Adaptive Immune System Julie Lowe BIO422 2014 julie.lowe@nih.gov

“Jobs” of the Immune System

“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 PAMP (Pathogen Associated Molecular Pattern) Receptor Signaling Cascade Transcription factors Cytokines/chemokines

PAMP + Receptor Complex Signaling Cascade Cytokine/ chemokine release Transcription factor activation

Levels of the Immune Response

Levels of the Immune Response

Adaptive Responses Are Specific to Individual “Epitopes” Antigen: the molecule recognized by the response The epitope is the specific part of the antigen recognized Each adaptive immune cell can only recognize one epitope

Epitopes are small parts of antigens Figure 24.2

Concept Questions Can an antigen have more than one epitope? Yes, almost always Can an epitope have more than one antigen? No You found two adaptive immune cells that respond to pilin. Are these cells specific for the same epitope? Not necessarily: they could respond to two different epitopes on the same antigen

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

Cellular Immune Response T cell Mediated Immunity

Roles of T cells in Host Defense CD8+ CD4+

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

Two types of MHC: MHCI and MHCII MHCI is present on all nucleated cells CD8+ cytotoxic T cells recognize MHCI MHCII is present on professional antigen presenting cells  pAPCs CD4+ helper T cells recognize MHCII Figure 24.20

Intracellular antigens are processed and displayed on MHCI for CD8+ cytotoxic T cells Figure 24.21

Extracellular antigens are processed and displayed on MHCII for CD4+ helper T cells Figure 24.21

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

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 major types: Th1 and Th2

CD8+ Cytotoxic T cells Death of cells infected with virus or cytoplasmic bacteria, cancer cell, etc.

CD4+ Helper T cells (Th) Th1 cells: activate phagocytes Th2 cells: activate B cells

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

Concept Question T helper 1 cells (Th1) are important for defense from… Extracellular pathogens Fungi only Viruses only Cytoplasmic pathogens Phagocytosed/Endosomal pathogens Change

T cell summary Cell Type Cytotoxic T cell Th1 Helper T cell Type of MHC MHCI MHCII Location of MHC All nucleated cells Professional antigen presenting cells Location of antigen Endogenous—within the cytoplasm of the cell Exogenous—present in the phagosome Type of epitope Small linear peptide Response to initial recognition Proliferate and activate to effector Activated cell recognizing epitope releases Granules—perforins, granzymes Cytokines Which… Kill the target cell Activate phagocytes (WBC) to kill phagocytosed microbes Activate B cells to proliferate, produce antibodies, and develop memory

Humoral Immune Response B cell Mediated Immunity

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 Membrane bound antibody Th2 cells help activation and are required for memory B cell differentiates to plasma cell, which produces antibodies

Antibody Structure Immunoglobulins (Ig) “Y” shaped proteins 4 polypeptides linked by disulfide bonds Two identical heavy chains Two identical light chains Has variable and constant regions Variable regions are responsible for recognizing the epitope

Antibody Structure Figure 24.7

Structure of Different Antibody Types

Functions of Antibodies

Concept Question B cells recognize _____ with membrane bound_____. Peptides only MHCs Whole antigens MHCs Peptides only Antibodies Carbohydrates only TLRs Whole antigens Antibodies change

Immunological Memory Secondary responses to infection

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 Vaccinations take advantage of memory responses

Concept Question When you’re exposed to a pathogen for the second time, your innate and adaptive immune responses will be Innate and adaptive both faster and stronger Adaptive faster and stronger but innate only faster Innate and adaptive both faster only Innate the same, adaptive both faster and stronger Innate the same, adaptive faster only

Immune System Summary

Adaptive Immune System

What types of adaptive responses would be best at fighting the listeria at A, B, and C?