ADAPTIVE IMMUNITY

COURSE TITLE: BASIC IMMUNOLOGY

COURSE CODE:MLS 305
(FIRST SEMESTER)

DR. UNYIME C. ESSIEN

 Types of Immunity

Innate
Adaptive(acquired) immunity
immunity

Naturally acquired Artificially acquired

Passive Passive
Active
Antibodies from Preformed Active
Antigens enter the
mother to baby antibodies Vaccination with
body naturally
through the introduced to the inoculated pathogens
through infection,
placenta or breast body e.g tetanus or products of
the body forms
milk (IgA) Antitoxin pathogens. Memory
antibodies.
cells.
 Types of Immunity

Innate Adaptive immunity

immunity

-Non-specific
-Present at birth -Specific
-Less -Specialized
specialized -More potent
-Present at birth -Develop after birth
-No memory -Memory
-Respond to -Response is different
foreign invaders depending on invader
in the same
way
 Adaptive Immunity

Cellular
Humoral Immunity Immunity (Cell
mediated)

B-cells T-cells

T-helper
T- cytotoxic
cells
Memory Plasma
cell cell
T-regulatory
cell or
Secondary suppressor
Antibodies cell
immune
response
stronger
GMADE
and faster
 Antigen

 Antigen is a substance that is recognized by host as foreign, as a

result stimulates immune response.
 Antigen can be foreign or self.
 Foreign antigens, this substances are not part of human body, the
originate outside the body they can be microbial agents (e.g.
capsule, cell wall, flagella, fimbriae, toxins of bacteria, the oat of
viruses, surface envelope, surface component of microbes).
 Foreign agents may also be non- microbial, that may arise from
animal, plant, pollen, blood cell from a donor, transplant tissues or
organ).
 Self antigens, immune system is able to distinguish between self
and foreign antigen.
 Epitope: The immune system does not recognize whole pathogens,
but portions or part of the pathogens. This portions or parts are
termed epitope or antigenic determinants.
 They are called antigenic determinant because the part or portion of
antigen that determine immune response.
 Each antigens has several epitopes.
 The chemical components of this antigens may be glycoprotein,
protein or polysaccharide.
 Recently, the term is used more broadly to describe any molecule
that reacts specifically with an antibody, a B-cell receptor, or a T-
cell receptor.
 Antigen
 Most antigens are T-dependent antigens, meaning that responding
to B cell requires a signal from a T-helper cell as part of the
activation process.
 T-dependent antigens characteristically have a protein component.
 In contrast, T-independent antigens can activate B cells without
T-helper cell help.
 T-independent antigens include lipopolysaccharide (LPS) and
molecules with identical repeating subunits, such as some
carbohydrates.
 Various antigens differ in their effectiveness in stimulating an
immune response. Proteins generally induce a strong response,
whereas lipids and nucleic acids often do not.
 The term immunogenic is used to describe the relative ability of an
antigen to elicit an immune response.
 Humoral Immunity

 The humoral immunity is also known as antibody or B-cells

mediated immunity.
 The B- lymphocytes are so called because they mature in the bone
marrow.
 Immature lymphocytes. These have not fully developed their
antigen-specific receptors.
 Naive lymphocytes. These have antigen receptors, but have not yet
encountered the antigen to which they are programmed to respond.
 Activated lymphocytes. These are able to proliferate; they
recognize that a specific antigen is present because their antigen
receptor has attached to it, and they have received the second signal
confirming that the antigen requires a response.
 Humoral Immunity

 Effector lymphocytes. These are descendants of activated

lymphocytes, armed with the ability to produce specific cytokines
or other protective substances.
 Plasma cells are effector B cells, T C cells are effector cytotoxic T
cells, and T H cells are effector helper T cells.
 Memory lymphocytes are long-lived descendants of activated
lymphocytes; they can quickly become activated when an antigen is
encountered again.
 Memory lymphocytes are responsible for the speed and
effectiveness of the secondary response.
 T- dependent B-cell activation

 Naive B cells are located secondary lymphoid organs, where they

encounter antigens.
 When a B cell’s antigen receptor (B-cell receptor) binds to a T-
dependent antigen, the B cell takes the antigen in by endocytosis,
enclosing it within an endosome.
 There, the antigen is degraded into peptide fragments that are then
delivered to protein structures called MHC class II molecules.
 The antigen is presented for inspection by T H cells a process
called antigen presentation.
 T H cells in the secondary lymphoid organs, scan the naive B cells
that are presenting antigens.
 T- dependent B-cell activation

 If a T H cell’s antigen receptor (T-cell receptor) binds (second signal

from T-H cell) one of the peptide fragments being presented by a B
cell, then that T cell activates the B cell.
 It does this by delivering cytokines to the B cell, initiating the process
of clonal (proliferation ie they multiply, generating a population of
cells that recognize the antigen) of that particular B cell.
 Some of the activated B cells continue dividing, others differentiate to
form antibody secreting plasma cells.
 Each plasma cell generally undergoes apoptosis after several days, but
activated B cells continue multiplying and differentiating, generating
increasing numbers of plasma cells as long as antigen is present.
 The result is a slow but steady increase in the titer (concentration) of
antibody molecules.
 T- dependent B-cell activation

 The first (primary) exposure and immune response to antigen as

explained is referred to as PRIMARY IMMUNE RESPONSE.

 Primary immune response may take about 10 to 14 days for a

significant concentration of antibodies to accumulate.

 During this delay, the person might experience signs and symptoms
of an infection, which could be life-threatening.

 Some B cells become memory B cells. These persist in the body for
years and accumulate in high enough numbers to give a fast
secondary response if the same antigen is encountered again later.
 T- dependent B-cell activation

 The antibody response begins to decrease as the antibodies clear the

antigen. As fewer molecules of antigen remain to stimulate the
lymphocytes, the activated lymphocytes undergo apoptosis.

 Memory B cells, however, are long-lived even in the absence of

antigen.
 T- dependent B-cell activation
 Secondary immune response
 The secondary response is much faster and more effective than the
primary response. In fact, repeat invaders are generally eliminated
before they cause noticeable harm.
 This is why a person who has recovered from a particular disease
typically has long-lasting immunity to the microbe that caused it.
 Vaccination takes advantage of secondary immune response.
 Memory B cells are responsible for the efficiency of the secondary
response. For one thing, there are more cells, memory B cells as
well as memory helper T cells that can respond to a specific
antigen.
 In addition, the memory B cells are able to scavenge even low
concentrations of antigen because their receptors have been fine-
tuned through affinity maturation.
 Secondary immune response

 When memory B cells become activated, some quickly differentiate

to form plasma cells, resulting in the rapid production of
antibodies.
 Additional exposures to the same antigen lead to an even stronger
response.
 Primary and secondary immune response to antigen

 Amount of antibody in serum is called the antibody titer.

 Primary response: Response of the body to the first contact with
an antigen. Mostly IgM
 Secondary response: any subsequent contact with the same
antigen. Rapidly very high antibody titer. Mostly IgG. Figure 1.0
 The first exposure to antigen elicits relatively low amounts of first
IgM, followed by IgG in the blood.
 The second exposure, which characterizes the memory of the
adaptive immune system, elicits rapid production of relatively large
quantities of IgG.
 T-independent B-cell activation

 T-independent antigens (polysaccharide, lipopolysaccharide,

glycolipids, nucleic acid) can activate B cells without the aid of T H
cells.
 T- independent B-activation does not provide memory.
Structure of Immunoglobulins
 Structure of Immunoglobulins

 Antibodies, also called immunoglobulins, are Y-shaped proteins

that have two general parts the arms and the stem.
 The two identical arms, called the fragment of antigen binding
(Fab) regions, bind antigen. The stem is the fragment
crystallizable (Fc) region.
 It consists of two copies of a high-molecular-weight polypeptide
chain, called the heavy chain, and two copies of a lower-
molecular-weight polypeptide chain, called the light chain.
 Each light chain is linked to a heavy chain by a disulfide bond.
 The variable region is the portion at the ends of the Fab regions;
it accounts for the antigen-binding specificity of the antibody.
 Part of this region is the antigen-binding site, the portion that
attaches to a specific epitope.
 Structure of Immunoglobulins
 Nevertheless, the antigen-antibody interaction is reversible, and the
molecules can separate, leaving both antigen and antibody
unchanged.
 The constant region includes the entire Fc region, as well as part
of the two Fab regions.
 There are five general types of constant regions, and these
correspond to the major classes (also called isotypes) of
immunoglobulin (Ig) molecules: IgM, IgG, IgA, IgD, and IgE.
 Protective Outcomes of Antibody-Antigen Binding

 The protective outcomes of antibody-antigen binding depend partly on the

antibody class, and include:
 (1) Neutralization. Toxins and viruses must bind specific molecules on a cell
surface before they can damage that cell.
 A toxin or virus coated with antibodies cannot attach to cells and is said to be
neutralized.
 (2) Opsonization. Phagocytic cells have receptors for the Fc region of IgG
molecules, making it easier for the phagocyte to engulf antibody-coated
antigens. Complement protein C3b is another examples of an opsonin.
 (3) Immobilization and prevention of adherence. Binding of antibodies to
flagella interferes with a microbe’s ability to move; binding to pili prevents a
bacterium from attaching to surfaces.
 These capabilities are often necessary for a pathogen to infect a host, so
antibodies that bind to flagella or pili prevent infection.
 Protective Outcomes of Antibody-Antigen Binding

 (4) Antibody-dependent cell mediated cytotoxicity (ADCC).

When multiple IgG molecules bind to a virally infected cell or a
tumor cell, that cell becomes a target for destruction by natural
killer (NK) cells.
 The NK cell attaches to the Fc regions of IgG and once attached,
kills the target cell by delivering compounds directly to it.
 ADCC mechanism
 When there is a large antigen target that cannot be internalized by
phagocyte, such as a virus infected cell or parasitic infection.
 Antibodies coat the target cell by binding to foreign antigen
expressed on the infected cell.
 The FC region are recognized by leukocyte that kill by cytotoxic
mechanism (e.g. NK cells and Eosinophils).
Protective Outcomes of Antibody-Antigen Binding

 This cells specific cell FC receptors on their cell surface.

 So they bind this antibodies by the FC receptors.
 This binding results in the degranulation of NK cell, cytotoxic
molecules are released to lyse the target cell.
 Classes of immunoglobulins

 Antibody molecules in all five major immunoglobulin classes.

 IgG
 IgG is the most abundant serum immunoglobulin, accounting for
about 80% to 85% of the total serum antibodies. It circulates in the
blood but exits the vessels to enter the tissues spaces ( lymph fluid,
CSF, peritoneal fluid, as well. Smaller size immunoglobulin
(146,000).
 It is a monomer. Half life in serum is 21 days
 Longest half life among antibody classes, provide long-term
immunity.
 It is divided to 4-subclasses; IgG1, IgG2, IgG3, IgG4.
 They numbered according to their abundance in the serum.
 Only class of immunoglobulin that can cross the placenta
 Classes of immunoglobulins

 Crossing the placenta enable the mother to transfer her immunity to

the fetus (passive immunity), until the immune system of the
mother is fully develop.
 Among the subclasses of IgG, except IgG2 all other are able to
cross the placenta and enter fetal circulation.
 The maternal antibodies present at birth gradually degrade over a
period of about 6 months, but during this time the infant begins
producing protective antibodies
 Coat antigens and act as opsonins. IgG1 and IgG3 are effective
opsonizing antibodies. Increase the efficiency of phagocytosis.
 It is important in ADCC.
 Effective neutralizing antibodies, ie. Neutralizing toxins of viruses
and bacteria.
 Classes of immunoglobulins

 IgG is also in colostrum, the first breast milk produced after giving
birth. The newborn’s intestinal tract absorbs this antibody.
 IgM
 IgM is the first class produced during the primary response to an
antigen. Half life (10 days). Account for 5–13% of serum antibodies.
 It occurs as a monomer and pentamer.
 As a monomer it is found in naïve and mature B-cells (also known as
membrane immunoglobulin, mIgM).
 The Pentamer is found in the blood stream.
 It is the principal class produced in response to some T-independent
antigens.

 Classes of immunoglobulins

 Provides direct protection by neutralizing viruses and toxins,

immobilizing motile organisms, preventing microbes from adhering
to cell surfaces, and cross-linking antigens.
 Its large size (970,000MW) prevents it from crossing from the
bloodstream into tissues, so its main role is to control bloodstream
infections.
 A total of 10 antigen-binding sites.
 Very effective neutralizers, prevent antigen from binding to host
cells.
 Do not act as opsonin nor play role in ADCC.
 Classes of immunoglobulins

 IgA
 Found in blood, but predominant in the body secretions .
 This form is important in mucosal immunity and is found on the
mucous membranes that line the gastrointestinal, genitourinary, and
respiratory tracts.
 Half-life of 6 days.
 It is also in secretions such as saliva, tears, and breast milk.
 Secretory IgA in breast milk protects breast-fed infants against
intestinal pathogens.
 Protection by secretory IgA is primarily due to the direct effect of
its binding. These include neutralizing toxins and viruses and
interfering with the attachment of microbes to host cells.
 Classes of immunoglobulins

 IgA is mainly produced by the plasma cells that reside in the

mucosa-associated lymphoid tissues (MALT).

 As IgA is transported across the mucosa (mucous membranes), a

polypeptide called the secretory component is added.

 This attaches the antibody to the layer of mucus that coats the
mucosal surface and protects it from destruction by enzymes there.

 Protects mucous membranes by neutralizing viruses and toxins,

immobilizing motile organisms, and preventing attachment of
microbes to cell surfaces.
 Classes of immunoglobulins

 IgD
 IgD accounts for less than 1% of all serum immunoglobulins. It is
involved with the development and maturation of the antibody
response, but its functions in serum have not been clearly defined.
 It is membrane bound antibody found on the surface of B-cells.
 IgE
 Is found in serum, is the least abundant immunoglobulin in serum
(<1%).
 IgE is barely detectable in serum, because most are tightly bound
via the Fc region to basophils and mast cells, rather than being free
in the circulation.
 Classes of immunoglobulins

 The bound IgE molecules allow these cells to detect and respond to
antigens.
 For example, when antigen binds to two adjacent IgE molecules
carried by a mast cell, the cell releases histamine and other
inflammatory mediators.
 Half-life 2days.
 IgE does not participate in opsonization.
 Play important role in allergic reaction.
 Also, defense against parasitic worms.
 IgE defense against parasitic worm

 When there is an invasion by parasitic worms, the T H-cell secrete

cytokine (IL-4) that stimulate B-cells to secrete IgE antibodies.
 The concentration IgE antibodies in the serum rises.
 This antibodies then coat the surface of the worms by binding to the
surface antigens.
 The bound IgE antibodies are recognized by eosinophils.
 Eosinophils bind to the coated antibody via the FC receptors.
 Once bind they eosinophils undergo degranulation, the release
granules destroy the parasitic worm.
 Role of IgE in allergic reaction

 When a susceptible individual is exposed an allergen for the first

time.
 B-cells are activated, B-cells differentiate into antibody secreting
cells (plasma cells).
 IgE are produced by B-cells.
 The IgE antibodies attach themselves to mast cell and basophils by
the FC region.
 Now the antigen binding sites in the IgE are free.
 On second exposure of the allergen.
 The allergen binds to the antigen binding site of the IgE.
 The binding of allergen result in degranulation of the cell.
 As a result of degranulation the is a rapid release of preformed
 Role of IgE in allergic reaction

 mediators such as histamine, this leads to allergic reaction.

 Antigen presenting cells
 Unlike the B-cell receptor, the T-cell receptor does not interact with
free antigen.
 Instead, the antigen must be “presented” by another host cell.
 The host cell does this by partly degrading (processing) the antigen
and then displaying (presenting) individual peptides of the
antigen’s proteins.
 The peptides are placed within a group of proteins called major
histocompatibility complex (MHC) molecules , which are on the
surface of the presenting cell.
 Two types of MHC molecules present antigen: MHC class I and
MHC class II.
 When a T cell recognizes an antigen, the cell is actually
recognizing both the peptide and MHC molecule simultaneously.
 Antigen presenting cells
 MHC class I molecules present endogenous antigens (antigens
made within the cell).
 MHC class II molecules present exogenous antigens (antigens
taken up by a cell).
 All nucleated cells produce MHC class I molecules, but only
specialized cell types (dendritic cells, B cells, and macrophages)
collectively referred to as antigen-presenting cells (APCs) make
MHC class II molecules.
 Cell mediated immunity

 There are three types of T-cells; T-Helper cell, T-Cytotoxic cell, and
T-Regulatory or suppressor cell.
 The T-cell populations involved in eliminating antigen are
cytotoxic T cells and helper T cells.
 These differ in their roles, and also how they recognize antigen.
Cytotoxic T cells recognize antigen presented on MHC class I
molecules, whereas helper T cells recognize antigen presented on
MHC class II molecules.
 Cell mediated immunity

 Because of these recognition characteristics, effector cytotoxic T

(TC) cells respond to endogenous antigens, whereas effector helper
T (TH ) cells respond to exogenous antigens.
 Cytotoxic and helper T cells are identical microscopically, so
scientists distinguish them based on the presence of surface
proteins called cluster of differentiation (CD) markers.
 Most cytotoxic T cells have the CD8 marker and are frequently
referred to as CD8 T cells; most helper T cells carry the CD4
marker and are often called CD4 T cells.
 Note that CD4 is also a receptor for HIV, which explains why the
virus infects helper T cells.
 Cell mediated immunity

 Dendritic cells, the scouts of innate immunity, play a crucial role in

T-cell activation.
 Immature dendritic cells reside in peripheral tissues, particularly
under the skin and mucosa, gathering various materials from those
areas.
 Dendritic cells located just below the mucosal barriers are even
able to send tentacle-like extensions between the epithelial cells of
the barriers.
 Using this action, the dendritic cells gather material from the
respiratory tract and the lumen of the intestine.
 Dendritic cells are able to “cross present” antigens, meaning they
can present peptides on both types of MHC molecules—class I and
class II—regardless of the origin.
 Cell mediated immunity

 This allows them to present antigen to, and therefore

activate, cytotoxic T cells as well as helper T cells.
 Once a T cell is activated, it undergoes clonal selection
and expansion, eventually forming effector cells and
memory cells.
 The effector helper T cells can take on different roles,
depending on the signals given by the dendritic cell.
 This results in at least three subsets of T H cells, T H 1, T
H 2, and T H 17 that produce different ranges of cytokines
and therefore promote different types of immune
responses.
 Cell mediated immunity

 In general, T H 1 cells promote a response effective against

intracellular invaders, T H 2 cells promote a response effective
against parasitic worms (helminths), and T H 17 cells promote a
response effective against extracellular invaders.

 If the “self” cell is infected with a replicating virus or

microorganism, however, then peptides from the invading microbe
will be presented on MHC class I molecules, and those will be
recognized by circulating T C cells.

 This makes the presenting cell a target for the lethal effector
functions of T C cells. The same thing can occur if the “self” cell is
producing abnormal proteins that characterize cancerous cells.
 Cell mediated immunity

 When a T C cell encounters a cell presenting a peptide it

recognizes, the T C cell binds to that cell, and then delivers a “death
package” to it.
 The T C cell does this by releasing perforin, a molecule that forms
pores in the target cell membrane, along with several proteases.
 The pores made by perforin allow the proteases to enter the target
cell, where they cause reactions that induce that cell to undergo
apoptosis.
 The Role of T H Cells in B-Cell Activation

 When a naive B cell binds antigen via its B-cell receptor,

the cell takes the antigen in by endocytosis.
 Proteins within the endosome are then degraded to
produce short peptides that can be loaded into the groove
of MHC class II molecules.
 If a T H cell encounters a B cell presenting a peptide it
recognizes, it delivers cytokines to that cell.
 These activate the B cell, allowing it to proliferate and
undergo class switching.
 The cytokines also drive the formation of memory B
cells.
 The Role of T H Cells in Macrophage Activation

 The steps of macrophage activation are very similar to those

described for B-cell activation.
 When macrophages engulf material, they enclose it within a
membrane-bound
 Phagosome. The proteins within the phagosome are then degraded,
and the resulting peptides presented on MHC class II molecules.
 If a T H cell recognizes one of the peptides, it delivers cytokines
that activate the macrophage.
 When a macrophage is activated, it gets larger, the plasma
membrane becomes ruffled and irregular, and the cell increases its
metabolism so that the lysosomes which contain antimicrobial
substances increase in number.
The Role of T H Cells in Macrophage Activation

 The activated macrophage also begins producing nitric oxide, a

potent antimicrobial chemical, along with various compounds that
can be released to destroy extracellular microorganisms.
 If the response is still not sufficient to control the infection,
activated macrophages fuse together, forming giant cells.
 These, along with other macrophages and T cells, can form
granulomas that wall off the offending agent, preventing
infectious microbes from escaping to infect other cells.
 Activated macrophages are important in the immune response
against the bacterium that causes tuberculosis ( Mycobacterium
tuberculosis ) and other microorganisms that can survive within
regular macrophages.