L14 Innate Defence Flashcards
Types of PRR
Free receptors present in the serum
Mannose Binding Lectin
Ficolins
Mannose Binding Lectin
- Binds to repetitive carbohydrate structure (mannan) found on a range of microbes
- Not found in vertebrates
- Activates lectin C’ pathway
- Opsonize microorganisms
Ficolins
- Contain carbohydrate recognition domains
- After binding to carbohydrates on a microbe, they activate complement through the lectin pathway and thus contribute to clearance of the microbe
What are the membrane bound phagocytic receptors?
PRR
• Receptor mediated
− Complement receptor
− Scavenger receptor : cellular break down products
− Mannose receptor
- Membrane enclosed endocytic vesicle phagosome
- Fuses with lysosome phagolysosome
Describe
membrane bound signaling receptors
PRR
Detect extracellular bacteria and microorganisms
• Toll-like receptors
-> down stream effects
• Cell surface and membranes of intracellular vesicles
• Recognize PAMPS
− Extracellular pathogens
− Endocytosed extracellular components
• Signaling induces the expression of inflammatory cytokines and chemokines
Describe Cytoplasmic signaling receptors
PRR
• Detect intracellular bacteria and virus
NOD-like receptors- intracellular sensors of bacterial infection
RIG-I like helicase – sensors of cytoplasmic RNAs
Cellular effectors of innate immunity
macrophages
neutrophils
NK
Dendritic cells
Dendritic cells Interdigitating DC (or just DC)
DC-Located under epithelia and interstitia of all tissues
− Capture microbes
− Transport to lymphoid organs
− Present antigen for recognition by lymphocytes
Dendritic cells
Follicular DC
FDC-Located in lymphoid follicles
− Trap antigen bound to antibody or complement
− Present antigen to B-cells
What are dendritic cells?
Antigen presenting cells:
(of the adaptive immune response?)
• Interdigitating DC (or just DC)
• Follicular DC
NK cells
• Arise from common lymphoid progenitor
• Innate immunity
• Receptors recognize molecules expressed on
− IgG coated target cells (ADCC- antibody dependent cytotoxicity
− Infected cells
− Stressed cells
includes cancer cells
− Cells with DNA damage
Host cells that is infected/stressed/damaged DNA down regulates MHC 1 -> identification for NK cells
• Eliminate irreparably damaged cells and potential
reservoirs of infection
• Avoid attacking normal host cells through recognition of class I MHC molecules on healthy cells
− Viral infections/ tumour cells up regulate MHC I
Complement activation
Classical pathway
requires an adaptive immune response
• Binding of IgM and IgG to pathogen induces conformational change in Fc region which initiates complement casacde
• Associated with adaptive immune response
Complement activation
Lectin pathway
innate immune response
• Activated when (PRR) bind to carbohydrate structures of certain pathogen
• Host derived soluble carbohydrate binding proteins (PRR) bind to carbohydrate structures of certain pathogen
Complement activation
Alternative pathway
• Bacterial cell walls and endotoxins
C3 effector process
complement activation
C3a being released, leading to chemical mediator recruitment and drawing to the site of injury
C3b being deposited on the microorganism->
Oposination- facilitate phagocytosis
Form MAC- pores in the membrane of the organism, cause direct death of microorganism
C3-opsoinsation
C5-inflammation
6,7,8-MAC