Basic immunological concepts 

and
Cells of the immune system

BBS755 Infection and Immunity

Feb 5, 2015
Lecture 2
Prof. Stern

Immunology: study of how an organism responds to pathogens

Protozoa Fungus Bacteria

Worms

Fungus Virus Virus Bacteria

Bacteria Bacteria
Bacteria

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What does the immune system need
to do to deal with these threats?
•  See everything
• Viruses, bacteria, fungi, protozoa, helminths

•  Look everywhere
• All tissues, extracelllular, intracellular

•  Mount an appropriate response

•  Make a self-nonself discrimination

The Responses
Innate immune Adaptive
response immune
response

Innate  response   Adap8ve  immune  

(e.g.  inflamma8on)   response  

Rapid Slower    
Indiscriminate Precise

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Characteristics of innate vs adaptive responses

Inflammation (Innate immunity): Adaptive immunity:

• Stereotyped response • Specialized responses
• Same cell - same receptor • Each cell has a different receptor
• Germ-line encoded receptors • Somatic cell receptor variation
• Immediate effect • Slower to respond,
• More easily subverted but “always gets their man”
• Evolutionarily older • Evolutionarily more recent

Specificity of innate versus adaptive

immunity
Innate: Limited # specificities
YY
Y

•  “Each policeman is looking for about the same

thing”
•  Limited number of different receptors looking for
conserved features of pathogens or injury (e.g.
bacterial cell wall components, DNA in cytosol)

Adaptive: Numerous highly selective specificities

•  “Each soldier is looking for a different thing”
•  Many different receptors & each cell has a different
receptor
Y

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 Specificity of innate versus adaptive
immunity
Innate: Limited # specificities

YY
Y
•  “Each policeman is looking for about the same
thing”
•  Limited number of different receptors looking for
conserved features of pathogens or injury
(e.g. bacterial cell wall components, DNA in cytosol)

Adaptive: Numerous highly selective specificities

•  “Each soldier is looking for a different thing”
•  Many different receptors & each cell has a different
receptor

U
Specificity and Memory

Two key features of the adaptive immune

system have puzzled, fascinated, and
inspired researchers :

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The immune system is amazingly
specific

vs.

isoleucine leucine Dinitrophenyl hapten

hapten: a small molecule covalently

coupled to a macromolecule to make
it “foreign” so it can be recognized
by the immune system

Nitrophenyl serum
albumin

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 Immunological memory

The immune system responds more quickly

and more effectively to pathogens to which it
has been previously exposed

Immunological memory

Thucydides, on the plague of Athens, 430 BC

“Yet is was with those who had recovered from the disease
that the sick and the dying found most compassion. These
knew what is was from experience, and had now no fear for
themselves, for the same person was never attacked twice -
never at least fatally.”

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Immune defenses

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 Immune defenses
First line of defense: barriers (epithelial surfaces)

Once barrier has been breached…

…immune system takes over

To deal with diverse threats, many

different defenses are needed
What are the components of the immune
response?
Soluble defenses: antibodies, complement proteins,
cytokines, chemokines, lipid mediators

Cells: lymphocytes, macrophages, dendritic cells,

granulocytes, mast cells

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 Immune defenses
•  Soluble molecules
Humoral immunity, from “humor” : according to
ancient theory, four bodily fluids or humors (blood,
phlegm, black bile, yellow bile) determined health
and temperament, with imbalances among the
humors responsible for pain and disease

•  serum antibodies (Abs)

•  serum complement (C’)

Immune defenses
•  Antibodies

Immunoglobulin G

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 Immune defenses
•  Antibody-mediated immunity

Opsonize:
fr. Greek opson,
condiment, delicacy
Complement:
a cascade of serum
proteins that results in
bacterial lysis and
immune recruitment

The complement system

Recognition of microbial surface

Proteolytic signaling cascade

All pathways lead to:

1) Covalent deposition of complement components on surface
2) Generation of pro-inflammatory peptides

Membrane damage Target for destruction Inflammation

by phagocytes
“opsinization”

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 Immune defenses
•  Cellular responses - T cells (CTL and NK cells)
directly lyse infected cells…

Credit: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY © James A. Sullivan CELLS alive!

… by induction of apoptosis to destroy infected cells 

and their contents

Immune defenses
•  Cellular responses – macrophages phagocytose
bacteria and fungi …

© James A. Sullivan CELLS alive!

… and kill them by phagosome-lysosome fusion

(pH ~5: proteases, lipases, lysozyme, antimicrobial
peptides, iron chelators )

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 Immune defenses
•  Cellular responses: neutrophils phagocytose and kill bacteria…

Neutrophil swarms require LTB4 and integrins at sites of cell © James A. Sullivan CELLS alive!
death in vivo Tim Lämmermann et al Nature 498, 371–375

… by releasing reactive oxygen (ROI) and nitrogen (RNI) species that react with
proteins, lipids and DNA. 
- superoxide (O2-) generated by the NADPH oxidase complex
-nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS)

How do we learn about the

immune system?
Many branches of experimental science have
contributed to our current understanding of
immunology
Chemistry
Biochemistry
Molecular biology
Microbiology
Microscopy
Cellular biology
Genetics
Population biology

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Levels of immunological investigation:
molecular
Antigen receptor
on T cell surface

Viral antigen
from influenza virus

MHC protein
on surface of infected cells

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Levels of immunological investigation:
cellular
bacteria macrophage

T cell

Levels of immunological investigation: 

tissue
Intravital imaging of a
lymph node
Immunity Vol 21, 231-339, 2004. 
Alex YC Huang, Hai Qi, Ronald Germain 

Illuminating the landscape of in vivo
immunity: insights from dynamic in
situ imaging of secondary lymphoid
tissues

Two-photon microscopy of a murine

lymph node. Images taken at 30s
intervals at a depth of ~100um
below the capsule. Total length of
movie = 25min (300x).
Image shows capture of CD4+ T
cells (red) and CD8+ T cells (green)
specific for chicken ovalbumin by
dendritic cells (yellow) expressing
ovalbumin peptides bound to cell
surface MHC II molecules.

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 Levels of immunological investigation: 
organism

Transgenic mice and gene knockout technology allow 

the function of a gene to be tested in vivo at the whole organism level

Levels of immunological investigation:

population

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 Summary of key points
•  Diverse threat from infectious agents
numerous, ubiquitous, adaptable

•  Innate (rapid, germ-line encoded) and adaptive (slower,

encoded by rearranged/mutated receptors) responses

•  Flexible, multilevel protection strategy

soluble defenses (humoral immunity)
phagocytes and cytoxic cells (cellular immunity)

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Cells of the immune system
There are a variety of types of
immune cells, but all arise from a
common bone-marrow progenitor

How can we tell the various immune

cells apart from one another?
1.  Morphology
2.  Surface molecules that are cell type-specific

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 Differentiation of immune cells

White blood cells Red blood

(immune cells) cells, platelets

(resting)

Lymphocytes
(adaptive immunity)

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 B and T Lymphocytes

•  Mediators of adaptive immunity

•  distinguish self / non-self
•  resting and activated appearance is different

Type of Lymphocytes

•  Killer T cells (CTL): recognition and lysis of infected cells

•  Helper T cells (TH1, TH2, TH17, Treg):
recognize infection,coordinate
response, activate or inhibit effector cells
•  B cells: antibody production
•  NK cells: lyse infected cells
•  Innate-like lymphocytes:
B-1 cell, γδ T cells, NKT cells

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 (resting)

Myeloid cells
phagocytes, granulocytes
(innate immunity)

Myeloid cells

• Mediators of innate immunity

• Secrete toxins to kill pathogens
• Release signals to alert and
attract other cells (cytokines,
chemokines, vasodialators)

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 (resting)

Antigen presenting cells

(bridge between adaptive and innate immunity)

Antigen presenting cells

Functions of APC
•  sentinels / warning
•  sample environment by
phagocytosis and surface
receptors
•  process antigens and
“present” them to helper T
cells

Other functions
•  Mφ: phagocytic effector cells
•  DC: carry antigens to lymph
nodes

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 Where are immune cells in the body?
Primary immune organs
Bone marrow
Thymus
Peripheral (secondary)
Lymphoid tissue
Lymphocytes
Macrophages
Dendritic cells
Blood
Granulocytes
Monocytes
Lymphocytes

Tissues
Macrophages
Dendritic cells
Mast cells

Summary of key points

• Immune cells arise from a common precursor
• Different types of immune cells have different
functions
• Phagocytic and secretory myeloid cells
(neutrophils, PMN, mast cells, basophils, mφ)
provide immediate response, sound alarm
• Lymphocytes (B, T, NK cells) are specialized for
specific antigen recognition
– Activated B cells secrete Ab
– Activated CTL lyse infected cells
– Activated TH cells recognize infection,
coordinate response

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 Stages of response to infection

Classic signs of inflammation

Calor, dolor, tumor, rubor

warmth, pain, swelling, redness

Aulus Cornelius Celsus
25 – 50 AD
De Medicina

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 Inflammation

•Induced by resident leukocytes, complement activation, or tissue damage

•Results in:
• Increased vascular diameter, local blood flow
• Upregulation of endothelial cell adhesion molecules
• recruitment of leukocytes from blood (extravasation)
• plasma leakage (edema)

Dendritic cells deliver tissue antigen

to lymph nodes
Figure and1-13
present it to
lymphocytes

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 Lymphocytes circulate
between blood and
lymphatic fluid

Antigen-presenting cells
carry antigens from tissues
to lymph nodes

Lymph nodes - 

and other peripheral lymphoid tissue -
where lymphocytes meet antigens

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 T cells searching for antigen in
lymph node

Meeting of lymphocytes and

antigen is important in the
conversion of naïve lymphocytes
to active forms that can perform
their respective immune
functions
Naïve: simple and guileless, unsuspecting
In immunology, having been never exposed to antigen

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 Summary of key points
•  Inflammation is a rapid response to penetration of the
epithelial barrier, and serves to deliver effector molecules
and cells to sites of infection
•  Inflammation is triggered by soluble mediators released
by tissue-resident leukocytes: mΦ, mast cells, and
causes monocytes, neutrophils, and lymphocytes to
extravasate near sites of infection
•  antigen presenting cells acquire antigens and carry
them to lymphatic tissue to initiate adaptive responses
•  naïve lymphocytes (B cells and T cells) meet antigens
on APC in lymph nodes, inducting lymphocyte maturation
•  yin/yang of immunity:
possibility of collateral damage by innate system
possibility of autoreactivity by adaptive system

The end

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