Introduction to the immune

system

By – Dr. Deepika Gupta

 Immunity
• Immunity (immunis- Latin-exempt, state of protection from
infectious diseases)
• Immunity is body's ability to resist or eliminate potentially
harmful foreign materials or abnormal cells
 History: what imparts Immunity?
• Thucydides, the great historian of the Peloponnesian War (430 BC)-
who had recovered from the plague could nurse the sick because
they would not contract the disease a second time

• Emil von Behring and Kitasato (1890)

– Serum from vaccinated animals was protective (diptheria)

• Metchinkoff (1880)
– Cell based Immunity

• Merrill Chase (1940)- Transfer of WBC (immunity to tuberculosis)

Both serum and cells contribute to immunity

 Immunology

• Study of the components and function of the

immune system

• Since 1901 there have been 20 Nobel Prizes for

immunology-related research.
 The immune system
• Crucial to human survival
• A functional system – NOT an organ system:
Molecules, cells, tissues and organs which provide
non-specific and specific protection
• Complex system – includes
– Skin – physical barrier
– Lining of mucus membranes – physical barrier
– Secretions – tears, mucus etc - antimicrobial
– Blood cells and vasculature – WBCs
– Bone marrow
– Liver – makes complement proteins
– Lymphatic system and lymphoid organs
– Most tissues – have resident immune cells
 Functions of the immune system

– Defense against invading pathogens (viruses &

bacteria)
– Removal of 'worn-out' cells (e.g., old RBCs) &
tissue debris (e.g., from injury or disease)
– Identification & destruction of abnormal or
mutant cells (primary defense against cancer)
– Rejection of 'foreign' cells (e.g., organ transplant)
– Inappropriate responses:
• Allergies - response to normally harmless substances
• Autoimmune diseases
Innate immunity vs Adaptive Immunity

Innate Immunity Adaptive Immunity

(first line of defense) (second line of defense)

• No time lag • A lag period

• Not antigen specific • Antigen specific

• No memory • Development
of memory
 NATURALLY ACQUIRED
IMMUNITY
• Active
– Antigens enter body naturally with response of
• Innate and adaptive immune systems
– Provides long term protection

• Passive
– Antibodies pass from mother to
• Fetus across placenta
• Infant in breast milk
– Provides immediate short term protection
 ARTIFICIALLY ACQUIRED
IMMUNITY
• Active
– Antigens enter body through vaccination with response
of
• Innate and adaptive immune systems
– Provides long term protection
• Passive
– Antibodies from immune individuals injected into body
• Referred to as
– Immune serum globulins (ISG)
– Immune globulins (IG)
– Gamma globulins
– Provides immediate short term protection
DEFENSE MECHANISMS OF THE
HUMAN HOST
Cells and Organs of the Immune System
Cells and Organs of the Immune System

• Cells – Leukocytes
a. Lymphocytes – specialized for adaptive immunity
b. Granulocytes/Agranulocytes – function in accessory roles in
adaptive immunity

• Immune Organs – 2 major groups

a. 1° lymphoid organs – where lymphocytes develop and mature
b. 2° lymphoid organs – where lymphocytes interact with Ag
 ORIGIN OF CELLS OF THE
IMMUNE SYSTEM
• Derived from common progenitor cell in bone marrow
– Pluripotent hematopoietic stem cell

• Progenitor Stem Cells

– Myeloid lineage
• Monocyte/macrophage, dendritic cells, PMN’s, mast
cells
– Lymphoid lineage
• Small and large lymphocytes
 Hematopoiesis
• HSC (Hematopoietic Stem Cell)
– Reside in Bone Marrow
– Pluripotent
– 1 HSC Per 50,000 BM Cells (~3x108 cells in Mouse
Bone Marrow)
– Extremely Proliferative If Need Arises
• HSC Differentiates to LPC (lymphoid progenitor
cell) or MSC (myeloid stem cell)
• Growth Factors and Cytokines Determine Path
• Once LPC or MSC, Committed
• Stromal Cells are Supporting Cells in BM
(endothelial, fat cells, fibroblasts, macrophages)
Immune cells: Myeloid Lineage
 Granulocytes

– Neutrophil
• Principal phagocytic cell of innate immunity
– Eosinophil
• Principal defender against parasites
– Basophil
• Functions similar to eosinophils and mast cells

Referred to as
1. Polymorphonuclear leukocytes
(PMN’s)
⮚ Nuclei are multilobed (2 to 5)

2. Granulocytes
⮚ Cytoplasmic granules
 Agranulocytes
Mononuclear Cells

• Mononuclear cells, Mast cells,

• Monocytes in Blood, MΦ in Tissues
– Monocytes 5-10 times smaller than MΦ
• Secretes cytokines and Produces Hydrolytic
Enzymes
• Activated By Phagocytosis or Cytokines (IFNγ)
• Antigen Presenting Capacity through MHC II
 Mononuclear Cells
– Monocytes
• Leukocytes with bean shaped or brain-like
convoluted nuclei
• Circulate in blood with half life of 8 hours
• Precursors of tissue macrophages

– Macrophages
• Mononuclear phagocytic cells in tissue
• Derive from blood monocytes
• Participate in innate and adaptive immunity
Monocyte vs MΦ
MΦ Effective APC
MΦ Capturing Bacteria
Immune cells: Lymphoid Lineage
 Lymphoid Cells
– B-cells, T-cells and NK cells
– 20-40% of body’s leukocytes
– 99% of lymph node
– If inactivated said to be naïve
– Nucleus occupies almost entire cell
– 6 μm diameter
 Lymphoid Cells
– Large lymphocytes (large granular lymphocytes)
• Natural killer (NK) cells (CD16, CD56)
• Innate immunity to viruses and other intracellular
pathogens
• Participate in antibody-dependent cell-mediated
cytotoxicity (ADCC)
– Small lymphocytes
• B cells (CD19)
• T cells (CD3, CD4 or CD8)
• Adaptive immunity
✔Lymphocytes refers to small lymphocytes
 NK Cells

• Do Not Express Classical Lymphocyte

Markers
• Predominantly NK Cells (CD56)
• Eliminate Tumor Cells and Virally Infected
Cells
 THE CLUSTER OF
DIFFERENTIATION (CD)
• A protocol for identification and investigation of cell
surface molecules
• CD number assigned on basis of 1 cell surface molecule
recognized by 2 specific monoclonal antibodies
• CD nomenclature established in 1982
– 1st International Workshop and Conference on Human
Leukocyte Differentiation Antigens (HLDA)
• Over 300 CD Markers
 THE CLUSTER OF
DIFFERENTIATION (CD)
• CD markers on leukocytes

Granulocyte CD45+, CD15+

Monocyte CD45+, CD14+
T lymphocyte CD45+, CD3+
T helper lymphocyte CD45+, CD3+, CD4+
T cytotoxic lymphocyte CD45+, CD3+, CD8+
B lymphocyte CD45+, CD19+
Natural killer cell CD45+, CD16+, CD56+, CD3-
 Dendritic Cells
• Scarce Cell Type
• Discovered in 1972
• Professional APCs
• Interstitial DCs, populate organs such as heart,
lungs, liver, intestines
• Interdigitating DCs, T-cell areas of lymph nodes
and Thymic medulla
Dendritic Cells

http:www.coleypharma.com
Developmental Pathway of DCs
Overview of the Immune System

Immune System

Innate Adaptive
(Nonspecific) (Specific)
1o line of defense 2o line of defense
Interactions between the two systems
The innate immune System

Innate Immune
System

External Internal
defenses defenses

Interactions between the two systems

 A typical immune response
INNATE IMMUNITY ACQUIRED IMMUNITY
Rapid responses to a Slower responses to
broad range of microbes specific microbes

External defenses Internal defenses

Phagocytic cells
Skin Humoral response
NK cells (antibodies)
Mucous membranes
Antimicrobial proteins
Secretions Cytokines,
Complements Cell-mediated response
Invading (cytotoxic
microbes Inflammatory response
lymphocytes)
(pathogens)
Innate immune system
External defenses
Anatomical Barriers - Mechanical Factors

• Skin

• Mucociliary escalator

• Flushing action of
saliva, tears, urine
Anatomical Barriers – Chemical factors
Antimicrobial HCl in stomach Lysozyme in tears /saliva
Peptides in sweat
Anatomical Barriers – Biological factors

Normal flora – microbes in many parts of

the body

Normal flora – > 1000 species of

bacteria

Normal flora – competes with pathogens

for nutrients and space
 A typical immune response
INNATE IMMUNITY ACQUIRED IMMUNITY
Rapid responses to a Slower responses to
broad range of microbes specific microbes

External defenses Internal defenses

Phagocytic cells
Skin Humoral response
NK cells (antibodies)
Mucous membranes
Antimicrobial proteins
Secretions Cytokines,
Complements Cell-mediated response
Invading (cytotoxic
microbes Inflammatory response
lymphocytes)
(pathogens)
Innate immune system
Internal defences
Innate immune system: components of Blood

Complement proteins
Extracellular
Cytokines

WBCs
 White blood cells (WBCs)
Macrophages

B-lymphocytes

T-lymphocytes

Natural killer(NK) cells

Mast cells
 Neutrophils in innate immune
response

• Most abundant WBCs (~50-60%)

• Efficient phagocytes

• Most important cells of the innate immune system

 Phagocytosis
• Phago = to eat
• Cyte = cell

• WBCs (eg. Neutrophils) – find, eat and digest

microbes !
 How do neutrophils find microbes ?

• https://youtu.be/I_xh-bkiv_c

• https://www.youtube.com/watch?v=ZUUfdP8
7Ssg
How do neutrophils eat and digest microbes
?

Granules
 What’s in the granules ?

Lysozyme – digests bacterial cell wall;

other antimicrobial proteins
Additional role of neutrophils

Triggers inflammatory response

 Monocytes

• Monocytes (~5% of
WBCs)
Lung Bone

• Migrate into the tissues

and become
Macrophages Liver Brain Intestine
 Macrophages

• “Big eaters”

• Phagocytosis of microbes in tissue

(neutrophils are present only in blood)

• Antigen presentation
 Natural killer cells
• Not B-lymphocytes / T-
lymphocytes

• Important part of the innate

immune system

• Kill virus /bacteria infected

cells (Intracellular
pathogens)

• Kills cancer cells

NK cells differentiate choose cells to kill ?

Uninfected cell /
Normal cell

Microbe infected cell /

cancer cell

Some cell surface proteins are

missing
 How does the killer kill ?

Kills both host cells and microbes

Release of granules with perforins and proteases
 Toll-like receptors (TLRs)
• Transmembrane proteins

• Present on macrophages / few other cells

• Conserved across vertebrates

• Important part of innate immune system

 TLRs – What do they do ?
They look out for microbes (or their components)

They bind to the microbes (or their components)

They trigger a cascade of events to kill or protect

against pathogens

THEY ARE INNATE IMMUNE SENSORS

TLRs – look out for microbes
TLRs – bind to microbes / components
of microbes
Which microbial components are
recognized by TLRs ?
What happens when a TLR bind to a microbe ?

Secretion of
Cytokines /
Interferon

Phagocytosis
Inflammation TLR binding of infected
to microbe cell

Apoptosis of
infected cell
 Summary: innate response – internal
defenses – Cellular (WBCs)

Come into play when the external defenses are breached

• Neutrophils

• Monocytes /macrophages

• NK cells

• TLRs
Innate immune system: components of Blood

Complement proteins

Cytokines

WBCs
 Cytokines
• Small proteins – secreted by
cells of the immune system

• Affect the behaviour of

other cells

• Signalling molecules

• Key players in innate and

acquired immunity
 Which cells release cytokines ?
Cells of the immune system:

• Neutrophils – when they encounter a pathogen

• Macrophages – when they encounter a pathogen

• NK cells – on encountering a microbe infected cell /tumour

cell

• Lymphocytes – when they are activated

 Examples of cytokines

• Interferons

• Interleukins

• Tumour necrosis factor (TNF)

 Interferons (IFN)
• Signalling proteins produced by virus infected monocytes and
lymphocytes

• Secreted proteins – Key anti-viral proteins

• “Interfere” with virus replication

• Warn the neighbouring cells that a virus is around...

• If we did not have IFNs – most of us may die of influenza virus

infection
How does IFN warn the neighbouring
cells ?

72
The infected cells release IFN

antiviral state

antiviral state antiviral state

antiviral state
73
Virus infects the neighbouring cells

antiviral state

antiviral state antiviral state

antiviral state
74
Prewarned cells are able to quickly
inhibit the virus

antiviral state

antiviral state antiviral state

antiviral state
75
How do Interferons inhibit viruses ?

Inactive host protein

Induction Virus ds-RNA
Activation

Host protein Active host protein

Cascade of events

Inhibition of
host protein
synthesis
Virus cannot replicate
 Interleukins
• Interleukins – 1-37

• Not stored inside cells

• Quickly synthesized and secreted in response to infection

• Key modulators of behaviour of immune cells

• Mostly secreted by T-lymphocytes & macrophages

 What to interleukins do ?

Proliferation of immune cells

Interleukins
Increase antibody production
Inflammation

Activation of immune cells

 Tumour necrosis factor (TNF)
TNF

Killing of cancer Fever

Inflammation
 Complement (C`)
• a large number of distinct plasma proteins that react with
one another (C1 - C9)

• Complement can bind to microbes and coat the microbes

• Essential part of innate immune response

• Enhances adaptive immune response (taught later)

 Complement proteins: role in innate
immune system
C`proteins

Facilitates phagocytosis Direct lysis of pathogens Inflammation

How do C` proteins facilitate phagocytosis ?
Bacteria coated with C` Neutrophils have C` receptors

Initiation of phagocytosis
 How do C` proteins lyse pathogens?
Membrane attack complex formed by
C` proteins
 Summary: innate response – internal
defenses

Cellular Extracellular

• Neutrophils • Cytokines

• Monocytes /macrophages
• Complement
• NK cells

• TLRs
 A typical immune response
INNATE IMMUNITY ACQUIRED IMMUNITY
Rapid responses to a Slower responses to
broad range of microbes specific microbes

External defenses Internal defenses

Phagocytic cells
Skin Humoral response
NK cells (antibodies)
Mucous membranes
Antimicrobial proteins
Secretions Cytokines,
Complements Cell-mediated response
Invading (cytotoxic
microbes Inflammatory response
lymphocytes)
(pathogens)