IMMUNOLOGY

Ma Yuanfang

Introduction
1. Immunology
2. Double language lecture
Why
How

Chapter 1

Overview of the
Immune system

The immune system is a remarkable

adaptive defense system that has evolved in
vertebrate to protect them from invading
pathogenic microorganisms and cancer.
It is able to generate an enormous variety
of cells and molecules capable of
specifically recognizing and eliminating an
apparently limitless variety of foreign
invaders.

Functionally, an immune response can be divided into two

related activitiesrecognition and response. Immune
recognition is remarkable for its specificity. The immune
system is able to recognize subtle chemical differences that
distinguish one foreign pathogen from another. Furthermore,
the system is able to discriminate between foreign molecules
and the bodys own cells and proteins. Once a foreign
organism has been recognized, the immune system recruits
a variety of cells and molecules to mount an appropriate
response, called an effector response, to eliminate or
neutralize the organism. In this way the system is able to
convert the initial recognition event into a variety of effector
responses, each uniquely suited for eliminating a particular
type of pathogen. Later exposure to the same foreign
organism induces a memory response, characterized by a
more rapid and heightened immune reaction that serves to
eliminate the pathogen and prevent disease.

Historical Perspective
The discipline of immunology grew out of
the observation that individuals who had
recovered from certain infectious diseases
were thereafter protected from the disease.
The Latin term immunis, meaning exempt,
is the source of the English word immunity,
meaning the state of protection from
infectious disease.

The first recorded attempts to induce

immunity deliberately were performed by the
Chinese and Turks in the fifteenth century.
Various reports suggest that the dried crusts
derived from smallpox pustules were either
inhaled into the nostrils or inserted into small
cuts in the skin (a technique called variolation).
In 1718, Lady Mary Wortley Montagu, the wife
of the British ambassador to Constantinople,
observed the positive effects of variolation on
the native population and had the technique
performed on her own children.

The method was significantly improved by the

English physician Edward Jenner, in 1798.
Intrigued by the fact that milkmaids who had
contracted the mild disease cowpox were
subsequently immune to smallpox, which is a
disfiguring and often fatal disease, Jenner
reasoned that introducing fluid from a cowpox
pustule into people (i.e., inoculating them)
might protect them from smallpox. To test this
idea, he inoculated an eight-year-old boy with
fluid from a cowpox pustule and later
intentionally infected the child with smallpox.
As predicted, the child did not develop
smallpox.

Jenners technique of inoculating with cowpox to

protect against smallpox spread quickly throughout
Europe. However, for many reasons, including a
lack of obvious disease targets and knowledge of
their causes, it was nearly a hundred years before
this technique was applied to other diseases.
Pasteur hypothesized and proved that aging
had weakened the virulence of the pathogen and
that such an attenuated strain might be
administered to protect against the disease. He
called this attenuated strain a vaccine (from the
Latin vacca, meaning cow), in honor of Jenners
work with cowpox inoculation.

1885, Pasteur
administered his first
vaccine to a human, a
young boy who had
been bitten repeatedly
by a rabid dog
The boy, Joseph
Meister, was
inoculated with a
series of attenuated
rabies virus
preparations. He lived
and later became a
custodian at the
Pasteur Institute.

1. Early Studies Revealed Humoral and Cellular

Components of the Immune System
Although Pasteur proved that vaccination
worked, he did not understand how. The
experimental work of Emil von Behring and
Shibasaburo Kitasato in 1890 gave the first
insights into the mechanism of immunity, earning
von Behring the Nobel prize in medicine in 1901
.Von Behring and Kitasato demonstrated that
serum(the liquid, noncellular component of
coagulated blood) from animals previously
immunized to diphtheria could transfer the
immune state to unimmunized animals.

In search of the protective agent, various

researchers during the next decade
demonstrated that an active component
from immune serum could neutralize toxins,
precipitate toxins, and agglutinate (clump)
bacteria. In each case, the active agent was
named for the activity it exhibited: antitoxin,
precipitin, and agglutinin, respectively.

Initially, a different serum component was

thought to be responsible for each activity, but
during the 1930s, mainly through the efforts of
Elvin Kabat, a fraction of serum first called
gamma-globulin (now immunoglobulin) was
shown to be responsible for all these activities.
The active molecules in the immunoglobulin
fraction are called antibodies. Because
immunity was mediated by antibodies contained
in body fluids (known at the time as humors), it
mwas called humoral immunity.

In due course, a controversy developed

between those who held to the concept of
humoral immunity and those who agreed with
Metchnikoff s concept of cell-mediated
immunity. It was later shown that both are
correctimmunity requires both cellular and
humoral responses. It was difficult to study the
activities of immune cells before the development
of modern tissue culture techniques, whereas
studies with serum took advantage of the ready
availability of blood and established biochemical
techniques. Because of these technical problems,
information about cellular immunity lagged behind
findings that concerned humoral immunity.

In 1883, even before the discovery that a

serum component could transfer immunity, Elie
Metchnikoff demonstrated that cells also
contribute to the immune state of an animal. He
observed that certain white blood cells, which he
termed phagocytes, were able to ingest
(phagocytose) microorganisms and other foreign
material. Noting that these phagocytic cells were
more active in animals that had been immunized,
Metchnikoff hypothesized that cells, rather than
serum components, were the major effector of
immunity.

In a key experiment in the 1940s,Merrill Chase

succeeded in transferring immunity against the
tuberculosis organism by transferring white blood
cells between guinea pigs. This demonstration
helped to rekindle interest in cellular immunity.
With the emergence of improved cell culture
techniques in the 1950s, the lymphocyte was
identified as the cell responsible for both cellular
and humoral immunity.

Soon thereafter, experiments with chickens

pioneered by Bruce Glick at Mississippi State
University indicated that there were two types of
lymphocytes: T lymphocytes derived from the
thymus mediated cellular immunity, and B
lymphocytes from the bursa of Fabricius were
involved in humoral immunity. The controversy
about the roles of humoral and cellular immunity
was resolved when the two systems were shown
to be intertwined, and that both systems were
necessary for the immune response.

2. Early Theories Attempted to Explain the

Specificity of the Antibody Antigen Interaction
One of the greatest enigmas facing early
immunologists was the specificity of the antibody
molecule for foreign material, or antigen.
The earliest conception of the selective theory
dates to Paul Ehrlich in 1900.
In the 1930s and 1940s, the selective theory
was challenged by various instructional theories,
in which antigen played a central role in
determining the specificity of the antibody
Molecule-disproved in the 1960s.

In the 1950s, selective theories resurfaced as

a result of new experimental data and were
refined into a theory that came to be known as
the clonalselection theory. According to this
theory, an individual lymphocyte expresses
membrane receptors that are specific for a
distinct antigen. This unique receptor specificity
is determined before the lymphocyte is exposed
to the antigen. Binding of antigen to its specific
receptor activates the cell, causing it to
proliferate into a clone of cells that have the
same immunologic specificity as the parent cell.

3. The Immune System Includes Innate and

Adaptive Components

Immunitythe state of protection from infectious

diseasehas both a less specific and more
specific component.
The less specific component, innate immunity,
provides the first line of defense against infection.
adaptive immunity, does not come into
play until there is an antigenic challenge to the
organism.

Innate (nonspecific) Immunity

1) The Skin and the Mucosal Surfaces Provide

Protective Barriers Against Infection

FIGURE 1-2 Electron micrograph of rod-shaped Escherichia coli

bacteria adhering to surface of epithelial cells of the urinary tract.

2) Physiologic Barriers to Infection Include

General Conditions and Specific Molecules
The physiologic barriers that contribute to innate
immunity include temperature, pH, and various
soluble and cell associated molecules.
high body temperature,
Gastric acidity
Lysozyme,
Interferon
Complement,

3)Cells That Ingest and Destroy Pathogens

Make Up a Phagocytic Barrier to Infection

4) Inflammation Represents a Complex Sequence of

Events That Stimulates Immune Responses
Tissue damage caused by a wound or by an invading
pathogenic microorganism induces a complex sequence of
eventscollectively known as the inflammatory response.

Adaptive Immunity
Adaptive immunity is capable of recognizing and
selectively eliminating specific foreign
microorganisms and molecules (i.e., foreign
antigens). Unlike innate immune responses, adaptive
immune responses are not the same in all members
of a species but are reactions to specific antigenic
challenges. Adaptive immunity displays four
characteristic attributes:
Antigenic specificity
Diversity
Immunologic memory
Self/nonself recognition

1)The Adaptive Immune System Requires

Cooperation Between Lymphocytes and AntigenPresenting Cells

Electron micrograph of an antigen-presenting

macrophage (right) associating with a T lymphocyte.

2) Humoral Immunity But Not Cellular Immunity Is

Transferred with Antibody
3) Antigen Is Recognized Differently by B and T
Lymphocytes
4) B and T Lymphocytes Utilize Similar Mechanisms
To Generate Diversity in Antigen Receptors

5) The Major Histocompatibility Molecules

Bind Antigenic Peptides

6) Complex Antigens Are Degraded (Processed) and

Displayed (Presented) with MHC Molecules on the
Cell Surface

7) Complex Antigens Are Degraded (Processed) and

Displayed (Presented) with MHC Molecules on the Cell
Surface

8) Antigen Selection of Lymphocytes Causes Clonal

Expansion

9) The Innate and Adaptive Immune Systems

Collaborate, Increasing the Efficiency of Immune
Responsiveness