bio 151 lec 3 2012 2013
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INNATE & ADAPTIVE IMMUNITY
Biology 151 Lecture 3
Tuesday, July 3, 2012
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INNATE IMMUNITY
•Recall: always present; ready to recognize and eliminate microbes (natural or native immunity)
• powerful early defense mechanism capable of controlling and eradicating infections
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HOW IT DIFFERS FROM ADAPTIVE IMMUNITY
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How do INNATE immunity recognize microbes?
• The components of innate immunity recognize structures that are shared by various classes of microbes and are not present on host cells
• e.g. phagocytes express receptors for bacterial lipopolysaccharide (LPS,also called endotoxin), which is present in many bacterial species but is not produced by mammalian cells
• The receptors of the innate immune system are encoded in the germline and are not produced by somatic recombination of genes
• e.g. germline-encoded pattern recognition receptors have evolved as a protective adaptation to potentially harmful microbe
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How do INNATE immunity recognize microbes?
• The innate immune system responds in the same way to repeat encounters with a microbe (no memory)
• The innate immune system does not react against the host
• rationale #1: because of the inherent specificity of innate immunity for microbial structures
• rationale #2: partly because mammalian cells express regulatory molecules that prevent innate immune reactions
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COMPONENTS OF THE INNATE IMMUNITY
• The innate immune system consist of epithelia which provide barriers to infection, cells in the circulation and tissues, and several plasma proteins
• These components play different but complementary roles in blocking the entry of microbes and in eliminating microbes that enter the tissues of the host
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EPITHELIAL BARRIERS• The common
portals entry of microbes: skin, gastrointestinal tract and respiratory tract
• They are protected by continuous epithelia that provide physical and chemical barriers against infections
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Tuesday, July 3, 2012
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YOUR WAYS...
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PHAGOCYTES
•The two types of circulating phagocytes: neutrophils and monocytes
• they are recruited to the sites of infection where they recognize and ingest microbes for intracellular killing
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WHAT’S IN YOUR BLOOD?
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1. Neutrophils: Phagocytic
2. Basophils: Produce histamine
3. Eosinophils: Toxic to parasites and some phagocytosis
4. Dendritic cells: Initiate adaptive immune response
5. Monocytes: Phagocytic as mature macrophages
a. Fixed macrophages in lungs, liver, and bronchi
b. Wandering macrophages roam tissues
6. Lymphocytes: Involved in specific immunity
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Tuesday, July 3, 2012
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NEUTROPHILS• also called polymorphonuclear leukocytes (PMNs)
• most abundant leukocytes in blood (4,000-10,000/mm)
• during infections productions increases rapidly (up to 20,000/mm)
• production is stimulated by cytokines (colony-stimulating factors/CSFs)
• first cell type to respond to most infections (bacterial and fungal)
• ingest microbes in the circulation, and they rapidly enter extravascular tissues at sites of infection where they also ingest microbes and die after a few hours
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MONOCYTES
• Less abundant than neutrophils (500-1,000/mm)
• ingest microbes in the blood and in tissues
•monocytes that enter extravascular tissues survive in these sites for long periods = in the tissues, these monocytes differentiate into cells called macrophages
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MONOCYTE MATURATION
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DURING A MICROBE ENCOUNTER
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MICROBE RECOGNITION
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HOW THEY KILL (1)
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HOW THEY KILL (2)
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MACROPHAGES: OTHER ROLES
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NATURAL KILLER (NK) CELLS• class of lymphocytes that respond
to intracellular microbes by killing infected cells and by producing the macrophage activating cytokine IFN-a
• comprise about 10% of the lymphocytes in the blood and peripheral lymphoid organs
• recognize host cells that have been altered by microbial infections
• NK cells and macrophages function cooperatively to eliminate intracellular microbes: macrophages ingest microbes and produce1L-12 = IL12 activates NK cells to secrete IFN-g = IFN-g in turn activates the macrophages to kill the ingested microbes
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INHIBITORY RECEPTORS OF NK CELLS
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THE COMPLEMENT SYSTEM
• a collection of circulating and membrane-associated proteins that are important in defense against microbes
• 3 pathways : alternative, classical and lectin
• ALTERNATIVE: triggered when some complement proteins are activated on microbial surfaces and cannot be controlled because complement regulatory proteins are not present on microbes (but are present on host cells). = INNATE
• CLASSICAL: triggered after antibodies bind to microbes or other antigens and is thus a component of the humoral arm of adaptive immunity
• LECTIN: activated when a plasma protein, mannose-binding lectin, binds to terminal mannose residues on the surface glycoproteins of microbes = lectin activates proteins of the classical pathway, but because it is initiated in the absence of antibody it is a component of innate immunity
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THE COMPLEMENT SYSTEM
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THE COMPLEMENT SYSTEM
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IMPORTANT FUNCTIONS
• C3b coats microbes and promotes the binding of these microbes to phagocytes, by virtue of receptors for C3b that are expressed on the phagocytes
• Some breakdown products of complement proteins are chemoattractants for neutrophils and monocytes and promote inflammation at the site of complement activation
• Complement activation culminates in the formation of a polymeric protein complex that inserts into the microbial cell membrane, forming pores that lead to the influx of water and ions and death of the microbe
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IMPORTANT FUNCTIONS
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CYTOKINES OF THE INNATE IMMUNITY
• In response to microbes, macrophages and other cells secrete proteins called cytokines that mediate many of the cellular reactions of innate immunity
• Macrophages responding to microbes produce cytokines that stimulate inflammation (leukocyte recruitment) and activate NK cells to produce the macrophage-activating cytokine IFN-g
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CYTOKINES OF THE INNATE IMMUNITY (1)
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CYTOKINES OF THE INNATE IMMUNITY (2)
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PLASMA PROTEINS OF THE INNATE IMMUNITY
• Plasma mannose-binding lectin (MBL): recognizes microbial carbohydrates and can coat microbes for phagocytosis or activate the complement cascade by the lectin pathway.
• belongs to the collectin family of proteins, which share homology to collagen and contain a carbohydrate-binding (lectin) domain
• Surfactant proteins (in the lung): protect the airways from infection
• belongs to the collectin family of proteins
• C-reactive protein (CRP): binds to phosphorylcholine on microboes and coat and coats the microbes for phagocytosis by macrophages, which express a receptor for CRP
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PLASMA PROTEINS OF THE INNATE IMMUNITY
• The circulating levels of many of these plasma protein increase rapidly after infection
• protective response or acute phase response to infection
• Extracellular bacteria and fungi are combated by phagocytes and the complement system and by acute phase proteins
• Defense against intracellular bacteria and viruses is mediated by phagocytes and NK cells, with cytokines providing the communications between the phagocytes and NK cells
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EVASION OF THE INNATE IMMUNITY BY MICROBES
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STIMULATING THE ADAPTIVE IMMUNE
RESPONSE
• lnnate immune responses generate molecules that function as "second signals” together with antigens, to activate T and B lymphocytes (co-stimulators)
• The requirement for these second signals ensures that adaptive immunity is elicited by microbes (the natural inducers of innate immune reactions) and not by non-microbial
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Tuesday, July 3, 2012
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NEXT: ADAPTIVE IMMUNITY
Tuesday, July 3, 2012