The Adaptive Immune Response
“Match me perfectly and I’m neutralized”
Kathy Huschle
Northland Community and Technical College
Adaptive Immune Response
in contrast to the innate immune response which we are
basically born with, the adaptive immune response is an
ever developing system
– it continues to mature throughout our life
Adaptive Immune Response
– in most cases as each new microbial
invader is encountered, our adaptive
immune response initiates a specific
attack against the invader
– generally this invader is remembered
and that “memory” is readily available
in the case of a second or subsequent
attack from the same invader
Adaptive Immune Response
this system is an extremely complex system to
which we will attempt to gain a basic understand
immunologists are continually discovering many
facts about the adaptive immune response
Adaptive Immune Response
the adaptive immune response
– is learned or acquired
– recognizes specific substances foreign to the
body
– is essential for life
Adaptive Immune Response
other terms used for the adaptive immune response
include
– acquired immunity
– specific immunity
though at one time thought to function exclusive of the
innate immune system, research is now discovering a
correlation between the two systems
regardless of a correlation or not, the failure of our
immune system results in mortality
Adaptive Immune Response
adaptive immune response is characterized by
– specificity
– memory
– learned ability to recognize (acquired) pathogens
which allows the body to usually only suffer once
from that particular pathogen
Components of the Adaptive Immune
System
antigens
antibodies
lymph system
lymphocytes
– B cells
– T cells
– NK cell (Natural Killer)
Antigen
Antibody
B cell
T cell
NK cell
Antigens
the term antigen derives from the two words antibody
generator
most antigens are proteins or large polysaccharides
Antigens
often a component of invading
microbes, such as the capsule,
cell wall, flagella, toxin
– particular chemical that will
activate the adaptive
immune response
Antigens found in autologous tumor
Antigens
invading microbes can
have many antigens on
its surface
pathogen
Antigens
when and antigen elicits an immune response it is
often referred to as a immunogen
epitope is the reactive portion of the antigen that reacts
chemically with an antibody to form the antigenantibody complex or immune complex
Antigens
two essential properties of antigens include
– immunogenicity
the ability to stimulate immune system
antigen-antibody
complex
Antigens
– specific reactivity
the ability to react with effector molecules
(antibody) to form an antigen-antibody complex
Antigens in red with green borders
Antibodies
glycoproteins that are also referred to as
immunoglobiulins
basic structure is a Y shaped molecule with 2 functional
parts
– Fab region
– Fc region
Fab region
Fc region
Antibodies
Fab region
– this is the part of the antibody that binds to the
antigen
Fc region
– the stem of the antibody that functions as a “red flag”
notifies the rest of the immune system: “here I am,
come and help”
Fab regions
The Fab portion of IgG binds to epitopes of a capsule.
The Fc portion can now attach the capsule to Fc receptors
on phagocytes for enhanced attachment. Once attached to
the phagocyte by way of IgG, the encapsulated bacterium
can be engulfed more efficiently and placed in a phagosome
Antibodies
protection gained from the formation of antigenantibody complexes basically comes down to the
tagging of foreign cells and molecules for destruction
by phagocytes and complement
Antibodies shown in different stains
Antibodies
the antibody molecule is not
damaging to the antigen
Melanoma antigens
Antibodies
foreign organisms and
toxins are rendered
harmless by
– neutralization
– immobilization and
prevention of adherence
– agglutination and
precipitation
– opsonization
– complement activation
– antibody-dependent
cellular cytosis (ADCC)
Respiratory syncytial virus antigens
Antibodies
neutralization
– blocks the adhesion of bacteria and
viruses by bathing the surface of the
cell with antibody
immobilization and prevention of
adherence
– antibodies binding to structures such
as flagella and pili can interfere with
mobility and attachment
Antibodies
agglutination and precipitation
– enhances phagocytosis by
gathering antigens into clumps
opsonization
– coating an antigen with antibody
enhances phagocytosis
Antibodies
complement activation
– enhances cell destruction by cell
lysis
antibody-dependent cellular
cytotxicity
– antibodies attach to target cells
causing destruction by nonspecific immune system cells
Antibodies
Antibodies
Antibodies
there are 5 classes of immunoglobulins
– each class plays a different role in the immune
response
IgG
IgM
IgA
IgD
IgE
Antibodies
IgG
– enhances phagocytosis
– neutralizes toxins and
viruses
– protects the fetus and
newborn
only immunoglobulin
that is transferred
across the placenta
Antibodies
IgG
– circulates in the blood,
but can easily exit to
the tissues
– most abundant
circulating antibody
IgG circulating in tissue
IgG
IgG reacts with epitopes on the host cell
membrane. Phagocytes then bind to the
Fc portion of the IgG and discharge their
lysosomes.
Antibodies
IgA
– provides localized protection on
mucosal surfaces
– found in mucus, tears, saliva,
sweat, blood, human milk
– protects surface tissues and
prevents adherence of
microorganisms
this is important in respiratory,
gastrointestinal and
genitourinary tract infections
Antibodies
IgM
– especially effective against
microorganisms and
clumping antigens
– these are the first
antibodies produced in
response to a mild
infection
– are circulating antibodies
found in the circulatory
system with IgG
IgM
IgG or IgM reacts with epitopes on the host cell
membrane and activates the classical complement
pathway. Membrane attack complex (MAC) then
causes lysis of the cell.
Antibodies
IgD
– function of these antibodies is not yet fully defined
– it’s presence on B cells functions in the initiation of an
immune response
Antibodies
IgE
– antibodies responsible
for allergic reaction
– possibly involved in the
lysis of parasitic worms
– found in the blood serum
– plays a role in the
initiation of the
inflammatory response
Lymphoid System
in regards to the immune
system the lymphatic
system consists of tissues
and organs that are
designed and located to
convey the B and T cells
into contact with all antigens
that enter the body
Lymphoid System
this process is accomplished
with the
– lymphatic vessels
– fluid of the lymphoid
system called lymph
– secondary lymph organs
such as tonsils, spleen,
lymph nodes
Lymphoid System
– primary lymph organs
bone marrow: the location of stem cells
that will eventually become B and T
cells, B cells mature in the bone
marrow
thymus: maturation of the T cells
Healthy bone marrow
Lymph node
Bone marrow with leukemia
Lymphoid System
notice how completely our
body is covered by the
lymphoid system
Lymphocytes
critical part of immune system responsible for
– detection of foreign antigens
– activate immune system
B lymphocytes
T lymphocytes
natural killer cells (NK cells)
B lymphocytes: B cells
antibody producing cells
that respond to an
antigen stimulation
develop from stem cells
located in the red bone
marrow of adults and the
liver of a fetus
B Cells dividing
B lymphocytes: B cells
following maturation, they
migrate to the lymphatic
tissue
B cell in lymph node
B lymphocytes: B cells
once in place in the lymphoid
organs, the B cells recognize
antigens by means of the
antigen receptors found on their
cell surfaces
basis for antibody-mediated
immunity
HIV antigens in yellow
B cells in red
B indicates a B cell
B cells
T lymphocytes: T cells
key cellular component of
immunity
develop from stem cells
found in the bone marrow
precursors to T cells
migrate to the thymus,
where they reach maturity
human T cells
T lymphocytes: T cells
following maturity, T cells migrate
to various lymph organs where
they await contact with antigens
basis for cell-mediated immunity
T cells (on left – orange,
on right – gray) killing
cancer cells (on left- mauve.
on right – red)
T cells
Natural Killer
Cells
these cells are not immunologically specific
– they do not need to be stimulated by an antigen
Natural Killer Cells
capable of destroying other cells, particularly
viruses-infected cells and tumor cells
also can attack large parasites
Clonal Selection of Lymphocytes
speaks to the ability of B cells and T cells to
differentiate to a population of cells capable of
recognizing an infinite number of antigens
– it is estimated that the human body has
approximately 1 billion B cells, yet each individual
cell is only capable of recognizing and responding
to one antigen
B cell differentiation
Clonal Selection of Lymphocytes
terms used to define various stages of clonal
selection include
– immature
– naïve
– activated
– effector
– memory
Clonal Selection of Lymphocytes
immature lymphocytes
– have not fully developed their antigen-specific
receptor
naïve lymphocytes
– have an antigen receptor, but have not
encountered the antigen
immature lymphocyte
Clonal Selection of Lymphocytes
activated lymphocytes
– have received confirmation of the danger of the
antigen and are able to proliferate more
lymphocytes specific for that antigen
effector lymphocytes
– descendents of activated lymphocytes
Activated lymphocyte
Clonal Selection of Lymphocytes
memory lymphocytes
– long-lived descendents of activated lymphocytes
– can revert back to activated lymphocytes with
stimulation from the same antigen
Antibody-Mediated Immunity
humoral or antibody-mediated immunity involves
antibodies that are produced by B cells
– the term humoral is derived from the word “humors”,
which is Latin for fluid
in response to foreign antigens, the B cell is activated to
produce a clone of plasma cells and memory cells
– plasma cells secrete antibodies
– memory cells recognize pathogens from previous
encounters
B memory cells are long lived and are ready to
mount an attack the next time that specific antigen
presents itself
Primary & Secondary Response
The body can make low levels of soluble
antibody about one week after exposure to
antigen. However, a second exposure to
antigen produces a much faster response,
and several orders of magnitude higher
levels of antibody. The ability of antibody to
bind antigen also increases in the secondary
response. The memory of antigen and
stimulated response is the basis for
vaccination
Antibody-Mediated Immunity
the antigen-antibody
complexes that are formed as a
result of antibodies produce by
B plasma cells attract
phagocytes
Bacteria in green
Antibody-Mediated Immunity
phagocytosis destroys the pathogen and control of
the disease is accomplished
Bacteria
Cell-Mediated Immunity
cell-mediated immunity involves specialized
lymphocytes that respond to intracellular antigens
T cells are responsible for managing cell-mediated
immunity
– after maturation in the thymus, T cells
differentiate into 2 groups
T-cytotoxic cells and T helper cells
Cytotoxic T cells
Helper T cell
Cell-Mediated Immunity
recognizes modified host cells
(abnormal cells)
– cell-mediated immunity is critical
to controlling infections where
pathogens reproduce in human
cell
viruses, bacteria (rickettes),
protozoa
important role in recognizing
and destroying abnormal
cells, such as tumor cells
T cells attacking cancer
Cell-Mediated Immunity
– T cells do not recognize free
antigens, the antigen must be
presented by a modified host cell
augments antibody-mediated
immunity
– eliminates cells infected with
viruses
– antibodies can’t penetrate a virus
within a host cell
T cells
Cell-Mediated Immunity
response to intracellular agents
includes
– antigen presentation
the antigen must be processed
(degraded) and then individual
peptides are displayed on the
surface of a glycoprotein called
a major histocompatibility
complex (MHC) molecule
this antigen processing is done
by antigen presenting cell
(APC)
Cell-Mediated Immunity
cytotoxic T cells recognize the non-self cell and
induce apoptosis (cell self death) in the viral infected
or other microbial infected cell
– this process also recognizes cancer cells and
destroys them
– unfortunately this process also recognizes and
destroys non-self tissue or organ transplants
Cell-Mediated Immunity
T-helper cells, often referred
to as CD4 cells, are
responsible for the “second
opinion” in immunity
– T-helper cells judge the
significance of the
antigen presented by the
antigen-presenting cells
(APC)
Cell-Mediated
Immunity
– after binding to an APC, T- helper
cells secrete cytokines that
activate other T cells and B cells
interleukin-2
macrophage chemotactic
factor
migration inhibition factor
macrophage activating factor
macrophage colony
stimulating factor
Cell-Mediated Immunity
interleukin-2
– stimulates the production of
more T cells
macrophage chemotactic factor
(MCF)
– attracts macrophages
(phagocytes) to the site of
infection or abnormality
migration inhibition factor (MIF)
– once at the infection site, MIF
inhibits the macrophages from
migrating elsewhere in the body
T cell (yellow) attracting
Macrophage (blue)
Cell-Mediated Immunity
macrophage activating factor (MAF)
– once at the infection site, MAF alters the function
of the macrophages
– increases their lysosomal activities
increases their ability to kill
Macrophage ingesting bacteria
Macrophage using
pseudopodia to grab
pathogen
Cell-Mediated Immunity
macrophage colony stimulating factor (CSF)
– regulates the production of macrophages at the
site
Macrophage and T cell
Macrophage & E.coli
T-Helper Cells
T helper cells also play a role in activating B
cells in antibody-mediated immunity
Helper T cells
Click icon to learn more about
T-cell dependent antigens
Overview of Antibody-Mediated
Immunity
initial response (bacteria with antigens enters the body)
B cells recognize
differentiate into plasma and memory cells
memory: recurring exposures
plasma produce antibodies
antigen/antibody complex forms
phagocytosis
control of disease
Overview of Cell-Mediated
modified host cell arrives
T cells activated
secrete cytokines
increase of T cell reproduction
attraction of macrophages (MCF)
inhibit migration (MIF)
activate phagocytosis (MAF)
control of disease
Overview of Immunity
Summary