The Innate Immune Response

What is the innate response?

the rapid, non specific first line of attack

What are the 3 components of the innate response?

1) complement cascade

2) phagocytosis by macrophages and neutrophils

3) natural killer cell activity

What 3 non-specific effectors are produced by the complement cascade?

1) MACs

2) Anaphylatoxins

3) Opsonisation

What does MAC stand for?

membrane attack complex

What is opsonisation?

the priming of pathogens for phagocytosis

What are the 3 complement activation pathways?

1) classical pathway

2) lectin/ mannose-binding pathway

3) alternative pathway

What activates the classical complement activation pathway?

antigen-antibody complexes

What is the role of serine proteases in the complement cascade?

they undergo proteolysis to activate factors

What enzymes are used in the complement cascade?

serine proteases

What is the name of the process where serine proteases cleave proteins into small peptide fragments?

proteolysis

What complement cascade factors are used as anaphylatoxins?

C3a, C4a, C5a

What complement cascade factor is used as an opsonin?

C3b

What two factor activations does the C1 factor catalyse in the classical complement pathway?

1) activation of C2 to C2a, producing C2b

2) activation of C4 to C4b, producing C4a

What factor activation does the C2a factor catalyse in the classical complement pathway?

activation of C3 to C3b, producing C3a

What factor activation does the C3b factor catalyse in the classical complement pathway?

activation of C5 to C5b, producing C5a

What do C5b, C6, C7, C8 and C9 go onto form in the complement cascade?

MAC

Where is mannose found?

pathogen lipid envelopes

Describe how the complement cascade is triggered by mannose:

mannose binding lectin binds to mannose on a pathogen stimulates MASP 1 and 2 to bind, activating C2 and C4

What does MASP stand for?

MBL-associated serine proteases

Give 6 examples of pathogens that activate the lectin or mannose binding pathway:

1) influenza A

2) HIV

3) Leishmania

4) salmonella

5) steptococci

6) Candida albicans

Describe how the alternative pathway triggers the complement cascade:

C3 automatically produces C3b which goes onto bind with factor B and properdin on the surface of pathogens which activates more C3 that activates C5

What molecules on pathogen's surface are key for activating the alternative complement cascade?

factor B and properdin

What do anaphylatoxins do? (2)

1) they trigger degranulation of endothelial cells, mast cells and phagocytes which activates them

2) they cause smooth muscle contraction and enhance vascular permeability

What 2 anaphylatoxins acts as chemoattractants for neutrophils:

C3a and C5a

What change does C3b undergo to become an opsonin?

it is cleaved to iC3b

Why can iC3b act as an opsonin?

macrophages contain receptors for iC3, facilitating phagocytosis

What 4 cells are involved in the innate cellular immune response?

1) neutrophils

2) macrophages

3) dendritic

4) NK cells

What are the three activation states of macrophages?

1) resting

2) primed

3) hyperactive

Give 3 locations where macrophages are found:

1) skin

2) lungs

3) intestines

Describe the resting activation state of macrophages:

macrophages collect tissue debris and eliminates apoptotic cells

Describe the primed activation state of macrophages:

they are increasingly phagocytotic with increased expression of MHC II and they are primed by interferon gamma produced by NK cells

Describe the hyperactive activation state of macrophages:

macrophages stop proliferating and become larger and increasingly phagocytic, stimulated with interferon gamma and lipopolysaccharide

What produces lipopolysaccharide?

Gram negative bacteria

What converts a resting macrophage to a primed macrophage?

interferon gamma

What converts a primed macrophage to a hyperactive macrophage?

lipopolysaccharide

What converts a resting macrophage to a hyperactive macrophage?

interferon and lipopolysaccharide

Where are neutrophils found?

blood

What 2 molecules are involved in the double-key mechanism of neutrophils?

selectin and ICAM

What receptor do neutrophils have for ICAM?

integrin receptors

Describe neutrophil activation:

selectin and ICAM on blood vessel endothelium binds to neutrophil receptors, bringing the neutrophil to a stop so it can infiltrate infected tissues

What activates integrin receptors on neutrophils?

C5a and lipopolysaccharide from inflamed tissue

What stimulates neutrophils to infiltrate infected tissues once they have been stopped in the endothelium?

F-Met found on bacterial proteins

What do neutrophils produce that activates NK cells?

TNF

What is F-Met?

N-terminal formyl methionine

Give 3 examples are where NK cells are found:

1) liver

2) blood

3) spleen

What receptors do NK cells have check cells for infection?

Fas

What receptor does Fas recognise on healthy cells?

MHC I

What do NK cells release if they find no MHC I complex on a cell?

perforin and granzyme B

What do NK cells release to activate macrophages?

interferon gamma