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INTRODUCTION

The introduction of pathogens and foreign proteins into the human body can stimulate immune recognition, leading to inflammatory and allergic responses. Aspects of these responses are subject to pharmacological modulation. Before describing the actions of pharmacological agents affecting allergy and immunity, this chapter describes the cellular and molecular basis of immune and allergic responses and the points of pharmacological intervention. Subsequent chapters in this section cover in detail the classes of agents that can alter allergic and immune responses, as well as the biology and pharmacology of inflammation.

ABBREVIATIONS

Abbreviations

APC: antigen-presenting cell

BCR: B-cell receptor

C#: complement component # (e.g., C3, C5)

CAR: chimeric antigen receptor

CLL: chronic lymphocytic leukemia

CR1: complement receptor 1

CTLA-4: cytotoxic T-lymphocyte–associated protein 4

DC: dendritic cell

DN: double negative

DP: double positive

ER: endoplasmic reticulum

GI: gastrointestinal

HLA: human leukocyte antigen

HSC: hematopoietic stem cell

ICI: immune checkpoint inhibitor

IFN: interferon

Ig: immunoglobulin

IL: interleukin

iNOS: inducible nitric oxide synthase: NOS2

IRF: interferon regulatory factor

ISG: interferon-stimulated gene

ISRE: interferon-stimulated response element

LT: long term

MADCAM-1: mucosal vascular addressin cell adhesion molecule 1

MALT: mucosa-associated lymphoid tissue

MHC: major histocompatibility complex

NF-κB: nuclear factor-κB

NK cell: natural killer cell

NO: nitric oxide

PAMP: pathogen-associated molecular pattern

PD-1: programmed cell death protein 1

PRR: pattern recognition receptor

Rh: rhesus

ROS: reactive oxygen species

SARS-CoV-2: severe acute respiratory syndrome coronavirus 2

scFv: single-chain variable fragment

ST: short term

TC: cytotoxic T cell

TCR: T-cell receptor

TH: helper T cell

TLR: toll-like receptor

TNFα: tumor necrosis factor α

TReg: T-regulatory cells

CELLS AND ORGANS OF THE IMMUNE SYSTEM

Hematopoiesis

All blood cells, including immune cells, originate from pluripotent hematopoietic stem cells (HSCs) of the bone marrow. HSCs are a population of undifferentiated progenitor cells that are capable of self-renewal. On exposure to cytokines and contact with the surrounding stromal cells, HSCs can differentiate into megakaryocytes (the source of platelets), erythrocytes (red blood cells), and leukocytes (white blood cells). This process is known as hematopoiesis (Figure 38–1).

Figure 38–1

Development of myeloid and lymphoid lineage cells from HSCs in the bone marrow. HSCs give rise to lineage-specific precursors, which differentiate into all myeloid and lymphoid cells.

The HSC pool can be divided in two populations: long-term (LT) and short-term (ST) HSCs. LT-HSCs are capable of lifelong self-renewal, allowing for continuous hematopoiesis throughout life. ST-HSCs have limited self-renewing capability and differentiate into multipotent progenitors—the common myeloid progenitor and the common lymphoid progenitor. The common myeloid progenitor gives rise to the myeloid lineage of cells that includes megakaryocytes, erythrocytes; granulocytes (neutrophils, eosinophils, basophils, mast cells), monocytes, macrophages, and dendritic cells (DCs). In contrast, the common lymphoid progenitor gives rise to the lymphoid lineage of cells ...

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