1.5.1 Humoral Immunity Flashcards
Describe the process of cross presentation.
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.
What are some of the chemical moieties that Ab’s can bind?
proteins, polysaccharides, lipids, nucleic acids
What is humoral immunity? What does it fight?
Humoral immunity is carried out by B cells and antibodies against extracellular pathogens.
Give some examples of extracellular pathogens that humoral immunity can combat.
Bacteria, Toxin, Viruses in the extracellular phase of their life cycle, Parasites
What allows one B cell to make 4000 plasma cells which can yield 10^12 Ab’s per day?
Clonal selection. Not as massive as T cell clonal expansion b/c B cells can produce numerous Ab’s.
Which isotypes of Ab are expressed by naive B cells?
IgM and IgD
As clonal expansion occurs, differentiation also occurs. What are some of the various types of differentiation?
Ab secretion, Isotype switching, affinity maturation, memory B cell
What are the common locations for B cell activation?
Spleen, tonsils, LN
Describe what can be found in the white and red pulp of the spleen.
White: leukocytes Red: hematologic function
Name these zones of the spleen where you can find B and T cells, respectively.
B cells: Follicle (follicular B cells) T cells: Periarteriolar lymphoid sheath, PALS
What anatomical zone makes the spleen unique from other lymphoid organs? What helps trap blood that moves through this zone?
Marginal zone; macrophages
What is the bullying model of the spleen?
Macrophages hold down the pathogen, and the B cells beat it up.
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).
Look at image
The recruitment of what to the ITAM motifs begins BCR signaling.
Src Kinases (Blk, Lyn, Fyn)
Describe the in order in which phosphorylated molecules are added onto the ITAMs.
ITAM, Syk, Btk, BLNK, PLCgamma2
What does PLCgamma2 cleave? Yielding which two molecules and their downstream txn factors?
PIP2; yielding DAG which goes through PKC-mediated pathways (NF-kappaB) and IP3 (NF-AT)
How is NF-kappaB activated?
- BCR ligation 2. PKC activates IkappaB kinase 3. Phosphorylation and ubiquitination of IkB 4. Degradation of IkB by 26S proteasome
What co-receptor can enhance BCR signalin by recruiting similar kinases but it required for B cell activation?
CR2
What does Factor I cleave?
C3b and C4b to form iC3b and iC4b; also cleaves iC3b to form C3d
C3d, which is produced via cleavage of C3b by Factor I, binds what receptor on B cells?
Co-receptor 2
What occurs in the B cell when B cells start to begin to respond to an antigen in the follicle?
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
Describe the germinal center rxn.
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
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?
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
What B cell differentiation responses to Ag are dependent upon CD4 cell help?
B cell proliferation, Ig isotype switching, somatic hypermuation/affinity maturation, plasma cell differentiation, memory B cell differentiation
What is isotype switching?
genomic rearrangements that result in the prod of different Ig isotype
What is somatic hypermutation?
The intro of point mutations into hypervariable regions of Ab genes (which can result in affinity maturation)
What regions are eliminated during isotype switching?
Constant regions
What cytokines induce the various types of Ig?
IgM: first Ab made, low affinity
IgE: IL-4, 5, 13
IgG: IFNgamma
IgA: TGFbeta
Describe pos/neg selection in terms of B cells. What process is it involved with and when are they pos/neg selected?
Affinity maturation Incr. affinity = Pos. selection Decr. affinity = Neg. selection
What type of cells are use Fc receptors and complement receptors to display Ag-Ab complexes to B cells during affinity maturation?
Follicular dendritic cells
What are the two types of Hyper-IgM syndrome? What is their cellular basis?
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
How do they arise? Where do long-lived plasma cells migrate to?
Germinal center reaction, BM
Describe the primary and secondary response.
Look at chart
What effect does Ig concentration have on Ig half life?
Increased Ig concentration, Decreased Ig half life
Cross linking of the BCR and what co-receptor turns off the B cell? How does it turn it off?
FcgammaRII, recruits phosphatases which limit the activation of B cells
What are the two types of Ab responses?
T-dependent: protein Ag, CD4 T cells activate and stimulate B cells through CD40 and cytokines T-independent: non-protein Ag, No CD4 help
Name the three types of B cells and their corresponding Ab response (Ab and plasma cell).
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
What are some features of T-independent Ag’s? Features of the response?
Ag: polysaccharides, repeating identical determinants, some TI Ag’s bind additional receptors Response: Less Ig class switch (IgM, IgG2), little somatic hypermutation, little memory
Differentiate the response to the two Haemophilus influenzae vaccines: HiB PS vaccine and HiB-DT vaccine.
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
What B cell is responsible for producing most of the IgM in the serum?
B-1 B cells, protects from bacterial invasion from the gut
What are isohemagglutinins?
The antigens associated with different blood types.
