Chapter 1

Properties and Overview

of Immune Responses
Xulong Zhang
Department of Immunology,
School of Basic Medical Sciences
Capital Medical University
2023.8.28
Immune in our body

X-linked SCID,
(XSCID)

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Immune in disease

Front. Immunol., 02 September 2020

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Immune in disease

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Immune in disease

1979 年 10 月 26 日
联合国世界卫生组织
在肯尼亚首都内罗毕
宣布，全世界已经消
灭了天花病。
明代吴又可医生编著
了《瘟疫论》，后来
国家免费医
治， 1961 年消灭天
花，比全球早 18 年！
唐开元年间（ 618 ～）
Edward Jenner (1749-1823) 种牛痘图
江南赵氏：鼻苗种痘法（清
《牛痘新书》）

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 Immune in disease

1953 年国家原卫生部将脊髓灰质炎列为法定报告传染病， 1964 年达到最高峰，发病率为

6.21/10 万。 1959 年，卫生部决定用接种疫苗的方法来预防。 1989 年中国政府响应第 41
届世界卫生大会关于 2000 年在全球消灭脊髓灰质炎的决议，确定了我国消灭脊髓灰质炎
的目标和策略。 2000 年 7 月，经国家消灭脊髓灰质炎证实委员会证实，确认中国已经成
功阻断本土脊髓灰质炎野病毒的传播，实现了消灭脊髓灰质炎的目标。这是继全球消灭天
花以后，世界公共卫生史上的又一壮举。
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Immune in disease
1994 年后我国再也没发现脊髓灰质炎病毒感染，比世界卫生组织规定
的时间提早 16 年。现在又将研制的疫苗出口给欠发达地区和一带一路
国家，为全球人类生命健康造福。

2011 年，李克强总理
喂孩子服食“糖 宝贝，接种疫苗啦！
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Immune in disease

Nat Rev Immunol

2021 Feb;21(2):73-82.
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Immune in disease

CAR-T

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Immune in disease

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Immune in disease

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Immune in disease

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Immune in disease

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The Nobel Prize in Immunology

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General process of
immune response

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General process of
immune response

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Contents

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 The concept and
function of immune

Protection from disease

Immune Immune system

immunitas
Immunity Organs, cells and molecules

Distinguish oneself and non-oneself Immune response

Collective and coordinated response
Innate immune response
Adaptive immune response
Tolerance Immune response
Immune function
Physiological response Defense
Surveillance
Body homeostasis
Homeostasis

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 The concept and
function of immune

Defense infectious microbes + Tissue injury or Infection

noninfectious foreign substances

Surveillance products of our own damaged Tumor or Infection

Immune function
and malignant (tumor) cells

Homeostasis Apoptosis Cells and Molecules Autoimmune responses

Immune response
a more inclusive definition of the immune response is a reaction to microbes and to molecules that are
recognized as foreign or abnormal, regardless of the physiologic or pathologic consequence of such a
reaction.

Immunology is the study of immune responses in this broader sense and of the cellular and
molecular events that occur after an organism encounters microbes and other foreign
macromolecules.

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Protective immunity

The concept of protective immunity may have

existed long before, as suggested by the
ancient Chinese custom of making children
resistant to smallpox by having them inhale
powders made from the skin lesions of patients
recovering from the disease.

Edward Jenner’s successful vaccination against smallpox

milkmaids who had recovered from

cowpox did not contract the more
serious smallpox.
观察能力，思考能力

Jenner’s landmark treatise on vaccination (Latin vaccinus, of or from cows) was published in 1798 20
Protective immunity

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Innate and Adaptive Immunity

Sequential and Coordinated Responses

that are called innate and adaptive immunity
Innate immunity (also called natural immunity or native immunity) is essential for defending
against microbes in the first few hours or days after infection, before adaptive immune responses
have developed. Innate immunity is mediated by mechanisms that are in place even before an
infection occurs (hence innate) and are capable of reacting rapidly to invading microbes.
PAMP/DAMP

In contrast to innate immunity, there are other immune responses that are stimulated by exposure to
infectious agents and increase in magnitude and defensive capabilities with each successive
exposure to a particular microbe. Because this form of immunity develops as a response to infection
and thus adapts to the infection, it is called adaptive immunity (also called specific immunity or
acquired immunity). stronger and more specialized
Antigen
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Innate and Adaptive Immunity

Immune
Immunity
Distinguish oneself and non-oneself

Tolerance Immune response

Physiological response
Body homeostasis

Glenn Dranoff. Nat Rev Cancer. 2004 Jan;4(1):11-22. 23

Innate and Adaptive Immunity

innate immunity
The phylogenetically oldest
Limited variability
Responds almost immediately to microbes and injured cells
Repeated exposures induce virtually identical innate immune responses
Immune The receptors of innate immunity are specific for structures that are common to
response groups of related microbes and do not distinguish fine differences among microbes
(1) physical and chemical barriers 、 (2) phagocytic cells(neutrophils, macrophages),
dendritic cells (DCs), mast cells, natural killer (NK cells), and other innate lymphoid
cells; and (3) blood proteins, including components of the complement system and
other mediators of inflammation

adaptive immunity
Only in vertebrates
Highly diverse antigen receptors
Specialized lymphoid tissues
Lymphocytes and their products
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Innate and Adaptive Immunity

tissue resident or
circulation

Inflammation:
recruiting phagocytes and
other leukocytes
blocking viral replication or
killing virus infected cells

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Adaptive Immune Responses
Cardinal Features of Adaptive Immune Responses

1. Specificity and diversity

Determinants or epitopes
TCR/BCR: distinguish subtle structural
differences between distinct epitopes

107 to 109

Clonal selection: Macfarlane Burnet in 1957

FIGURE 1.2 Specificity, memory, and contraction of adaptive immune responses. 26

Adaptive Immune Responses

2. Memory

long-lived memory cells

specific for the antigen

FIGURE 1.2 Specificity, memory, and contraction of adaptive immune responses. 27

Adaptive Immune Responses

3. Nonreactivity to self (self-tolerance)

Immune tolerance
Immune suppression autoimmune diseases
immunodeficiency

4. Systemic, provide protection at distant sites

5. Regulated by a system of positive and negative feedback loops

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Innate and Adaptive Immunity

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Innate and Adaptive Immunity

FIGURE 1.1 Innate and adaptive immunity. 30

Humoral and Cell-Mediated Immunity

Overview of Humoral and Cell-Mediated Immunity

Humoral immunity
Adaptive
immunity

Cell-mediated immunity

mediated by different types of lymphocytes

function to eliminate different types of microbes

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Humoral immunity

Two types of adaptive immunity

Humoral immunity:
mediated by antibodies, produced by B lymphocytes

blood and mucosal secretions

recognize microbial antigens

1. Neutralize the infectivity of the microbes
2. Target microbes for elimination by
phagocytes and the complement system

microbes and their toxins located outside cells

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Humoral immunity

B lymphocytes
Recognize antigens: BCR membrane-bound form of antibody + unique antigen specificity
Proliferate and differentiate into plasma cells:
protein antigens: requires activating signals (help) from CD4+ T
many nonprotein antigens (Polysaccharides and lipids) without the participation of helper T
Secrete different classes of antibodies
protein antigens: --IgM, IgG, IgA, IgE heavy-chain class (or isotype) switching + affinity maturation
many nonprotein antigens (Polysaccharides and lipids) s ------IgM

Distinct functions:
Neutralizing the microbes-------vaccination
Mediating phagocytosis------neutrophils and macrophages
IgG and IgM activate the complement system,
Complement products promote phagocytosis and destruction of microbes.
Neutralizes microbes in the lumens of mucosal tissues-----IgA
Maternal IgG is actively transported across the placenta and protects the newborn

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Humoral immunity

Protective immunity
Active immunity-----vaccination
the host’s response to the microbe

Passive immunity
transfer of antibodies
Conferring resistance rapidly, without having to wait for
an active immune response to develop
1. Transfer of maternal antibodies through the
placenta to the fetus
2. Lethal toxins
rabies infection and snake bites the first Nobel Prize in Physiology or
Emil von Behring and Shibasaburo Kitasato in 1890 Medicine to von Behring
侧链学说 the 1890s Paul Ehrlich Antibodies + antigens
Immunodiagnosis: Detect antibody in individuals
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 Cell-mediated immunity

Two types of adaptive immunity

Cell-mediated immunity:
mediated by T lymphocytes

microbes are ingested but survive within phagocytes

viruses, infect and replicate in various host cells

destruction of microbes inside phagocytes

killing of infected cells to eliminate reservoirs of infection

Immunodiagnosis: measuring reactions to these substances

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Initiation and Development of
Adaptive Immune Responses
1. Recognition of antigen
2. Activation of lymphocytes
3. Elimination of antigen
4. Contracts (declines)
5. Memory

Captured and displayed to specific lymphocytes

antigen-presenting cells (APCs)
dendritic cells (DCs)
capture
transport
present

Naive lymphocytes
Express antigen receptors
Clonal expansion
Effector cells
Memory cells
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Cell-Mediated Immunity
T lymphocytes, the cells of cell-mediated immunity
Recognize the antigens of cell-associated microbes: T lymphocytes have a restricted specificity for antigens
ONLY recognize peptides derived from foreign proteins that are bound to host proteins called major
histocompatibility complex (MHC) molecules (not soluble antigens), which are expressed on the surfaces of
other cells.
different types of T cells: helper T cells and cytotoxic (or cytolytic) T lymphocytes (CTLs)
Helper T cells function mainly by secreted cytokines and membrane molecules, which activate other cells to
kill microbes,
CTLs produce molecules that directly kill infected host cells.
Regulatory T cells, function mainly to inhibit immune responses.
Naive T lymphocytes differentiate into effector cells in secondary lymphoid organs, and migrate to sites of
infection.
Help phagocytes to destroy these microbes or kill the infected cells.
CD4+ helper T cells produced cytokines, recruit leukocytes, stimulate production of microbicidal substances in
phagocytes, kill the infectious pathogens.
CD4+ helper T cells secrete cytokines that help B cells to produce a type of antibody called IgE and activate
leukocytes called eosinophils, which are able to kill helminths that may be too large to be phagocytosed.
CD8+ CTLs kill cells harboring microbes in the cytoplasm by destroying the infected cells
CTLs eliminate the reservoirs of infection and kill tumor cells

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Summary

Defense

Surveillance

Homeostasis

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Summary
the early reactions
innate immunity Macrophages, ….
PAMP/DAMP nonspecific
Immune Directed recognize
Recruiting Active immunity
Immunity Limited immunologic memory passive immunity
the later responses
T/B lymphocytes
adaptive immunity TCR/BCR specific diverse repertoire
antigen-presenting cells
proliferating and differentiating into effector cells
Definition immunologic memory
Components Humoral immunity ：
Functions B lymphocytes/plasma cells, defense against extracellular microbes
Antibodies neutralize the infectivity of microbes and promote the elimination of microbes by phagocytes
and by activation of the complement system
Cell-mediated immunity:
T lymphocytes and their products, defense against intracellular microbes.
CD4+ Th lymphocytes help macrophages to eliminate ingested microbes and help B
cells to produce antibodies. CD8+ cytotoxic T lymphocytes kill cells harboring intracellular pathogens, thus
eliminating reservoirs of infection.
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Summary

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Further Reading

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Further Reading

Trends in Immunology, August 2021, Vol. 42, No. 8

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Further Reading

Figure 1. Architecture of the IL-12 Cytokine Family

Nat Immunol. ; 13(8): 722–728. IL-12 Family Cytokines

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Further Reading

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