Lecture 4: Adaptive Immunity

Front 1

where are mature antibody secreting plasma cells generally found

Back 1

bone marrow

Front 2

what differs between the primary and secondary antibody response

Back 2

secondary is quicker and more powerful (more Ab), IgG rather than IgM, greater Ab affinity due to somatic hypermutation affinity maturation

Front 3

what antigenic features provoke stronger reaction

Back 3

difference from self, larger antigen (more epitopes), high dose

Front 4

what type of antigen can directly provoke B cell action

Back 4

only carbohydrate bacterial wall type antigens

Front 5

how do mature lymphocytes locate to peripheral lymph nodes

Back 5

exit circulation in a manner similar to neutrophil extravasation

Front 6

where in the spleen do mature T cells locate and what aids this

Back 6

T cell CCR7 (chemokine receptor) binds to CCL19 and CCL21 (chemokines) in white pulp

Front 7

where in the spleen do mature B cells locate and what aids this

Back 7

B cell CXCR5 (chemokine receptor) binds to CXCL13 (chemokine) on stromal cells of the follicles

Front 8

4 types of CD4 T cells

Back 8

Th1 Th2 Treg and Th17

Front 9

Th1 cells do what

Back 9

promote cell mediated immune response- macrophage activation, CD8 response etc

Front 10

Th2 cells do what

Back 10

promote Ab response

Front 11

what dictates whether a T cell becomes Th1 or 2

Back 11

the nature of the activating APC

Front 12

3 main APC types

Back 12

monocyte/macrophage, B cell, dendritic cell

Front 13

initiation of adaptive immune system

Back 13

innate immune response (inflammation) attracts APC's into tissues, pick up antigen, transport to local lymph nodes in lymph, encounters and activates T cells at corticomedllary junction

Front 14

what do APC's use to discriminate antigen for uptake

Back 14

PRR (pattern recognition receptors) recognse common pathogen signatures or PAMP's (pathogen assoicated molecular patterns)

Front 15

2 types of PRR

Back 15

membrane bound and cytoplasmic

Front 16

2 examples of cytoplasmic PRR and what they bind

Back 16

NOD1 and NOD2 bind bacterial wall componnets

Front 17

2 types of membrane bound PRR

Back 17

C-type lectins and toll-like receptors TLR

Front 18

2 examples of C-type lectins and what they bind

Back 18

mannose receptor, DC-SIGN, bind pathogen surface carbohydrates

Front 19

what are TLR's

Back 19

a type of membrane-bound PRR, 13 types, APC's express several types, bind to virus and bacterial PAMPs

Front 20

how does a T cell become activated from it's naive state? receptors etc

Back 20

Signal 1- APC MHC with peptide binds to CD4/CD8 and associated CD3 signals
signal 2- APC B7 family binds to CD28 on T cell

Front 21

what happens to a T cell that receives signal 1 but not 2

Back 21

anergy, peripheral tolerance, will no longer react to that antigen

Front 22

what ensures that T cells only react to antigen presented by APC

Back 22

B7 only expressed on APC

Front 23

what happens to a DC as it is matures

Back 23

B7 on surface, greater MHC expression and ability to activate T cells, stop phagocytosis

Front 24

causes of DC maturation

Back 24

PRR interaction with PAMP, IFNa/b, IL-1, TNFa stimulation, opsonised bacteria binding to DC complement receptors

Front 25

what cytokines do mast cells release that can activate DC

Back 25

IL-1, TNFa

Front 26

what cytokine do infected cell release that can activate DC

Back 26

IFNa/b

Front 27

where do mature DC's go

Back 27

leave site of infection/inflammation in lymph go to LN's

Front 28

after receiving signal 1 and 2 Maturing T cells express what and produces what cytokine

Back 28

IL-2 receptor and produces IL-2, autocrine stimulation to reproduce clones

Front 29

what determines Th1 or 2 development

Back 29

the APC's cytokine production, this depends on the type of stimulation the APC recieved- the most appropriate immune response to the pathogen is illicited.

Front 30

what APC cytokine will promote Th1 and inhibit Th2, and what will the Th1 produce

Back 30

IL12, proliferating Th1 produce IFNg which further retards Th2 growth

Front 31

what happens regarding Th1/2 proliferation if IL12 is not released by the APC

Back 31

Th2 stimulated and produce IL4 which suppresses Th1

Front 32

BCR bound to peptide can be taken into the cell similarly to the exogenous pathway, how is it ensured that this does not induce a response if the antigen is harmless

Back 32

T cell co-stimulus is also required from a T cell activated to the same antigen.

Front 33

where does T cell activation of B cells occur

Back 33

thymic paracortex

Front 34

B cell activation signal 1

Back 34

antigen binding to BCR

Front 35

B cell activation signal 2

Back 35

B cell Cd40 binds to Cd154 on activated T cell

Front 36

once signal 1 and 2 received by B cell what does it express and receive

Back 36

receptors for Tcell cytokines, T cells produce IL4 and 5 inducing B cell proliferation

Front 37

where does B cell proliferation occur

Back 37

Thymic follicle in the cortex

Front 38

After signal 1 and 2 are received proliferating B cellsgo where

Back 38

germinal centre of the thymus

Front 39

what happens in the germinal centre reaction

Back 39

cycles of affinity maturation, somatic hypermutation of Ig's to improve BRC 'fit'

Front 40

what cell are the BCR's tested against during affinity maturation

Back 40

follicular dendritic cells, presents immune complexes on surface, only those that bind get survival signal. after cycles of this fit improves.

Front 41

how do B cells decide which isotype of Ig to produce

Back 41

interact with follicular helper T cells and are influenced by T cell cytokines to dictate which Ig isotype to produce

Front 42

which Ig is produced under stimulus of T cell TGFb

Back 42

IgA

Front 43

T cell IL4 causes which B cell Ig isotype to be produced

Back 43

IgE

Front 44

initiation of CD8 response

Back 44

APC's present antigen on MHC1 and travel to lymph nodes where it presents to CD8 cells, also phagocytose virus and present on MHC2 causing Th1 response. APC-CD4 interaction releases chemokine CCL3 attracting CD8. Th1 cell and CD8 cell both now bound to APC, CD4 derived IL2 activates CD8

Front 45

what does IL-2 cause CD8 cells to do

Back 45

proliferate, and produce perforin and granzymes, alter chemokine receptor expression so travel to site of infection

Front 46

what happens when active CD8 reaches site of infection

Back 46

binds to infected cells MHC1-antigen complex, releases perforin to create pores and granzymes enter cell causing caspase activation and apoptosis (similar to MAC in complement)