Objectives – Adaptive Immunity To understand the importance of both the innate and adaptive immune system in controlling pathogens To understand the function/role of Th1 versus Th2 versus Th17 To understand the architecture of the secondary lymphoid tissue and the role that various regions play in the adaptive response. To understand why different pathogens require a different adaptive response.

Review Adaptive immunity – requires innate, but infections that get by innate will overwhelm host if adaptive is not present. Role of adhesion molecules to get cells in correct place.

Review Th1 vs Th2 vs Th17 has taught us that appropriate response is important if host is to control disease Leprosy/Leishmania example Erythroblastosis fetalis example Autoimmune disease (MS/RA) example Much effort is directed at understanding what controls Th1,Th2 or Th17– so that this can be done clinically.

Objectives -- Memory To understand how memory is important for species survival List the components important in maintaining memory. Define original antigenic sin and what it means to the immune response to a pathogen.

Review -- continued The memory component of the adaptive immune response is important both from an evolutionary point of view as well as clinical. Survival of species and allows survivors to treat those who have disease Vaccination requires memory Memory means faster response with higher affinity Ab – meaning response to lower pathogen levels.

Concept of “Original Antigenic Sin” Primary response is prevented when secondary response is available. Can work to disadvantage in situations where pathogen is highly mutatable e.g. influenza virus. New and highly immunogenic epitopes go unused.

Objectives—Failure of Bodies Defenses List methods that pathogens can use to subvert the immune system. To understand how the immune system can actually contribute to the disease.

Review -- continued Pathogens have developed “tricks” to get around memory – altered coats, high mutation rates, going into cytoplasm, special vesicle, coating with serum proteins, make cytokine like molecules – are just some examples. Disease can result from too much IR – bacterial sepsis example.

Review -- continued Inherited immunodeficiencies give great advantages to pathogen – though severity of condition depends upon what is lost. Understand treatment options for condition Some can cause few problems B cell (antibody only) – IVIg – wheras SCID or lack of innate immunity – BM transplant.

Spectrum of Immunodeficiency Diseases Type of Infections DEFICIENCY Bacterial Viral Fungal Protozoan Antibody deficiency +++ + - + T cell/Combined +++ +++ +++ +++ Complement +++ - - - Phagocytic +++ - ++ -

Treatment of Immune Disorders Disease Therapy Antibody Deficiency Immunoglobulins (IVIG) SCID BMT Enzyme Therapy Interleukin-2 infusion Gene therapy (ADA) WASP BMT CGD Interferon- LAD BMT BMT = Bone Marrow Transplantation

Review -- continued Vaccines – a triumph of immunology! Started with Jenner and observation that cowpox protected against smallpox. Attenuated now used—especially for viruses as stimulates a protective response much like virulent agent. Success can essentially eliminate disease. Historically – vaccines stimulate the antibody response – new research aims to stimulate the CTL more effectively.