Download Presentation 3 Innate Immunity

LECTURE 3: INNATE
IMMUNITY
DR. SYEDA SALEHA HASSAN
BIOT 307
1-09-2014
LECTURE OBJECTIVES
• Understand the concept of innate
immunity
• Describe the characteristics of the
response
• Understand recognition processes
• Describe the cells involved and
their effector functions
INNATE IMMUNITY
Innate immunity is a non specific defense mechanism
that a host uses immediately or within several hours
after exposure to antigen
0-4 hours Innate immunity (natural immunity)
4-96 Early, induced response
>96 hours Acquired immunity (adaptive immunity)
CHARACTERISTICS
• This is the immunity you are born with!
• Designed to be very fast- within hours
• Ancient evolution-components of innate immunity
found in invertebrates-amoeba, snails, fruit flies
• Responds exactly the same way every time
• Uses a handful of molecules to recognise that
infection is present
• Induces and directs the acquired immune response
COMPONENTS OF THE INNATE
IMMUNE SYSTEM
• Physical/anatomical barriers
Skin, GI tract, respiratory tract, mucosal epithelia
• Secreted compounds
Antibacterial compounds, complement, natural
antibodies, cytokines
• Cellular components
Phagocytes, NK cells
GOALS OF THE IMMUNE SYSTEM
Prevent entry of the pathogen!
PATHOGEN PREVENTION
Skin: dry outer protective
layer, difficult for
pathogens to penetrate,
fatty acid production
inhibits microbes on skin
Respiratory tract: cells
joined tightly togethertight junctions, cilia,
mucus
GI tract: peristalsis,
hydrochloric acid
production, low pH
PATHOGEN PREVENTION
Tears, sweat, saliva: lysozyme, destroys bacterial walls
GI tract: acid hydrolysis, bacterial
digestion/degradation
Microbial competition: bacteria that normally live in
the body can prevent the pathogen from growing
Skin-Staphylococcus epidermis
GI tract-lactobacilli
GOALS OF THE INNATE IMMUNE SYSTEM
Recognise the pathogen
THE INNATE IMMUNE RESPONSE DOES NOT
RECOGNISE EVERY POSSIBLE ANTIGEN
• Recognises a few highly
conserved molecular
structures present in
many different
microorganisms
Pathogen Associated
Molecular
Patterns=PAMPS
• Present in the
microorganism but not
the host
• Essential for the survival
of the pathogen e.g.
Lipopolysaccharide
from Gram negative
bacteria
LIPOTEICHOIC ACID FROM GRAM
NEGATIVE BACTERIA
• Peptidoglycan found in
bacterial
cell walls
• ds RNA
unique to
most viruses
PATTERN RECOGNITION RECEPTORS=PRR
1. Collectins
2. Toll like receptors
COLLECTINS
• Family of proteins
present in solution
• Collagen-like region
and a lectin like
region=collectin
• Collagen-like region
interacts with
effector parts of the
immune system
• Lectin region binds
to sugar molecules
on surface of
pathogen e.g.
mannose
TOLL LIKE RECEPTORS (TLR)
• Toll proteins first identified in the fruit fly
• Drosophila melanogaster
• At least 11 mammalian homologues
TOLL LIKE RECEPTORS
EFFECTOR MECHANISMS OF THE
INNATE IMMUNE RESPONSE
• Phagocytosis
• Cytokine/chemokine production
• Inflammation
• Pathogen destruction
PHAGOCYTOSIS
• Monocyte/macrophage-Mature from circulating
monocytes found in large numbers in the GI tract,
lung, liver, spleen. Relatively long-lived.
• Neutrophils-Short-lived, found only in blood.
PHAGOCYTOSIS
Recognition of
the pathogen
by receptors on
the phagocyte
leads to
ingestion and
destruction
Receptors:
PRR
Complement
receptors
KILLING MECHANISMS OF
MACROPHAGES & NEUTROPHILS
• Reactive oxygen intermediates (more in neutrophils)
• Following phagocytosis there is an increase in oxygen
uptake i.e. respiratory burst
• Oxygen is reduced by NADPH oxidase to form
hydroxyl radicals and hypochlorite
DNA damage and alterations in bacterial membranes
KILLING MECHANISMS OF
MACROPHAGES AND NEUTROPHILS
• Reactive nitrogen intermediates (more
in macrophages)
• L-arginine to L-citrulline generates NO
radicals
• Catalysed by the enzyme inducible
nitric oxide synthase (iNOS, NOS2)
induced by cytokines and bacterial
components
CYTOKINES
• “Intracellular messengers”
• Proteins that are produced by many cells in the
body that control immune defences by binding to
specific receptors
• Can be activating or deactivating
• IL-1 (interleukin 1), IL-6 (interleukin 6) causes
inflammation and fever
• TNF-α(tumour necrosis factor α) causes fever and
macrophage activation
• IL-12 causes CD4 T cell differentiation
CHEMOKINES
• Class of cytokines with chemoattractant properties
• Promote inflammation by enabling cells to adhere
to the surface of blood vessels and migrate to the
infected tissue
• IL-8 produced by macrophages and endothelial
cells
• MCP (monocyte chemoattractant protein)
INTERFERONS
• Type I interferons (IFN-Υand IFN-β)
• Produced in response to virally infected cells
Natural killer cells-kill virally infected cells and tumour
cells, responsive to TNF-αand IL-12. Produce IFN-Υ.
• Critical cytokine-activates macrophages,
upregulates MHC molecules, together with IL-12
stimulates differentiation of CD4 Th1 cells