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71 Cards in this Set
- Front
- Back
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Overview of properties of innate immune system |
static broad range no enhancement no memory receptors selected over evolution recognizes broad groups of related microbes and other threats |
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Overview of properties of the adaptive immune system |
dynamic individualized fine tuned learns memory receptors selected in individual animal during maturation recognizes specific single molecules |
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A productive immune response relies on |
identification and expansion of clones that express antigen receptors that can bind specific relevant antigens
Also relies on existing diversity |
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each individual clone expresses |
one specific antigen receptor |
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as a population lymphocytes express |
>5 x 10^7 different antigen receptors |
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adaptive immune system must be capable of |
distinguishing among millions of antigens/epitopes |
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Innate mechanisms for extracellular threats |
complement activation phagocytosis by phagocytes extracellular killing |
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innate effectors for intracellular threats |
NK cell cytotoxicity |
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Adaptive effectors for extracellular threats |
B cells Helper T-cells Antibodies (humoral) |
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Adaptive effectors for intracellular threats |
Cytotoxic T cells Helper T cells Macrophages |
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function of B lymphocytes |
Neutralization of microbes phagocytosis complement activation |
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antigen recognition of CD4 (Th lymphocyte) |
MHC2 microbial antigen presented by antigen presenting cell |
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effector functions for CD4 cells |
Activation of macrophages inflammation activation (proliferation and differentiation) of T and B lymphocytes |
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Antigen recognition for CD8 cytotoxic T lymphocytes |
MHC1 infected cell expressing microbial antigen |
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effector functions of CD8 cells |
killing infected cells |
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antigen |
any molecule that can be recognized by the acquired immune system
Can be bound to an antibody or T cell receptor |
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which molecule group mostly makes up antigens |
proteins (lots of different AA means lots of possible variation) |
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Properties of antigens |
organic complex large degradable by proteases contain epitopes - only small part is antigenic |
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why is it important that antigens are degradable |
proteases break the proteins into smaller peptides Need peptides to react with MHC |
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exogenous vs endogenous antigens |
not all foreign things are antigenic some endogenous things may be antigenic (autoimmune) |
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immunogens |
the same thing as an antigen |
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hapten |
very small piece of protein that is too small to be an antigen on its own |
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epitope |
antigenic determinant part of antigen that is recognized by an antibody |
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two types of epitopes |
continuous (linear) - all parts are together on the antigen Discontinuous (conformational) - parts of epitope are split up around the antigen |
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number of epitopes on an antigen |
multiple |
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type of epitope MHC recognizes |
continuous only |
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type of epitopes T-cells have |
linear only |
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type of epitopes B cells have |
linear and conformational |
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MHC = |
major histocompatability complex |
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Other names for MHC |
lymphocyte antigens HLA = human lymphocyte antigen BLA = bovine lymphocyte antigen |
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where is MHC important |
transplantation medicine (rejection) general disease susceptibility factor |
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MHC definition |
polymorphic heterodimeric membrane proteins that display both self and non-self antigens for recognition by lymphocytes |
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purpose of MHC |
cell surface markers present on surface of all cells
essential component of humoral and cell mediated immunity |
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most T-lymphocytes only recognize antigen when |
bound to MHC molecule (MHC restriction) |
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MHC are determined by and are responsible for |
genetically determined
responsible for individual variation of immune function |
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MHC is present in |
all vertebrates (low diversity in chickens) |
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purpose of genetic diversity |
bind and present many antigens at individual level
basically all antigens on population level |
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many gene loci encode for |
MHC |
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hypervariability provides |
protection at a population level |
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Big picture of reason for MHC |
can deal with many different antigens, but not all complexity, redundancy / non-specificity |
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T and B cells mount |
antigen specific response |
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big advantage of MHC |
at a population level new threat some will still survive |
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inbreeding problems |
small array of MHC decreased population resistance more susceptible to new threats |
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Binding properties of MHC |
Peptide binding clefts Bind only polypeptides Low specificity of binding (bind to wide variety of peptides) Stability and surface localization rely on bound peptide Binding interaction is long lived |
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Class 1 MHC |
all nucleated cells present cytoplasmic antigens to cytotoxic T-cells (CD8+) Important for killing of virally infected cells, intracellular, bacteria, and neoplastic cells |
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class 2 MHC |
antigen presenting cells only present phagocytosed antigens to T-helper cells |
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structure of MHC1 |
one alpha and one beta 2 chain narrow antigen binding cleft Only alpha chain is transmembrane |
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structure of MHC2 |
one alpha 1 and one beta 1 chain both chains are transmembrane antigen binding cleft is wide |
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MHC 1 peptides |
8 - 10 peptide residues only four are important which form non-covalent interactions |
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purpose of MHC1 and 2 peptides |
create degenerate specificity and functional redundancy many antigens can be presented |
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MHC2 peptides |
binding cleft is wider so bigger peptides with more variability 2 peptide residues are important (12-24 total) which form non-covalent interactions |
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properties of antigen presenting cells |
express MHC2 present exogenous antigens |
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DCs are responsible for |
presenting antigen in a primary immune response |
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DCs can present |
MHC1 and MHC2 |
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Information about what is going on inside the cell come from |
MHC1 |
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information about what is going on outside the cell comes from |
MHC2 |
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DCs can determine what's going on where |
both intracellular and extracellular |
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MHC1 antigen presentation |
present endogenous antigens to CD8+ and T-lymphocytes sample endogenous antigens in cytoplasm
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MHC 1 binding cleft can accomodate |
polypeptides 8-10 mm in acids |
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all nucleate cells present |
MHC1 restricted antien |
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Crosspresentation |
Process through which DCs play a major role in presenting MHC1 restricted antigen to naive CD8+ T-lymphocytes |
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Proteasome and MHC1 |
quality control in ER and cytosol produces small peptides translocated into ER by transporters (TAP) loaded on MHC1 |
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phagosomes mature into |
phagolysosome |
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endosome pathway |
early recycling endosomes late endosome lysosome (all of above can progress into phagosome maturation) |
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MHC2 antigen presentation |
present exogenous antigens to CD4+ T-lymphocytes (T-helper) Antigens are captured by endocytosis or phagocytosis and processed in endosomes or phagsomes Only performed by antigen presenting cells |
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MHC2 binding site can accommodate |
peptides of 12-24 AA in length |
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antigen presenting cells include |
macrophages dendritic cells T-lymphocytes |
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Mechanism through which DCs can stimulate a primary immune response to intracellular infections |
crosspresentation |
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peptides generated where for MHC2 processing |
in endosome and or phagosome by endosomal or lysosomal proteases |
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peptides generated where for MHC1 |
in cytoplasm by proteosome |
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MHC2 is loaded where |
in specialized endosome/vesicles |
