Immunotherapy for Infectious Diseases

Fungal Infections 305
Table 2
Categories of Immunotherapies under Development or in Current Use
Replacement
Granulocyte transfusions
IVIG
Nonspecific augmentative
Granulocyte transfusions from CSF-stimulated donors
G-CSF
GM-CSF
M-CSF
IFN-�
Specific augmentative
Vaccines
Specific antibody
Fungal extract
Transfer factor
Abbreviations: CSF, colony-stimulating factor; G, granulocyte; IFN-�, interferon-�; IVIG, intravenous
immunoglobulin; M, macrophage.
stimulate immune function against specific pathogens by eliciting new immune responses
or augmenting existing responses. The different types of immune therapies described in
this chapter are listed in Table 2. However, the distinctions between the various forms of
immune therapy are blurred by the complexity and redundancy of the immune system. For
example, replacement immune therapies can augment the immune system, whereas specific
immunotherapy can have nonspecific effects. Administration of colony-stimulating
factors (CSFs) to neutropenic patients for the purpose of stimulating bone marrow recovery
may also enhance the function of host effector cells, and such therapy has both replacement
and augmentative qualities. Hence, categorization of immune therapies as
replacement, augmentative, specific, and nonspecific is done with the knowledge that these
labels may need revision as we learn more about the complex interrelationships between
the components of the immune system.
At this time there are no immunotherapies for fungal infections that are part of standard
antifungal therapeutic protocols. Most, if not all, immunotherapies for fungal
infections can be characterized under the label of experimental therapy. Nevertheless,
this is an area of intense interest, and the field is evolving rapidly. For other recent
reviews on the subject of immunotherapy for fungal infections see refs. 1–7.
IMMUNOCOMPROMISED HOSTS AND FUNGAL INFECTIONS
When evaluating therapies, it is important to consider two features of fungal infections:
(1) fungal pathogens are highly diverse organisms; and (2) susceptibility to individual
fungal infections usually depends on the type of immune defect present. Fungal
pathogens are free-living organisms that are acquired from either the environment or
the endogenous flora. The mechanisms of pathogenesis differ for the various fungal
pathogens. For example, Aspergillus sp. produce powerful hydrolytic enzymes that
destroy tissue, whereas Cryptococcus neoformans cells classically elicit a weak inflammatory
response. Differences in pathogenic strategies used by the different fungal