BMS2052 Lecture Notes - Lecture 10: Tlr2, Antigen Presentation, Interleukin 4
30 May 2018
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Week 4. Pathogenicity and the Host Response
INNATE IMMUNITY
• Innate immunity is essential early in infection – acts hours after infection (does bulk of work)
• How does the innate immune system recognise pathogens?
o Complement:
Collection of circulating serum proteins
Most are proteases hih leae oe aother to for opleet asade
Consequence of activation: inflammation, opsonisation (phagocytosis) and
bacterial lysis
Can help in 3 ways:
1. Pore in membrane
2. Inflammatory – recruitment of WBC
3. Opsonisation – makes more attractive to phagocytosis
find more resources at oneclass.com
find more resources at oneclass.com
Activated in 3 ways:
1. Alternative pathway
-C3 is activated and binds directly to pathogen surface
2. Lectin pathway
-C3 is activated by mannose binding lectin to bound mannose residues
found exclusively on surface of microbes (causes lysis)
3. Classical pathway
-C3 is activated by Ab (IgM and IgG) bound to antigen
o Through pattern recognition receptors:
Recognise PAMPs (pattern associated molecular patterns) on microbes
Germline encoded – no somatic recombination
Single innate immune cell expresses several different PRR
PRR are encoded by many protein families and can be expressed at cell surface,
in endosomes and in cytoplasm
Triggering can lead to an inflammatory response, phagocytosis and oxidative
burst
o Key pro-inflammatory cytokines:
IL-1, IL-6, TNF-alpha, IL-12, and chemokines (eg. CXCL8)
• Cytokines:
o Secreted proteins that function as mediators of immune and inflammatory reactions
o Major mechanism by which immune cells communicate
o Paracrine or autocrine
o Act by binding to specific receptors expressed on surface of cells
o Binding to receptor induces signal transduction and gene transcription
find more resources at oneclass.com
find more resources at oneclass.com
• Pro-inflammatory cytokines and chemokines promote leukocyte recruitment:
o Neutrophils are the first responders and arrive at site of infection within hours
o Monocytes take 2-3 days
o 1. PAMPS -> 2. Chemokines/cytokines -> 3. Macrophages can communicate with
vascular endothelium -> 4. Neutrophils adhere to integrins (usually low affinity but high
affinity with chemokine secretion)
o Cytokines: activate the vascular endothelium
o Selectins: adhesion molecules that allow Leucocytes to roll on the vascular endothelium
o Chemokines: activate integrins to become high affinity
o Integrins: adhesion molecules that allow leucocytes to stably adhere
o Leucocytes transmigrate out of the vasculature and follow a chemotactic gradient
towards the site of infection
• Triggering PRR can lead to Type I interferon production:
o Type I IFN = IFNa and IFNb
o Cytokines with potent antiviral activity
o Also activates NK cells and dendritic cells
Note: IFNY is type II not type I
• NK cells recognise stressed/infected cells that lose expression of MHC I:
o NK are activated by Type I interferon
o Activated receptors recognise stress ligands on infected cells
o Inhibitory receptors recognise class I MHC
o Infected cells usually lose MHC I due to viral infection
• Phagocytes are important in anti-bacterial immunity
Macrophage: slow, deal with slow chronic infections, also antigen presentation
Neutrophil: immediate, good for extracellular bacteria
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Innate immunity is essential early in infection acts hours after infection (does bulk of work: how does the innate immune system recognise pathogens, complement: Most are proteases (cid:449)hi(cid:272)h (cid:272)lea(cid:448)e o(cid:374)e a(cid:374)other to for(cid:373) (cid:858)(cid:272)o(cid:373)ple(cid:373)e(cid:374)t (cid:272)as(cid:272)ade(cid:859) Consequence of activation: inflammation, opsonisation (phagocytosis) and bacterial lysis. Can help in 3 ways: pore in membrane, inflammatory recruitment of wbc, opsonisation makes more attractive to phagocytosis. Activated in 3 ways: alternative pathway. C3 is activated and binds directly to pathogen surface: lectin pathway. C3 is activated by mannose binding lectin to bound mannose residues found exclusively on surface of microbes (causes lysis: classical pathway. C3 is activated by ab (igm and igg) bound to antigen: through pattern recognition receptors: Recognise pamps (pattern associated molecular patterns) on microbes. Prr are encoded by many protein families and can be expressed at cell surface, Single innate immune cell expresses several different prr in endosomes and in cytoplasm.
