Innate Immunity
Rui He
Department of Immunology
Shanghai Medical School
Fudan University
Components of Immunity
Innate Immunity:
non-specific, also called natural or native immunity
Adaptive Immunity:
specific, also called acquired immunity
Features of Innate and Adaptive Immunity
Innate AdaptiveCharacteristics
Specificity For structures shared by groups of related microbes
For antigens of microbes and for nonmicrobial antigens
Diversity Limited; germline-encoded Very large; receptors are produced by somatic recombination of gene segments
Memory None Yes
Nonreactivity to self
Yes Yes
Components
Cellular and chemical barriers
Skin, mucosal epithelia; antimicrobial chemicals
Lymphocytes in epithelia; antibodies secreted at epithelial surfaces
Blood proteins Complement, others Antibodies
Cells Phagocytes (macrophages, neutrophils), natural killer cells
Lymphocytes
The physiologic function of immune system
Innate Immunity: the early reactions
Adaptive Immunity: the later responses
Defense against infectious microbes
FUNCTIONS COMPONENTS
Innate immunity recognition The influence on adaptive immunity
Innate Immunity
OVERVIEW
The first line of defense against infection
An evolutionarily older defense strategy, found in all
classes of plants and animals
Preexist infection or exposure to foreign antigen
Respond immediately after recognition of microbes
Respond in essentially the same way to repeated infection
Initial response to microbes to prevent infection with elimination of danger
Innate components also important in adaptive immunity
Stimulates adaptive responses
FUNCTIONS
Components of innate immune system
Components Principal FunctionsEpithelial barriers
Epithelial layers Prevent microbial entry
Defensins Microbial killing
Intraepithelial lymphocytes
Microbial killing
Circulating effector cells
Neutrophils Early phagocytosis and killing of microbes
Macrophages Efficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation
NK cells Lysis of infected cells, activation of macrophages
Circulating effector proteins
Complement Killing of microbes, opsonization of microbes, activation of leukocytes
Mannose-binding lectin (collectin)
Opsonization of microbes, activation of complement (lectin pathway)
C-reactive protein (pentraxin)
Opsonization of microbes, activation of complement
Cytokines
Epithelial barriers
Skin
Mucosal surfaces of the gastrointestinal tracts (GI)
Mucosal surfaces of the respiratory tracts
Physical barriers
Antimicrobial Peptides
Defensins
Cystein-rich peptides with 29-34 amino acids
Present in the skin and abundant in neutrophil granules
Broad-spectrum antibiotics
Upregulated by inflammatory cytokines
Cryptocidines
Secreted by the epithelium of the intestine
Locally sterilize the lumen of intestine
Intraepithelial lymphocytes
Intraepithelial T cells
Present in the epidermis of the skin and in mucosal epithelia
cells and NKT cells
Serve as sentinels at common sites of microbial invasion
B-1 cells
Present in peritoneal cavity
Produce NATURAL antibodies
Components of innate immune system
Components Principal Functions
Epithelial barriersEpithelial layers Prevent microbial entry
Defensins Microbial killing
Intraepithelial lymphocytes
Microbial killing
Circulating effector cellsNeutrophils Early phagocytosis and killing of microbes
Macrophages Efficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation
NK cells Lysis of infected cells, activation of macrophages
Circulating effector proteinsComplement Killing of microbes, opsonization of microbes, activation of
leukocytes
Mannose-binding lectin (collectin)
Opsonization of microbes, activation of complement (lectin pathway)
C-reactive protein (pentraxin)
Opsonization of microbes, activation of complement
Cytokines
Phagocytes
Cell types
Neutrophils and Macrophages
Primary functions
Identify, ingest, and destroy microbes
NeutrophilsPolymorphonuclear neutrophils (PMNs)
The most abundant population of circulating leukocytes
Mediate the earliest phases of inflammatory responses
Neutrophils
Macrophages
Name of cell Location
Alveolar macrophagespulmonary alveolus of lungs
Histiocytes connective tissue
Kupffer cells liver
Microglia neural tissue
Epithelioid cells granulomas
Osteoclasts bone
Sinusoidal lining cells spleen
Dominant effector cells of the later stages of innate immune
responses
Play central role in both innate and adaptive immune
responses
Macrophages
1. Active recruitment of the cells to sites of infection
2. Recognition of microbes
3. Phagocytosis
4. Destruction of ingested microbes
The steps of functional responses of phagocytes
© 2005 Elsevier
Recruitment of leukocytes
Phagocytosis
A cytoskeleton-dependent cellular process of phagocytes of engulfing large particles
Bound microbes are ingested into vesicles called phagosome
Destruction of phagocytosed microbes
Where
Phagolysosome
Killing Mechanisms
1. Reactive oxygen intermediates (ROIs)
2. Reactive nitrogen intermediates: mainly NO
3. Preformed antimicrobials
BUT, these mechanisms also can cause host tissue injury
Effector functions of macrophage
Natural Killer cells (NK cells)
A type of cytotoxic lymphocytes
The principal physiologic role
1. Defense against infections by viruses and some other intracelluar
microbes
2. Rejection of tumors
The mechanism of effector function
Perforin
Granzyme
Components of innate immune system
Components Principal Functions
Epithelial barriersEpithelial layers Prevent microbial entry
Defensins Microbial killing
Intraepithelial lymphocytes Microbial killing
Circulating effector cellsNeutrophils Early phagocytosis and killing of microbes
Macrophages Efficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation
NK cells Lysis of infected cells, activation of macrophages
Circulating effector proteinsComplement Killing of microbes, opsonization of microbes, activation of
leukocytes
Mannose-binding lectin (collectin)
Opsonization of microbes, activation of complement (lectin pathway)
C-reactive protein (pentraxin)
Opsonization of microbes, activation of complement
Cytokines
The complement system
A complex series of some plasma proteins
Pathways of complement activation
1. Classical Pathway
2. Alternative Pathway
3. The lectin Pathway
Pathways of complement activation. The activation of the complement system may be initiated by three distinct pathways, all of which lead to the production of C3b (the early steps). C3b initiates the late steps of complement activation,
culminating in the production of peptides that stimulate inflammation (C5a) and polymerized C9, which forms the membrane attack complex, so called because it creates holes in plasma membranes. The principal functions of major
proteins produced at different steps are shown. The activation, functions, and regulation of the complement system are discussed in much more detail in Chapter 14.
The effect of complement activation
Opsonization of pathogen
Recruitment of leukocytes
Killing of pathogens
Cytokines
Cell source:
macrophages, neutrophils, and NK cells, endothelial cells, some epithelial cells
Functions
1. Recruit and activate leukocytes
2. Produce systemic alterations that contribute to potentiate antimicrobial responses
Proteins secreted by the cells of innate and adaptive immunity that mediate many of the functions of these cells.
Cytokines
TNF, IL-1 Inflammation
IFN-γ Macrophage activation
IL-12 IFN-γ production by NK cells and T cells
IL-15 Proliferation of NK cells
IL-10, TGF-β Control of inflammation
In severe infection, excess systemic cytokine production is harmful and may even cause death of the host
The first line of host defense against microbes
The mechanisms of innate immunity exist before exposure to microbes
The components of the innate immune system include epithelial barriers,leukocytes, circulating effector proteins and cytokines
Neutrophils and macrophages are phagocytes that kill ingested microbesby producing ROIs, nitric oxide, and enzymes in phagolysosomes
NK cells are lymphocytes that defend against intracelluar microbes by killing infected cells and providing a source of the macrophage-activatingcytokine IFN-γ
The complement system is activated by microbes, and products of complement
activation promote phagocytosis and killing of microbes and stimulate inflammation
Different cytokines of innate immunity recruit and activate leukocytes, enhance the microbicidal activities of phagocytes, and stimulate NK cells and T cell responses
Summary
To be continued
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