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B CELL

B CELL. Public Health MSc 6th week , 2014. DEFINITIONS. Antigen (Ag) - any substance, which is recognized by the mature immune system of a given organism antigenicity - specific reactivity with cells or molecules of the immune system ( weak antigen vs. strong antigen )

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B CELL

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  1. B CELL Public Health MSc 6th week, 2014

  2. DEFINITIONS • Antigen (Ag) - any substance, which is recognized by the mature immune system of a given organism • antigenicity - specific reactivity with cells or molecules of the immune system (weakantigen vs. strongantigen) • immunogenicity - capability to elicit an immune response • tolerogenicity - capability to induce immunological tolerance

  3. ANTIGENIC DETERMINANT (=EPITOPE) part of the antigen that directly interacts with the antigen-specific receptors of lymphocytes (TCRorBCR/antibody)

  4. B cell epitope(recognized by B cells) T cell epitope(recognized by T cells) proteins polysaccharides lipids DNA steroids etc. (even artificial molecules) cell or matrix associated or soluble proteins mainly(8-23 amino acids) requires processing and presentation by APCs

  5. Severalepitops of onemicrobescan be recognizedbydifferent B cells

  6. ADAPTIVE IMMUNE SYSTEM Diversity of receptor strucure How can the antigen receptors of lymphocytes recognize extremly diverse antigens approx.10 – 1000 million(107 - 9) differentantigen receptors, uniquespecificity of B cells approx. 10 – 1000 million(107 - 9) differentantigen receptors, uniquespecificity of T cells

  7. Random hands, millions of variations

  8. Random selection of genesegmentsensuresmillionsofdifferentreceptors(variabledomains) Happensduringthematuration of B cellsintheredbonemarrow

  9. VARIABILITY OF B-CELL ANTIGEN RECEPTORS AND ANTIBODIES VH JH D V-Domains C-Domains VL JL VH-D-JH VL-JL B cells of one individual 1 2 3 4

  10. Estimates of combinatorial diversity Taking account of functional V D and J genes: 65 VH x 27 DH x 6JH = 10,530 combinations 40 Vk x 5 Jk = 200combinations 30 Vl x 4 Jl = 120 combinations = 320 different light chains If H and L chains pair randomly as H2L2 i.e. 10,530x 320 = 3,369,600 possibilities Due only to COMBINATORIAL diversity In practice, some H + L combinations do not occur as they are unstable Certain V and J genes are also used more frequently than others. There are other mechanisms that add diversity at the junctions between genes - JUNCTIONAL diversity GENERATES A POTENTIAL B-CELL REPERTOIRE

  11. Severalantibodiesareexpressedon B cells(arround 100.000) butall of themhas thesamespecificity

  12. Forms of immunoglobulins: • membrane-bound (expressedasBCRonthesurface of B cells) • soluble (secretedbyplasmacells [antibody]) • Membrane bound and soluble Igsrecognize the same antigenwhenoriginatedfromthesame B cell Differentiation Secreted antibodies Plazma cell

  13. B – CELL ACTIVATION Where and how do all these things take place?

  14. SECONDARY LYMPHOID ORGANS/TISSUES Sites of lymphocyteactivation and terminaldifferentiation • LYMPH NODES • SPLEEN • TONSILS (Waldeyer’s ring) • Diffuse lymphoid layers under the epithelial barriers: • SALT (skin-associated lymphoid tissue) • MALT (mucosa-associated lymphoid tissue) • BALT (bronchus-associated lymphoid tissue) • GALT (gut-associated lymphoid tissue)

  15. B cells in blood T cell area B cell area Efferent lymph B-cell recycling in the absence of antigen (lymph node)

  16. B cells proliferate rapidly B cells leave blood & enter lymph node via high endothelial venules Antigen enters node in afferent lymphatic Y Y Y Y Y Y Y Y Y Y Y Y Y Y Germinal centre releases B cells that differentiate into plasma cells Y Y Y Y GERMINAL CENTRE Transient structure of Intense proliferation Recirculating B cells are trapped by foreign antigens in lymphoid organs

  17. when B cells recognize their antigens originated from the afferent lymphatics, they start to migrate to the boarder of the B cell zone for the help of helper T cells

  18. After helper T cells become activated by APCs (mostly DCs) in the T cell zone, and they differentiate into effector cells, they start to migrate to the boarder of the T cell zone to help the activation of B cells

  19. T-DEPENDENT ACTIVATION OF B CELLS MHC-II + peptide T CELL B CELL onlyworksinthepresence of pathogenicproteins! cytokines

  20. T-INDEPENDENT ACTIVATION OF B CELLS aggregation of multiple BCRs  cross-phosphorylation  signaling

  21. GC reaction: • proliferation (clonal expansion) of activated B cells • affinity maturation (stronger binding to epitopes) • isotype switch (different effector functions) • memory B cell formation (from improved clones) • Only by the help of Th cells!

  22. AFFINITY MATURATION

  23. B cells compete for the antigen High affinity B cells can grab the antigen and get survival signals while low affinity cells will lack those and undergo apoptosis  selection of high affinity clones

  24. Antigen recognition by specific BCR induces clonal expansion and differentiation of the sepcific B cells. Circulation Restricted lifespan (few days) Apoptosis Activation Clonal expansion Differencaition Plasma cells Antibody production Memory B cells Specific B cells Non-specific B cells

  25. Antigen recognition by specific BCR induces clonal expansion and differentiation of the sepcific B cells. Activation of specific B cells 1. Clonalexpansion MEMORY B CELLS Plasma cells, antibody production 2.Differentiation

  26. Antigen recognition by specific BCR induces clonal expansion of the sepcific B cells. Ag Activation Clonalexpansion B cell Antigen receptor, BCR Clonalantigenreceptors areexpressedexclusivelyonT- and Blymphfocyties.

  27. Ag Ag POLYCLONAL RESPONSE B cellrepertoire Specific, activated B cells Plasma cells Antigen specific antibodies

  28. EFFECTOR FUNCTIONS OF ANTIBODIES Antibody-mediated immune responses • NEUTRALIZATION • OPSONIZATION • opsonizedphagocytosis (IgG) • ADCC (NK cell-mediatedkilling) (IgG) • mast cell degranulation (IgE) • COMPLEMENT ACTIVATION

  29. Antigen recognition by specific BCR induces clonal expansion and differentiation of the sepcific B cells. Activation 1. Clonalexpansion MEMORY B cells Plasma cells 2.Differentiation

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