen (NWSM) Some oligonucleotides

Phaseolus vulgaris Canavalia ensiformis Phytolacca americana Streptococcus Nocardia opaca Bacterial or synthetic

T cells (human) T cells (mouse) T and B cells B cells B cells B cells

Bacteria cell wall products and analogs - bind a number of receptors on lymphocytes

Lipopolysaccharides (LPS) Peptidoglycan Lipoproteins Porin proteins Dextran sulfate

Polyene antibiotics Amphotericin B

Calcium ionophores - alter calcium signals A23187 lonomycin

Gram-negative bacteria

Bacteria

Bacteria

Neisseria

Synthetic

Streptomyces

Streptomyces Streptomyces

Phosphorylation modifiers - increase stimulatory phosphorylation events Phorbol myristate acetate Croton tiglium

Pervanadate Inorganic salt + H202

B cells B cells B cells B cells B cells

B cells (T cells) T cells

T and B cells

T and B cells T and B cells

Antigen-receptor ligands - bind to non-variable portions of the receptor mechanism

(Fab')2 anti-immunoglobulin anti-lg-dextran (Fab')2 anti-T cell receptor Staphylococcal enterotoxin TSST - toxic shock toxin Superantigens (MMTV) Protein A

Ligands for costimulator molecules Anti-CD28/CTLA4 and B7 Anti-CD40 and CD40L Anti-CD21 /complement Anti-CD2

Mammalian B cells

Mammalian + synthetic B cells

Mammalian T cells

Staphylococcus T cells

Streptococcus T cells

Retroviruses T cells

Staphylococcus aureus B cells bind to lymphocytes and favor stimulation

Mammalian T cells

Mammalian B cells

Mammalian B cells

Mammalian T cells

Transforming agents infect cells and cause continued growth and/or activation

Epstein Barr virus Virus B cells

HumanT lymphotropic virus Virus T and B cells

Human immunodeficiency virus Virus B cells

Monocytes

T and B cells T cells ±T cells

NK/macrophages

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