LMP299Y1 Lecture Notes - Alpha Beta Gamma, Interferon Gamma, Tumor Necrosis Factor Alpha

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3 Jun 2013
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LMP403 January 9, 2013
Two major effective arms of immune system = T cells, B cells
Thymus made up of seven pairs of thymic lobes in avian, where T cells would mature and differentiate
In mammalian system, in pair of lobes in thymus
For B cells, in avians bursa fabricious but no equivalent invagination in intestines in mammalian cells
bone marrow
Side chain theory
Antigen sensitive cells have cell surface side chains (now called receptors)
When stimulated, produces more similar chains
Error: B cells express receptors of ONE specificity other antigens cannot stimulate the cell to produce
more antibodies
B-cell Ig receptor green antigen interacting with B cell
Cell cell interactions hen cells collide, through receptors, recognize the type of cells interacting with
Surface associated immunoglobulins
Carboxyl terminal anchoring the Ig molecule on the cell surface
In circulating Ig, there are intrachain disulfide bonds linking the two heavy chains, so they do not come
apart but in cell-surface Ig receptor, they are already anchored, so do not need intrachain disulfide
bonds
T cell system
T cell receptor Tak Mak, Davis
Major histocompatibility complex
MHC governs recognition of T cells in interacting with other cells
MHC made up of two classes of molecules class one molecule has three loci ABC, class two three loci
DP DQ DR. Under each locus, there are many alleles each locus is multiple-alleic so people in room
likely have different combination of alleles
Under each locus, hundreds of alleles
Perfect match is statistically impossible unless identical twins
Histocompatibility complex so called because when this genetic site determined, it was thought that the
products were associated with graft rejection
MHC governs immune recognition ***
MHC in all mammalian species called Human lymphocyte antigen in humans
Class I ABC antigen made up of a single alpha chain with three extracellular domains; alpha chain
cannot be expressed unless in non-covalent association with beta two microglubulin
Each antigen made up of about fifty-seven thousand molecular sites class 1 antigens expressed on all
nucleated cells recognized by suppressor T cells that bear CD8
Class 2 two chains does not need beta two macroglobulin; restricted to B cells and macrophages, not
universal; recognized by helper T cells bearing CD4 antigen
MHC
- Structure alpha one and alpha two chains folded in alpha helices come together to form a
receptor that will interact with antigen
- More variable where hypervariable regions are
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- N intermal of alpha one and two are less variable and the beta two microglubin and alpha three
form the support for the two outermore domains for antigen recognition
T cell system
T cell receptor system is made up of seven chains CD3 form a pedestal for holding the alpha and beta
chains into proper confirguration and conformation for antigen recognition gamma, delta, epsilon in
association with zeta dimer to allow T cell receptor to be phosphorylated
Made up of at least seven chains but this is not sufficient for T cell receptor to recognize an antigen
Antigen recognition requires CD4 and CD8 ?? DOUBLE CHECK THIS
B cells can freely associate with antigen, but T cells cannot see antigen unless it is presented in MHC
So antigen must be associated with MHC only way T cell receptor will recognize antigen
The recognition of antigen would essentially create a signal for the T cell to be ready to be triggered
CD4/8 recognizes non variant portion of _____ - they are not variable, so can only recognize specific
structure on MHC
CD4 or 8 is associated with an intracytoplasmic tyrosine protein kinase when T cell receptor recognizes
antigen in context of MHC CD4 or 8 recognize MHC as well under this combined recognition, triggers
or activates p56 tyrosine kinase to phosphorylate zeta chains once phosphorylated, zeta chains send
signals to T cell
CD4 =/= CD8
CD8 is dimer; CD4 is dimer, three imunobulugin domains, and a less im unoglubulin like domain
(triangle)
-
After destroying tumour cell, can engage another target
Two other cytotoxic cell types = NK cells have NK receptor; killer cells recognition depends on antibody
sitting on Fc receptor of K cells
Antimicrobial immune mechanisms
- Complement is innate but can be adaptive (if activated by classical pathway, involving antibody
binding antigen)
- Macrophages phagocytosis is also innate
- Inflammation when complement system is activated, triggers release of ___, release of
histamine, ergo inflammatory response
Adaptive response ex. Immune complex promotes an innate response in complement activation to
really manage the microbial infection
How the immune system deals with extracellular bacteria through adaptive immune response
extracellular bacteria are circulating bacteria that are not hiding in cells, fully exposed and therefore the
most effective mechanism is antibody neutralization
C3b or C3b equivalent complement activation
Inflammation products associated with complement activation that trigger inflammation C3a, c4a,
c5a are hemotactic, are cleavage products from complement that draw neutrophils, monocytes to site
of infection promote extravascularization of circulating cells anaphilatoxin, so also trigger mast cells
release histamine
Third biological effect of complement is bacterial lysis membrane attack complex made up of C5 and
C9 constitute a transmembrane channel allowing water soluble substance to enter cell to burst the cell
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