Innate Immunity

1
Innate Immunity

• Lab Days Again
• Pass forms along and then forwards

2
Innate Immunity lecture 4/5

• Innate immune system refers to defence systems
  permanently in place.
• Only when these are overcome does adaptive immune
  response kick in.
• The adaptive response, while slow to respond on
  first exposure to a foreign antigen, has the
  characteristic of memory, such that on subsequent
  exposure a rapid response ensues.
•  

•  

3
(No Transcript)
4
Innate defences

• 1Differences in susceptibility to certain
  pathogens
• 2Anatomical defences
• 3 Microbial antagonism
• 4 Tissue bactericides, including complement,
  acute phase proteins and lysozyme
• 5 Inflammation (ability to undergo an
  inflammatory response)
• 6 Phagocytosis

5
Differences in Susceptibility

• Absence of tissue/cell receptors for attachment
• Temperature of host
• Lack of nutritional requirements
• Lack of target site for toxins

6
Individual resistance in same species

• Age
• Sex
• Stress
• Diet, malnutrition
• Inter-current disease or trauma
• Therapy against other diseases

7
Physical Barriers

• Skin
• Mucous Membranes
• Respiratory tract
• Mouth, stomach and intestinal tract
• Uro-genital tract
• Eyes (conjunctiva)

8
Microbial antagonism

• Competition with non-indigenous species
• Specific antagonism - bacteriocins
• Non-specific antagonism - metabolites
• Mimsp47-48

9
Tissue bactericides and complement

• Lysozyme
• Complement
• Basic proteins/peptides
• Lactoferrin/transferrin
• Peroxidase
• Fibronectin

• Interferons
• Interleukins

10
Complement

• Innate and inducible defence
• Triggered cascade enzyme system
• Central role played by C3 convertase

11
Alternative pathway

• Normal plasma- C3 spontaneous activation to
  release C3b
• C3b BgtgtgtgtgtgtC3bBb
• C3bBb normally broken down rapidly
• In the presence of bacterial surfaces C3bBb
  stabilised
• Positive feedback loop

12
Complement

• Microbial products stabilise C3 convertase
• Build up of C3b acts as opsonin
• Tight regulation

13
(No Transcript)
14
Complement synergises with phagocytesgtinflammmator
y response

• C3b and C3 convertase act on C5
• C5a and C3a triger
• Vascular permeabilisationAllows exudation of
  fluid and plasma components
• Chemotactic factorsAttract leukocytes
  (granulocytes/neutrophils)
• Mast cell degranulation
• Arachidonic acid pathway

15
Acute inflammatory response

• Capillary dilation- erythema
• Exudation of plasma proteins and fluid-edema
• Accumulation of neutrophils
• Focuses phagocytes on opsonised invader

16
(No Transcript)
17
(No Transcript)
18
Mast cell mediators

• HistamineVasodilation, capillary permeability,
  bronchoconstriction
• HeparinAnticoagulant
• ChemokinesAttract phagocytes including
  polymorphs and monocyte/macropahges

19
Destruction of invader

• Opsonisation leads to uptake by phagocyteor
• Destruction by membrane attack complex

20
(No Transcript)
21
(No Transcript)
22
Membrane attack

• C5b membrane bound
• Binds C6,7,8
• This complex allows C9 partial unfolding and
  insertion in membrane to make an
• Annular channel
• Influx of Na leads to lysis

23
(No Transcript)
24
(No Transcript)
25
E-M of MAC in Shigella dysentariae
26
Summary of complement functions

• Generation of inflammatory factors
• Attraction of phagocytes
• Enhancement of phagocytosis
• Lysis of bacterial or virus infected cells
• Read about in Mims 53-57

27
Professional phagocytes

• Macrophages and polymorphonuclear phagocytes
  (neutrophils/granulocytes)
• Distribution

28
(No Transcript)
29
Types of mononuclear phagocytes
30
Phagocytes

• Macrophages long lived
• Neutrophils short lived - no mitochondria -
• Contain granules with powerful enzymes
• Primary-myeloperoxidase, lysozyme,cationic
  proteins
• Secondary-lactoferrin and lysozyme
• Tertiary-acid hydrolases

31
Phagocytes

• Monocytes 3-7 of circulating white blood cells
  - actively phagocytic and bactericidal
• Migrate into tissues and differentiate to
  macrophages -inflammatory stimuli

32
Phagocytosis

• Delivery of phagocyte to site of infection
• Adherence-lectin like receptors or complement
• Ingestion-pseudopodial extensions
• Phagolysosome- fusion with endosomes
• Intracellular killing-enzymes,pH, O2,NO
• Intracellular digestion

33
(No Transcript)
34
http//ntri.tamuk.edu/immunology/mac.mov
35
Acute phase response

• Acute phase proteins.
• When macrophages are triggered into inflammatory
  state by opsonised microbes, C5a, and toxins,
  they release pro-inflammatory cytokines IL-1,
  IL-6 and TNF.
• These trigger the release of acute phase
  proteins, such as C-reactive protein which
  assists complement fixation.
• Fever/pyrexia

36
Interferons and NK cells

• Interferons
• Involved in antiviral response, by triggering
  synthesis of protective enzymes such as polyA
  synthase.
• NK Cells
• Primarily involved in destroying viral infected
  cells. Triggered by glycoproteins on viral
  infected cells, and kill via perforin and
  granzyme B.

37
Reading for innate immunity

• Mims, Chapter 4
• P47-62