Lecture 16 Cellular Cooperation and Antigen Recognition

Cellular Cooperation T H B antigen antigen Antibody secretion by plasma cells Plasma Cells Antigen presenting cell Antigen presentation to T and B cells by APC T cells elaborate cytokines to facilitate B cell proliferation and maturation

Antigen Presenting Cells Must be capable of processing antigen from extracellular and intracellular pathogens Must be capable of processing antigen from extracellular and intracellular pathogens Must present processed antigen on MHC class I & II molecules Must present processed antigen on MHC class I & II molecules Must express co-stimulatory molecules (cytokines) Must express co-stimulatory molecules (cytokines)

Types of Professional Antigen Presenting Cells Macrophages/monocytes Macrophages/monocytes Dendritic cells (e.g.., Langerhan’s cells) Dendritic cells (e.g.., Langerhan’s cells) B cells B cells

Properties of Professional Antigen- Presenting Cells

Cellular Cooperation and Antigen Recognition APC ExtracellularAntigen CD4 + Helper T Lymphocyte Class II MHC- associatedantigen +

The Role of Adjuvants Depot effect Depot effect antigen persists for long period antigen persists for long period resistance to rapid degradation resistance to rapid degradation Macrophage activation Macrophage activation production of non-specific enhancing factors production of non-specific enhancing factors Non-specific T cell signal Non-specific T cell signal provides "second" signal to B cell normally provided by T cell provides "second" signal to B cell normally provided by T cell

Types of Adjuvants Freund's Complete Adjuvant (Water-in-oil emulsion) Freund's Complete Adjuvant (Water-in-oil emulsion) mineral oil mineral oil emulsifying agent emulsifying agent microbial preparation (eg. heat-killed extract of Mycobacterium tuberculosis) microbial preparation (eg. heat-killed extract of Mycobacterium tuberculosis) aqueous phase containing antigen aqueous phase containing antigen Aluminum Hydroxide Gel Aluminum Hydroxide Gel Microbial Adjuvants Microbial Adjuvants C. parvum C. parvum BCG BCG Peptides and Synthetic Polymers Peptides and Synthetic Polymers

Effector Mechanisms Mechanisms that are used by the immune system to eliminate pathogens (or other substances) from the body Mechanisms that are used by the immune system to eliminate pathogens (or other substances) from the body Cellular effector mechanisms Cellular effector mechanisms Activated T cells Activated T cells Natural killer cells Natural killer cells Humoral effector mechanisms (antibody) Humoral effector mechanisms (antibody) Neutralization Neutralization Opsonization Opsonization Complement activation Complement activation Antibody-dependent cell-mediated cytotoxicity (ADCC) Antibody-dependent cell-mediated cytotoxicity (ADCC)

Effector Activity Against Pathogens

Cytokines Polypeptides produced by a variety of cell types including T lymphocytes. Polypeptides produced by a variety of cell types including T lymphocytes. Cytokine production is triggered by specific receptor binding and subsequent signal transduction pathways Cytokine production is triggered by specific receptor binding and subsequent signal transduction pathways Cytokine repertoire is dependent on cell type triggered, receptors present on that cell type. Cytokine repertoire is dependent on cell type triggered, receptors present on that cell type. Cytokines act on cells that possess receptors for them. Cytokines act on cells that possess receptors for them.

Lymphocyte Migration, Activation, and Effector Function Depends on Cell-Adhesion Molecules A variety of cell surface polypeptides serve as receptors to ensure appropriate cell-cell interactions. These polypeptide include: A variety of cell surface polypeptides serve as receptors to ensure appropriate cell-cell interactions. These polypeptide include: Selectins Selectins Integrins Integrins Immunoglobulin Superfamily Immunoglobulin Superfamily Mucin-like Vascular Addressins Mucin-like Vascular Addressins

T-cell Mediated Cytotoxicity Necrosis Necrosis Programmed cell death or apoptosis Programmed cell death or apoptosis

Summary Effector cells and antibodies play critical roles in almost all adaptive immune responses Effector cells and antibodies play critical roles in almost all adaptive immune responses Antigen-presenting cells play critical role in processing and presenting antigen to T cells Antigen-presenting cells play critical role in processing and presenting antigen to T cells Cytokines are released by a variety of cell types and regulate a variety of biological effects Cytokines are released by a variety of cell types and regulate a variety of biological effects T-cell mediated cell death is largely via apoptosis T-cell mediated cell death is largely via apoptosis