Ch. 10 & 11 BOC Review: Immunology and Hypersensitivity

Vocabulary and key concepts regarding tumor immunology, various types of graft rejection, tumor evasion mechanisms, and the four types of hypersensitivity reactions.

Neoantigens

Newly expressed in tumor but not normal cells; generated by somatic mutations that can be recognized by the host immune system; mutations usually play no role in tumorigenesis and are called passenger mutations; most common targets for adaptive immune responses.

Cancer-testis antigen

Proteins encoded by genes that are normally expressed in male germ cells in the testis; male germ cells do not express MHC molecules so peptides from these proteins aren’t normally presented to T cells; when expressed by tumor cells, they can be presented to T cells by tumor-cell MHC CI molecules.

Tumor suppressor genes

Genes that suppress cell division; mutations can confer a growth advantage to tumor, enabling outgrowth of neoplastic clones. Note: myeloid-derived suppressor cells are developmentally related to neutrophils and monocytes and have anti-inflammatory functions.

Oncogenes

Mutated or overexpressed gene that has the potential to cause cancer; products of oncogenes activate cell division.

Oncoviral proteins

Tumor antigens encoded by viral oncogenes that have a critical role in the oncogenic process; because they are foreign, they can evoke a T cell response.

Differentiation Antigens

Encoded by genes that are expressed only in particular types of tissues; normal proteins expressed by tissue of tumor origin; examples include pigments produced in melanocytes and melanoma cells.

Chimeric antigen receptor (CAR) therapy

Receptor expressed in CAR-T cells consisting of an extracellular Ig part that recognizes a surface antigen on tumor cells and intracellular signaling domains from the TCR complex and costimulatory receptors; avoids limitations of MHC restriction.

Syngeneic graft/isograft

Transplant from 1 individual to another who is genetically identical to donor (e.g., identical twins); donor and recipient are histocompatible; the recipient does not mount an immune response against it.

Allograft

Transplant from one individual to an MHC-disparate individual of the same species; recognized as foreign due to MHC polymorphisms and rejected without immunosuppression; antigens targeted are called alloantigens.

Xenograft

Transplant between a donor and a recipient from a different species; targets of rejection are called xenoantigens and exhibit the most vigorous rejection.

Indirect allorecognition

Occurs when allogeneic MHC molecules from graft cells are taken up and processed by recipient APCs, and fragments of the allogeneic MHC molecules are presented by recipient (self) MHC molecules.

Direct allorecognition

Occurs when recipient T cells bind directly to intact allogeneic MHC molecules on graft donor dendritic cells (DCs).

Minor histocompatibility antigens

Polymorphic normal cellular proteins, which are non-HLA; differ in amino acid sequences between individuals and lead to rejection because T cells are never selected to be tolerant to them.

Graft vs Host Disease (GVHD)

Major complication of HSCT; acute GVHD occurs within $100$ days and chronic GVHD begins after the first $100$ days; symptoms include depigmentation, sloughing of epithelial cells, and liver failure.

Graft vs Leukemia Effect

Beneficial side of HSCs transplant where mature T cells and/or NK cells in the graft recognize minor histocompatibility antigens or tumor-specific antigens on recipient leukemia cells and attack them.

Hyperacute rejection

Occurs within minutes to hours after transplantation; preformed antibodies react with alloantigen on vascular endothelium, activate complement, and trigger rapid intravascular thrombosis and necrosis.

Accelerated rejection

Occurs within days due to reactivation of memory cells resulting from prior exposure to an alloantigen now expressed on the current donor.

Acute rejection

Occurs within days or weeks; involves alloreactive $CD8$ T cells (CMI) or alloantibodies (HMI) reactive with graft endothelial and parenchymal cells.

Chronic rejection

Occurs over months or years; T cells reactive with graft alloantigens produce cytokines inducing inflammation/proliferation of smooth muscle cells, leading to luminal occlusion and fibrosis.

Oncofetal antigens

Category of tumor markers including Alpha-fetoprotein ($AFP$) and Carcinoembryonic protein ($CEA$).

Hypersensitivity

Adaptive immune response that causes tissue injury and disease due to excessive or aberrant immune responses; can be directed against foreign or self-antigens.

Type I Hypersensitivity

Immediate hypersensitivity mediated by $IgE$ antibodies; effector cells include Th2 cells, mast cells, and eosinophils; response time is $15-30$ minutes (e.g., allergic rhinitis).

Type II Hypersensitivity

Antibody-mediated disease involving $IgM$ and $IgG$; mechanisms include opsonization, phagocytosis, and complement/$Fc$ receptor-mediated leukocyte recruitment (e.g., Hemolytic anemia).

Type III Hypersensitivity

Immune complex-mediated diseases involve $IgG$ and soluble antigens; response time is $3-8$ hours; involves complement and $Fc$ receptor-mediated recruitment of leukocytes (e.g., Serum sickness).

Type IV Hypersensitivity

T cell-mediated diseases; involves $Th1$, $Th2$, $CTL$, or $Th17$ cells; response time is $48-72$ hours; mechanisms include macrophage activation and direct target cell lysis (e.g., Contact dermatitis).