Adaptive Immune System Eric Scott BIO422 10/19/15 escot127@email.unc.edu

Objectives Describe the roles of various types of lymphoctyes in an adaptive immune response. Define antigen and antibody Distinguish the response to intracellular pathogens from the response to extracellular pathogens

“Jobs” of the Immune System Recognize that invaders are present Recognize that these are different than self Recruit more cells/factors to fight invaders Kill the invaders Block any toxins produced by the invaders Learn from past encounters to increase future effectiveness

Overview of Host Response to Pathogens

Time Course of an Immune Response

Levels of the Immune Response

Levels of the Immune Response

Adaptive Responses Are Specific to Individual Molecules Antigen: the molecule recognized by the response Each cell can only recognize one antigen

Two Branches of Adaptive Response Cellular immunity Main cells are T cells Used against intracellular pathogens Humoral immunity B cells and antibodies Used against extracellular microbes and toxins

Cellular Immune Response T cell Mediated Immunity Cellular Immune Response

How do T cells recognize antigen? T cell receptor Recognizes small parts of proteins “presented” on MHC molecules MHC is present on antigen presenting cells

Starts with phagocytes recognizing antigen

Antigen is processed and displayed: MHCI

Antigen is processed and displayed: MHCII

Initial recognition by pAPCs Professional antigen presenting cells Dendritic cells, macrophages, and B cell Offer activating signals to T cells—primes for activity

Types of T cells Cytotoxic T cells: CD8+ T cells Recognize antigens on MHCI Releases granules to kills target cells Helper T cells: CD4+ T cells Recognize antigens on MHCII Secrete cytokines to activate other cells Two types: Th1 and Th2

Cytotoxic T cells (Tc)

Helper T cells (Th) Th1 Cells: activate phagocytes Th2 Cells: activate B cells

Concept Question Cytotoxic T cells are important for defense from… Bacteria only Intracellular pathogens Viruses only Fungus only Extracellular pathogens

Concept Question What do helper T cells recognize? Exogenous peptides on MHCI Carbohydrates on bacteria cells Exogenous peptides on MHCII Endogenous peptides on MHCII Endogenous peptides on MHCI

Humoral Immune Response B cell Mediated Immunity Humoral Immune Response

B cells Produce Antibodies Defense from extracellular pathogens and toxins Recognize antigen in native form

Activation of B cells B cell receptor (BCR) recognizes antigen Th2 cells help activation B cell differentiates to plasma cell Produces antibodies

Antibody Structure Immunoglobulins (Ig) Functions Neutralize pathogens and toxins Lead to phagocytosis Activation of complement

Types of antibodies

Types of Antibodies Functional Activity IgM IgD IgG IgA IgE Neutralization +  ++ Phagocytosis +++ Natural killer cell killing Mast cell activation Complement activation Location BCR & Serum BCR (minor) Serum & tissue Mucus & tissue Mast cells

Immunological Memory

Timing of Adaptive Response

Immunological Memory

Secondary Immune Response

Memory Responses Small populations of B and T cells retained from first exposure Survive for a long time Begin faster than first response Stronger than first response

Immune System Summary

Adaptive Immune System

Adaptive immunity T B T B T B B B T T T B T T Immune response microbes MB MB Y Memory B cells MB MB T Y B Y T Y Y Y T B PC B Y B Y PC Y T T B PC T T B Y T B cells PCs Germinal Centers Immune response T cells Y antibodies To begin with, T cells, B cells and in many ways plasmacytoid dendritic cells (pDCs) are apart of the adaptive immune system. Upon stimulation by foreign microbes in the environment, B cells are activated and move into follicles called germinal centers. Within the germinal centers B cells receive T cell help clonally expand and may differentiate into either memory B Cells or plasma cells. Plasma cells that produce antibodies that bind the foreign antigen resulting in its elimination from the host. In addition effector T cells role is to eliminate invading microbes. pDCs produce proinflammatory cytokines to help eliminate microbes. Together these three cell types help rid the body of harmful antigens. Type I IFN Y Y E-T E-T Y Y E-T Y Y pDC Y Y Eliminates microbes Eliminates microbes

Adaptive immunity T B T T = B B B B T T T B T T autoimmune response Dying cells Self antigen Y MB MB Y autoreactive Memory B cells MB MB T B Y Y T Y Y Y T = B Y B Y PC PC B Y autoreactive PCs PC T T B T T B Y T B cells Y Germinal Centers autoimmune response T cells Y Y autoAbs Y Y Y To begin with, T cells, B cells and for the most part pDCs are apart of the adaptive immune systems. With the help of T cells, B cells are activated and differentiate into plasma cells that produce antibodies. In addition effector T cells role is to eliminate invading microbes. pDCs produce proinflammatory cytokines to help eliminate microbes. Together these three cell types help rid the body of harmful antigens. However in the case of autoimmunity, these three cell types have a devastating effect. Type I IFN E-T E-T Y Y E-T Y Y Y pDC Y Self antigen immune complexes Tissue damage/organ failure Activate autoreactive T cells

Autoimmunity Autoimmune responses are incited by specific self-antigens that are expressed on normal host tissues Autoimmune diseases may be organ-specific and have aberrant immune antibody responses directed against antigen(s) associated only within target organs being damaged. Type I diabetes mellitus is an example of organ-specific autoimmunity where CD4+ T cells and CD8+ T cells destroy pancreatic beta cells in genetically predisposed individuals Autoimmune diseases can be classified as systemic (non-organ specific) and have antibody directed against an antigen not associated with any particular target organ. Systemic Lupus Erythematosus (SLE) is an example of systemic autoimmunity

Systemic Lupus Erythematosus (SLE) SLE is a chronic autoimmune disease characterized by the production of auto-Abs to intracellular proteins and nucleic acids. It is the prototype of the systemic autoimmune diseases characterized by multi-organ involvement. The prevalence of SLE in the United States range as high as 1.5 million with an incidence ranging from 1.8 to 7.6 cases per 100,000 persons per year in the United States (Rus V. 2001). SLE affects women more often than men, at a ratio of about 10:1, with minority women being affected three times more often than caucasians (Rus V. 2001). Renal involvement is a principal cause of morbidity and mortality in SLE, but the underlying immunopathological mechanisms of nephritis are still largely unknown Read slide