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36 Cards in this Set
- Front
- Back
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fate of Ag and organ distribuion depends largely on
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the route of entry and
nature of material |
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usually bulk of Ag introduced into an individual is
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degraded and eliminated as aa's and/or small peptides
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foreign substances either may enter body
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naturally or may be introduced artificially
most frequently, gain entrance through the respiratory or GI tract although they may enter naturally through other body surfaces, including he mucous membranes and skin, or by transplacental passage |
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artificial intro of foreignness occurs by
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injection
inhalers oral/GI surgical intervention ( transplanation ) |
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Ag poral of entry and innitial lymphoid tissues involved
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IV: spleen
respiratory: MMALT GI: GALT skin or muscle: lymph nodes |
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Ag transport to secondary lymphoid tissue
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free Ag internalized by resident APC's (blood and/or lymph node)
transported by APCs: mac or dendritic cells langerhan's cell specialized dendritic cell resides in skin major unction Ag processing/presentation and Ag ransport to secondary lymphoid tissues |
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function of Ag transport to secondary lymphoid tissue
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filter and concentrate Ag
activate specific and B cells and expand cell populations generate Ab generate memory seed other lymphoid tissue |
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schematic structure of lymph node
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collagenous capsule
subcapsular sinus- lined by endothelial and phagocytic cells cortex with primary follicle and germinal center of secondary follicle paracortex with medullary cords that extend into medulla capsule extends via trabeculae bw cortex medulla hilus with efferent lymphatic and artery and vein going into high endothelial venule afferent lymphatic goes into collagenous capsule high endothelial venule b/c cortex and paracortex |
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T cell rich area in lymph node
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paracortex/medullary cords
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where are DC's found in lymph node
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paracortex/medullary cords
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b cell rich area n lymph node
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cortex
makes primary and secondary follicles (GC) |
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organization of lymphoid tissue in spleen
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capsule
has trabecular A and V in trabeculae venous sinuses in red pulp white pulp composed of periarteriolar lymphoid shealths: PALS, frequently containing lymphoid follicles - surrounded by marinal zone which contains numerous macs, APC's, slowly recirculating B cell and NK cells t cell rich area in GC of secondary follicle B cell rich area in marinal zone dendritic cells in PAL's |
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organization of M cell in intestinal FAE
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lymphocytes and occasional macs in intracellular pocket
endocytosed Ags are passed via this pocket into subepithelial tissues M cell b/w enterocytes M cell has B and T lymphocytes T cell rich area in middle and B cell outer |
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dendritic cells interact with
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T helper cells
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Langerhan's cells
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APC
reside in dermis and presents Ag transport Ag to lymphoid tissue and present Ag go to paracortex: cell rich and communicate with T cells (present Ag) through class II class II presents peptide must have T cell R, which fits into class II peptide goes from skin to afferent lymphatic vessel to lymph nodes, spleen and MALT |
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MHC
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structures found on surface of all cells and express peptides contained within their binding grooves
means of communication for directing T cell activity by binding their T cell R - either CD4 + T helper cells or CD8+ cytotoxic cells |
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MHC class I with peptide activates
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T cytotoxic cells though class I R
foreign promotes killing normal maintains no activation |
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MHC class II with peptide activates
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T helper cells through their T cell R
- Th1 and Th2 promotes "helperc cytokines" |
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Class I normal and foreign peptides
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peptides generated within cell
added to class I molecules as they are synthesized I and peptide transported directly to cell surface become potential target for T cytotoxic cells |
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presentation of intracellular antigenic peptides by MHC
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class I molecules
result of series of Rxns 1. Ag's degraded by proteasome 2. resuting peptides translocated via transported associated with Ag presentation (TAP) into ER lmen and loaded onto class I molecules 3. peptides-MHC class I complexes are released from ER and transported via olgi to PM for Ag presentation to CD8+ T cells |
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native MHC class ii molecules
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found on APC's
expressed on cell surface synthesized in ER transported and stored in cytoplasmic vesicle (anchored in PM) invariant chain "cap" on peptide binding region |
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Ag peptides binding and II expression
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external Ag engulfed:endosome
protein - peptides vesicle endosome fusion II and peptides expressed on cell surface: ligand for CD4 T helpercells |
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Class II alpha and beta chains assemble in ER and form complex with
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invariant chain: li
the li-MHC class II heterotrimer is transported through the golgi to the class II compartment, either directly and/or via PMM endocytosed proteins and li are degraded by resident proteases in MIIC class II assoiated li peptide: CLIP, fragment of li remains in peptide binding grooves of II dimer and is exchanged for an antigenic peptide with the help of dedicated chaperone HLA-DM class II molecules are then transported to PM to present antigenic peptides to CD4+ T cells |
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T cell activation by
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sees Ag with two epitopes
DC in T dependent areas produce IL1: T cell activator increase T cel R and produce co stimulatory R with CD28 and B7 talk (2nd signal)= activated Toll R's on APC; Ag internalized ; processed peptides; MHC II upregulate IL-2 R; increases affinity and produced more t cell sellected via T cell Rs activated T cells express CD 28 ; match II peptide and CD-28/B7 T cell releases, produces IL2 and increases its IL2 R and affinity this can produce a swollen node produces CTLA4; increases affinity for B7 stop proliferating signal |
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B cells activated by
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free Ag; makes Ab and becomes APC: DC, macs and B cells
surface Ig cross link Ag (epitope) patch and cap Sig & Ag internalizes complex into vesicle processes into peptides; fuses with II vesicle & expressed on cell surface expresses CD40, a 2nd signal T helper cells now B cell needs T cell help and proliferate and make lots of Abs T cell makes cyokines, IL4: B cell proliferation; make other cytokine R for switching some go to plasma cells and make IgM; some cytokines make them switch to IgG memory cells made too |
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Ab production
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clonal selection of B cell populations in response to Ag is by surface Ig R and epitope recognition
Ab producing plasma cell produces and secretes AB with ONE specificity |
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primary and secondary T dependent Ag responses
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clonal expansion of activated B cells and Ig isotype production
cytokines released by T helper cells induce isotype switching activation. cell signaling : CD40-CD40L expansion: b cell growth factors maturation: Ig class (isotype) switch change isotype, NOT IDIOTYPE infuenced by cytokines "loop" out DNA (excise) memory cells if encounter IL-4: makes IgG1 and IgE if encounter TGF-B: IgG2b, AgA if encounter IFN-gamma: IgG2a and IgG3 |
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Ig (isotype) class switching
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human Ig heavy chain gene locus: IGH
initially, B cells transcribe a VDJ gene and mu heavy chain that is spliced to produce mRNA for IgM under influence of T cells and cytokines, class switching may occurr each heavy chain gene except CD (which encodes IgD) is preceded by a switch region when switching occurs, recombination b/w these regions takes place, with loss of intervening C genes plasma cell does not class switch! just selected B cells |
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Ab production in T dependent responses
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lag phase (before you can mesure Ab in serum)
IgM (3/4 days) to IgG switch (about 7 days; peaks a 14 and hangs till 20 days) - IgG has longer half life than M idiotypic speciicity - never changes; only ISOTYPE switch |
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Ab affinity with Ag boost
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rapid increased EgG production
increased Ab affinity select high affinity sig-expressing B cells create high affinity memory cells - affinity determined by 5 hypervariable regions that can bind epitope |
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with Ag boost, affinity of IgM response
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is constant
affinity maturation of IgG response depends on dose of secondary Ag - low Ag does produce higher affinity clones compete effectively for limiting amount of Ag |
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immunological memory
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follicular DC's
- B cells with immune complexes (how handled by DC and create memory) - Ag presentation - follicular T cells (CD4+ Thf) |
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primary and secondary immune response to T independent Ag characteristics
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poor Ab production
low affinity and short lived |
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Ag types in immune repsonse to T independent Ag
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polymeric Ag's: polysaccharides and lipids
B cell activation - cross link multiple sIg's - not processed into II efficiently - no MHC II communication with Th-2 cells |
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quality and quantity of Ab in T independent immune response
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IgM
no class switching no t cell helper cytokines |
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immunological memory in T independent immune response
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little to none
no t cell activation by APCs: poor II binding no B cell proliferation or memory cell development secondary response same as primary |
