Foundations in

Microbiology
Sixth Edition
Chapter 15
Adaptive, Specific
Immunity and
Immunization
Lecture PowerPoint to accompany
Talaro
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
2
Specific Immunity Adaptive Line
of Defense
Third line of defense acquired
Production of specific antibodies by dual system of B
and T lymphocytes in response to an encounter with
a foreign molecule, called an antigen
Two features that characterize specific immunity:
specificity antibodies produced, function only against
the antigen that they were produced in response to
memory lymphocytes are programmed to recall their
first encounter with an antigen and respond rapidly to
subsequent encounters


3
Classifying Immunities
Active immunity results when a person is
challenged with antigen that stimulates production of
antibodies; creates memory, takes time and is lasting
Passive immunity preformed antibodies are
donated to an individual; does not create memory, acts
immediately, and is short term.
Natural immunity acquired as part of normal life
experiences
Artificial immunity - acquired through a medical
procedure such as a vaccine
4
Natural active immunity acquired upon
infection and recovery
Natural passive immunity acquired by a
child through placenta and breast milk
Artificial active immunity acquired
through inoculation with a selected Ag
Artificial passive immunity
administration of immune serum or globulin
5
6
Overview of Specific Immune
Responses
Separate but related activities of the specific immune
response:
Development and differentiation of the immune
system
Lymphocytes and antigens
The challenge of B and T lymphocytes by antigens
B lymphocytes and the production and activities of
antibodies
T lymphocyte responses
7
8
Development of the Immune
Response System
Cell receptors or markers confer specificity and
identity of a cell.
Major functions of receptors are:
1. To perceive and attach to nonself or foreign
molecules
2. To promote the recognition of self molecules
3. To receive and transmit chemical messages
among other cells of the system
4. To aid in cellular development

9
Major Histocompatibility Complex (MHC)
Receptors found on all cells except RBCs
Also known as human leukocyte antigen
(HLA)
Plays a role in recognition of self by the
immune system and in rejection of foreign
tissue
10
Functions of MHC
Genes for MHC clustered in a multigene
complex:
Class I markers that display unique characteristics
of self molecules and regulation of immune
reactions
required for T lymphocytes
Class II receptors that recognize and react with
foreign antigens; located primarily on macrophages
and B cells
involved in presenting antigen to T-cells
11
Lymphocyte Receptors
Lymphocytes role in surveillance and
recognition is a function of their receptors.
B-cell receptors bind free antigens
T-cell receptors bind processed antigens

12
Clonal Selection Theory
Lymphocytes use 500 genes to produce a
tremendous variety of specific receptors.
Undifferentiated lymphocytes undergo
genetic mutations and recombinations while
they proliferate in the embryo.
Form a billion different clones with the
ability to react with a tremendous variety of
antigens

13
In the bone marrow, lymphocytic stem cells
differentiate into either T or B cells.
B cells stay in the bone marrow.
T cells migrate to the thymus.
Both T and B cells migrate to secondary
lymphoid tissue.
14
15
Lymphocyte specificity is preprogrammed,
existing in the genetic makeup before an antigen
has ever entered the system.
Each genetically different type of lymphocyte
expresses a single specificity.
First introduction of each type of antigen into the
immune system selects a genetically distinct
lymphocyte.
Causes it to expand into a clone of cells that can
react to that antigen
16
17
Specific B-Cell Receptor:
Immunoglobulin
Receptor genes of B cells govern immunoglobulin (Ig)
synthesis.
Large glycoproteins that serve as specific receptors of
B cells
Composed of 4 polypeptide chains:
2 identical heavy chains (H)
2 identical light chains (L)
Y shaped arrangement ends of the forks formed by
light and heavy chains contain a wide range of
variable antigen binding sites
Variable regions
Constant regions
18
19
Development of Receptors
Immunoglobulin genes lie on 3 different chromosomes
Undifferentiated lymphocyte has 150 different genes
for the variable region of light chains and 250 for the
variable region and diversity region of the heavy chain
During development, recombination causes only the
selected V and D genes to be active in the mature cell.
Once synthesized, immunoglobulin is transported to
cell membrane and inserted there to act as a receptor.

20
21
T-Cell Receptors for Antigen
Formed by genetic recombination, with
variable and constant regions
2 parallel polypeptide chains
small, without humoral functions
22
23
B-cell Maturation
Directed by bone marrow sites that harbor
stromal cells, which nurture the lymphocyte
stem cells and provide hormonal signals
Millions of distinct B cells develop and
home to specific sites in the lymph nodes,
spleen, and GALT
Come into contact with antigens throughout
life
24
T-Cell Maturation
Maturation is directed by the thymus gland
and its hormones.
7 classes of T-cell receptors termed CD -
cluster of differentiation
Mature T cells migrate to lymphoid organs
and occupy specific sites.
25
Entrance and Processing of Antigens
and Clonal Selection
Antigen (Ag) is a substance that provokes an
immune response in specific lymphocytes.
Also called an immunogen
Property of behaving as an antigen is
antigenicity
26
Characteristics of Antigens

Perceived as foreign, not a normal constituent
of the body
Foreign cells and large complex molecules
over 10,000 MW are most antigenic.
Antigenic determinant, epitope small
molecular group that is recognized by
lymphocytes
Antigen has many antigenic determinants.
27
28
Foreign molecules less than 1,000 MW,
called haptens
Not antigenic unless attached to a larger
carrier

29
30
Special Categories of Antigens
Alloantigens cell surface markers of one
individual that are antigens to another of that
same species
Superantigens potent T cell stimulators;
provoke an overwhelming response
Allergen antigen that provokes allergy
Autoantigens molecules on self tissues for
which tolerance is inadequate


31
Antigen Processing and Presentation
to Lymphocytes
T-cell dependent antigens must be processed by
phagocytes called antigen presenting cells (APC).
APCs modify the antigen so it is more immunogenic
and recognizable; then the Ag is moved to the APC
surface and bound to MHC receptor.
Antigen presentation involves a direct collaboration
among an APC, a T helper cell and an antigen-specific
B or T cell.
Interleukin-1 is secreted by APC to activate T
H
cells.
Interleukin-2 is produced by T
H
to activate B and other T
cells.

32
33
B-cell Activation and Antibody
Production
Once B cells process the Ag, interact with
T
H
cells and are stimulated by growth and
differentiation factors, they enter the cell
cycle in preparation for mitosis and clonal
expansion.
Divisions give rise to plasma cells that
secrete antibodies and memory cells that
can react to the same antigen later.
34
35
Antibody Structure and Functions
Immunoglobulins
Large Y-shaped protein
Consist of 4 polypeptide chains
Contains 2 identical fragments (Fab) with
ends that bind to specific antigen
Fc binds to various cells and molecules of
the immune system.
36
37
Antibody-Antigen Interactions
Principle antibody activity is to unite with the Ag to call
attention to, or neutralize the Ag for which it was
formed.
Opsonization process of coating microorganisms or
other particles with specific antibodies so they are more
readily recognized by phagocytes
Agglutination Ab aggregation; cross-linking cells or
particles into large clumps
Neutralization Abs fill the surface receptors on a
virus or the active site on a microbial enzyme to prevent
it from attaching
Antitoxins are a special type of Ab that neutralize a bacterial
exotoxin.

38
39
Functions of the Fc Fragment
Fc fragment binds to cells macrophages,
neutrophils, eosinophils, mast cells,
basophils, and lymphocytes.
40
41
Classes of Immunoglobulins
5 classes of immunoglobulins (Ig):
1. IgG
2. IgA
3. IgM
4. IgD
5. IgE
42
43
Antibodies in Serum
If separated by electrophoresis, globulin
separates into 4 bands:
Alpha-1 (-1), alpha-2 (-2), beta (), and
gamma ()
Most are antibodies.
is composed primarily of IgG; and -2
are a mixture of IgG, IgA, and IgM.
44
45
Primary and Secondary Responses to
Antigens
Primary response after first exposure to an
Ag immune system produces IgM and a gradual
increase in Ab titer (concentration of antibodies)
with the production of IgG
Secondary response after second contact with
the same Ag, immune system produces a more
rapid, stronger response due to memory cells
anamnestic response

46
47
Monoclonal Antibodies
Pure preparation of antibody
Single specificity antibodies formed by
fusing a mouse B cell with a cancer cell.
Used in diagnosis of disease, identification
of microbes and therapy
48
49
T Cells & Cell Mediated Immunity
Cell mediated immunity requires the direct
involvement of T lymphocytes.
T cells act directly against Ag and foreign cells
when presented in association with an MHC
carrier.
T cells secrete cytokines that act on other cells.
Sensitized T cells proliferate into long-lasting
memory T cells.
50
Types of T cells
1. T helper cells (CD4 or T
H
) most prevalent type
of T cell; regulate immune reaction to antigens,
including other T and B cells; also involved in
activating macrophages and improving
opsonization; differentiate into T helper 1 (T
H
1)
cells or T helper 2 (T
H
2) cells
2. Cytotoxic T cells (CD8 or T
C
) destroy foreign
or abnormal cells by secreting perforins that lyse
cells.
3. Natural killer cells lack specificity; circulate
through the spleen, blood, and lungs
51
52
Immunization: Manipulating
Immunity
Passive immunity immune serum globulin
(ISG), gamma globulin, contains immunoglobulin
extracted from pooled blood; immunotherapy
Treatment of choice in preventing measles and
hepatitis A and in replacing antibodies in
immunodeficient patients
Sera produced in horses are available for
diphtheria, botulism, and spider and snake bites.
Acts immediately; protection lasts 2-3 months

53
Vaccination
Artificial active immunity deliberately
exposing a person to material that is
antigenic but not pathogenic
Principle is to stimulate a primary and
secondary anamnestic response to prepare
the immune system for future exposure to a
virulent pathogen
Response to a future exposure will be
immediate, powerful, and sustained.
54
Vaccine Preparation
Most vaccines are prepared from:
1. Killed whole cells or inactivated viruses
2. Live, attenuated cells or viruses
3. Antigenic molecules derived from bacterial
cells or viruses
4. Genetically engineered microbes or microbial
agents
55
56
Killed or Inactivated Vaccines
Cultivate the desired strain, treat it with
formalin or some other agent that kills the
agent but does not destroy its antigenicity.
Often require a larger dose and more
boosters to be effective

57
Live Attenuated Cells or Viruses
Process that substantially lessens or negates the
virulence of viruses or bacteria eliminates virulence
factors
Advantages of live preparations are:
organisms can multiply and produce infection (but not
disease) like the natural organism
They confer long-lasting protection.
usually require fewer doses and boosters
Disadvantages include:
require special storage, can be transmitted to other people,
can conceivably mutate back to virulent strain

58
Antigenic Molecules
Acellular or subcellular vaccines (subunit
if a virus)
Exact antigenic determinants can be used when
known:
capsules pneumococcus, meningococcus
surface protein anthrax, hepatitis B
exotoxins diphtheria, tetanus
Antigen can be taken from cultures, produced
by genetic engineering, or synthesized.


59
Genetically Engineered Vaccines
Insert genes for pathogens antigen into plasmid
vector, and clone them in an appropriate host.
stimulated the clone host to synthesize and secrete a
protein product (antigen), harvest and purify the
protein hepatitis
Trojan horse vaccine genetic material from
a pathogen is inserted into a live carrier
nonpathogen; the recombinant expresses the
foreign genes
experimental vaccines for AIDS, herpes simplex 2,
leprosy, tuberculosis

60
Genetically Engineered Vaccines
DNA vaccines create recombination by inserting
microbial DNA into plasmid vector
Human cells will pick up the plasmid and express
the microbial DNA as proteins causing B and T
cells to respond, be sensitized, and form memory
cells.
experimental vaccines for Lyme disease, hepatitis C,
herpes simplex, influenza, tuberculosis, malaria

61
62
Route of Administration ad Side
Effects
Most administered by injection; few oral, nasal
Some vaccines require adjuvant to enhance
immunogenicity and prolong retention of antigen.
Stringent requirements for development of vaccines
More benefit than risk
Possible side effects include local reaction at injection
site, fever, allergies; rarely back-mutation to a
virulent strain, neurological effects.

63
Herd Immunity
Immune individuals will not harbor it,
reducing the occurrence of pathogens
herd immunity.
Less likely that an nonimmunized person
will encounter the pathogen