MICB-708 Immunogenetics in Health and Disease
Spring for 2017-2018
Ohuiginc, Colm
The course will consist of a lecture series composed of the following themes: Distinction of self and non-self – why is it important. Origins of innate and of adaptive immunity. Generation of diversity for T-cell and B-cell receptors and for major histocompatibility (HLA) systems. The genetic and the molecular basis of disease associations with HLA. Understanding why HLA is the most critical locus for so many complex diseases. Genetics of natural killer cell receptors. Phases in cancer: elimination, equilibrium and escape. Cancer genome project: driver and passenger mutations. Immunotherapy in cancer. The microbiome in immunity and cancer.

The students will be guided to understanding the origins and functions of the systems that protect the body from invasion. The course will explore the unique genetic systems that generate the wide diversity of antigen receptors which learn how to recognize molecular features distinguishing our proteins and metabolites from those of invading parasites, microbes and viruses. The genetics of the human leukocyte antigen (HLA) system is explored, as well as that of the T-cell and B-cell receptors. Genome wide association studies (GWAS) indicate the strongest associations with diverse diseases ranging from the infectious (e.g. leprosy, viral control of HIV and HBV) to the complex and autoimmune (e.g.
narcolepsy, rheumatoid arthritis, diabetes, multiple sclerosis, schizophrenia, psoriasis, irritable bowel disease) occur in the HLA region. The molecular and evolutionary reasons that make the HLA an epicenter of disease are explained and individual disease associations studied in addition to the role of HLA polymorphisms in transplant histocompatibility. Connections between cancer and immunity are explored. The elimination of aberrant cells can be compromised by the occurrence of lesions sheltered from the immune system in cancer. Equilibrium occurs in which altered-self remains un-eliminated while chronic inflammation generates a tumor microenvironment that promotes growth and ultimately migration of cancerous cells. The students explore the technologies (next generation and single cell sequencing) that have enabled the simultaneous profiling of genetic and metabolic markers in multiple cancers. The roles of the microbiome in responses to therapy are examined. Immunotherapy (Science breakthrough of 2013) is explored. The targeting of checkpoint inhibitors is shown to promote the renewal of immune function against the tumor cells and their elimination from the body.
Credits: 2
Prerequisites: None
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