OVERVIEW OF THE

IMMUNE RESPONSE
BAS 115: Immunology
Topic #1
Michael Dorrington
Course Administration
Mike Dorrington
dorrinmg@gmail.com
Office Hours
By appointment only. Will occur either
before or after class.
Part-time faculty office (Rm 2111)
Grading
2 Exams (one midterm, one final)
40/60 weighting
Immunology
The study of the physiological mechanisms
that humans and other animals use to
defend their bodies from invasion by other
organisms
Overview of the Immune Response
We are surrounded by a myriad of
potentially harmful microbial agents =
pathogens

Bacteria
Viruses
Fungi
Parasites


Overview of the Immune Response
However..
in normal individuals most infections are
of limited duration and leave little (if any)
permanent damage

Due to: immune system responding to
and eliminating the pathogen
Intrinsic Barriers
Mechanical
Skin
Epithelium
Chemical
Enzymes
Oil
Microbiological
Normal Flora
Overview of the Immune Response
Immune system has 2 functional
divisions:

1. Innate 1
st
line of defence

2. Adaptive comes into play if innate
defences are breached

Overview of the Immune Response
All of the elements of innate/natural
immunity:

1. Do not increase in response to re-
exposure or chronic exposure to a
microbe
2. Do not discriminate between foreign
substances*
Overview of the Immune Response
However.

Elements of acquired/adaptive immunity
induced by exposure to foreign substances
are:

1. Specific for a given pathogen

2. Increase both qualitatively and
quantitatively following primary exposure to
a given pathogen
Overview of the Immune Response
The ultimate defence against a
pathogen (whether elicited by the
innate or adaptive immune system) is
to reduce invaders genes from an
active polymer to inactive monomers

Break big things into little things
This is accomplished by phagocyte cells
Overview of the Immune Response
Steps in Phagocytosis:

1. Adhesion grabbing
2. Ingestion engulfing
3. Digestion breaking down
Innate-Activated Phagocytosis
Overview of the Immune Response
Almost every component of the immune
system contributes to:
1. Recognizing pathogens
2. Destroying pathogens
3. Communicating between these two
activities
Hallmarks of Adaptive Immune Responses
1. Specificity

2. Diversity

3. Memory

4. Self/Non-self Discrimination

5. Self Limitation
Hallmarks of Adaptive Immune Responses
1. Specificity

Immune responses are specific for
distinct antigens

antigenic determinant/epitope:
- portion of the molecule recognized
Hallmarks of Adaptive Immune Responses
2. Diversity

Vertebrate immune system can
recognize ~10
16
distinct antigens

This is accomplished by sets of
corresponding recognition molecules
(receptors) on immune cells
Antibody
T cell receptors
Hallmarks of Adaptive Immune Responses
2. Diversity (cont.)

lymphocyte receptor repertoire:
- the set of antigen (Ag) receptors in a
given individuals immune system
Hallmarks of Adaptive Immune Responses
3. Memory

Exposure of the adaptive immune system to Ag
increases its ability to respond to the same or
closely related antigen following re-exposure

Secondary immune responses =
Faster
Larger
Qualitatively different

Hallmarks of Adaptive Immune Responses
4. Self-Limitation

Adaptive immune responses are
transient
Immune responses are tightly
regulated and controlled


Hallmarks of Adaptive Immune Responses
5. Self/Non-self Discrimination

The immune system can tell foreign from
self
Immune responses to self can result in
autoimmunity
Immunological unresponsiveness to self is
termed tolerance


Clonal Selection Hypothesis
The central principle of adaptive
immunity!

Is comprised of 4 basic principles

Types of Adaptive Immune Responses
1. Humoral
Mediated by antibodies (Ab)
Produced by bone marrow derived or B
lymphocytes

2. Cell-mediated
Mediated by thymus-derived or T lymphocyte

N.B. BOTH humoral and cell-mediated immune
responses involve lymphocytes
Types of Adaptive Immune Responses
Humoral
Immunity
Cell-Mediated
Immunity
Antigen
Extracellular
pathogen & toxins
Intracellular microbes
Responding
Lymphocyte
B lymphocytes T lymphocytes
Effector
Mechanism
Ab killing
Transferred By:
serum Lymphocytes
Cells and Tissues of The
Immune System
Cells & Tissues of the Immune System
All cellular elements of the blood (WBCs, RBCs and
platelets) are derived from the same progenitor:

Pluripotent Stem Cells

Myeloid progenitor Common lymphoid progenitor
- monocytes - B lymphocytes
(macrophages, dendritic cells) - T lymphocytes
- granulocytes (PMNs) - NK cells
- Mast Cells

Myeloid Progenitor
Monocytes/macrophages
Macrophages are one of 2 phagocytic cells in
the body
Macrophage is the mature form of monocyte
Monocytes circulate in the blood &
differentiate into macrophages upon
migration into tissue
Macrophages often produce the cytokines
that initiate the inflammatory response
Myeloid Progenitor
Dendritic Cells

Resident in the bodys tissues
During infection, leave tissue (with
infectious cargo) and travel to lymph
nodes
Important in T cell activation during
adaptive immune responses
Myeloid Progenitor
Mast Cells

Differentiate in tissue from a blood-
derived precursor
Orchestrate allergic responses
Important in mucosal immune
responses
Myeloid Progenitor
Granulocytes (PMNs)

a) Neutrophils
- Phagocytic
- Most numerous cellular component of innate immune
system

b) Eosinophils
- defense against parasites

c) Basophils
- with mast cells, protect mucosal body surfaces & release
histamine in allergic responses

Common Lymphoid Progenitor
Produces lymphocytes

B cells: - bone marrow derived
- upon activation differentiate into Ab-
secreting plasma cells

T cells: - thymus-derived
- become either helper T cells (T
H
) or
cytotoxic T lymphocytes (CTL)
T Lymphocytes
T
H
Cells:
Activate other cells (macrophages, B
cells)

CTL:
Kill virus infected cells
Common Lymphoid Progenitor
T and B lymphocytes look alike, each
having receptors for specific antigen

NK cells: lack Ag-specific receptors
Important in the innate immune system
Kill infected/altered cells
Lymphoid Tissues
Organized tissues where lymphocytes
interact with non-lymphoid cells

Important in the initiation and maturation of
adaptive immune responses

2 types of lymphoid tissues
Primary lymphoid organs
Secondary lymphoid organs
Primary Lymphoid Organs
Where lymphocytes are generated
Includes bone marrow & thymus
Both B and T cells are generated in the
bone marrow but only B cells mature
there
Once lymphocytes mature they leave
the 1
o
lymphoid organs and are capable
of responding to Ag
Secondary Lymphoid Organs
Where adaptive immune responses are
initiated & Ag/Ab encounter each other
Exist to bring Ag and lymphocytes together

Lymph nodes:
Organized lymphoid structures
Collect ECF (lymph) and return it to the blood (in vessels
called lymphatics)
Afferent lymphatics drain lymph and Ags from tissues,
carrying it to the nodes where Ag is trapped
A. Lymph Node Structure
Bean-shaped outer cortex, inner
medulla
Lymph enters via afferent lymphatics,
percolates through node & exits via
efferent lymphatics in medulla
Nave lymphocytes exit blood via high
endothelial venules (HEV)
High Endothelial Venules (HEV)
Specialized section of post-capillary venules
Plump endothelial cells protrude into vessel
In LNs found in paracortex and some areas of
cortex
Lymphocytes display increased adhesiveness
to HEV
A. Lymph Node Structure
Medulla: consists of macrophages and
plasma cells

B cells: - found in follicles
- some follicles contain germinal
centers where B cells proliferate in
response to Ag

T cells: found in paracortical area

B. Spleen
Fist-sized organ located behind stomach

Collects blood born Ag & also destroys aged RBCs

Organ is divided into red pulp & white pulp

Red pulp:
where old RBCs are destroyed

White pulp:
where lymphocytes surround arterioles entering organ
Further subdivided into corona and periarteriole lymphoid
sheath (PALS)
Asplenia & Splenectomy
Genetic defect causing asplenia not yet
identified
Clinical consequence:
Susceptibility to bacteremia caused by
encapsulated bacteria caused by failure of
the immune response to these common
extracellular bacteria when they enter the
blood stream
C. Mucosa-associated Lymphoid Tissue
Gut- and bronchial- associated
lymphoid tissues (GALT & BALT)
Purpose is to collect Ag from mucosal
surfaces
Specialized lymphoid tissue at the
bodys wet surfaces required due to
large surface area, rich with potential
pathogens
C. Mucosa-associated Lymphoid Tissue
Gut-Associated Lymphoid Tissue (GALT)
Includes tonsils, adenoids, appendix
and Peyers Patches (PP)
PPs collect Ag from epithelial surfaces
of GI tract via M cells
PPs composed of distinct T and B cell
areas
Lymphocyte Recirculation
Nave lymphocyte recirculation pattern:

B & T lymphocytes lymphocytes
mature In b.m. & thymus in blood

PLN
superior
vena cava

thoracic efferent
duct lymphatics
Lymphocyte Recirculation
If an infection occurs in periphery:

a) Ag enters local draining LN via afferent lymphatics.
Ag gets trapped and is displayed to recirculating
lymphocytes

b) Lymphocytes that specifically recognize the Ag are
arrested in the LN, where proliferation and
differentiation to effector lymphoid cells occurs

c) Specific effector cells leave the LN via efferent
lymphatics