Innate and Adaptive Immunity

Innate Immunity

The innate immune system is the most evolutionarily conserved arm of the immune system and it generates rapid, non-specific inflammatory responses in response to signals from Pattern Recognition Receptors (PRR).
Pathogen Associated Molecular Patterns (PAMPs) are conserved molecular structures of bacteria, viruses and other pathogens that bind to PRRs.
The innate immune response has an important role in controlling infections during the first 7 days after an infection.
Many of the cells in the innate immune system (such as dendritic cells, macrophages, mast cells, neutrophils, basophils and eosinophils) produce cytokines or interact with other cells directly in order to activate the adaptive immune system.
There are other cell types, such as gamma-delta T cells and Natural Killer (NK) cells that are lymphocytes without antigen specificity, and therefore are considered to be innate cells with some similarities to effector lymphocytes.
The effector mechanisms used to clear an infection depend on the type of pathogen that has initiated the immune response.

The adaptive immune system is based on clonal selection of lymphocytes with antigen receptors (B cell receptors and T cell receptors).
Antigen receptors are genetically rearranged clonal receptors that bind to antigen displayed in Major Histocompatibility Complex (MHC) molecules on antigen-presenting cells.
During the course of an adaptive immune response, memory T and B cells are generated which allow for more rapid and effective response to reinfection.
Immunologic memory is the hallmark of adaptive immunity because it allows vertebrates to survive in a world where they are re-exposed to pathogens throughout their lifetimes.

The ultimate goal for cancer immunotherapy is to induce immunologic memory against a tumor. However, just as it is difficult to vaccinate patients with HIV because the HIV virus continues to evolve, it is difficult to induce immunologic memory against a tumor that continues to acquire mutations which allow for immune escape.
In addition, T cells that are chronically exposed to antigen during a viral infection, or in the presence of a tumor, often upregulate inhibitory molecules, such as Programmed Cell Death Protein-1 (PD-1), to inhibit T cell activation. Hence, PD-1 expression is characteristic of an "exhausted" T cell phenotype.
While tumor vaccines have been effective in some contexts, one of their drawbacks is that they target specific tumor antigens and rely on the generation of an adaptive immune response against that specific antigen to control tumor growth.
Therefore, one of the main reasons that the checkpoint inhibitors are so effective is that they do not target T cells against specific tumor antigens but instead target inhibitory receptors (such as PD-1) that are present on any activated T cells. By blocking this inhibitory effect, these immunotherapies are able to reinvigorate "exhausted" tumor-specific T cells.