Chapter 2 innate immunity lecture 2
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Transcript of Chapter 2 innate immunity lecture 2
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Chapter 2:Innate
Immunity
Dr. Hafez Sumairi
Learning outcomes
1.How does the innate immune system recognizemicrobes and damaged cells?
2.How do the different components of innateimmunity function to combat different types ofmicrobes?
3.How do innate immune reactions stimulate adaptiveimmune responses?
Recognition ofmicrobes by the innateimmune systemInnate immunity also called natural, ornative, immunity, non specific
Adaptive or specific
Recognition of microbes by the innateimmune system• The components of innate immunity recognize structures that are shared by
various classes of microbes and are not present on host cellsPathogen-associated molecular patterns (PAMP)• Are shared by microbes of the same type
• Bacterial lipopolysaccharide (LPS)• Terminal mannose residues• Double-stranded RNA• Un-methylated CpG oligonucleotides
Pattern recognition receptors.• The receptors of innate immunity that recognize these shared structuresDamage-associated molecular patterns (DAMP)
Cellular receptors for microbes
• On phagocytes, dendritic cells,lymphocytes and epithelial andendothelial cells
• In different cellularcompartments
• Types• Toll-like receptors (TLRs)• Others
Cellular receptorsfor microbes typesToll-like receptors (TLRs)
Signal transduction
Components of innate immunity
1.Epithelia• Continuous epithelia that
provide physical andchemical barriers againstinfection
2.Cells in the circulation
3.Tissues4.Plasma proteins
Epithelia components
Cellular components of innate immunity
Phagocytes:• Neutrophils
• Polymorphonuclear leukocytes [PMNs]• Most abundant leukocytes in the blood• First cell type to respond, particularly bacterial
and fungal infections• Die after a few hours of ingestion
• Monocytes/macrophages• Survive in extravascular sites for long periods• Mononuclear phagocyte system• Produce cytokines
• Initiate and regulate inflammation,• Ingest and destroy microbes• Clear dead tissues• Initiate the process of tissue repair• APC
Cellular components of innate immunityMonocytes/macrophages
Cellular componentsof innate immunity• Monocytes/macrophages
• Activation• Functions
Cellular componentsof innate immunity• Monocytes/macrophages
Cellular components of innate immunity
• Dendritic Cells• Cytokines
• Initiate inflammation• Stimulate adaptive immune responses
• Mast Cells• Cytoplasmic granules
• Vasoactive amines such as• Histamine that cause vasodilation and increased capillary permeability• Proteolytic enzymes that can kill bacteria or inactivate microbial toxins.
• Skin and mucosal epithelium• Activated by
• Microbial products binding to TLRs• Special antibody
• Products• Synthesize and secrete
• Lipid mediators (e.g., prostaglandins)• Cytokines (e.g., TNF), which stimulate inflammation.• Products also provide defense against helminths and are responsible for symptoms of allergic diseases
Cellular componentsof innate immunity• Natural Killer Cells (NK) cells are
a class of (10%) lymphocytes that• Recognize infected and stressed
cells• Respond by killing these cells and
by secreting the macrophageactivating cytokine IFN-γ
• Cytoplasmic granules• Unique surface proteins• Eliminate cellular reservoirs of
infection
Cellular componentsof innate immunity• The activation of NK cells
is determined by a balancebetween engagement ofactivating and inhibitoryreceptors• IL12• IL15• Type I IFNs
Other classes of lymphocytes
1. Receptors have limited diversity2. Rapid responses• T cells
• γδ T cells are present in epithelia• NK-T cells• They recognize microbial lipids bound to a class I MHC–related molecule called CD1
• B cells• B-1 cells
• Found mostly in the peritoneal cavity and mucosal tissues• Natural antibodies (IgM)• Carbohydrates Ag
• Marginal-zone B cells• Carbohydrates Ag
Complement system• The complement system is a
collection of circulating andmembrane-associated proteinsthat are important in defenseagainst microbes.
• Proteolytic enzymes• Three functions
1. Opsonization2. C5a and C3a, are chemo-
attractants3. Formation of a polymeric protein
complex (MAC)
Other plasma proteins of innate immunity
Acute-phase response1. Plasma mannose binding lectin (MBL)
• MBL belongs to a family of proteins called the collectins, because they arestructurally similar to collagen and contain a carbohydrate-binding (lectin)domain.
2. Surfactant proteins• Belong to the collectin family and protect the airways from infection.
3. C-reactive protein (CRP)• Binds to phosphorylcholine on microbes and opsonizes the microbes for
phagocytosis by macrophages, which express a receptor for CRP
Cytokines of InnateImmunityInterleukins• These molecules are
produced by leukocytes andact on leukocytes.
• Are responsible forcommunications betweenleukocytes and betweenleukocytes and other cells
Innate immune reactions
1. The acute inflammatory response• Extracellular bacteria and fungi• Neutrophils and monocytes are recruited• Complement system
2. Antiviral defense mechanisms.• Type I interferons and natural killer cells.
Inflammation• It is a tissue reaction that rapidly delivers
mediators of host defense—circulatingcells and proteins—to the locations wherethey are needed, the sites of infection andtissue damage
Multiple steps
1. Recruitment of cells
2. Leakage of plasma proteins throughblood vessels
3. Engulfment of microbes and deadmaterial by phagocytes,
4. Destruction of these potentially harmfulsubstances.
Phagocytosis anddestruction ofmicrobes• Phagocytosis is a
process of ingestionof particles largerthan 0.5 µm indiameter.
• Chronicgranulomatousdisease (CGD)
Antiviral Defense• Type I interferons
induce resistance toviral infection andreplication, called anantiviral state
• Type I IFNs enhancethe ability of NK cellsto kill infected cells.
• Enhanced apoptosis
Microbial evasion of innate immunity
Regulation of innate immune responses
• Anti-inflammatory cytokines by macrophages and dendritic cells,• Interleukin-10 (IL-10), which inhibits the microbicidal and pro-inflammatory
functions of macrophages (classical pathway of macrophage activation),• IL-1 receptor antagonist, which blocks the actions of IL-1• Suppressors of cytokine signaling (SOCS), which block the responses of cells
to various cytokines, including IFNs.
Role of innate immunity in stimulatingadaptive immune responses• In experimental situations or for
vaccination the antigens need to beadministered with substances calledadjuvants that elicit the sameinnate immune reactions asmicrobes do.
• Types of second signals• T cells activation
1. Co-stimulators2. IL-12, IL-1, and IL-6
• B cells activation1. Complement product C3d serves as
the second signal for humoralimmune responses.
Thank you