Immunology: Basic Principles of
Adaptive Immunity and
Immunizations
2007
Adaptive Immunity
Recognize non self
 Respond to a foreign invader
 Distinguish between invaders(
potential pathogen)

Antigen
Is a substance( molecule) that the
body identifies as foreign and it
mounts an immune response.
 It is also known as an immunogen
 Most antigens are proteins
 Some are glycoproteins,
nucleoproteins, or polysaccharides

Proteins as antigens
Proteins are
generally more
immunogenic
 Their structure is
more complex
 Large proteins may
have several
epitopes or
antigenic
determinants

Hepatitis antigens
Hepatitis surface
antigen is a
molecule attached
to the exterior or
the virus
 Evokes an immune
response
 First antigen
detectable

Haptens
Haptens are
smaller molecules
that can be
antigenic if they
bind to a larger
molecule
 The antigen is the
result of the
combination.
Neither is
antigenic by itself

Antibody
Antibodies are
molecules that are
produced as a
response to foreign
invaders
 It is specific for an
antigen
 It has the capacity
to bind to the
antigen

Titer



Titers are the
quantitiy of an antigen
required to evoke an
immune response
It is quantifiable
Measured in clinical
situations to
determine
immunity,the presence
of disease,the course
of an infection
Antibody titer
( definition and importance)



Quantity to bind to
and neutralize a
particular quantity of
an antigen
Rubella is a virus that
produces teratogenic
effects in a fetus
Rubella titers are
diagnostically
significant in young
women planning on
pregnancy
Effector Response
Recognition of a non self presence
causes a series of response
reactions
 Divided into
a. Humoral response – Based upon the
presence to antibodies
b.Cellular response – based upon the
activity of special cells such as T
lymphocytes

Development of the immune
system( Immune cells)
T cells are are
differentiated in the
thymus
 They are located in
lymph nodes
 They are the majority of
circulating lymphocytes

Differentiation of stem
cells into lymphocytes is
influenced by other
tissues
 B cells are differentiated
in the bone marrow
 Found in the lymph nodes,
spleen, gut associated
lymphoid tissues( GALT)

B CELLS
T CELLS
T lymphocytes and cellular
immunity
Attack and destroy
 Produce cytokines that enhance
specific immunity and non specific
mechanisms of defense

T lymphocytes
T lymphocytes






Cytotoxic T cells – destroy
virally infected cells and
tumor cells
Helper T cells – they divide
rapidly and secrete cytokines
Memory T cells – They are
antigen specific cells
Regulatory T cells( suppressor
T cells) – Cell mediated
immunity
Natural Killer Cells – Connects
the innate and the adaptive
immune system
Other subsets of cells
Natural Killer Cells( Doc Kaiser
Microbiology)
Apoptosis( Doc Kaiser Microbology)
MHC - 1

Endogenous antigens, such as viral proteins, pass through
proteasomes where they are degraded into a series of
peptides.
2. The peptides are transported into the rough endoplasmic
reticulum (ER) by a transporter protein called TAP.
3. The peptides then bind to the grooves of newly
synthesized MHC-I molecules.
4. The endoplasmic reticulum transports the MHC-I
molecules with bound peptides to the Golgi complex.
5. The Golgi complex, in turn, transports the MHC-I/peptide
complexes by way of an exocytic vesicle to the cytoplasmic
membrane where they become anchored. Here, the peptide
and MHC-I/peptide complexes can be recognized by CTLs by
way of TCRs and CD8 molecules having a complementary
shape.
MHC I and viruses
Humoral immunity



The result of
circulating immunities
When stimulated by an
antigenm the B
lymphocytes initate a
process that leads to
the release of
antibodies
Most effective at
defending the body
against viruses and
bacteria

a.
b.
c.
d.
Works on the
basis of
Specificity
Diversity
Memory
Self vs. Non self
Humoral immunity
Dependent upon
the ability of white
blood cells to
recognize specific
antigens
 Antigens are
generally exposed
on the outer
surface of a
pathogen or are
toxins

Antibody Response
Each B cell carries an
antibody on its outer
membrane
 It has the ability to
bind to a specific
antigen
 The binding of an
antigen sensitizes or
activates the B cells
 This causes the cells
to divide may times


a.
b.
The B cell divides to
produce
Plasma cells that
actively produce
antibodies at a rapid
rate
They also produce a
memory cell that
retains the
information
necessary to produce
the antibody
B cells
After the binding
of the antigen to
the antibody, the B
cells processes the
antigen, by
breaking it into
tiny fragments
 The fragments bind
to molecules on the
surface of the B
cell MHCII

APC( Antigen Presenting Cell)
Antigen Presentation and
MHC II



The antigen is
presented on the
surface of the B cell
by MHC II
The T cells are
activated to produce
interleukin 2
The activation further
stimulates the
production of more B
cells - memory cells
MHC I and II
There are five classes of
Immunoglobulins - The basic
form of antibodies
IgG
 IgA
 IgM
 IgD
 IgE

Basic structure
Basic unit is a Y
shaped structure
 They are composed
of four polypeptide
chains
 The chains are held
together by
disulfide bonds
 They possess both
variable and
constant regions

IgG
IgG-The main class of
antibodies
 Produced as a
secondary response
 Attach to antigens on
microorganisms and
their receptors attach
to phagocytic cells
 They work effectively
with phagocytic cells
 The tails section also
activates complement
 Crosses the placenta

QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
IgM
Pentameric structure(
secreted by Plasma
cells)
 Monmeric on the
surface of B cells
 It is the first
antibody made in
response to an
infection
 It has ten antigen
binding regions
 Activates complement
and causes clumping of
microbes

IgA







Occurs in bodily
secretions
Found in breast milk
Attaches to the lining
of the digestive,
respiratory, and
gastrointestinal tract
Transported through
epithelial cells
Attaches to microbes
before they invade
tissues
Activates complement
Exists as a dimer
IgD
Found primarily on
the membranes of
B cells
 It may help in
immune responses
 It also may be
active in allergic
responses

IgE





Has specially affinity for
receptors on the
basophils
In the blood or mast cells
in the tissues
When IgE binds to
antigens, the associated B
cells secrete specific
molecules that are
related to allergic
responses
Histamine is one of these
molecules
IgE is found primarily in
tissues and bodily fluids
Immune Disorders- SCIDS
SCIDS



Most cases of SCID are
due to mutations in the
gene encoding the common
gamma chain (γc),
A protein that is shared by
the receptors for
InterleukinsIL-2, IL-4, IL7, IL-9 and IL-15.
These interleukins and
their receptors are
involved in the development
and differentiation of T
and B



Another well-known form
of SCID is caused by a
defective enzyme,
adenosine deaminase
(ADA),
Necessary for the
breakdown of purines. Lack
of ADA causes
accumulation of dATP.
This metabolite will inhibit
the activity of
ribonucleotide diphosphate
reductase, the enzyme that
reduces ribonucleotides to
generate
deoxyribonucleotides
Genetic Diseases of the
Immune System
Severe combined
immunodeficiency
 Multiple types
 X linked and
autosomal
 Affect both
cellular and
humoral aspects of
the immune system

T cell-negative (T-), B
cell-negative (B-),
natural killer cellpositive (NK+)
Gene map locus
11p13, 11p13
SCIDS
Immune Disorders
Immune disorders
#301000, WISKOTTALDRICH SYNDROME;
WAS
 The manifestations of
Wiskott-Aldrich
syndrome are eczema,
thrombocytopenia,
proneness to infection,
and bloody diarrhea.
 Death usually occurs
before age 10 years.
 Bone Marrow transplants
are a treatment
possibility

Genetics of Immunoglobulins
Generation of Immunoglobulins
Genetics of Immunoglobulins




Genes for the
constant region
Genes for the variable
region
Light and heavy
chained molecules are
synthesized separately
The diversity of
antibody-binding sites
comes from the
random combinations
of variable gene
segments that join
with constant gene
segments
Naturally Acquired Active
immunity
The immune system responds to an
invader by producing antibodies and
activated lymphocytes
 This can produce a life long immunity

Naturally Acquired Passive
Immunity
Antibodies transferred across the
placenta to the fetus
 Transfer of antibodies through the
colostrum in the breast milk
 Both of these provide temporary
immunity to an infant

Artificially Acquired Passive
Immunity
When antibodies made by other hosts are
introduced into a new host
 An example of this is rattlesnake antivenin
injection
 Antivenins are antibodies produced by
other animals such as horses or cows
 The host does not make new antibodies the antibodies supplied circulate for as
long as a month and are eventually
destroyed in the host

Venom
Rattlesnake venom
is a mixture of
enzymes that
possess the ability
to destroy cells
 Can be a neurotoxin
as well
 Injected like a
hypodermic

Antivenin
Antivenin is a
polyvalent
preparation of
globulins prepared
by the
fractionation of
horse’s serum
 It is a mixture of
globulins from
different types of
rattlesnakes

One of antigens in rattlesnake
venom
Artificially Acquired Active
Immunity
When an individual is exposed to a
vaccine
a. The vaccine might include
attenuated
( weakened) organism, portions of the
organism, toxins, subunits of
antigenic portions of the organism

Chicken Pox – Varicella
Zoster





Chickenpox begins
as a cold
Sneezing, coughing,
and a runny nose
Two days later a
rash begins
Usually begins on
the chest and face
It may spread all
over the body
Chicken Pox




Infection spread by
aerosolized droplets
It is contagious 1-2
days prior to the onset
of symptoms
It takes 20 days to
develop symptoms
It takes 5-10 days for
the immune system to
defeat the virus




All children between 12 and 18 months of age should
have one dose of chickenpox vaccine.
Children who have had chickenpox do not need the
vaccine.
No tests need to be administered to determine immune
status - a parent's recollection of the disease is
considered a reliable measure of previous infection and
therefore immunity.･
Children between 19 months and their 13th birthday
who have not had chickenpox should be vaccinated with
a single dose.･People 13 and older who have not had
chickenpox should get two doses of the vaccine 4 to 8
weeks apart.
Primary Immune Response
In humoral
immunity the
primary response
occurs when the
antigen is first
recognized by host
B cells
 B cells divide to
form plasma cells
 Antibodies begin to
appear - IgM

Cytokines trigger
the proliferation of
B cells
 IgG synthesis
accelerates
 Memory cells are
formed

Secondary Response
The secondary response occurs when
the immune system sees an antigen
for the second time
 Memory cells divide more rapidly than
B cells
 IgM is still produced first, but in
smaller quantities than the secondary
response
 IgG is produced second, but in
greater amounts

Response of B cells
T independent antigens - This
response only produces IgM and no B
memory cells are formed
 T- dependent antigens - B cell
becomes the antigen presenting cell,
makes contact with the T helper cell
and the T helper then produces
lymphokines that stimulate thethe B
cell to differentiate

Primary and Secondary
Inactivation of the antigen( microbe)
Neutralization IgG is the main
neutralizer of
these infections
 Prevents the toxin
from doing further
damage
 Antibiotics are
required to kill the
microbe causing
the infection

Viruses can be
inactivated by
neutralization
 Viruses with
envelopes can be
removed by
complement

Neutralization Reaction
http://people.eku.edu/ritchisong/neutralization2.gif
Neutralization of a toxin
Agglutination reactions
Bacteria are large
particles
 When they react
with bacteria they
can clump
 IgM causes strong
agglutination
reactions
 IgG also causes
agglutination

Ingestion by macrophages
Both agglutination
and neutralization
effectively
inactivate the
microbe by binding
to the antigenic
site
 Macrophages can
then ingest the
pathogen

COMPLEMENT





Pathway for the
elimination of
microbes
Cascade
Lysis of cells
Augmentation of
immune response
Disposal of waste
by products
Complement action


Perforin is a cytolytic
protein found in the
granules of CD8 T cells and
NK. Upon degranulation,
perforin inserts itself into
the target cell's plasma
membrane forming a pore
This finally results in the
lysis of a cell
Classical Complement Pathway