Summary module guide exercises
immunology
Theme 2 innate immunity
Main functions of the innate immune system
• To eliminate, prevent and control invading microbes
• Activation of the adaptive immune response (and complement)
• Tissue repair and elimination of damages cells
PAMPs and DAMPs: pathogen/damage associated molecular patterns
Characteristics of PAMPs
• They are conserved
• Distinct from self-antigens
• Essential for the pathogen’s life
• Shared by a large group of pathogens
11 different PAMP receptors (pattern recognition receptor = PRRs)
,And the different PAMPs and DAMPs
TLRs are toll-like receptors that are a subset of membrane-associated PRRs. Each TLR subset
recognizes specific PAMPs
,The complement system can be activated immediately after contact with the microbe by the
alternative, the lectin or, if pre-existing antibodies bind to the microbe, the classical pathway.
Alternative pathway
• Spontaneous C3 hydrolysis and inactivation of C3b in fluid phase. C3b, once cleaved is either
inactivated by hydrolysis or forms covalent bonds with cell surfaces
• C3b on cell surface bind factor B → factor B cleaved by factor D into Bb that associates with
C3b, and Ba
• C3bBb complex forms C3 convertase and is stabilized by properdin → preferentially
stabilized on microbial cell surfaces
, • C3 convertase amplifies the pathway → C3a triggers inflammation by binding receptors on
nearby leukocytes
• C3b binds to C3bBb to form C3b2Bb = C5 convertase
• C5 convertase cleaves C5 into C5a that triggers inflammation and C5b, initiating the late
stages of complement activation
Lectin pathway:
• Same as classical pathway, but earlier, and instead of C1 binding to antibody Fc tails, MBL
binds to antigen
Classical pathway
• Antibodies bind multivalent microbial antigen
• C1 ( = C1r2C1s2) bind antibody Fc region
• C4 comes in contact with C1 enzymes that cleave C4
• C4 becomes C4a and bound C4b by cleavage C1 (amplification)
• C4b than attaches to antigenic surface
• C2 comes into contact with C1 enzyme that cleaves iit into C2b and bound C2a
• C2a binds to C4b to form C4b2a ( = classical pathway C3 convertase)
• C3 convertase cleaves C3 into C3a that causes inflammation and C3b that binds to the C2a
part (amplification) → forms C4b2a3b which is a C5 convertase
• C5 convertase cleaves C5 to form C5a that causes inflammation, and C5b that attaches to
C4b2a3b for initiation of the late stages of complement activation
The three key functions of the complement system are opsonization and subsequent phagocytosis
and cytolysis of microbes, and triggering inflammation. Cytolysis is not possible if the microbe is
encapsulated, therefore the cell wall is too thick.
immunology
Theme 2 innate immunity
Main functions of the innate immune system
• To eliminate, prevent and control invading microbes
• Activation of the adaptive immune response (and complement)
• Tissue repair and elimination of damages cells
PAMPs and DAMPs: pathogen/damage associated molecular patterns
Characteristics of PAMPs
• They are conserved
• Distinct from self-antigens
• Essential for the pathogen’s life
• Shared by a large group of pathogens
11 different PAMP receptors (pattern recognition receptor = PRRs)
,And the different PAMPs and DAMPs
TLRs are toll-like receptors that are a subset of membrane-associated PRRs. Each TLR subset
recognizes specific PAMPs
,The complement system can be activated immediately after contact with the microbe by the
alternative, the lectin or, if pre-existing antibodies bind to the microbe, the classical pathway.
Alternative pathway
• Spontaneous C3 hydrolysis and inactivation of C3b in fluid phase. C3b, once cleaved is either
inactivated by hydrolysis or forms covalent bonds with cell surfaces
• C3b on cell surface bind factor B → factor B cleaved by factor D into Bb that associates with
C3b, and Ba
• C3bBb complex forms C3 convertase and is stabilized by properdin → preferentially
stabilized on microbial cell surfaces
, • C3 convertase amplifies the pathway → C3a triggers inflammation by binding receptors on
nearby leukocytes
• C3b binds to C3bBb to form C3b2Bb = C5 convertase
• C5 convertase cleaves C5 into C5a that triggers inflammation and C5b, initiating the late
stages of complement activation
Lectin pathway:
• Same as classical pathway, but earlier, and instead of C1 binding to antibody Fc tails, MBL
binds to antigen
Classical pathway
• Antibodies bind multivalent microbial antigen
• C1 ( = C1r2C1s2) bind antibody Fc region
• C4 comes in contact with C1 enzymes that cleave C4
• C4 becomes C4a and bound C4b by cleavage C1 (amplification)
• C4b than attaches to antigenic surface
• C2 comes into contact with C1 enzyme that cleaves iit into C2b and bound C2a
• C2a binds to C4b to form C4b2a ( = classical pathway C3 convertase)
• C3 convertase cleaves C3 into C3a that causes inflammation and C3b that binds to the C2a
part (amplification) → forms C4b2a3b which is a C5 convertase
• C5 convertase cleaves C5 to form C5a that causes inflammation, and C5b that attaches to
C4b2a3b for initiation of the late stages of complement activation
The three key functions of the complement system are opsonization and subsequent phagocytosis
and cytolysis of microbes, and triggering inflammation. Cytolysis is not possible if the microbe is
encapsulated, therefore the cell wall is too thick.
