MDSC 321 Second Midterm Exam
Latest Update
Types of Antigens - Answer - Infection(bad foreign)
- gut flora(good foreign)
- cancer(bad self)
- autoimmunity(good self)
what's recognizes antigens? - Answer - adaptive immune system
- innate only can recongize PAMPS
what are antigens? - Answer - molecule that can interact(specifically) w
immunoglobulin(Ig) receptor of B cells(or T cell receptor complexed w MHC)
- cells see it
immunogen - Answer - molecule that induces specific immune response
- all immunogens are antigens
- not all antigens are immunogens
- in a western blot detected by antibodies, there are only antigens and no immunogens
because no immune response
- a ligand for B cells in vivo would be antigen and immunogen because response can be
initiated
humoral immunogens - Answer - B cells
- proteins>polysaccahrides> lipids/nucleic acid
cells mediated immunogens - Answer - T cells
- proteins, some lipids, some glycolipids
- slow and picky
- need help
- proteins not recognized directly
- processed peptides from protein seen in association w MHC molecules, lipids w an
MHC-like molecule CD1
,what are the 4 properties of an immunogen? - Answer - foreigness
- molecular size
- chemical heterogeneity
- degradability
foreigness - Answer - to be an immunogen, molecule must be seen as non self
- degree of immunogenicity depends on degree of foreigness
- greater the phylogenetic distance btw species typically greater chance of
immunogenicity
- eg. bovine serum albumin injected into chickens/goats
what are exceptions of the foreigness property of an immunogen? - Answer - highly
conserved molecules like collogen or cytochrome c may not be immunogenic even in
distant species
- some self molecules, normally sequestered from immune system, will raise an immune
response(eg. sperm or lens tissue) in animal they come from
molecular size - Answer - correlation btw size and immunogenicity
- best immunogens in the range of 100,000 Da
- small molecules 5-10, 000 Da generally poor immunogens
- need to be large enough to be processed
chemical heterogeneity - Answer - size alone doesn't make good immunogen
- synthetic homopolymers not immunogenic regardless of size
- large co-polymers can be immunogenic and adding aromatic amino acids increases
the chance
- proteins w higher complexity in primary structure and those showing secondary,
tertiary and quaternary structure increase immunogenicity
degradability - Answer - protein degraded to be presented by MHC molecules to
activate T cells
- factors influencing this process affect immunogenicity
- insoluble>soluble bc more likely to be phago. and processed
- large>small (more processing and more epitopes)
- L amino acids>D amino acids(works w processing enzymes
,how can we make an antigen more immunogenic? - Answer adjuvants
adjuvants - Answer - change envir. for better response
- to help
- substance that when injected w Ag, it enhances immunogenicity of Ag
- resulting in higher antibody titer and longer lasting immune response
- not specific to an antigen but can be used w many diff. antigens
adjuvant mechanism step 1 - Answer - stimulate immune response
- freund's complete adjuvant, containing muramyl dipeptides from cell walls of heat
killed myobacteria stimulate macrophage activity
- increase in IL-1 helps activate helper T cells
- synthetic polyribonucleotides and baterial LPS stimulates non specific lymphocyte
proliferation
- some stimulate local chronic inflammation and granuloma formation(freund's
complete)
adjuvant mechanism step 2 - Answer - prolong exposure to Ag
- alum and freund's adjuvant bind and precipitate Ag to keep in system longer and allow
for slow realease of Ag
- increase time of exposure from few days to few weeks
- precipitation increases size of Ag to facilitate phago.
adjuvant mechanism step 3 - Answer - co stimulatory signal
- helper T cells when stimulated by Ag need second co stimululatory signal
- freud's adjuvant, LPS and other factors up regulate co stimulatory signal systems
epitopes - Answer - lymphocytes dont recognize entire antigens
- they recognize small discrete sites on macromolecules called antigenic determinants
or epitopes
- epitopes seen by b cells and t cells differ in many diff ways
- antibodies see diff spots of epitopes
B cell epitopes - Answer - b cells bind Ag directly via cell surface immunoglobulin(Ig)
- Ag can be almost anything like sugars, lipids, proteins, nucleic acids, heavy metals
, - epitope size defined by binding size of Ab
- complex proteins w many overlapping b cells epitopes
- not all epitopes induce a response(Immunodominance)
Epitopes in solution binding to B cells - Answer - for Ag in solution:
- epitopes must be topographically accessible on native molecular
surface(hydrophillic)(but there are exceptions)
- epitopes have to be flexible and mobile for agglutination(often on bends and loop
structure of proteins)
- epitopes can be sequential or non-sequential(conformational)
how is epitope size defined by binding size of Ab? - Answer - complementary binding
btw Ag-Ab limits epitope size
- 6-7 amino acids or sugars fit into deep pocket structures of linear epitope binding sites
- conformational epitopes of globular proteins cover much more space on flatter surface
binding sites of Ab
- conformational epitopes may consist of 15-22 aa
- whatever shape/size fits into pocket of Ab is what it sees
linear vs. conformational epitopes - Answer - linear is sequential
- conformational is non-sequential
- conformational has distinct pieces of protien
- linear is one singular piece of protein
- if chopped up and digested, linear epitopes still work but conformational don't because
they depend on their 3 dimentional structure for functionality as linear dont
different structures of enzymes - Answer - primary structure: amino acid residues
- secondary: alpha helix
- tertiary: polypeptide chain
- quaternary: assembled subunits
T cell epitopes - Answer - recognize only protein(and some glycolipid) epitopes
- dont recognize soluble native Ag
- recognize only processed Ag whose peptide fragments are presented in association w
Latest Update
Types of Antigens - Answer - Infection(bad foreign)
- gut flora(good foreign)
- cancer(bad self)
- autoimmunity(good self)
what's recognizes antigens? - Answer - adaptive immune system
- innate only can recongize PAMPS
what are antigens? - Answer - molecule that can interact(specifically) w
immunoglobulin(Ig) receptor of B cells(or T cell receptor complexed w MHC)
- cells see it
immunogen - Answer - molecule that induces specific immune response
- all immunogens are antigens
- not all antigens are immunogens
- in a western blot detected by antibodies, there are only antigens and no immunogens
because no immune response
- a ligand for B cells in vivo would be antigen and immunogen because response can be
initiated
humoral immunogens - Answer - B cells
- proteins>polysaccahrides> lipids/nucleic acid
cells mediated immunogens - Answer - T cells
- proteins, some lipids, some glycolipids
- slow and picky
- need help
- proteins not recognized directly
- processed peptides from protein seen in association w MHC molecules, lipids w an
MHC-like molecule CD1
,what are the 4 properties of an immunogen? - Answer - foreigness
- molecular size
- chemical heterogeneity
- degradability
foreigness - Answer - to be an immunogen, molecule must be seen as non self
- degree of immunogenicity depends on degree of foreigness
- greater the phylogenetic distance btw species typically greater chance of
immunogenicity
- eg. bovine serum albumin injected into chickens/goats
what are exceptions of the foreigness property of an immunogen? - Answer - highly
conserved molecules like collogen or cytochrome c may not be immunogenic even in
distant species
- some self molecules, normally sequestered from immune system, will raise an immune
response(eg. sperm or lens tissue) in animal they come from
molecular size - Answer - correlation btw size and immunogenicity
- best immunogens in the range of 100,000 Da
- small molecules 5-10, 000 Da generally poor immunogens
- need to be large enough to be processed
chemical heterogeneity - Answer - size alone doesn't make good immunogen
- synthetic homopolymers not immunogenic regardless of size
- large co-polymers can be immunogenic and adding aromatic amino acids increases
the chance
- proteins w higher complexity in primary structure and those showing secondary,
tertiary and quaternary structure increase immunogenicity
degradability - Answer - protein degraded to be presented by MHC molecules to
activate T cells
- factors influencing this process affect immunogenicity
- insoluble>soluble bc more likely to be phago. and processed
- large>small (more processing and more epitopes)
- L amino acids>D amino acids(works w processing enzymes
,how can we make an antigen more immunogenic? - Answer adjuvants
adjuvants - Answer - change envir. for better response
- to help
- substance that when injected w Ag, it enhances immunogenicity of Ag
- resulting in higher antibody titer and longer lasting immune response
- not specific to an antigen but can be used w many diff. antigens
adjuvant mechanism step 1 - Answer - stimulate immune response
- freund's complete adjuvant, containing muramyl dipeptides from cell walls of heat
killed myobacteria stimulate macrophage activity
- increase in IL-1 helps activate helper T cells
- synthetic polyribonucleotides and baterial LPS stimulates non specific lymphocyte
proliferation
- some stimulate local chronic inflammation and granuloma formation(freund's
complete)
adjuvant mechanism step 2 - Answer - prolong exposure to Ag
- alum and freund's adjuvant bind and precipitate Ag to keep in system longer and allow
for slow realease of Ag
- increase time of exposure from few days to few weeks
- precipitation increases size of Ag to facilitate phago.
adjuvant mechanism step 3 - Answer - co stimulatory signal
- helper T cells when stimulated by Ag need second co stimululatory signal
- freud's adjuvant, LPS and other factors up regulate co stimulatory signal systems
epitopes - Answer - lymphocytes dont recognize entire antigens
- they recognize small discrete sites on macromolecules called antigenic determinants
or epitopes
- epitopes seen by b cells and t cells differ in many diff ways
- antibodies see diff spots of epitopes
B cell epitopes - Answer - b cells bind Ag directly via cell surface immunoglobulin(Ig)
- Ag can be almost anything like sugars, lipids, proteins, nucleic acids, heavy metals
, - epitope size defined by binding size of Ab
- complex proteins w many overlapping b cells epitopes
- not all epitopes induce a response(Immunodominance)
Epitopes in solution binding to B cells - Answer - for Ag in solution:
- epitopes must be topographically accessible on native molecular
surface(hydrophillic)(but there are exceptions)
- epitopes have to be flexible and mobile for agglutination(often on bends and loop
structure of proteins)
- epitopes can be sequential or non-sequential(conformational)
how is epitope size defined by binding size of Ab? - Answer - complementary binding
btw Ag-Ab limits epitope size
- 6-7 amino acids or sugars fit into deep pocket structures of linear epitope binding sites
- conformational epitopes of globular proteins cover much more space on flatter surface
binding sites of Ab
- conformational epitopes may consist of 15-22 aa
- whatever shape/size fits into pocket of Ab is what it sees
linear vs. conformational epitopes - Answer - linear is sequential
- conformational is non-sequential
- conformational has distinct pieces of protien
- linear is one singular piece of protein
- if chopped up and digested, linear epitopes still work but conformational don't because
they depend on their 3 dimentional structure for functionality as linear dont
different structures of enzymes - Answer - primary structure: amino acid residues
- secondary: alpha helix
- tertiary: polypeptide chain
- quaternary: assembled subunits
T cell epitopes - Answer - recognize only protein(and some glycolipid) epitopes
- dont recognize soluble native Ag
- recognize only processed Ag whose peptide fragments are presented in association w