Bio 151 lec 3 2012 2013

INNATE & ADAPTIVE IMMUNITY

Biology 151 Lecture 3

Tuesday, July 3, 2012

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

HOW IT DIFFERS FROM ADAPTIVE IMMUNITY

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

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

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

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

YOUR WAYS...

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

WHAT’S IN YOUR BLOOD?

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

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

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

MONOCYTE MATURATION

DURING A MICROBE ENCOUNTER

MICROBE RECOGNITION

HOW THEY KILL (1)

HOW THEY KILL (2)

MACROPHAGES: OTHER ROLES

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

INHIBITORY RECEPTORS OF NK CELLS

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

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

IMPORTANT FUNCTIONS

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

CYTOKINES OF THE INNATE IMMUNITY (1)

CYTOKINES OF THE INNATE IMMUNITY (2)

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

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

EVASION OF THE INNATE IMMUNITY BY MICROBES

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

NEXT: ADAPTIVE IMMUNITY

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