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BASIC PRINCIPLES OF ADAPTIVE
IMMUNITY AND IMMUNIZATION
CHAPTER 17
Copyright © 2012 John Wiley &
Sons, Inc. All rights reserved.
CHAPTER 17 IMMUNOLOGY I: BASIC PRINCIPLES
OF ADAPTIVE IMMUNITY AND IMMUNIZATION
Immunology and immunity- Immunology is the
study of specific immunity and how the immune system
responds to specific infectious agents.
The immune system consists of various cells,
especially lymphocytes and organs such as the thymus that
help provide the host with specific immunity to infectious
agents.
Types of Immunity
Innate immunity- One kind of innate immunity is species immunity, which is common to
all members of a species. For example, all humans have immunity to many infectious
agents that cause disease in pets and domestic animals, and animals have similar
immunity to some human diseases. -determined by genetic and physiological factors is
always present and is for a lifetime
Adaptive immunity -immunity obtained in some manner other than by heredity.
Adaptive immunityNaturally acquired adaptive immunity- is most often obtained through having a specific
disease and is mediated by antigens (disease agent) and antibodies (proteins made by the
body to specifically interact with that agent). Typically antibodies form 5 to 14 days
following exposure to antigen. Depending on the antigen can last from months to a lifetime
Artificially acquired adaptive immunity- produced in response to being vaccinated.
Passive immunity- is created when ready-made antibodies are introduced into the body.
Typically lasts from days to weeks.
Naturally acquired passive immunity- mothers milk-colostrum
Artificially acquired passive immunity- antibodies made by other hosts are introduced
into a new host (anti-venom, gamma-globulin, tetanus-antibodies)
Panton-Valentine Leukocidin is an important virulence factor for
methicillin resistant staphylococcus
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50%
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50%
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A. True
B. False
How to Develop New Antibiotics THE bacteria are winning. Every year, according to the Centers for
Disease Control and Prevention, at least two million people are infected with bacteria that can’t be wiped
out with antibiotics, and as a result, 23,000 people die. Direct health care costs from these illnesses are
estimated to be as high as $20 billion annually. Just last week, the U.C.L.A. Health System announced that
nearly 180 patients may have been exposed to the CRE superbug that was linked to two deaths in one of its
hospitals. Today, 30 percent of severe strep pneumonia infections are resistant to multiple drugs and 30
percent of gonorrhea infections are resistant to all antibiotics. And drug-resistant enterobacteriaceae,
enterococcus, acinetobacter and a slew of other unpronounceable bacteria pose serious threats. The
development of antibiotics has been glacial. We need a completely new approach. he number of F.D.A.approved antibiotics has decreased steadily in the past two decades. The big pharmaceutical companies
have largely stopped work on these drugs. Pfizer, long the leader in developing antibiotics, closed its
antibiotic research operations in 2011. Smaller biotech companies now account for 80 percent of
antibiotic development. There are now about 40 new antibiotics in development. That might sound
promising — but not when compared with the 771 new drugs and vaccines in clinical trials or awaiting F.D.A.
review for cancer. And most of these antibiotics are unlikely to come out of the testing process as F.D.A.approved drugs. The big problem is profitability. Unlike drugs for cholesterol or high blood pressure, or
insulin for diabetes, which are taken every day for life, antibiotics tend to be given for a short time, a week
or at most a few months. So profits have to be made on brief usage. Furthermore, any new antibiotics that
might be developed to fight these drug-resistant bacteria are likely to be used very sparingly under highly
controlled circumstances, to slow the development of resistant bacteria and extend their usefulness. This
also limits the amount that can be sold. Because it costs at least $1 billion to develop a new drug, the prize
money could provide a 100 percent return — even before sales. From the government perspective, such a
prize would be highly efficient: no payment for research that fizzles. Researchers win only with an approved
product. Even if they generated just one new antibiotic class per year, the $2-billion-per-year payment would
be a reasonable investment for a problem that costs the health care system $20 billion per year.
Whole virus vaccine for Ebola found to effectively protect monkeys The vaccine, detailed in the
journal Science, was developed using a novel experimental platform at the University of WisconsinMadison that allowed the researchers to safely study the virus in laboratory conditions. A group of
scientists have developed a whole Ebola virus vaccine that can successfully protect monkeys from the
virus and is capable of preparing the immune system with the full range of viral proteins and genes.
"In terms of efficacy, this affords excellent protection," says Prof. Yoshihiro Kawaoka, a professor of
pathobiological sciences at the University of Wisconsin-Madison School of Veterinary Medicine. "It is
also a very safe vaccine." Whole virus vaccines have been used in the past to prevent other serious
diseases, including hepatitis, human papillomavirus-mediated cervical cancer, influenza and polio.
Using inactivated whole viruses provides the immune system with the complete range of viral
proteins and genes, improving the likelihood of the virus triggering a strong immune response. Earlier
attempts to develop an inactivated whole Ebola virus vaccine, using irradiation and the preservative
formalin, were ultimately unsuccessful and failed to protect monkeys from the virus. As a result,
these attempts were abandoned. Developing a new experimental platform from which to work with
the virus has helped these researchers to be successful this time round. Devised in 2008, the new
system enabled the team to work safely with Ebola virus by deleting a key gene called VP30 which
allows the virus to make a protein required for it to reproduce. Using monkey kidney cells engineered
by the researchers to express VP30, the team could safely use the virus as a starting point for the
development of treatment for it. The whole virus vaccine devised by Kawaoka and his team was also
chemically inactivated with hydrogen peroxide. While the researchers have overcome the problems
experienced by previous attempts at developing a whole virus vaccine, it will still be some time
before the vaccine is ready to be rolled out. Human trials need to be conducted, and these are both
complex and highly expensive.
Obama Seeks to Double Funding to Fight Antibiotic ResistanceWASHINGTON —
President Obama on Friday urged Congress to double the funding to confront the
danger of antibiotic-resistant bacteria, calling it a major public health issue that, if left
unchecked, would “cause tens of thousands of deaths, millions of illnesses.” The
administration also issued a new plan for attacking the problem, part of a national
strategy that Mr. Obama laid out in an executive order in September. The plan calls for
improved surveillance of outbreaks, better diagnostic tests and new research on
alternative drugs. It also urges government agencies to bolster systems to track the
consumption of antibiotics and to reduce inappropriate use in people and animals. The
new plan’s strength, experts said, is its actions to curb use in humans. It calls on federal
agencies like the Centers for Disease Control and Prevention to create a tougher
surveillance system to monitor the use of antibiotics in hospitals and other medical
settings. It includes specific steps that hospitals participating in Medicaid and Medicare
must take to reduce inappropriate use. “The news here is that the administration is
setting specific, annual milestones for tackling the problem,” said Allan Coukell, the
senior director for health programs at the Pew Charitable Trusts, a Washington-based
research and advocacy group that contributed to the administration strategy outlined in
September. Americans use more antibiotics than people in other industrialized nations,
with rates more than twice those in Germany and the Netherlands, according to Pew.
The White House said the president wanted to double the amount of federal funding for
combating and preventing antibiotic resistance to more than $1.2 billion. The plan calls
for “enhanced summary reports on the sale of distribution and antibiotics” used in food
Adaptive Immunity
• Natural
• Artificial
• Active
• Passive
© 2012 John Wiley &
Fig. 17.1 The Copyright
various
types of immunity
Sons, Inc. All rights reserved.
Antibodies bind to specific chemical groups or
structures termed epitopes or antigenic determinants.
A single protein may have many epitopes.
H-antigen
O antigen
Gram-negative bacterium with several different antigenic determinants
Fig. 17.2 A typical antigen-antibody reaction
Antigens and AntibodiesAntigen- An antigen is a substance the body recognizes
as foreign and against which it mounts an immune response.
Most antigens are proteins greater than 10,000 MW. Some
antigens are polysaccharides, and a few are glycoproteins or
nucleoproteins
Epitopes- large complex proteins can have
several antigenic determinants (places where the polyclonal
antibody binds).
Haptene- haptene can react with an antibody but
by itself cannot illicit the production of an antibody (typically
because it is too low molecular weight).
Antibody- a protein produced in response to an antigen
that is capable of binding specifically to the antigen.
Cells and Tissues of the Immune System
Lymphocytes that are processed and mature in tissue referred to
as bursal-equivalent tissue become B lymphocytes or B cells.
Functional B cells are found in all lymphoid tissues-lymph
nodes, spleen tonsils adenoids, and gut-associated lymphoid
tissue. B cells account for about one-fourth of the lymphocytes
circulating in the blood. Other stem cells migrate to the thymus,
where they undergo differentiation into thymus-derived cells
called T lymphocytes or T cells. In adults when the thymus
becomes less active differentiation of T cells is thought to occur
in bone marrow or tissues under the influence of hormones from
the thymus
Fig. 17.3 Differentiation of stem cells into B
cells and T cells.
The bursa of Fabricius- In chickens this is where B cells develops
and is the origin of the term B-cell in mammals.
Fig. 17.4 The bursa of Fabricius
I will not ask you the percentage of B and T cells in the various tissues. Know that: 1, the
spleen contains about equal amounts of B and T cells, Peyer’s patches in digestive tract
important source of B cells and that most other tissues are weighted in T cells.
Dual Nature of the Immune System
Humoral immunity- carried out by antibodies,
produced by B cells, circulating in the serum. Humoral
immunity is most effective in defending the body against
bacterial toxins, bacteria, and viruses before they enter
cells.
Cell-mediated immunity is carried out by T cells. It is
most effective in clearing the body of virus-infected cells, but
also in defending against fungi and parasites, cancer and
foreign tissues such as transplanted organs.
Recognition and self versus non-self.
How the body recognizes an antigen
How the body distinguishes between a
foreign antigen and the body's own antigens
Questions?
email the course director:
Dr. Sarah D’Orazio
([email protected])
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Bacterial Pathogenesis
Course topics:
u Defining virulence: what is a bacterial pathogen?
u Overview of innate and adaptive immune mechanisms
u In vitro and in vivo approaches to measure infectivity & virulence
u Mechanisms for extracellular survival in the host
u Adherence, motility & biofilms
u Bacterial toxins and secretion systems
u Intracellular bacteria: life in the cytosol vs. escape from the vacuole
u How bacteria become resistant to antibiotics
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course prerequisites: BIO308 (BIO208 with permission) & BIO315
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The B cell
specificity is
largely
determined
during
developmentalthough some
adjustments are
made
following
exposure to
antigen
Clonal selection hypothesis. According to this theory, one of many B cells responds to a particular antigen
and begins to divide, thereby producing a large population of identical B cells (a clone). All cells of such a
clone produce the same antibody against the original epitope. B memory cells are also produced.
http://www.youtube.com/watch?v=Ys_V6FcYD5I
Clonal selection youtube
Fig. 17.5 Clonal selection hypothesis
This process which occurs during embryonic development and results in removal of
those lymphocytes that have receptors for self antigens. If you did not have this
system you would reject your own tissues.
Fig. 17.6 Clonal deletion
Humoral Immunity (antibody production). In a typical
immune response, helper T cells facilitate growth and
differentiation of plasma cells -which produce antibody
(humoral immunity). After about a week this reaction reaches
a peak and then subsides, largely because suppressor T cells
inhibit further antibody production.
I am a low molecular weight molecule. I cannot by myself illicit the
production of antibody. However, if antibody is produced when I am
linked to a protein I can react with that antibody. I am a haptene
se
50%
Fa
l
50%
Tr
ue
A. True
B. False
Enterovirus 68 May Be Linked to Paralysis in Children, Study Says A new strain
of a common respiratory virus may be responsible for partly paralyzing scores
of children nationwide, researchers reported on Monday. Researchers at the
University of California, San Francisco, analyzed genetic sequences of
enterovirus 68 cultured from 25 children in Colorado and California with limb
paralysis, also called acute flaccid myelitis. The researchers concluded that the
viruses were a novel strain of enterovirus 68, which they called B1. Using a
method called “molecular clock analysis,” the team estimated that the B1
strain emerged four and half years ago. On balance, he said, that strengthens
the case that the B1 strain of enterovirus — detected in roughly half of the
children’s nasal secretions — was linked to their paralysis. One sibling pair — a
school-age girl and her younger brother — were both infected with identical B1
strains of enterovirus 68 and got colds, Dr. Chiu and his colleagues found. The
girl suffered paralysis in both arms and her trunk. Her brother experienced no
lasting effects. Enterovirus 68 may be a contributor to the children’s paralysis,
said Priya Duggal, the director of the genetic epidemiology program at Johns
Hopkins Bloomberg School of Public Health, who had nothing to do with the
study. “But it must not be acting alone, because children with the same virus
and siblings with the same clade have different outcomes.”
Fecal transplantation for patients with Clostridium difficile infection may
be a more effective treatment strategy than previously thought,
according to a new study.,, the study reveals that fecal transplantation
makes long-term healthy changes to the gut bacteria of patients
infected with C. difficile - a finding they say could have important
regulatory implications for the procedure. C. difficile infections are a
major health concern in the US. According to the Centers for Disease
Control and Prevention (CDC), the bacterium caused around half a
million infections in 2011 and killed around 29,000 people within 30
days of diagnosis. While many C. difficile infections can be treated with
antibiotics, the infection can keep coming back for some patients. In
these cases, fecal microbiota transplantation (FMT) may be
recommended. The researchers found that the gut bacteria of patients
who underwent FMT was normalized shortly after the procedure. They
were surprised to find, however, that while the composition of
patients' gut bacteria changed following FMT, it remained healthy for
up to 21 weeks.
Each antibody binds to a specific
antigen; an interaction similar to a
lock and key
antibody binding site
Variable
regiondetermines
Ab specificity
Constant
region
determines the
particular class
that an
immunoglobuli
n belongs to
Antibodies or immunoglobulins (Ig), are Y-shaped protein molecules composed of four
polypeptide chains- two identical light (L) chains and two identical heavy (H) chains. The
chemical structure of the constant region determines the particular class that an
immunoglobulin belongs to,. The variable regions of each chain have a particular shape
and charge enable the molecule to bind a particular antigen, i.e., the variable region is what
confers the specificity to the antibody.
Fig. 17.7 Antibody structure
Fig. 17.7 continued
Additional Constant Region Attributes:
1,Complement binding site-complement binds to antigen-antibody complex at that site
2, Site of bonding to macrophages- how antibody facilitate opsonization, i.e., ab binds to the surface
of the capsule of a bacterium which inturn can be taken up by a macrophage by binding to this site
of the antibody
3. Ability to cross the placenta- Enables IgG to cross the placenta
1
2
3
4
5
IgM and IgD serve as
receptors on B cells to
which Ag binds.
IgA is secreted across
epithelium-typically in
mucus secretions
1-ag/ab-triggers complement
2-protect newborn
5-immunoglobulin associated with allergy
3-facilitate phagocytosis
4- act as receptor for
antigen presenting cells
Secretory piece associated with IgA Confers the unique ability of that antibody to traverse the epithelial
layer and be in secretions (mucus)
Fig. 17.8 The structures of the different classes of antibodies
Points of this slide:
1.
induction
period
2.
3.
B cells initially produce
IgM in higher quantity
than IgG
The peak of IgG then
follows that of IgM (there
may be switching from
production of IgM to
production of IgG by
cytokines)
Following second exposure
to the same antigen the level
of IgM roughly the same as
the first exposure, however,
the level of IgG is greatly
enhanced because it is
generated from a clone of
memory cells. There are
no memory cells for IgM
This figure shows the correlation of antibody concentrations with the activities of B cells. Cytokines trigger
the class switching from IgM to IgG
Fig. 17.9 Primary and secondary responses to antigen
T-independent
antigens only produce
IgM hence, there is
no “memory”
response.
Fig. 17.9 Primary and secondary responses to an antigen
neutralization
Opsonization-this is how
Ab facilitate the uptake
of S. pneumoniae, i.e., Ab
allows macrophage to
engulf the org. See Fig.
17.7 for site on ab that
binds to the macrophage
surface.
Cell lysis IgG
or M plus
complement
form an
attack
complex
Fig. 17.10 Antibodies produced by humoral immune responses eliminate
Foreign agents in three ways
lymphoid
Fig. 17.11 Summary of humoral immunity
Figure 17-10- Antibodies produced by humoral immune responses
eliminate foreign agents in three ways.
1) neutralization of pathogens and toxins by IgA or
IgG
2) opsonization of bacteria by IgG and
3) cell lysis initiated by IgM or IgG immune complexes
allows for the formation of membrane attack complexes
involving complement proteins.
Below are the numbers
of Unassigned Devices
131959
23294D
57E484
595143
5c7B7A
7F57F
82C91
90CA7
T-independent antigens only trigger the production of IgG
50%
Fa
lse
e
50%
Tr
u
A. True
B. False
Growth of global antibiotic use for livestock raises concerns about drug resistance A new study predicts the next
15 years will see a startling increase in worldwide use of antibiotics in livestock, raising serious concerns
about the effect this will have on a growing global health problem - drug-resistant pathogens or superbugs.
Antibiotics are used widely in the farming of food animals to treat disease and increase productivity. In the
US, antibiotic consumption in animals accounts for up to 80% of antibiotic sales. While studies suggest such
practice fuels the spread of drug-resistant pathogens in animals and humans, the lack of reliable global data
makes it hard to both measure the size of the problem and come up with solutions. n the Proceedings of the
National Academy of Sciences, they present their findings in the form of a global map of antibiotic use in
livestock, covering a total of 228 countries. Senior study author Dr. Ramanan Laxminarayan, a senior
research scholar at the Princeton Environmental Institute at Princeton University, NJ, says:"The invention of
antibiotics was a major public health revolution of the 20th century. Their effectiveness - and the lives of
millions of people around the world - are now in danger due to the increasing global problem of antibiotic
resistance, which is being driven by antibiotic consumption."The researchers estimate "conservatively"
that the total global consumption of antibiotics by livestock in 2010 was 63,151 tons, and that by 2030,
this figure will be 67% larger overall.
They suggest most of the growth (66%) will be due to increases in the number of animals raised for food driven mostly by rising demand in middle-income countries, and partly (34%) due to a shift toward largescale, intensive or "factory" farming where antibiotics are used routinely.
In Brazil, China, India, Russia and South Africa the increase will be dramatic, mostly because of these two
factors. These five countries will see a 99% increase in antibiotic consumption but only a 13% growth in
their human populations over the same period. "Antibiotic resistance is a dangerous and growing global
public health threat that isn't showing any signs of slowing down. Our findings advance our understanding
of the consequences of the rampant growth of livestock antibiotic use and its effects on human health - a
crucial step towards addressing the problem of resistance."
Common bacteria on verge of becoming antibiotic-resistant superbugs Antibiotic resistance is poised to spread
globally among bacteria frequently implicated in respiratory and urinary infections in hospital settings,
according to new research at Washington University School of Medicine in St. Louis. The study shows that
two genes that confer resistance against a particularly strong class of antibiotics can be shared easily among a
family of bacteria responsible for a significant portion of hospital-associated infections. Drug-resistant germs
in the same family of bacteria recently infected several patients at two Los Angeles hospitals. The infections
have been linked to medical scopes believed to have been contaminated with bacteria that can resist
carbapenems, potent antibiotics that are supposed to be used only in gravely ill patients or those infected by
resistant bacteria. "Carbapenems are one of our last resorts for treating bacterial infections, what we use when
nothing else works," said senior author Gautam Dantas, PhD, associate professor of pathology and
immunology. "Given what we know now, I don't think it's overstating the case to say that for certain types of
infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we
rely on to treat bacterial infections are no longer effective." The researchers studied a family of bacteria
called Enterobacteriaceae, which includes E. coli, Klebsiella pneumoniae and Enterobacter. Some
strains of these bacteria do not cause illness and can help keep the body healthy. But in people with
weakened immune systems, infections with carbapenem-resistant versions of these bacteria can be
deadly. Two genes are primarily responsible for carbapenem-resistant versions of these disease-causing
bacteria. One gene, KPC, was detected in New York in 2001 and quickly spread around most of the world,
with the exception of India, Pakistan and other South Asian countries. This gene was present in the bacteria
that recently contaminated medical equipment in a Los Angeles hospital where two patients died. A second
carbapenem resistance gene, NDM-1, was identified in 2006 in New Delhi, India. It was soon detected
throughout South Asia, and most patients infected by bacteria with NDM-1 have had an epidemiological link
to South Asian countries. The researchers identified a few key instances in which the plasmids carrying
NDM-1 or KPC were nearly identical, meaning they easily could facilitate the spread of antibiotic
resistance between disease-causing bacteria found in the United States and South Asia. Recent evidence
suggests that this intermingling already may be happening in parts of China.
Why the Flu Sometimes Kills Many people catch the flu every year and, after several days, recover. But for
some, the disease becomes life threatening. Researchers now know one reason why. In 2011, the parents of a
2-year-old girl with labored breathing carried their daughter into a French hospital. She was admitted, tested,
and eventually diagnosed with the flu. Influenza is dangerous in children because of their still-developing
immune systems, but some cases like this one, can be more severe, requiring hospitalization. Now, using
next-generation sequencing and stem cell technologies, researchers from The Rockefeller University
have found the Achilles heel in this child’s immune system that allowed for such a serious first
encounter with the flu. When Casanova and his colleagues learned of this girl's condition, they focused on
identifying genes that might be responsible for her particular vulnerability to flu by first sequencing both her
and her parents' protein-coding DNA. By focusing on mutations in genes related to the immune system that
were unique to the girl, the researchers identified interferon regulatory factor 7 (IRF7) as the culprit. In
this case, she had inherited a different mutation from each parent, whose heterozygous status protected them
from the same response to the flu she experienced but made her susceptible to flu. Normally, the transcription
factor IRF7 drives expression of genes essential to the anti-viral response. To investigate IRF7 function in the
patient's cells, the team exposed her blood samples to different viruses and confirmed that they did not
produce interferons in response. In contrast, her parents' cells produced a healthy response, showing that only
one copy of the gene is necessary. The research team then collected skin cells from the child, reprogrammed
them into iPS cells, and differentiated these into lung cells where they could study the effects of influenza.
They found that the virus replicated significantly more in the child's cells than in cells from healthy donors.
The study not only identified the genetic underpinnings of this severe influenza infection in the young girl,
but also suggested a possible treatment, advancing physicians one step closer towards personalized medicine
for influenza. "Had we known the patient had IRF7 deficiency when she was admitted, perhaps she would
have benefited from recombinant alpha interferon, in addition to the Tamiflu and oxygen that she was given,"
said Casanova.
Production of monoclonal antibodies. Only the hybridoma cells grown in culture will survive.
Because unfused spleen cells cannot divide in culture, and unfused mouse myeloma cells cannot
synthesize nucleic acid (have been selected for this property). When fused together (hybridoma)
they can grow.
Spleen cells do not grow
in tissue culture by themselves
http://www.youtube.com/watch?v=c_krTc9M1WU
Fig. 17.12 Production of monoclonal antibodies
Myeloma cells are selected
such that they cannot make
nucleic acid by themselves
Cell-Mediated Immunity- In contrast to humoral immunity,
which involves B cells and immunoglobulins, cell-mediated
immunity involves the direct actions of T cells. In cellmediated immunity, T cells interact directly with other
cells that display foreign antigens. The cell-mediated
immune response involves the differentiation and actions of
different types of T cells and the production of chemical
mediators called lymphokines.
The cell mediated immune reaction-
Activation of helper T cells
•
•
HIVattacks
here
•
•
TH cells have receptors that
recognize the peptide fragment
on MHC class II. Binding
causes the TH cells to become
active.
The activated T cells then
differentiate into either TH1 or
TH2 cells.
TH1 cells activate infected
macrophages to destroy
internal bacterial infections.
TH2 cells activate B cells by
binding to MHC class II:
peptide presented by the B
cells, activate the B cells to
produce Ab.
http://www.youtube.com/watch?v=Xhoiu0w1-Js&feature=related
Activation of cytotoxic T Cells
Presenting the same peptide fragment on
MHC class I to TC cells activates these
cells to attack infected cells, especially
abnormal or virus-infected cells.
Figure 17.13 The reactions in cell-mediated immunity
Helper T cells can be further divided
into Ts (tumor suppressor) and Td
cells (delayed hypersensitivity) by the
combined action of IL-1 (from
macrophages and IL-2 (from TH
cells)).
After T cells are challenged by antigens, the cells differentiate into one of several types of
functioning T cells.
Fig. 17.14 Types of T cells
Macrophages that have processed
an antigen secrete the
lymphokine IL-1 which activates
helper T cells (TH). Activated TH
cells produce another cytokine,
Il-2, which activate other T cells
suppressor T (TS) cells, delayed
hypersensitivity T cells (TD),
and cytotoxic (killer) T cells
(TC).
Fig. 17.15 Summary of cell-mediated immunity
Activated TD cells also release various lymphokines
including:
1. Macrophage chemotactic factor,
which helps macrophage find microbes
2. Macrophage activating factor, which
stimulates phagocytic activity and the production of
anti-bacterial compounds, e.g., H2O2, O23. Migration inhibiting factor, which
prevents macrophage from leaving sites of infection
4. Macrophage aggregation factor,
which causes macrophages to congregate at such sites
TD cells also participate in delayed hypersensitivity
which will be discussed in chapter 18.
How killer cells killCytotoxic T cells act mainly on virally infected cells,
whereas
NK cells act mainly on tumor cells, cells of transplanted
tissues, and possible on cells infected with intracellular
agents such as rickettsias and chlamydias.
Cytotoxic T cells bind to antigens presented by macrophages
and then attack virus-infected cells.
In contrast, NK cells bind directly to malignant or other
target cells without the help of macrophages.
Both kinds of killer cells contain granules of a lethal
protein, perforin, which is released when they bind to a
target cell. Perforin bores holes in the target cell.
Given their strong cytolytic activity and the potential for auto-reactivity, NK cell
activity is tightly regulated. NK cells must receive an activating signal, which can
come in a variety of forms, the most important of which are listed below.
•1. Cytokines
•The cytokines play a crucial role in NK cell activation. As these are stress molecules
released by cells upon viral infection, they serve to signal to the NK cell the presence of
viral pathogens. Cytokines involved in NK activation include IL-12, IL-15, IL-18, IL-2,
and CCL5.
•2. Fc receptor
•NK cells, along with macrophages and several other cell types, express the Fc receptor
(FcR) molecule (FC-gamma-RIII = CD16), an activating biochemical receptor that
binds the Fc portion of antibodies. This allows NK cells to target cells against which a
humoral response has been mobilized and to lyse cells through Antibody-depdendent
cellular cytotoxicity (ADCC).
•3. Activating and inhibitory receptors
Aside from the Fc receptor, NK cells express a variety of receptors that serve either to
activate or to suppress their cytolytic activity. These receptors bind to various ligands on
target cells, both endogenous and exogenous, and have an important role in regulating
the NK cell response.
The action of cytokines may autocrine, paracrine and endocrine. Cytokines are critical to the development and functioning
of both the innate and adaptive immune response, although not limited to just the immune system. They are often secreted
by immune cells that have encountered a pathogen, thereby activating and recruiting further immune cells to increase the
system's response to the pathogen. Cytokines are also involved in several developmental processes during embryogenesis.
Interleukins are a group of cytokines (secreted signaling molecules)
Table 17.5 Characteristics of B cells, T cells and Macrophages
Immunization
Active immunization- is the process of inducing active
immunity (vaccines or toxoids). A vaccine in a substance that
contains an antigen to which the immune system responds.
Passive Immunization- Antiserum- serum containing
antibodies- gamma globulin, or hyperimmune
serum, Can also use animals, such as a horse, for
preformed tetanus antibodies that have been raised
commercially by injections of toxoid. (serum sickness is
one danger of this type of immunization (will discuss in
the next chapter).
Immune serum globulin (gamma globulin)- pooled
gamma globulin fraction from many individualsprovides passive immunity to a number of common
disease such as mumps, measles, hepatitis B, tetanus,
rabies, and pertusis (whopping cough). hyperimmune
sera contains especially high titers against a particular
agent obtained from donors with a high titer of antibody
against that agent. Antitoxins- to combat snake or
spider venoms
Immunity to Various Kinds of Pathogens
Bacteria- Antibodies can work with
complement to opsonize bacteria (coat with
antibody) for later phagocytosis or lysis by other
cells of the immune system. Or they can neutralize
bacterial toxins or inactivate bacterial enzymes.
A- Viruses at epithelial
surfaces bathed in IgA in
mucos which inactivates the
virus by blocking its binding
site
B- Viruses inside blood
vessels
(antibody agglutinates, or
blocks
virus from finding receptor)
C- Viruses inside cells that
display viral antigens
(cytotoxic T cells (Tc)
destroy the cells.
D- Sometime more damage
results from immune
response (killing of virus
infected cells) than would
have been caused by the
virus alone. Many upper
respiratory viral infection
trigger a host of defense
mechanisms, e.g.,
inflammation, sloughing of
cells, mucus production that
are worse than the action of
the virus killing some cells.
Fig. 17.17 How the immune system combats viruses