Principles - Innate Immune System 1) Proteins Flashcards
What produces acute phase proteins?
liver
What do acute phase proteins do?
mediate inflammatory response Activate macrophages Influence chemotaxis Act as opsonins Role in tissue repair and remodelling
What is C reactive protein?
acute phase protein which acts as opsonin for phagocytes and facilitates binding of complement proteins
Levels rise dramatically in response to infection
What is a normal level or CRP?
<5mg/l
What are cytokines?
diverse collection of solubule proteins and peptides which modulate behaviour of cells at low concentrations
What are the names of the cytokine families?
interferons, interleukins, colony stimulating factors, chemokines (and others)
What are interferons important in?
limitation of viral infections
What are interleukins?
produced by T cells, these direct cells to divide or differentiate
What is interleukin 2 important for?
T cell differentiation and activation
What are colony stimulation factors for?
directing the division or differention of bone marrow stem cells e.g act on myeloid cells
What are chemokines for?
direct movement of cells in the body
When is TNFa formed?
during the acute phase response, important in inflammation
What can TNFa activate?
endothelial cells
How many proteins does the complement system consist of?
about 30
Where are complement proteins produced?
liver
When does precursor A become an active enzyme?
when cleaved
Is the complement system involved in innate or acquire immune system?
both
What is lupus?
an immunopathological disease which is the result of problems with the complement system function
What does C3 deficiency result in?
repeated deep seated bacterial infections
What is C5 cleaved to?
C5a and C5b
How many pathways are there of complement activation?
3
Which complement proteins are involved in chemotaxis?
C5a and C3a
Which complement proteins are involved in opsonisation and cell activation?
C3b
What are the names of the 3 pathways in complement activation?
Classical, Lectin and Alternative
What activates the classical pathways?
antibodies
What happens in activation of the classical pathway?
antibodies (IgG or IgM) bind to C1, leading to a conformational change in c1
What is the order in which the proteins are activated in the classical pathway?
c1, c4, c2, c3
What is the classical pathway particularly important for?
clearing bacterial infection
protection against autoimmunity
What happens in the Lectin Pathway?
Lectin binds specifically to carbohydrates, whihc bind to Mannose-Binding Lectin
What does the Lectin Pathway bypass the need for?
antibodies
What do all 3 pathways lead to being activated?
c3
What occurs in the Alternative Pathway?
There is a spontaneous hydrolysis of c3 and binding of c3 to bacterial cell wall components, resulting in c3 being cleaved into active fragments
What is the alternative pathway dependant on?
activator surfaces (NOT the adaptive immune response)
What are examples of bacterial cell wall components c3 is bound to in the alternative pathway?
lipopolysaccharide of gram negative bacteria
teichoic acid of gram positive bacteria
What is the alternative pathway vital for?
protection against meningococcus and other encapsulated bacteria
What is the major amplification step in the complement cascade?
activation of c3
What does the activation of c3 trigger?
formation of final common pathway, complements c5-9 assemble to form the membrane attack complex
What does the membrane attack complex lead to?
osmotic cell lysis
What happens to C3a?
released into interstitium, is involved in increasing vascular permeability and mediating inflammation
What does C3b do?
Is an opsonin - coats bacteria and leads to phagocytosis
Promotes specific antibody formation by plasma cells
Dissolve the antibodies that trigger the cascade
How can the complement system be regulated by biochemical properies of complement components?
Only cleaved proteins are active
and these have a very short half life
How can the complement system be regulated by complement inhibitors?
Soluble inhibitors (C1 inhibitor, Factor 1, Factor H and c4 binding protein) Inhibitors bound to cell membranes (CD59 and DAF)
What does CD59 do?
prevents insertion of membrane attack complex
What does DAF do?
competes for C4 fragments
Who are complement deficiences most common in?
Asian and Middle Eastern populations
What are complement deficiences most commonly?
alternative pathway and final common pathway deficiencies
