The effectors of innate immunity (W11)

Question 1

what is complement

Answer 1

set of soluble proteins in blood called C1, -> C9
triggered enzyme cascade

Question 2

3 types of complement activation pathways

Answer 2

classical
mannose-binding lectin
alternative

Question 3

3 types of complement effector pathways

Answer 3

anaphylatoxins (inflammation)
membrane attack complex (lysis)
opsonisation

Question 4

classic pathway of complement activation?

Answer 4

only occurs when there are antibodies present specific to a foreign antigen
antibodies bind to complement component Clq activating subsequent complement components

Question 5

alternative pathway of complement activation?

Answer 5

complete component C3 spontaneously activates and binds to nearby membranes
host cell control proteins deactivate C3 but bacterial cells do not

Question 6

mannose-binding lectin pathway of complement activation?

Answer 6

activation through mannose-binding lectin binding to mannose or similar carbs on bacteria
mannose is not present on host cells

Question 7

what occurs in complete lysis

Answer 7

Membrane Attack Complex (MAC) forms in membrane of bacteria
C6-C9 form pore for water to enter and ions to exit cell
bacteria swells and bursts

Question 8

complement-mediated anaphylatoxins?

Answer 8

soluble complement components (anaphylatoxins) are released on complement activation, causing blood vessels to become leaky (oedema) allowing infiltration of plasma proteins, recruitment of immune cells, activation of mast cells

Question 9

opsonisation?

Answer 9

complement opsonin binds to bacteria
phagocytes bind to complement through complement receptors
encourages phagocytosis

Question 10

complement cascade?

Answer 10

C1 complex of 2 antibodies bound to target cell antigen
activates C2 & C4 and cleaves them in half, C2b &C4b form C3 convertase
(above is classical, below is alternative)
C3 convertase hydrolyses C3 splitting it into C3b & C3a
C3b activates C5 into C5a & C5b
membrane attack complex (pore) formed by C5b, C6-C9
C3a & C5a (anaphylatoxins) acting on endothelial cells

Question 11

types of phagocytes

Answer 11

neutrophils
macrophages
dendritic cells

Question 12

neutrophils features

Answer 12

rapid recruit to scene
good at killing
short lived
main part of pus
limited to circulation

Question 13

macrophages features

Answer 13

good at killing when activated
involved in tissue healing, clearing dead cells, metabolism
reside in tissue (supplemented by monocytes
produce cytokines needed to pull in neutrophils

Question 14

dendritic cells function

Answer 14

reside in tissues
rare
pick up antigens in tissue and take to T cells

Question 15

process of neutrophils getting from circulation to site of inflammation?

Answer 15

extravastation

Question 16

process of extravastation?

Answer 16

blood vessel endothelium altered by inflammatory cytokines
neutrophil rolls along endothelium then firmly adheres and exits between cells (diapedesis)
neutrophils then follow chemokine gradient to site of inflammation

Question 17

phagocytosis?

Answer 17

phagocyte engulfs pathogen forming phagosome
lysosome containing toxic products fuses with phagosome to create a phagolysosome
more lysosomes fuse and pump in H+ ions, proteases, oxygen radicals, nitric oxide, pre-forming proteins
neutrophils also make HOCl (bleach)

Question 18

antigen definition

Answer 18

molecule that is recognised by the adaptive immune system

Question 19

how does antigen-specificity come about

Answer 19

adaptive immune cells randomly generate unique receptors that recognise specific antigens

Question 20

when do dendritic cells mature and what occurs

Answer 20

when they sense danger.
improve antigen presentation and upregulate chemokine receptors
migrate to lymphatics (following naturally present chemokine gradients) and into lymph node where the antigen is presented to T cells

Question 21

adaptive leukocytes and recognition of antigens? (signal 1)

Answer 21

B cell receptor - recognises soluble antigen in normal form
T cell receptor - antigen must be cut into peptides by dendritic cells and ‘presented’ with MHC molecules on the dendrites surface to be recognised

Question 22

how is signal 2 passed on between dendrite and T cell

Answer 22

costimulation!
CD28 (most important costimulatory molecule receptor) on T cell binds with B7 (ligand) on dendritic cell

Question 23

how does negative selection occur

Answer 23

when T cells are produced in the thymus they are presented with all the bodies ‘self’ antigens, and if a T cell recognises any it is given the signal to die, therefore the remaining T cells only recognise ‘non self’ antigens.

Question 24

what occurs to T cells in the lymph nodes if they recognise ‘self’ antigens? when does this occur?

Answer 24

anergy (permanent stasis) or death
This occurs when there is a small signal one and absence of signal 2

Question 25

what is signal 3?

Answer 25

production of cytokines (specific to pathogen type) from the dendritic cell (or other innate immune cells) which then act on the T cell and drives differentiation (when also activated with signal 1 and 2) towards particular effector cell type. This allows specialisation of the adaptive immune response - develop T cells better at killing bacteria, fungi, etc