Effector Responses

Question 1

What is crosstalk in this context?

Answer 1

Cytokines and antibodies signalling to cells of the immune response after their production by it, to avoid damage to self and save energy

Question 2

Innate cellular response?

Answer 2

Fast and non-specific
Cells mostly derive from common myeloid progenitor cells
i.e. neutrophils, macrophages etc

Question 3

What are the phagocytes?

Answer 3

Macrophages
DCs
Neutrophils

Question 4

Macrophages?

Answer 4

Tissue-resident, formed from monocytes in bone marrow
Also produced during development from embryonic cells
Main phagocytes, using surface receptors and chemotaxis

Question 5

Neutrophils?

Answer 5

Has dense granules, makes up 90% of our circulating granulocyte pop
Short life span - when dead, cells form pus
Phagocytosis, also use chemotaxis

Question 6

What are the granulocytes?

Answer 6

Neutrophils
Eosinophils
Basophils

Question 7

Eosinophils?

Answer 7

2-5% of WBS

Release toxic granules and chemical mediators; eosinophil cationic protein and major basic protein

Question 8

Basophils?

Answer 8

0.2% of wbs

Release histamine, prostaglandins, heparin, leukotrienes

Question 9

Mast cells?

Answer 9

Found in tissues, they are like basophils
Cell-surface receptors bind Fc of IgE
Multivalent binding - granule release

Question 10

Natural killer cells?

Answer 10

Produce cytotoxic molecules
Inhibitory receptors = MHCI, expressed on all cells normally
Excitatory receptors for ligands only work when MHCI is downregulated in abnormal cells

They also inhibit viral replication, producing interferons

Question 11

Complement innate response?

Answer 11

Antibody independent killing

Uses 30 different soluble proteins (inactive precursors circulate from the liver)

Question 12

Activation of complement?

Answer 12

Proteolytic cleavage into 2/more parts
Smaller fragment may mediate inflammation
Larger fragment has active enzyme site and binding site for next protein in cascade

Question 13

Pathways of complement? End point of all?

Answer 13

Classical
Alternative
Lectin
All form C3 convertase, cleaving C3 into C3b (bound to affected cell) and C3a for inflammation

Question 14

Classical pathway?

Answer 14

IgM (planar form), as a pentamer, binds antigens on bacteria = staple form
C1q binds one IgM
Or C1q binds at least two IgG molecules

C1r activated, cleaving serine proteases C1s.
C1s cleave C4 to a and b, which bind the surface
C4b binds C2, cleaved by C1s to C2 a and b = C4b2a complex
This is an active C3 convertase, able to cleaved up to 1000 molecules of C3
Most C3b binds microbial surface

Question 15

Alternative pathway?

Answer 15

Complement binds pathogen surface directly
C3 binds water via spontaneous hydrolysis, letting it bind factor B
Factor D cleaves B into Ba and Bd
C3(H20)Bb = C3 convertase
Only active if bound to cell surface

Question 16

Lectin pathway?

Answer 16

Complement binds mannose binding proteins on pathogens
with mannose binding lectin, present in serum
MBL associated proteases (MASPs) bind MBL = complex, cleaving C4 and C2 to form C4a2b in same way as classical

Question 17

Effector response of complement?

Answer 17

Induces cell lysis
Opsonisation of pathogen
C3a induces chemotaxis and inflammation
Immune complex clearance (soluble antigen complexes where too few antibodies mean no phagocytosis - complement aggregates these)

Question 18

Effector function of CD4+ T cells?

Answer 18

Differentiation to Th1 and Th2

Question 19

Th1 effector?

Answer 19

Intracellular pathogens
Activate macrophages via secretion of IFN-y and CD40 ligand
Macrophages then upregulate MHCII to activate T cells

Also produces:
IL3 and GM-CSF = macrophage differentiation in marrow
IL2 = T cell proliferation
Fas ligand or LTa = killing of infected cells

Can also stimulate antibody production for extracellular action

Question 20

What is delayed-type hypersensitivity?

Answer 20

Activation of T cells in absence of co-stimulation, through macrophages MHCII binding - much slower, needs attachment to last for some time

Question 21

Th2 effectors?

Answer 21

Large extracellular pathogens that cannot be phagocytosed

Master TF GATA-3 expressed, to help B cells produce antibody (secreting IL4,5,6 – IgE production from plasma cells)

Activate basophils, eosinophils and mast cells through cytokines directly, or IgE production from B cells

Question 22

Th17 effectors?

Answer 22

Extracellular bacteria/fungi
Recruits other cells with IL17 (induces cytokine secretion)
IL22 - antimicrobial peptides

Question 23

CD8+ T cell effector function?

Answer 23

Migrate from lymph to circulation to scan every MHCI in body for infection, without need for second signal as already active

Bind loosely, recognise antigen and reorganise cytoskeleton to localise granules to point of contact
Releases granules to diffuse across synapse = apoptosis
Rapid
Very selective

Also produce IFNy for macrophage activation
TNF-a helps this
LT-a directs killing

Question 24

CD4+ and CD8+ cross talk?

Answer 24

e.g. in infected macrophages
CD8+ CTLs activate with IFNy or kill
Th1 cells activated with IFNy, increasing macrophage differentiation
Th1 cells produce IL2 to stimulate T cell production, increasing cytotoxic lymphocytes (CTLs)

Question 25

Antibody effector mechanisms?

Answer 25

Neutralisation
Agglutination
Opsonisation
ADCC
Activation of complement 
Specialised responses

Question 26

ADCC?

Answer 26

Antibody-dependent cell-mediated cytotoxicity
Binds infected cell/large extracellular pathogen when phagocytosis not possible
Fc receptors allow immune cells to bind for cell death e.g. through better granule release

Question 27

Specialised antibody responses?

Answer 27

e.g. IgE-mediated mast cell activation

Cross-linking antigen by IgE = granules, lipid mediators and cytokines released for recruitment and inflammation

Question 28

Pathogen responses to immune effects?

Answer 28

Mutations to avoid antibodies
Hiding within cells/mimicking host cells
May directly regulate immune response (parasitic worms)

Question 29

Parasitic regulation?

Answer 29

Secrete cytokine-like molecules to regulate host immunity e.g. TGFB-like molecules for Treg induction