Vaccination is arguably the greatest success of immunology, having eradicated or virtually eliminated several human diseases. It is the single most successful manipulation of the immune system so far, because it takes advantage of the immune system’s natural specificity and inducibility. But important human infectious diseases remain that lack effective vaccines. Most effective vaccines are based on attenuated live microorganisms, but such vaccines carry some risk and are potentially lethal to immunosuppressed or immunodeficient individuals. New techniques are being developed to generate genetically attenuated pathogens for use as vaccines, particularly for malaria and tuberculosis. While most current viral vaccines are based on live attenuated virus, many bacterial vaccines are based on components of the microorganism, including components of the toxins that it produces. Protective responses to carbohydrate antigens, which in very young children do not provoke lasting immunity, can be enhanced by conjugation of the carbohydrate to a protein. Vaccines based on peptides, particularly very long peptides, are just emerging from the experimental stage and are beginning to be tested in humans. A vaccine’s immunogenicity often depends on adjuvants that can help, directly or indirectly, to activate antigen-presenting cells that are necessary for the initiation of immune responses. Adjuvants activate these cells by engaging the innate immune system and providing ligands for TLRs and other innate sensors on antigen-presenting cells. The development of oral vaccines is particularly important for stimulating immunity to the many pathogens that enter through the mucosa.
Summary to Chapter 16.
One of the great future challenges in immunology is to be able to control the immune system so that unwanted immune responses can be suppressed and desirable responses elicited. Current methods of suppressing unwanted responses rely, to a great extent, on drugs that suppress adaptive immunity indiscriminately and are thus inherently flawed. We have seen in this book that the immune system can suppress its own responses in an antigen-specific manner and that, by studying these endogenous regulatory events, it has been possible to devise strategies to manipulate specific responses while sparing general immune competence. New treatments, including many monoclonal antibodies, have emerged as clinically important therapies to selectively suppress the responses that lead to allergy, autoimmunity, or the rejection of grafted organs. Similarly, as we understand more about tumors and infectious agents, better strategies to mobilize the immune system against cancer and infection are becoming possible. To achieve all this, we need to learn more about the induction of immunity and the biology of the immune system, and to apply what we have learned to human disease.
Questions.
16.1 Multiple Choice: Which of the following immunomodulators has a similar mechanism to azathioprine?
A. Mycophenolate
B. Cyclophosphamide
C. Abatacept
D. Rapamycin 16.2 Matching: Match the following immunomodulating antibodies with their respective mechanism of action.
16.3 True or False: Chimeric antigen receptor (CAR) T cells are cells that have been retrovirally transduced with a tumor-specific T-cell receptor in order to treat a leukemia.
16.4 Multiple Choice: Which statement is false?
A. The vaccine Provenge is prepared using the patient’s own antigen-loaded dendritic cells to induce therapeutic antitumor T-cell responses.
B. Clinical trials of vaccines against HPV-16 and HPV18 (associated with 70% of cervical cancers) were 100% effective in preventing cervical cancers caused by these viruses.
C. Cell-based cancer vaccines can use the patient’s tumor as a source of antigens. In order to enhance immunogenicity these can be mixed with adjuvants such as CpG, which binds to TLR-7.