Creative Commons Attribution-Noncommercial-Sharealike License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License.
Your use of this

material constitutes acceptance of that license and the conditions of use of materials on this site.
Copyright 2006, The Johns Hopkins University and Gary Ketner. All rights reserved. Use of these materials
permitted only in accordance with license rights granted. Materials provided AS IS; no representations or
warranties provided. User assumes all responsibility for use, and all liability related thereto, and must independently
review all materials for accuracy and efficacy. May contain materials owned by others. User is responsible for
obtaining permissions for use from third parties as needed.
Host Response to Infection:

The Immune Response and Vaccination
Gary Ketner, PhD
Johns Hopkins University
Section A
Introduction to Innate Immunity
The Immune System
Central to survival after infection

Central to public health
Immunity can be manipulated to protect both
individuals and populations by vaccination
Effective use of vaccination depends upon knowledge
of immune system function
Nature of the vaccine (live, subunit, vectored)
Characteristics of the type of immunity induced
Target antigens
Innate Immunity
Inborn
Effective without prior exposure to an infectious agent
Nonspecific
First-line defense
Continued
Innate Immunity
Physical barriers
Skin
Cornea
Mucus layers (with
clearance)
Outflow (urine, for
example)
Chemical barriers
Stomach acid
Fatty acids on skin
Lysozyme in tears
Active mechanisms
Intracellular
X Interferons
X Apoptosis
Organismal
X Complement
X Phagocytosis
Phagocytosis
Active process that destroys invading pathogens

Mediated by specialized cells (phagocytes)
Macrophages, neutrophils
Phagocytes engulf potential pathogens
Efficient engulfment depends on receptors for
common bacterial cell wall components
Once engulfed, pathogens are killed and digested
Some pathogens are resistant (TB)
Continued
Phagocytosis
Active process that destroys

invading pathogens
Mediated by specialized cells
(phagocytes)
Macrophages, neutrophils
Phagocytes engulf potential
pathogens
Efficient engulfment
depends on receptors for
common bacterial cell
wall components
Once engulfed, pathogens are
killed and digested
Phagocytosis
Phagocytes are located

in strategic places
Skin, blood, gut
Phagocytes are
chemotactic (attracted
to sites of injury)
Phagocytes can be
activated to become
better killers
Section B
Effector Mechanisms of Adaptive Immunity
Adaptive Immunity
Arises as a
consequence of
exposure to a
particular target
(virus, protein, toxin)
Specific for that target
Arises after a delay of
a few days
Potent
Exhibits memory
Rapid, large
reappearance upon
a second exposure
11
Adaptive Immunity Primary and Secondary Responses
12
Adaptive Immunity
Humoral: mediated by protein molecules called

antibodies
Cell-mediated immunity (CMI): due to the action of
specialized immune system cells
13
Humoral Immunity
Mediated mostly by protein molecules called

antibodies (Ab), also called immunoglobulin (Ig)
Antibodies generally are found in extracellular fluids
Blood, lymph, mucus
Antibodies are active against agents with an
extracellular phase, including some viruses, toxins, and
bacterial infections
Not all pathogens have obligatory extracellular
phases
X In some cases, extracellular exposure is brief
X Antibodies tend to be ineffective against such
agents
14
Antigen Binding by Antibody
Antibodies act by physically

binding to their targets called
antigens (Ag)
Antibody binding to antigen
occurs because of a close
physical fit between the
antibody and the target
antigen (epitope)
Binding is extremely
specifica given antibody
binds only to one (or a few
closely related) antigens
Binding results in inactivation
or destruction of the target
Ab
Antigen
(lysozyme)
15
Antibody Structure (IgG)
Four protein chains

Two heavy
Two light
The heavy chains
are identical to
each other
The light chains are
identical to each
other
The chains are held
together by disulphide
bonds
Continued
16
Each chain has

constant (C) and
variable (V) regions
The variable regions
differ among antibody
species in amino acid
sequenceand therefore
shape
Antibodies bind antigens
by the variable regions
The variation in shape is
responsible for differences in
specificity of different antibody species
Continued
17
It is estimated that there

can be about 1011
different variable region
amino acid sequences,
and so about 1011
antibody specificities
At a given time, about
109 are found in an
individual
Antibody diversity is
generated by DNA
rearrangements that
occur during immune
development
18
Antibody Structure (IgM, IgA)
There are several different types of antibody, each

with specific functions
Two examples are IgM and IgA, which are
important antibodies on mucosal surfaces
19
Neutralization by Antibody
Neutralization occurs when antibody binding to a

target interferes directly with function
Human rhinovirus
20
Opsonization by Antibody
Phagocytosis can be made much more efficient by

antibody
21
Additional Functions of Antibody
Complement fixation
Antibody-dependent cytotoxicity
Both depend on the binding of Ab to the outside of a
cellular target to recruit effectors that kill the cell
22
Cell-Mediated Immunity (CMI)
The primary effectors of CMI are cytotoxic T cells (killer

T cells, CD8+ T cells, CTLs)
Activated macrophages also participate
Cytotoxic T cells kill other cells
The primary targets of cytotoxic T cells are usually
pathogen-infected cells
Like humoral immunity, CMI depends on specific
recognition of an antigen by a protein: T-cell receptor
23
T-Cell Receptor (TcR)
Primary recognition
molecule in CMI
Similar in structure to
antibody
Two chains
V and C regions
Membrane-bound
24
Recognition by TcR
TcR recognizes antigen

by shape
Recognition is of
antigen fragments,
bound to another
specialized immune
system protein, the
MHC I antigen
This is called
presentation
MHC I is found on the
surface of essentially all
cells
25
Antigen Presentation
The targets of CMI tend

to be pathogen-infected
cells
Presentation is the
consequence of a
specific mechanism:
Processing
Intracellular loading
of MHC I
Transport to the cell
surface
26
Killing by CMI
Antigen is presented
Antigen is recognized by cytotoxic T cell
The T cell releases pore-forming proteins
The target cell dies, killing the internal pathogen
27
Humoral vs. Cell-Mediated Immunity
Humoral immunity
Antibody-mediated
Effective in extracellular spaces
CMI
Mediated by T cells
Effective against intracellular pathogens
Kills infected host cells
28
Section C
Induction of Adaptive Immunity
Induction of an Immune Response
Induction of the humoral and CMI responses involve

parallel mechanisms:
Effectors arise from initially nave precursor cells (B
and T cells)
Precursors bear surface receptors with specificities
generated at random (Ig, TcR)
Nave precursors differentiate (acquire effector
function) because of interaction between antigen
and receptors
Development begins with an interaction between
the pathogen and professional antigen-presenting
cells (APCs)
30
Professional APCs
Situated for immediate interception of pathogens

Biologically tuned to effectively initiate a response
Specialized to deal with different threats
31
Macrophages
Stationed in skin, gut, and

circulation
Phagocytic
Surface receptors are preset
to recognize common
bacterial cell components
Engulf, kill, process, and
present
Present using MHC II
32
B Cells
Stationed in lymph
nodes and in the
circulation
Surface receptor is
membrane-bound
antibody
Antibody specificities are
randomly generated
Antigens binding
stimulates phagocytosis
Antigens are processed
and presented on MHC II
33
Dendritic Cells
Stationed in skin
Particularly susceptible
to infection by viruses
Present internallyproduced antigens on
MHC I
34
Maturation of T Cells
T cells are produced as nave precursors

No effector function
Random TcR specificities
Maturation is triggered by encountering a cell
presenting a recognizable antigen
Maturation of T cells involves primarily:
Acquisition of effector function
Proliferation of cells with specificities that suit the
pathogen at hand (clonal expansion)
35
Nave T cells circulate, sampling the antigens

presented on APCs
Sampling involves brief physical interaction
between the antigen (in the context of MHC) and
the T cell TcR
If the antigen is not recognized, the interaction is short
lived, and the T cell moves on
36
If the antigen is recognized, binding is tight and long

lived
Stimulatory signals are exchanged (cytokines)
The T cell proliferates
Effector mechanisms are developed
Memory cells are produced
37
Cytotoxic T Cells and Helper T Cells
There are two kinds of T cells:

Cytotoxic T cells ( TC or CD8+)
Helper T cells ( TH or CD4+)
These differ in function and therefore develop
different effector functions
TC kills virus infected cells and develops cytotoxic
mechanisms discussed earlier
TH assists in the immune response (below) and
develops helper mechanisms (increased ability to
secrete cytokines)
38
Cytotoxic T Cells and Helper T Cells
TH and TC cells arise similarlybut from different nave

precursors
Also, TC development is stimulated by antigen
presented on MHC I by dendritic cells
TH by antigen presented on MHC II
39
Maturation of B Cells
Antibodies are the products of plasma cells, which

mature from B cells
Nave B cells with random surface antibody
specificities circulate, sampling the antigens present
If an antigen recognized by the nave B cell is
encountered, its bind is internalized, and it is
presented on MHC II
Modest proliferation also occurs, and partial
activation toward the plasma cell state
The B cell is now primed for differentiation, needing
only help from a TH cell
40
Maturation of B Cells
The primed B cell continues to circulate, presenting its

processed antigen to passing T cells
Since it presents on MHC II, only TH cells are
interested
When a cognate TH cell is finally encountered, signals
are exchanged (as for T-cell maturation above)
Cell proliferation occurs
Differentiation to plasma cells and IgG production
begins
X (Refinement of specificity)
Memory cells are produced
41
Secondary Immune Response
Arises from memory cells

Arises quickly because the activation steps have
occurred and need not be repeated
Is large because of the increased number of starting
cells
42
Section D
Poliovirus Pathogenesis: A Review
Poliovirus Pathogenesis: A Review
Transmission by fecal-oral route via contaminated

water
Primary replication/multiplication is in lymphoid cells
(specialized cells of the immune system), especially in
the gut
Virus is shed primarily into the gut and is excreted in
the feces
Some virus also enters the blood and reaches other
susceptible cells; these include anterior horn cells
(motor neurons), which innervate muscle
Destruction of these cells can result in paralysis
Disease is not a consequence of an essential step in
the viruss life cycle
44
Immunology and the Polio Vaccine
Two polio vaccines were developed with support from

the March of Dimes campaign initiated in 1938 and
sponsored by President Franklin Roosevelt, a paralytic
polio victim
1. Killed virus (Salk), licensed in 1955
2. Attenuated live virus (Sabin), licensed in 1962
Continued
45
The two vaccines have very different immune

consequences
What immunity is induced by each vaccine?
What APCs are initially involved? how do they
present antigen?
What T cells does each stimulate?
What sort of immunity does each ultimately
produce?
Continued
46
What protection is conferred by each vaccine?

Against disease?
Against viral replication?
Does each of these vaccines protect an individual
against disease?
Continued
47
What practical public health advantages does each

vaccine have?
What is current U.S. polio vaccine policy?
48

Creative Commons Attribution-Noncommercial-Sharealike License

Uploaded by

Copyright:

Available Formats

Creative Commons Attribution-Noncommercial-Sharealike License

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Creative Commons Attribution-Noncommercial-Sharealike License

Uploaded by

Copyright:

Available Formats

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License.

Your use of this

Host Response to Infection:

The Immune System

Central to survival after infection

Active process that destroys invading pathogens

Active process that destroys

Phagocytes are located

Adaptive Immunity Primary and Secondary Responses

Humoral: mediated by protein molecules called

Mediated mostly by protein molecules called

Antigen Binding by Antibody

Antibodies act by physically

Antibody Structure (IgG)

Four protein chains

Antibody Structure (IgG)

Each chain has

Antibody Structure (IgG)

It is estimated that there

Antibody Structure (IgM, IgA)

There are several different types of antibody, each

Neutralization occurs when antibody binding to a

Phagocytosis can be made much more efficient by

Additional Functions of Antibody

Cell-Mediated Immunity (CMI)

The primary effectors of CMI are cytotoxic T cells (killer

T-Cell Receptor (TcR)

TcR recognizes antigen

The targets of CMI tend

Humoral vs. Cell-Mediated Immunity

Induction of an Immune Response

Induction of the humoral and CMI responses involve

Situated for immediate interception of pathogens

Stationed in skin, gut, and

T cells are produced as nave precursors

Nave T cells circulate, sampling the antigens

If the antigen is recognized, binding is tight and long

Cytotoxic T Cells and Helper T Cells

There are two kinds of T cells:

Cytotoxic T Cells and Helper T Cells

TH and TC cells arise similarlybut from different nave

Antibodies are the products of plasma cells, which

The primed B cell continues to circulate, presenting its

Secondary Immune Response

Arises from memory cells

Poliovirus Pathogenesis: A Review

Transmission by fecal-oral route via contaminated

Immunology and the Polio Vaccine

Two polio vaccines were developed with support from

Immunology and the Polio Vaccine

The two vaccines have very different immune

Immunology and the Polio Vaccine

What protection is conferred by each vaccine?

Immunology and the Polio Vaccine

What practical public health advantages does each

You might also like