1.5.1 Humoral Immunity

Question 1

Describe the process of cross presentation.

Answer 1

An intracellular pathogen (e.g. virus) infects a cell other than a DC. The DC ingests the infected the infected cell along with its pathogen. The pathogen is then processed and presented on the MHC class I of the DC. Thus, in short, the DC was able to consume an intracellular pathogen and present it on MHC class I.

Question 2

What are some of the chemical moieties that Ab’s can bind?

Answer 2

proteins, polysaccharides, lipids, nucleic acids

Question 3

What is humoral immunity? What does it fight?

Answer 3

Humoral immunity is carried out by B cells and antibodies against extracellular pathogens.

Question 4

Give some examples of extracellular pathogens that humoral immunity can combat.

Answer 4

Bacteria, Toxin, Viruses in the extracellular phase of their life cycle, Parasites

Question 5

What allows one B cell to make 4000 plasma cells which can yield 10^12 Ab’s per day?

Answer 5

Clonal selection. Not as massive as T cell clonal expansion b/c B cells can produce numerous Ab’s.

Question 6

Which isotypes of Ab are expressed by naive B cells?

Answer 6

IgM and IgD

Question 7

As clonal expansion occurs, differentiation also occurs. What are some of the various types of differentiation?

Answer 7

Ab secretion, Isotype switching, affinity maturation, memory B cell

Question 8

What are the common locations for B cell activation?

Answer 8

Spleen, tonsils, LN

Question 9

Describe what can be found in the white and red pulp of the spleen.

Answer 9

White: leukocytes Red: hematologic function

Question 10

Name these zones of the spleen where you can find B and T cells, respectively.

Answer 10

B cells: Follicle (follicular B cells) T cells: Periarteriolar lymphoid sheath, PALS

Question 11

What anatomical zone makes the spleen unique from other lymphoid organs? What helps trap blood that moves through this zone?

Answer 11

Marginal zone; macrophages

Question 12

What is the bullying model of the spleen?

Answer 12

Macrophages hold down the pathogen, and the B cells beat it up.

Question 13

Describe the cellular processes that follow the binding of a BCR to a pathogen (starting with the kinase and ending with the resulting txn factors).

Answer 13

Look at image

Question 14

The recruitment of what to the ITAM motifs begins BCR signaling.

Answer 14

Src Kinases (Blk, Lyn, Fyn)

Question 15

Describe the in order in which phosphorylated molecules are added onto the ITAMs.

Answer 15

ITAM, Syk, Btk, BLNK, PLCgamma2

Question 16

What does PLCgamma2 cleave? Yielding which two molecules and their downstream txn factors?

Answer 16

PIP2; yielding DAG which goes through PKC-mediated pathways (NF-kappaB) and IP3 (NF-AT)

Question 17

How is NF-kappaB activated?

Answer 17

1. BCR ligation 2. PKC activates IkappaB kinase 3. Phosphorylation and ubiquitination of IkB 4. Degradation of IkB by 26S proteasome

Question 18

What co-receptor can enhance BCR signalin by recruiting similar kinases but it required for B cell activation?

Answer 18

CR2

Question 19

What does Factor I cleave?

Answer 19

C3b and C4b to form iC3b and iC4b; also cleaves iC3b to form C3d

Question 20

C3d, which is produced via cleavage of C3b by Factor I, binds what receptor on B cells?

Answer 20

Co-receptor 2

Question 21

What occurs in the B cell when B cells start to begin to respond to an antigen in the follicle?

Answer 21

Enter cell cycle, make some IgM, express B7-1 and B7-2, internalize and process Ag for MHC class II presentation, Migrate toward T cells

Question 22

Describe the germinal center rxn.

Answer 22

1) T and B cells are activated independently 2) T and B cells migrate toward eachother 3a) B cells present Ag to T cells 3b) T cells express CD40L and cytokines (IL-4) 3c) Ab prod is initiated (IgM) 4) T and B cells migrate back to follicle 4a) T cells that were re-activated by the B cells are Follicular Helper T (Tfh) cells

Question 23

What occurs when B-T cells interact in the extrafollicular focus without the CD40-CD40L interaction? What occurs when B-T cells interact in the extrafollicular focus with the CD40-CD40L interaction?

Answer 23

Without CD40-CD40L interaction, B cell Ag presentation to activated helper T cells With CD40-CD40L interaction, activation of B cells by CD40 ligand cytokines -> B cell proliferation, initial Ab prod, germinal center reaction

Question 24

What B cell differentiation responses to Ag are dependent upon CD4 cell help?

Answer 24

B cell proliferation, Ig isotype switching, somatic hypermuation/affinity maturation, plasma cell differentiation, memory B cell differentiation

Question 25

What is isotype switching?

Answer 25

genomic rearrangements that result in the prod of different Ig isotype

Question 26

What is somatic hypermutation?

Answer 26

The intro of point mutations into hypervariable regions of Ab genes (which can result in affinity maturation)

Question 27

What regions are eliminated during isotype switching?

Answer 27

Constant regions

Question 28

What cytokines induce the various types of Ig?

Answer 28

IgM: first Ab made, low affinity IgE: IL-4, 5, 13 IgG: IFNgamma IgA: TGFbeta

Question 29

Describe pos/neg selection in terms of B cells. What process is it involved with and when are they pos/neg selected?

Answer 29

Affinity maturation Incr. affinity = Pos. selection Decr. affinity = Neg. selection

Question 30

What type of cells are use Fc receptors and complement receptors to display Ag-Ab complexes to B cells during affinity maturation?

Answer 30

Follicular dendritic cells

Question 31

What are the two types of Hyper-IgM syndrome? What is their cellular basis?

Answer 31

Type 1 (T cell deficiency): Absence of Cd154 (CD40L co-receptor) on T Cells, poor signaling for Ig class switching Type 2 (B cell deficiency): Deficiency of activation-induced cytidine deaminase (AID), poor class switching and somatic hypermutation

Question 32

How do they arise? Where do long-lived plasma cells migrate to?

Answer 32

Germinal center reaction, BM

Question 33

Describe the primary and secondary response.

Answer 33

Look at chart

Question 34

What effect does Ig concentration have on Ig half life?

Answer 34

Increased Ig concentration, Decreased Ig half life

Question 35

Cross linking of the BCR and what co-receptor turns off the B cell? How does it turn it off?

Answer 35

FcgammaRII, recruits phosphatases which limit the activation of B cells

Question 36

What are the two types of Ab responses?

Answer 36

T-dependent: protein Ag, CD4 T cells activate and stimulate B cells through CD40 and cytokines T-independent: non-protein Ag, No CD4 help

Question 37

Name the three types of B cells and their corresponding Ab response (Ab and plasma cell).

Answer 37

Follicular B cells: isotype-switched, high affinity Ab, long-lived plasma cells Marginal Zone B cells: mainly IgM, short-lived plasma cells B-1 Cells: mainly IgM, short-lived plasma cells

Question 38

What are some features of T-independent Ag's? Features of the response?

Answer 38

Ag: polysaccharides, repeating identical determinants, some TI Ag's bind additional receptors Response: Less Ig class switch (IgM, IgG2), little somatic hypermutation, little memory

Question 39

Differentiate the response to the two Haemophilus influenzae vaccines: HiB PS vaccine and HiB-DT vaccine.

Answer 39

HiB PS: T-independent, capsular polysacc, induces IgM, low affinity Ab, poor memory Hib-DT: T-dependent, PS covalently linked to DT, IgG\>\>\>IgM, higher affinity Ab, Memory B cells

Question 40

What B cell is responsible for producing most of the IgM in the serum?

Answer 40

B-1 B cells, protects from bacterial invasion from the gut

Question 41

What are isohemagglutinins?

Answer 41

The antigens associated with different blood types.