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Immuno Lec 5

Pro B Cell H Chain Rearrangement. DJ. mew surrogate light chain.
Pre B Cell Pre-BCR. L-Chain Rearrangement, V and J come together. functional light chain is now available, move to surface.
Immature B cell You have IgM on surface. First Antibody. Negative Selection(central tolerance) then B cells move into periphery.
Naive Mature B cell Moves into periphery. IgD is translated. no foreign antigens.
Plasma Cell Activated by specific antigen. Always generates memory cells when becoming activated.
Pre B Cell Receptor heavy chain and surrogate light chain
B cell maturation requirements Recombinases RAG1 and RAG2 TDT Bruton's Tyrosine Kinase Iga and Igb Transcription Factors
Recombinases RAG1 and RAG2. endonuclease, cleaves signal sequences in DNA, initiate recombination events.
TDT Terminal Deoxytransferase. Adds NTs once recombinases open up. Allows you to cause frameshift mutations and increase diversity.
Bruton's tyrosine Kinase Mediates signal transduction during B cell development. lets cell know heavy chain is on surface.
Iga and Igb Associated with heavy chain. Signal transduction.
Lymph node superficial cortex - B cells. 1* = resting. 2* = prliferating. germinal center. deep cortex - T cells.
splenectomy main concern: infection with encapsulated bacteria
Spleen no afferent lymphatics. Red pulp and white pulp.
Red pulp macrophages. Phagocytosis. Ab mediated opsoninzation.
White pulp Lymphatic tissue around arterioles. PALS - T nodules - B
Antigen entry through skin goes through lymph to lymph nodes
Antigen entry through GI, Uro, Resp. through lymph and to MALT
Antigen entry through blood through blood to spleen
B cell activation 2 Signals. B cell = APC. 1st signal = Ag binds BCR. 2nd signal = B cell processes Ag, presents with MHCII, TH2 recognizes, engages with MHCII. CD40L engages with CD40 on surface, Th2 also secretes IL-4. Linked recognition
Linked recognition B cells are activated by T cells that recognize the same antigen(any epitope)
Peripheral Tolerance tolerance to those antigens not encountered in the 1* lymphoid organs
Anergic cell cant express Ig on surface does not receive 2nd signal.
Antigen Any substance that binds with antibody
Immunogen Any substance that binds with antibody and elicits an Immune response
Hapten small molecule that can bind with antibody, no immune response. Too small to associate with MHC. Binds, taken in, does not associate. B cell cant receive help, becomes anergic. you have to conjugate with carrier to make it immunogenic.
Hapten carrier conjugate Conjugate a hapten to a peptide. you create an immunogen. allows the whole complex to be processed and some of the hapten to be conjugated to peptides will be presented on MHCII.
Factors favoring immunogenicity <5000D, complex molecule, different than self protein, strong interaction with MHC, and delivery with adjuvants
Adjuvants Substance that increases immunogenicity of substance mixed with it. They work in two ways. 1) prolong life of immunogen in body 2) non specifically stimulate immune response bc they are bacterial components.
T cell dependent antigen require T cell help
T cell independent antigen Dont require help to activate B cell. usually multivalent with repeating epitopes. Crosslink on B cell surface receptor, stimulates B cell. Early in response to bacteria. Only for IgM. You can't class switch (no t cell) so its only IgM.
Upon activation of a B cell it migrates to B cell areas and forms germinal centers
What occurs in germinal centers? Proliferation, Differentiation, class switching, somatic hypermutation.
Proliferation in Germinal Centers. Naive B cell gets second signal. THen proliferation occurs.
Differentiation in Germinal Centers. Newly activated B cells become plasma cells. First Ab produced is IgM, but also IgD, but you won't see IgD because it is turned over almost immediately.
class Switching in Germinal Centers. B cell expresses IgM, class switches, now secretes IgG(or anything). Same specificity, but now the molecule associates with different H Chain. can be direct or sequential.
C Gene organization(class switching) in Germinal Centers Only B cells. DNA loss occurs. Can't go backwards. site specific DNA recombination. You loop out middle signals. M and D are attached.
Il-4 in Class switching IgG and IgE
Il-5 in class switching IgA
Somatic hypermutation in Germinal Centers. Point mutations in VDJ region of Heavy Chain. Dark zone of FDC with centroblasts. active cell division here. Some will have higher and some will have lower affinity.
Affinity Maturation in Germinal Centers. Carried out by cells in FDC. they hold onto antigen for months-years. Screen new B cells as they leave germinal center. If high affinity, will stimulate to divide. If not, won't stimulate and will die. light zone. centrocytes.
Somatic Hypermutation occurs in the variable region of heavy and light chain.
Created by: nady