Immune Depletion, Immune Modulation, and Immunosuppression in MS: A Review

Introduction

Architecture of the Immune System: Focus on Innate Immunity

Innate Immune System Features

Architecture of the Immune System: Focus on Adaptive Immunity

T-Cell Development

B-Cell Ontogeny

B Cells: Antigen Presentation, Cytokine Release, and Antibody Secretion

Regulatory and Proinflammatory Features of B Cells

Effector Function of T Cells

Immunity in the Periphery and CNS

Adaptive Immune Response in MS

Initiation of T-Cell Responses in MS: Scenario 1

Initiation of T-Cell Responses in MS: Scenario 2

Initiation of T-Cell Responses in MS: Scenario 2 (cont)

Different Functions of Macrophages

Potential Role of NK Cells in MS

CNS Inflammation in MS

Compartmentalized Inflammation in Progressive MS

CNS Lymphatic Vessels

Ectopic Lymphoid Follicles in Meninges

MS: A T-Cell- or B-Cell-Driven Disease?

A Soluble Demyelinating Factor in MS?

Targeting the Immune System in MS

Immunosuppressive DMTs

Immunomodulatory DMTs

Immune-Trafficking DMT—Blockade

Immune-Trafficking DMT—Entrapment

Immune-Depleting DMTs

Overlap of DMT Classification

Daclizumab: Enhancement of Endogenous Mechanisms of Immune Tolerance

What Is the Most Promising Strategy for the Treatment of RRMS?

ORATORIO Primary and Secondary Endpoints: 12- and 24-Week CDP

INFORMS: Fingolimod in PPMS

EXPAND Trial: Siponimod in SPMS

Anti-CD20 Therapy in MS: MOA

Conclusions

Abbreviations

Abbreviations (cont)

Abbreviations (cont)