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Flashcards in The Humoral Response Deck (40):
1

What mediated effector functions of humoral response?

Antibodies produced by activated B cells: they neutralize the extracellular microbes

2

Overview of humoral response!

mature B cell: IgM and IgD being expressed

Activate when helper T cell signals to activate (3signals)

Clonal expansion

Differentiation:
1) some become plasma cells
2) some class switch and affinity mature
3) sub pop becomes memory B cells

3

The differentiation possibilities of B cells?

1) become plasma cells: active antibody secretion, IgM (IgM is first produced)

2) class switch and affinity mature under direction of helper T cells
Affinity mature: change FAB region so it binds stronger --> HIGH AFFINITY IgG****

3) sub pop becomes memory B cells to activate in a secondary response

4

What are the three signals of B cell activation?

1) BCR complex recognizes antigen (NOT MHC DEPENDENT, FREE ANTIGENS ONLY)

2) complement receptor CR2 binds C3d (complement activation product)--> drives activation
*esp strong if both signal 2) and antigen recognition

3) t-dependent antigen signal provided by TH cells = CD40-CD40 ligand (CD40 is on B cell, ligand on helper T)

5

Humoral response deals with:

Extra cellular microbes

Humoral response must neutralize and eliminate extra cellular microbes

6

Overview of B cell antigen recognition (what needs to bind?)

Cd3 bound to microbe binds CR2
Microbial antigen binds BCR
Together= recognition

Single receptor complex binding is usually not enough to actually activate B cell, need signals from Ig and Cr2 complex

7

What happens after B cell activation?

Proliferates
Plasma, class switch, affinity mature, and memory cells

IgM secretion is eventually replace by IgG (class switching)--> population of IgG making cells outgrows IgM producing population

8

B cell responses to antigen? And significance?

Entry into cell cycle= clonal expansion

INC expression of cytokine receptors= can respond to Helper T cell secreted cytokines

Migration out of lymphoid follicles= interaction with helper T cells

Secretion of low levels of IgM= early phase of humoral response

9

T-dependent versus T-independent B cell antigens?

T-dependent (thymus):
-proteins (think how T cells only recognize proteins, and this type of activation depends on T cell function
-***if recognizes protein--> needs T cell help
-isotope switching YES
-affinity maturation YES
-memory cells made YES

T-independent:
-polysaccharides, nucleic acids, glycolipids, polymeric antigens
-low level isotope switching
-little to no affinity maturation
-memory cells only made when dealing with some polysaccharide antigens

10

What are polymeric antigens and how can they activate T cells?

What is the downside to this type of activation?

Antigens with same repeating unit, long polymers bind and cross link BCR 's, bringing them together and causing a large signal

Downside: T cell cannot communicate so cannot class switch or affinity mature, so only IgM is made

11

How do B cells activate via t-dependent antigens?

Recognizes globular protein, only engages one receptor of Y: no cross linking

Cell takes that receptor, pulls it in, makes MHC class II and becomes APC

T cell must then recognize and tell it to activate

Most are t dependent

12

B cell antigens are large or small complexes?

Large complexes!!

13

3 types of B cells: location and antibody production? Main antigen? Effector functions?

Follicular B cells (B2):
-location: follicles of secondary lymph nodes, adult humoral response
-antigen: recognize T- dependent antigens
-can do all antibody isotopes
-effector function: long lived plasma cells

B-1 cells:
-location: peritoneal and pleural cavity fluid AND mucosal tissue
-formed early in life, short lived, self populate
-antigens: polymorphic, T-independent
-only IgM
-express CD5
-plasma cells

Marginal zone:
-location: marginal zone of splenic white pulp
-resting mature cells
-antigens: T-independent
-IgM only
-plasma cells

14

T and B cell interaction

B cell binds globular protein, internalizes and presents as APC

B cell enters border T-B cell region

Dendritic cell activates T cell

Activated T cell activates B cell w/same antigen

B cell makes IgM, back to follicle, makes germinal center: also starts class switching and affinity maturing

15

What does the follicular dendritic cell do?

Holds antigens so B cells can retest receptors after affinity maturing (sits in follicle)

IF doesn't bind: does
IF works better: lineage expanded for that cell

16

T and B cell interaction simple version

B cell encounters its antigen
Processes via MHC2
Presents to active T cell (CD4)
T cell recognizes: if CD40 (on B) and CD40 ligand (on T) AND MHC/antigen interaction both match
Cytokines secreted by T cell signal antibody class switching to B cell

17

Where does affinity maturation occur?

In the germinal center

18

Where does affinity maturation occur?
What occurs?

In the germinal center

Receptor binding FAB region, random mutations within CD-R-1-3 region (complementarity determining region)

Then test if it got better or worse at binding: FDC

19

What enzyme is most responsible for affinity maturation and class switching?

AID (similar in function to RAG enzyme for VDJ)

Activation-induced deaminase

20

Antibody class switching process?

Similar to VDJ

Switch regions are chosen (fold DNA, cut it out, then that switch region is closest)
***this process mediated by AID

T cell tells which to switch to via cytokines

Ones cuz out of DNA can no longer be made

21

What are the 5 isotopes of antibodies?

IgM (first used)
IgD
IgG
IgE
IgA

22

Which cytokines are needed for IgE, IgG, and IgA?

IL-4 = IgE

IFN-y = IgG

TGF-B = IgA

23

Antibody effector functions and their natural sequence of expression?

IgD: developmental marker, if presented it is mature, if IgM presented still immature don't know effector functions

1) IgM: first produced, pentamer (5 Ys linked), BEST one at activating complement
2) IgG: best and most features: best at neutralization, best at opsonization (upregulated phagocytosis), directly responsible for ADCC (tags for NK to kill infected cell), ONLY one that can gross placenta, most abundant in serum
3) IgA: dimer, secretion antibody, for neutralization
4) IgE: allergic response/parasite antibody (helminths) think TH2 (they are connected)

24

Antibody locations

IgA: transport across epithelium (mucosal tissue immunity: gastrointestinal and respiratory tracts)

IgG: transport across placenta, most abundant in serum, extra vascular sites

IgM: found in blood and lymph (first responder/made)

IgE: body linings: defense against parasites and mast cell de granulation (allergic response)

25

What is the J chain?

Protein responsible for allowing multimedia antibodies to link together

26

Why is IgM best at activating complement?

Because has 5 C1s (it's a pentamer) so more C1s in hand lead to more C4 activation. Numbers alone make it easier for C1 to bind

27

What is neutralization?
Important for?
Example?

When antibodies bind to something and prevent it from exerting its effects

Important for toxins and venom!

Another ex: prevents virus from binding and infecting a cell

28

What is opsonization? How does it work? What are Fc receptor's roles?

Upregulated phagocytosis

1)IgG binds microbe
2) opsonized microbe binds to phagocyte via Fc receptors
3) Fc receptor signals activate phagocyte
4) microbe is phagocytosed and killed

*Fc receptor binds the bound antibody (opsonized antibody)

29

OpsonizationFc receptor affinity for Ig: bigger number =

Stronger binding

IgE to Fc is strongest --> opsonization target is mast cells, eosinophils, basophils= allergic and parasite response

30

What is ADCC? Which antibody is involved?

Antibody dependent cellular cytotoxicity = NK cell recognizes infected cell and kills it

IgG

31

What is responsible for the allergic response?

TH2 + IgE

TH2 secretes IL-5, which acts on eosinophils to make more of their granules
Then, helminth (example) cross links, causes de granulation = allergic response

32

How does IgA transport across epithelial cells occur?

Poly-Ig receptor binds to J chain
These are endocytosed, travel across cell, and are released in the lumen side

33

If someone is IgA deficient, which antibody could make up for the lack of IgAs crossing the mucosal epithelial barrier?

IgM could because it also had a J chain

34

Why does IgG have longest half life and most abundant in serum?

Because body cells protect it by endocytosing and protecting them in vehicle for a while then recycling to cell surface, thus maintaining high serum levels

35

Antibody transport:
Placenta
Liver
Endothelial cells
Gut

Placenta: binds IgG and transports it across

Liver: regulates IgG blood levels

Endothelial cells: regulate blood IgG levels by protection it

Gut: neonatal IgG transport into circulation

36

What is the neonatal Fc receptor? How does it work?

FcRn= neonatal Fc receptor

It is used to grab and bring antibodies in: either to hold or transfer across to neonate to get to their serum, or can be degraded in lysosome

37

What is immune complex clearance?

After antibodies bind and neutralize a threat, they have formed an immune comes, which is a lattice shape (bigger the better) made of antibody antigen and complement

RBC receptors grab on and hold, goes to liver and spleen, where macrophages grab it and destroy it (via their Fc receptors)

CR1 binds the complexes *****

38

What is antibody feedback and why is is necessary?

Necessary because we shouldn't waste the energy to fix up new antibodies when a cell has already gone through affinity maturation for the same antigen

It is the inhibition of a B cell response when we already have antibodies against that antigen

Feedback mechanism

Antigen-antibody complex binds BOTH B cell Ig AND Fc receptor (Fc receptor binds antibody bound antigen) and thus send inhibition signal to turn the B cell signaling off

39

Primary vs secondary antibody response?

Primary: IgM to start, then IgG, plasma cells in bone marrow, develop memory

Secondary: almost exclusively IgG, memory already so faster stronger because B cells have already affinity matured and class switched (their antibodies)

40

Ways to avoid humoral immunity?

How does heroes avoid cell mediated response?

1) antigenic variation (viruses such as flu and herpes)
2) inhibit complement activation: many bacteria can shut down classical cascade
3) am resist phagocytosis: anything with capsule, many bacteria (ex pneumococcus)

Heroes: shuts down MHC class 1