Transcript Adaptive Immunity

Innate Immunity
Rui He
[email protected]
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
Adaptive
Characteristics
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
Defense against infectious microbes
Innate Immunity:
the early reactions
Adaptive Immunity:
the later responses
Innate Immunity
 FUNCTIONS
 COMPONENTS
 Innate immunity recognition
 The influence on adaptive 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
FUNCTIONS
 Initial response to microbes to prevent infection
with elimination of danger
 Innate components also important in adaptive immunity
 Stimulates adaptive responses
Components of innate immune system
Components
Principal Functions
Epithelial 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
Physical barriers
 Skin
 Mucosal surfaces of the gastrointestinal tracts (GI)
 Mucosal surfaces of the respiratory tracts
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 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
Phagocytes
 Cell types
Neutrophils and Macrophages
 Primary functions
Identify, ingest, and destroy microbes
Neutrophils
Polymorphonuclear neutrophils (PMNs)
Neutrophils
 The most abundant population of circulating leukocytes
 Mediate the earliest phases of inflammatory responses
Macrophages
Name of cell
Alveolar macrophages
Histiocytes
Kupffer cells
Microglia
Epithelioid cells
Osteoclasts
Sinusoidal lining cells
Location
pulmonary alveolus of
lungs
connective tissue
liver
neural tissue
granulomas
bone
spleen
Macrophages
 Dominant effector cells of the later stages of innate immune
responses
 Play central role in both innate and adaptive immune
responses
The steps of functional responses of phagocytes
1. Active recruitment of the cells to sites of infection
2. Recognition of microbes
3. Phagocytosis
4. Destruction of ingested microbes
Recruitment of leukocytes
© 2005 Elsevier
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 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
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
Proteins secreted by the cells of innate and adaptive immunity that
mediate many of the functions of these cells.
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
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
Summary
 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
To be continued