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INTRODUCTION

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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.

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ABBREVIATIONS

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Abbreviations

Ag: antigen

APC: antigen presenting cell

BCR: B-cell receptor

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

CD: cluster of differentiation

CLL: chronic lymphocytic leukemia

CR#: complement receptor #

CTL: cytotoxic T lymphocyte

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

DC: dendritic cell

HLA: human leukocyte antigen

HSC: hematopoietic stem cell

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

LTB4: Leukotriene B4

MADCAM-1: mucosal vascular addressin cell adhesion molecule 1

MALT: mucosa-associated lymphoid tissue

MHC: major histocompatibility complex

NK cell: natural killer cell

NO: nitric oxide

NSAID: nonsteroidal anti-inflammatory drug

PAMP: pathogen-associated molecular pattern

PD1: programmed cell death protein 1

PRR: pattern recognition receptor

Rh: rhesus

ROS: reactive oxygen species

ST: short term

TAP: transporter associated with antigen processing

TC: cytotoxic T cell

TCR: T-cell receptor

TFH: follicular helper T cells

TH: helper T cell

TLR: toll-like receptor

TNF-α: tumor necrosis factor alpha

TReg: T-regulatory cells

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CELLS AND ORGANS OF THE IMMUNE SYSTEM

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Hematopoiesis

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All blood cells, including immune cells, originate from pluripotent hematapoietic 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 34–1).

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Figure 34–1

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.

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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 (CMP) and the common lymphoid progenitor (CLP). The CMP 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 CLP gives rise to the lymphoid lineage of cells that includes natural killer (NK) ...

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