INNATE IMMUNITY: COMPONENTS,

CELLULAR RECEPTORS

By Dr. Oyaro
 Learning objectives
1. List the various components of the innate
immunity and explain the functions of each
component (mechanism of action)
2. Differentiate between PAMPS and PRR
 What is immunity?
• Immunity is body's ability to resist or eliminate
potentially harmful foreign materials (pathogens or
abnormal cells (tumor/cancer)
 Functions of the Immune system
• consists of following functions:
1. Defense against invading pathogens (viruses,
bacteria, protozoa, parasites,fungi)
2. Removal of 'worn-out' cells (e.g., old RBCs) &
tissue debris (e.g., from injury or disease)
3. Identification & destruction of abnormal or
mutant cells (primary defense against cancer)
4. Rejection of 'foreign' cells (e.g., organ transplant)
Inappropriate responses:
• Allergies - response to normally harmless substances
• Autoimmune diseases (self-antigens/molecules)
 The immune system
A functional system – NOT an organ system:
Complex system – well coordinated and includes;
• Skin – physical barrier
• Lining of mucus membranes – physical barrier
• Secretions – tears, PH,mucus etc - antimicrobial
• Blood cells and vasculature – WBCs (innate/specific)
• Bone marrow (HSC/origin of all immune cells)
• Liver – makes complement proteins
• Lymphatic system and lymphoid organs
• Most tissues – have resident immune cells
All cells in the immune
system are derived
from stem cells and
either myeloid or
lymphoid precursors
under the control of
cytokines
 Lymphoid System

• Primary lymphoid organs

– Bone marrow
– Thymus

• Secondary lymphoid organs

• Lymph nodes
• Spleen
Primary lymphoid organs:

Thymus: encapsulated organ where T

cells mature and are selected based
in part on their ability to not
recognize the host

Bone Marrow: site of remaining

hematopoiesis, B cells mature here,
mostly in skull, ribs, sternum and
pelvis
 Thymus
• Structure
– Gross
• Bi-lobed
• Lies above heart
– Microscopic
• Capsular
• Lobules with outer cortex and inner
medulla
 Thymus
• Function
– Takes in immature T cells and puts
out mature (immunocompetent) T
cells
– Increased diversity of T cells
– T cell selection (positive/negative)
 Bone marrow
• Structure
– Microscopic
• Less well defined than thymus
• Role of stromal cells

• Function
– Hematopoiesis
– B cell maturation
– B cell selection
– Puts out mature, naive B cells
Lymphatic vessels:
Drain the entire body to regional lymph
nodes – is a secondary circulatory system
moving antigen to lymph nodes where B
and T cells can respond
 Lymphatic System

• Network of vessels
– Collects fluid from tissues (interstitial fluid-
bathes cells) but lymph-enters the lymphatic
vessels. In blood-plasma
– Major cell is lymphocyte
– Unidirectional
– Often first place where antigens are detected
 Lymph Nodes
• Function
– 1st line of response to antigens
– Harbors B cells (cortex) and T cells,DCs
(paracortex)
– Secondary follicle (Germinal center) is site of B
cell proliferation, mutation, differentiation
– After Ag stimualtion lymphocyte numbers up in
different lymphatic vessel
– Lympadenopathy (enlargement of L.N)
 Spleen
• Structure
– Gross
• Ovoid organ in upper left quadrant of abdomen
– Microscopic
• Compartmentalized
– Red pulp (Macrophages, worn-out RBCs)
– White pulp (B & T lymphocytes) and macrophages
– Site of Ag presentation
• Major cell types (white pulp)
– Lymphocytes
– Macrophages
– Dendritic cells
– RBCs
 Tonsils
• Follicular structure
• Contains lymphocytes, macrophages,
mast cells
• Germinal centers appear in response to
Ag
• Protective role in upper respiratory
infection (URI)
 Appendix
• Associated with intestines
• Responds to Ag
• Role in GI immune response
 MALT
• Lymphoid tissues below epithelium
• Presence of B cells
• Ag presented through unique cell (M cell)
• Preferentially responds with IgA antibody
Neutrophils, mast cells
basophils and
eosinophils are
important granulocytic
cells involved in
phagocytosis or release
of innate immune
inflammatory
mediators
Neutrophils, normally found in
circulation, migrate out of blood
vessels to sites of infection in effort to
phagocytose invading bacteria
Mast cells release
histamine, cytokines
and other inflammatory
mediators when IgE
bound to the surface of
the cell is crosslinked by
an allergen
Monocytes are quiescent
precursors to macrophages and
are found in all tissues in the
body. On activation by invading
pathogens, cytokines etc.,
monocytes differentiate into
macrophages (an angry
monocyte) that can
phagocytose pathogens and
present antigen to T cells to
engage the adaptive immune
response
T and B cells are the main cell types of the adaptive immune
system. B cells express membrane bound antibody (IgM) on
their surface to recognize intact (unprocessed) antigen. T
cells express a T cell receptor that recognizes processed
antigen bound to the MHC molecules
Classification of the Immune System

Immune System

Innate Adaptive
(Nonspecific) (Specific)
1o line of defense 2o line of defense
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

Skin Phagocytic cells

Humoral response
Mucous membranes Antimicrobial proteins (antibodies)

Secretions Inflammatory response

Invading
microbes Natural killer cells Cell-mediated response
Complement
(pathogens) (cytotoxic
lymphocytes)
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
The innate immune System

Innate Immune
System

External Internal
defenses defenses

Interactions between the two systems

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
 Innate immune system
internal defences (blood cells & molecules)
Innate immune system: components of Blood

Complement proteins

Coagulation 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 !
 Monocytes

• Monocytes (~5% of WBCs)

• Migrate into the tissues and

become Macrophages

Lung Bone

Liver Brain intestine

 Macrophages

• “Big eaters”Phagocytosis of microbes in tissue

(neutrophils are present only in blood)
• Antigen presentation
• Activates other immune cells by secreting
cytokines
 Natural killer cells
• Not B-lymphocytes / T-lymphocytes

• Important part of the innate immune system

• Kill virus infected cells (Intracellular

pathogens)

• Kills cancer cells (NK-KIRs)

 Innate immune cell receptors
• The ability to sense the presence of
microorganisms that could cause potentially
dangerous infections is a widespread property
of cells, tissues and body fluids of all
multicellular organisms. This process is
called innate immune recognition.
• This recognition process is the first crucial step
triggering the complex sequence of events by
which the body protects itself against infection
 PAMPS VS PRR
• The receptors usually recognize components
of microorganisms that are not found on cells
of the host, e.g. components of bacterial cell
wall, bacterial flagella or viral nucleic acids
(PAMPS) e.g. components of bacterial cell
wall, bacterial flagella or viral nucleic acids
• Receptors that recognize PAMPS are called
pattern recognition receptors (PRRs).
 How does the killer kill ?

Kills both host cells and microbes

Release of granules with perforins and proteases

 PRR (Toll-like receptors (TLRs)
• Transmembrane proteins
• Present on macrophages / few other cells
• Conserved across vertebrates
• Important part of innate immune system

• N/B: Pattern recognition receptors (PRR)

interacts with PAMPs (pathogen associated
molecular patterns) on the surface of pathogens
 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

Which microbial components are
recognized by TLRs ?
What happens when a TLR bind to a microbe ?

m une Secretion of
d im Cytokines /
nc e nse
a o
Enh resp Interferon

Phagocytosis
Inflammation TLR binding of infected
to microbe cell

d
fe cte
o f in
Apoptosis of i l l ing cell
K
infected cell
 Other receptors
• RIG-1 is an example of a family of molecules that
recognize RNA viruses such as influenza, picornaviruses
(common cold) and Japanese encephalitis virus, and
then switch on the production of interferons and other
antiviral proteins.
• NOD-like receptors: NOD1 and NOD2 receptors
recognize fragments of bacterial cell wall
proteoglycans, and are found at particularly high
amounts in the epithelial cells that line the gut
 Cytokines
• Small proteins – secreted by
cells of the immune system

• Affect the behaviour of other

cells (activates other sells)

• 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/monocytes – when they encounter a pathogen

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

cell

• Lymphocytes (B & T cells) – when they are activated

 Examples of cytokines
• Interferons

• Interleukins

• Tumour necrosis factor (TNF)

 Interferons (IFN)
• Signalling proteins produced by virus infected cells

• 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
 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 thro’ C9)

• Complement can bind to microbes and coat the microbes

• Essential part of innate immune response

• Enhances adaptive immune resposne (taught later)

 Complement proteins: role in innate
immune system
C`proteins

Facilitates phagocytosis Direct lysis of pathogens Inflammation

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

Initiation of phagocytosis
 How do C` proteins lyse pathogens?

Membrane attack complex formed by c` proteins

Thank you!