3. Defence against infection Flashcards
What different things can be human pathogens?
bacteria
viruses
fungi
protozoa
parasites
worms
what cells does HIV1 infect?
T cells, macrophages, dendritic cells
what is the number 1 killer if you have AIDS?
Tuberculosis
what organism can cause toxic stock syndrome?
S. aureus
What happens to pathogens that are too big to be phagocytosed?
Large IgE presence and eosinophils release toxic granules
What can vary depending on the lifecycle of the pathogen?
site of infection - intracellular vs extracellular
Why are pathogens vulnerable when outside the cell?
attack from: innate cells, antibodies, and the complement
what receptors do innate immune cells express?
pattern recognition receptors
What receptors do adaptive lymphocytes express?
specific BCR and TCR
1 receptor for 1 antigen
how quickly does the innate immune system react?
rapidly within minuets
why is adaptive immunity slower to act?
clonal expansion of individual b and t cells takes time, over several days
does innate immunity change after repeated exposure?
no
How do t and b cells get their specific receptors?
genetic rearrangement
why is innate response important?
it limits the infection to local tissues
why is adaptive immunity important?
it clears the infection
what is the role of macrophages in the initial immune response?
recognise the bacteria as foreign and mount an immune response
cause wound healing to commence
what is the role of dendritic cells in the initial immune response?
takes up the bacteria and becomes an antigen-presenting cell then travels to the lymph node
what is the role of dendritic cells in the activation of t cells?
dendritic cells enter the lymph node and present the antigen to the specific T to activate them and cause clonal expansion
what is the role of activated t cells in the lymph node?
encounter the b cells to activate and trigger antibody production
Where to activated B and T cells go?
they leave the lymph node and circulate in the blood to the site of infection
what are the physical barriers?
skin, hair, nails
mucosal membranes
mechanical barriers like cilia moving mucus
what are the chemical barriers?
fatty acids on the skin
enzymes like lysozyme and pepsin
low pH
antibacterial peptides
what are the microbiological barriers?
normal microbiota competing for nutrients and space
production of antibacterial substances like defensins
Is the complement innate or adaptive?
innate
what are the complement proteins produced as?
inactive precursors called zymogens
what activates the complement zymogens?
each component cleaved and then activating the next
what is C3 in the complement?
a key starting component for the cascade
what is produced when C3 is spontaneously cleaved in serum?
C3a and C3b
what is C3a?
soluble in serum
What does C3b do?
forms a thioester bond to bacterial membrane
What does C3b bind once it is attached to the bacterial membrane?
Factor B
what happens to factor B once it is bound to C3b?
it is cleaved by factor D to produce Bb and Ba fragments
Bb remains attached to C3b making C3bBb
what is C3bBb?
a C3 convertase which makes more C3a and C3b
also made is (C3b)2Bb which is what?
a C5 convertase that makes C5a and C5b
what are the 3 ways to activate the complement?
classical pathway, alternative pathway, mannose-binding lectin pathway
where is mannose-binding lectin normally found?
in the plasma at low concentration
what is a cytokine that macrophages produce that triggers the release of proteins from hepatocytes?
IL-6
where is mannose-binding lectin released from?
hepatocytes
where to mannose binding lectins bind?
mannose residues on bacterial surfaces
what else can mannose-binding lectins bind?
Fucose
N-acetylglucosamine
both on bacteria
what does binding to the mannose cause?
activation of serine protease MASP-1 and MASP-2
what do MASP-1 and MASP-2 do?
cleave complement components C2 and C4
what does C4b do ?
Covalently binds to the bacterial surface
what is C4bC2a?
a C3 convertase
what is C4bC2aC3b?
A C5 convertase
what is C2a an exception to?
the rule that A fragments are soluble
where do ficolins bind?
acetylated sugars on bacteria membrane
what does ficolin binding cause?
activation of serine protease MASP-1 and MASP-2
what do C3a and C5a do?
recruit macrophages and neutrophils to cause inflammation
how does C3b trigger phagocytosis?
Binds to complement receptors on phagocytes
what does C5b and other components form?
membrane attack complex
how does the membrane attack complex form?
C8 penetrates the lipid bilayer and recruits up to 16 C9 fragments which form a pore to lyse the bacteria
what do defects in C3 and its activation lead to?
pyogenic infections like staph and strep
what to defects in membrane attack complex cause?
Susceptibility to Neisseria infections
Neisseria meningitidis
Neisseria gonorrhoea
