Cumulative Learning Objectives

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Somatic recombination occurs in what cells?
B and T cells
Junctional diversity occurs in what cells?
B and T cells
Somatic hypermutation occurs in what cells?
B cells
Isotype switching occurs in what cells?
B cells
Affinity maturation occurs in what cells?
B cells
What does somatic recombination accomplish?
-Creates combinatorial diversity
-Uses RAG-1/RAG-2 for recombination in BCR and TCR
What does somatic hypermutation accomplish?
increase points of mutation that are initiated bu the AID enzyme through the heavy and light chain variable regions;
1 point mutation/V region/ Cell devision
Is somatic hypermutation more common in B-1 or B-2 lymphocytes?
High in B-2, low in B-1
How does somatic hypermutation play a role in germinal centers?
Germinal center: where activated B cells undergo somatic hypermutation to become centroblasts
How does somatic hypermutation and isotype switching play a role in centroblasts?
become small non-proliferating centroblasts after being isotype switched and undergoing somatic hypermutation
What cell interaction triggers isotype switching and somatic hypermutation?
Triggered by T cell interaction/ linked recognition
What controls isotype switching?
what are where the pathogen is
Describe the process of isotype switching
-B cell receptor binds
-Gene is turned on
-AID introduces cytokine to uracil
-the base from uracil nucleotide is removed by UNG
-APE1 leaves a hole where there is missing DNA
-Looping occurs and DNA strand recombination is promote
-rearranged V region is matched with a new C region
What is the IL that is an isotype switch factor?
IL-5 from Th2
What are that cognate pairs?
B cell and Tfh form a cognate pair and trigger isotype switching and somatic hypermutation
Explain the relevance of isotype switching in somatic hypermutation in T-dependant and T-independant B cell interactions
Isotype: occurs
Hypermutation: occurs

Isotype: minimum, mostly IgM
Hypermutation: NONE

What are the 4 cytokines that cause plasma cells located in the cut to isotype switch to IgA production
TGF-beta –> BAFF, IL-10 –> IL-10, APRIL
What is negative selection?
What is positive selection?
Neg: removal of lymphocytes that recognizes self-antigen, makes sure T cell doesn’t attack self-antigen

Pos: guarantees that a T cell is capable of binding/ recognizing an MHC class

What is receptor editing?
What chain does it occur in?
What does it prevent?
Editing the light chain is edited; self-reactive B cells in bone marrow edit their antigen binding site; prevents negative selection
Do the following cells go through positive or negative selection?
-B cells
-Alpha-Beta T cells
-Gamma-Delta T cells
-B cells: negative

-Alpha-Beta T cells: both

-Gamma-Delta T cells: neither

Does negative or positive selection occur first?
What cells mediate negative selection of T cells?
What about positive ?
Neg: cortical epithelial cells
Pos: DC, macrophages, thymocytes
What is central tolerance?
deletion of self reactive T lymphocytes in the thymus through negative selection
What is the two-signal hypothesis?
states that a T cell must receive a minimum of two signals to respond to an antigen
What are the two signals that T cells must receive according to the two-signal hypothesis?
1) primary through MHC
2) Co-stimulatory signal through molecules on APC; need B7 for APCs to express co-stimulatory molecule)
What would happen if the two-signal hypothesis was not satisfied?
The T cell is not activated
What is linked recognition?
T cell interaction; T and B cells specific for different epitopes of the same antigen can cooperate
What cells participate in linked recognition?
T cells and B cells
How is linked recognition responsible for epitope spreading?
the sloppiness of T cell’s held to B cells
What are the cytokines required for a naive (CD4+) T cell to activate?
What cytokines are released by Th1?
IL-2, IFN-gamma, GM-CSF
What cytokines are released by Th2?
IL-4, IL-5, and IL-13
What cytokines create the Th1 subset?
IL-12 and IFN-gamma
What cytokines create the Th2 subset?
What cytokines create the Th17 subset?
IL-6 and IL-21
What cytokines create the Treg subset?
What cytokines create the Tfh subset?
IL-16, TGF-beta, IL-23
What cytokines are released by Treg?
TGF-beta and IL-10
What cytokines are released by Th17?
IL-6 and IL-17
What cytokines are released by Tfh?
What cells function as professional APCs?
dentritic, macrophages, and B cells
What cells function as phagocytes?
neutrophils and macrophages
(aslo basophils and eosinophils)
What are the common CD markers for T cells?
CD3, CD4, CD8
What are the common CD markers for B cells?
CD19, CD21, CD84
What are the common CD markers for NK cells?
CD16, CD56
What CD markers are on Cytotoxic T Cells?
CD8, CD3
What CD markers are on Helper T cells?
CD4, CD3
What CD markers are on gamma-delta T cells?
True or False:
NK cells lack CD3
True (only have Cd16 and CD56)
What is innate Immunity?
-rapid response
-limited specificities
-constant during a response
-no memory
What is adaptive immunity?
-slow response
-numerous specificities
-improves during a response
-memory formed
What cells are active in innate immunity?
alpha-2-macroglobulins, pentraxins, defensins
What cells are active in adaptive immunity?
B cells and T cells
What are the advantages of adaptive immunity?
improves over time, can remember how to fight reoccurring pathogens
What is the role of TLR in innate immune responses
activate inflammatory cytokine production, recognize an array of microbial components, activates cytokine gene expression in infected cell
What are features of B-1 B lymphocytes?
-produced in a fetus
-self renewing
-high levels of spontaneous Ig production
-secretes more IgM
-no somatic hypermutation
-Responds to carb antigens
What are features of B-2 B lymphocytes?
-Produced after birth
-Produced in bone marrow throughout lifetime
-Low levels of spontaneous Ig production
-Secretes more IgG
-High levels of somatic hypermutation
-Responds to protein antigens
What two CD markers can identify a B-1 cell from B and T cells?
CD5 and CD19/CD20
What are features of T-dependant B lymphocyte antibody responses?
-B cell reaction antigens require T cell help for proper response
-isotype switching occurs
-somatic hypermutation occurs
-affinity maturation occurs
What are features of T-independant B lymphocyte antibody responses?
-No T cells
-Low affinity
-Minimal isotype switching
-No somatic hypermutation
-No memory
What are characteristics of alpha-beta T cells?
-express both CD4 and CD8
-recognize peptide antigens
-presented by MHC I and II
-TCR diversity
-Abundant in blood
-Adaptive immunity
What are characteristics of gamma-delta T cells?
-express CD3 only
-recognize non-peptide antigens
-presented by MHC I
-Plentiful in tissues
-Function in tissue homeostasis, protection, and repair
What are the signaling molecules for BCR and TCR?
BCR: Ig-alpha and Ig-beta
TCR: CD3, CD4, and CD8
What is the structure of BCR and TCR?
BCR: two heavy chains, two light chains
TCR: single alpha and single beta chain
What proteins compose a complete BCR?
Vh, Vl, Ch, Cl
(variable light and heavy, constant light and heavy)
Ig-alpha and Ig-beta
What cell receptor variable domains contain junctional diversity?
both BCR and TCR
What are the 5 main antibody isotypes?
What antibody isotype has the highest concentration in mucus?
Which antibody isotype is transported across blood vessel endothelial cells and delivered to tissues?
Which antibody isotype appears as a dimer?

The J-Chain

What antibodies are expressed on the surface of naive B lymphocytes?
IgM and IgD
What antibody is transported through breast milk?
Which antibody is transported through the placenta from mother to baby?
What antibody must be a pentamer to be affective and why?
IgM b/c of low affinity
What antibody is the largest/ has the highest molecular weight?
What antibody is the most abundant in serum and body fluids?
What three antibodies together that compose 99% of all blood/body fluids?
IgG, IgM, IgA
What two antibodies can bind/fix complement?
IgG, IgM
What antibody is primarily found in the respiratory tract?
What antibody is best at neutralization?
IgG and IgA
What antibody is best at opsonization?
What antibody is best at sensitizing for NK killing?
What antibody is best at sensitizing mast cells?
What antibody is best at activating complement?
IgG and IgM
What FcR does IgG bind to?
what FcR does IgE bind to?
What FcR does IgA bind to?
What initiates the activation of the alternative pathway?
triggered by spontaneous hydrolysis of C3
What initiates the activation of the lectin pathway?
triggered by mannose-binding lectin being bound to pathogen surface
What initiates the activation of the classical pathway?
C-reactive protein or antibody binds to antigen on pathogen’s surface
What are components of the membrane attack complexes (MAC) of complement?
When do the three complement pathways converge?
when C3b is present
What type of bond does complement form? What about antibody?
Complement is covalent
Antibody is non-covalent
What are the two primary lymphoid cites?
Bone Marrow (B cells)
Thymus (T Cells)
What are the secondary lymphoid tissues?
lymph nodes, Peyer’s patch, spleen, adenoids, tonsils
What occurs in primary lymph tissues?
cells of the adaptive immune system are made
What occurs in secondary lymph tissues?
B and T cells become activated by an antigen
A lymph follicle containing a germinal center is called a:
secondary lymphoid follicle

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