Applied BioLogics

The Basics of Transfer Factor

Applied BioLogics and Inflammation

Transfer factors are natural, microscopic molecules that reside in the bodies of all animals. They are messengers, passing immunity information about the presence of an immune threat—whether external or internal—and how to properly respond, from immune cell to immune cell.

Transfer factors are produced by lymphocytes with cell-mediated immunity function. They carry the parent lymphocyte’s antigen-specific cell-mediated immunity (delayed-type hypersensitivity) to unsensitized, or naive, lymphocytes. They can also increase the nonantigen-specific immunostimulatory activity of the recipient lymphocytes.

Transfer factors transfer immunity information—recognition of pathogens and appropriate immune response—with inducer, suppressor and antigen-specific factors.

  • The inducer factor allows transfer factor to aid the adaptive immune response to viral infections, parasites, malignancies, bacterial and mycobacterial disease, fungal infection, autoimmune disorders and neurological disease. This factor can transfer an immune response in under 24 hours and significantly reduce or eliminate symptoms of illness.
  • The suppressor factor keeps the immune system from over-responding, such as to pollens and other foreign bodies, as well as to itself as in the case of an autoimmune disorder.
  • The antigen-specific factor carries critical tags that the immune system uses to identify foreign microbes and cells.

Transfer factors are found in even the most primitive immune systems. As such, transfer factors’ inducer and suppressor factors are universal and can transfer immunity across species barriers. Hence, transfer factors from a cow can confer immunity in a human. The antigen-specific factor can transfer immunity between species when crossover occurs between antigen-specific pathogens, such as in smallpox and cowpox, E. coli, etc.

 

Featured Article

Natural killer cells are made, not born
First evidence of immune cell's activation potential in infection, tumor control

News Release
February 2, 2004
The Rockefeller University

Call it the immune system's version of nature versus nurture.

For years, scientists regarded natural killer cells as a blunt instrument of the body's immune defense system. Born to kill, these cells were thought to travel straight from the bone marrow, where they are manufactured, to the blood, circulating there and infiltrating the sites of early tumors or infectious agents in the body.

Now, Rockefeller University scientists, led by Christian Münz, Ph.D., have learned otherwise. Natural killer cells, Münz and his colleagues say, have to be nurtured. Their ability to destroy tumor and infected cells is not present at birth.

This new insight paves the road to changes in bone marrow and stem cell transplant procedures and will enable scientists to pursue research into activating natural killer cells to help the body fight emerging infections and tumors.

In two separate papers in the February issue of The Journal of Immunology, Münz, postdoctoral associate Guido Ferlazzo, Ph.D., and their colleagues show that natural killer cells accumulate mostly in "secondary lymphoid tissues" - the tonsils, lymph nodes and spleen - after emerging from the bone marrow. There, the natural killer cells await activation (probably after stimulation by sentinel dendritic cells) before they react in two distinct modes. In one mode, they promptly secrete cytokines, chemical messenger proteins, which modulate emerging T and B immune cell responses. In the other, they become potent killers of tumors and virus-infected cells. While natural killer cells do provide a crucial first defense against many infectious agents and tumor cells, they do so with more discrimination than raw determination.

"Natural killer cells burst forth from the the tonsils, lymph nodes and spleen, and destroy infected and cancerous cells while the immune system's T and B cells are still mobilizing," says Münz. "Without natural killer cells, threatening conditions can get a strong foothold before the adaptive immune response kicks in."

Leading oncologists treating human leukemias and lymphomas already track natural killer cell activities after bone marrow and stem cell transplants. James Young, M.D., a researcher at Rockefeller's neighboring Memorial Sloan-Kettering Cancer Center's Allogenic Bone Marrow and Stem Cell Transplant Service, is one of them. "The emerging data on the activation of natural killer cells, their distinct functions in the body and their cellular targets, are helping to move the study of natural killer cells in transplantation and cancer from conjecture to sound hypotheses," he says.

The findings by Münz and his colleagues not only explain why a natural killer burst is important - the burst likely results from mobilization of natural killer cells from lymphoid tissues, and these activated immune cells are discriminating enough to recognize, through a full repertoire of surface receptors, virus-infected and tumor cells - it also affirms a potential strategic change in bone marrow or stem cell donor matching.

Bone marrow donors are selected based on the similarity of their white blood cell profiles: the closer the match to the patient, the better. But that's likely less important when doctors can harness the donor's natural killer cells to fight both residual cancer cells and residual immune system cells of the patient. Certain mismatches between donor and recipient can actually encourage the donor's natural killer cells to deliver an extra punch to the cancer and the threatening graft-versus-host disease, the updated logic goes.

Münz and his colleagues did not develop the bone marrow donor match strategy, but part of their aim in understanding where and how natural killers hang out, was to determine how the cells are recruited to combat cancer and other emerging diseases in the body. The Rockefeller scientists are in close contact with clinicians interested in tailoring immune cells - such as natural killers - in treating human leukemias.

The current Journal of Immunology publications

also contribute to strategies for dealing with the viral menace known as Epstein-Barr virus, a member of the herpes family of viruses. Though most infections are latent, active Epstein-Barr is the source of infectious mononucleosis in many teenagers.

Epstein-Barr also is a human cancer-causing virus. The virus hijacks the immune system's B cells in an elaborate chemical signaling mimicry of normal B cells. The result often is B cell tumors like Hodgkin's disease and Burkitt's lymphoma. Münz and his colleagues know that the natural killer cell response, or burst, is important in establishing immune control against the cancer causing Epstein-Barr virus.

"We have seen that Epstein-Barr virus transformation of B cells can be delayed by a strong natural killer cell burst," says Münz. "Now we are studying how this herpes virus may be targeted by natural killer cell responses." By learning both what molecular signals activate natural killer cells in their dialogue with dendritic cells and how viruses can be targeted by natural killer cells, Münz and his colleagues may be able to artificially stimulate natural killer cells to heighten their effect and ward off emerging Epstein-Barr virus associated malignancies.

"We're trying to get a sum of all signals that activate natural killer cells against viruses and tumors and do not cause harm to healthy human tissues," says Münz. "In the past five years, we've learned enough about these cells to extend hopes of their eventual usefulness in medical treatments."

This research was funded by the Leukemia & Lymphoma Society and the New York Academy of Medicine.

Transfer factor as an adjuvant to non-small cell lung cancer (NSCLC) therapy.

Pilotti V, Mastrorilli M, Pizza G, De Vinci C, Busutti L, Palareti A, Gozzetti G, Cavallari A.

Istituto di Clinica Chirurgica II, S. Orsola-Malpighi, Bologna, Italy.

The rationale for using transfer factor (TF) in lung cancer patients is that the possibility of improving their cell-mediated immunity to tumour associated antigens (TAA) may improve their survival. From Jan 1984 to Jan 1995, 99 non-small cell lung cancer (NSCLC) resected patients were monthly treated with TF, extracted from the lymphocytes of blood bank donors. In the same period, 257 NSCLC resected patients were considered as non-treated controls. The survival rates of the TF treated group appear significantly improved both for patients in stages 3a and 3b, and patients with histological subtype "large cell carcinoma" (P < 0.02). Survival of TF treated patients is also significantly higher (P < 0.02) for patients with lymph node involvement (N2 disease). The results of this study suggest that the administration of TF to NSCLC resected patients may improve survival.

Publication Types:

  • Clinical Trial
  • Controlled Clinical Trial

PMID: 8993769 [PubMed - indexed for MEDLINE]

Structural nature and functions of transfer factors.

Kirkpatrick CH.

Conrad D. Stephenson Laboratory for Research in Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.

Transfer factors are molecules that "educate" recipients to express cell-mediated immunity. This effect is antigen-specific. The most consistent effects of transfer factors on the immune system are expression of delayed-type hypersensitivity and production of lymphokines such as macrophage migration inhibitory factor (MIF), which is probably identical to gamma-interferon in response to exposure to antigen. Transfer factors bind to antigens in an immunologically specific manner. This discovery has enabled us to isolate individual transfer factors from mixtures that contain several transfer factors. This reactivity probably explains the specificity of individual transfer factors, and it has provided a method for purification of individual transfer factors to apparent homogeneity. The purified materials are immunologically active and antigen-specific. They have molecular weights of approximately 5,000 Da and appear to be composed entirely of amino acids. Transfer factors appear to offer a novel means of molecular immunotherapy for certain patients with defective cell-mediated immunity.

Publication Types:

  • Review

PMID: 8363241 [PubMed - indexed for MEDLINE]

 

Department of Pathology, University of Chicago, Chicago, IL, USA.

It is now little disputed that most if not all cancer cells express antigens that can be recognized by specific CD8(+) T lymphocytes. However, a central question in the field of anti-tumor immunity is why such antigen-expressing tumors are not spontaneously eliminated by the immune system. While in some cases, this lack of rejection may be due to immunologic ignorance, induction of anti-tumor T-cell responses in many patients has been detected in the peripheral blood, either spontaneously or in response to vaccination, without accompanying tumor rejection. These observations argue for the importance of barriers downstream from initial T-cell priming that need to be addressed to translate immune responses into clinical tumor regression. Recent data suggest that the proper trafficking of effector T cells into the tumor microenvironment may not always occur. T cells that do effectively home to tumor metastases are often found to be dysfunctional, pointing toward immunosuppressive mechanisms in the tumor microenvironment. T-cell anergy due to insufficient B7 costimulation, extrinsic suppression by regulatory cell populations, inhibition by ligands such as programmed death ligand-1, metabolic dysregulation by enzymes such as indoleamine-2,3-dioxygenase, and the action of soluble inhibitory factors such as transforming growth factor-beta have all been clearly implicated in generating this suppressive microenvironment. Identification of these downstream processes points to new therapeutic targets that should be manipulated to facilitate the effector phase of anti-tumor immune responses in concert with vaccination or T-cell adoptive transfer.

PMID: 16972901 [PubMed - in process]