Innate Immunity

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Immunology 473a (2006)
Innate Immunity Sung O. Kim Sibens-Drake
Research Institute, Rm 119 Phone [phone]
E-Mail skim283_at_schulich.uwo.ca
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Topics 1. Overview (Innate immunity) From
plant to human 2. Complement system/Phagocytosis
3. Toll-like receptors I 4. Toll-like
receptors II and NOD like receptors 5.
Intracellular nucleic acid sensing (eg. RLHs) and
the interferon response Tutorial

• Reference book and articles
• Immunobiology (6th ED), Janeway, Chapter 2 and
  15
• Review articles indicated in each section
• Lecture note (http//instruct.uwo.ca/microbiology
  /473a/)

• Exam will be on the contents presented in lecture
  slides

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Metchnikoff, who identified phagocytes (first in
invertebrates Later in vertebrates) is often
considered the father of innate immunity.
Because innate defense mechanisms are
phylogenetically ancient, innate immunity is
often considered primitive immunity.
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Beginning of Immunology cellular vs. humoral
immunity
Early 1900s
EIya Metchnikoff Pasteur Institute in Paris
Paul Ehrlich Berlin School
Nature review Mol. Cell. Biol. 4897 (2003)
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Definition
Innate immunity is a complex heritable system of
defense that confers most resistance to microbes
or foreign objects

• Complex Many receptors, multiple signal
  cascades and various outcomes. RAG mutations
  wipe out adaptive immunity, but no single
  mutation can kill innate immunity.
• Heritable Innate immunity utilizes germ-line
  encoded receptors, whereas adaptive immunity
  utilizes somatically recombined receptors and
  clonal selections. Also called natural
  immunity or innate resistance. The genome of
  the host will seize upon any mechanism it can to
  defend itself.
• Microbes Immunity against virus to parasites
• Foreign components Microbial components and
  altered endogenous origins
• Some of the genes that confer innate immunity
  are dedicated others are multifunctional.
  Example Toll (in Drosophila) also plays
  important roles in development. TLRs are also
  expressed in adaptive immune cells and regulate
  their function.

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• Innate immunity in Kingdom plantae (ref Lecture
  note posted and review articles within)

• Plants are lacking adaptive immunity and
  specialized innate immune cells
• such as MF, neutrophils, and DC mostly at the
  level of single cell
• redundant layers of protective mechanisms
  constitutive barriers such as wax layers, rigid
  cell walls, anti-microbial enzymes, or secondary
  metabolites
• fast response to limit the area and restrict its
  spreading via necrotic cell death (hypersensitive
  response) pathogens do not have much chance to
  obtain virulence factors

• Infections in plants are infrequent and usually
  do not cause problems in general. However, it can
  be a problem if monoculture settings such as in
  agriculture, resulting in decrease of crops.

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general
PLANTS IMMUNITY
Pathogen specific
Gene-for-gene immunity
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Example of race-specifc elicitor (Avr) and
resistance (R) gene in tomato plants
- Pto gene
Pto gene
Symptoms of speck disease and resistance in
tomato leaves inoculated with P. syringae pv.
tomato
Microbes Infection (2000)21591
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Examples general and gene-for-gene
(race-specific) elicitors and immunity receptors
in plants
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• Plants effector systems

1. Hypersensitive responses

• react to pathogen within minutes, causing cell
  death, cell wall fortification, callose
  deposition, release antimicrobial agents (lytic
  enzymes chitinase, glucanase, proteases,
  defensins and phytoalexin etc)
• Genes for the antibacterial and antifungal
  molecules are called
• pathogenesis-related gene (PR).
• At least 11 families PR genes have been
  identified

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The innate immunity in Kingdom animalia (Chapter
15, p665-681)
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Cells of the innate immune system (Chapter 2,
p37-45, 89-95)

• Professional phagocytes
• Granulocytes neutrophils
• Agranulocytes monocytes/macrophages
• Dendritic cells (? Controversial)

• Primarily secretory cells Mast cells,
  eosinophils and basophils lyctic enzymes, free
  radicals,

• Lymphoid elements evolved to fulfill innate
  rather than adaptive functions
• NK cells (CD56 (NK1.1) CD3- cells)
• NKT cells (Va14-Ja18 TCR (Va14i) and NK1.1
  cells)
• B1 B cells
• ?d T cells

• Epithelial cells and almost every cell in body
  ---- the interferon response

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• B1 B cells
• CD5, T cell independent IgM production
• High in peritoneum and lung cavities
• Recognize bacterial antigen phosphorylcholine
  and self antigens DNA etc
• ?d T cells
• ?d heterodimer TCR (limited pairing)
• localized in skin and intestinal tract
• function is not clear but may recognize blood
  cancer cells and bacteria infected cells.
• Produce type II IFN and tissue growth factors
• Natural killer T cells (NKT cells)
• CD56/NKR-P1C and express invariable TCR (Va14
  in mouse or Va24 in humans)
• Activated by CD1d bound a-galactosylceramide and
  (bacterial) glycolipids
• Produces cytokines and regulate other immune
  cells
• NK cells
• CD56 (human)/NKR-P1C(mouse), CD3- cells
• Peripheral blood (5-20 of lymphocytes), spleen
• Innate immune to protect against virus, bacteria
  and tumors
• Secretion of various cytokines, chemokines and
  cell mediated cytotoxicity

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Bone marrow hematopoietic stem cells
Lymphoid progenitor
Myeloid progenitor
Red blood cells (erythrocytes) platelets
(Polymorphonuclear cells)
Phagocytes

• 1.75 x 1011 erythrocytes/day
• 7 x 1010 leukocytes/day
• ½ cup of compacted neutrophils/day

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Executors of innate immunity

• Antimicrobial polypeptides
• eg. Defensins produced by neutrophils,
• macrophages and mucosal epithelium
• and disrupt bacterial surface membranes
• Antimicrobial enzymes eg. lysozyme
• Reactive oxygen and NO species
• Complement
• Immune regulators chemokines and cytokines
• Cell autonomous process eg. Type I interferons
  which can be produced by many somatic cells

Secretion of defensins by paneth cells within
intestinal crypts serves as a primary barrier to
bacterial infection. (Oullette at UC Irvine)
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The temporal pattern of a developing immune
response
Minutes
Hours
Days/Weeks
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• Summary
• Brief history of immunology Definition of innate
  immunity
• Plant immunity Key terms/definitions used in
  plant immunology
• Phylogenetics of immunity in animals beginning
  of adaptive, TLRs
• Innate immune cells in mammals cell types
• Temporal response of immune responses