2 Immuno: Adaptive Immunity: Antigens

Front 1

antigen definition

Back 1

substance that is capable, under the appropriate conditions, of inducing a specific immune response

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antigen interations

Back 2

interacts with the following products of the immune response it generates:
1. recognized by specific antibody
2. recognized by specific T lymphocytes, binds at T cell receptor (TCR)
- only a portion of the larger molecule actually binds with the Ab or the T cell receptor

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antigenicity

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ability of an antigen to bind with immune components (antibody and TCR)
- doesn't necessarily = immunogenicity

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immunogenicity

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- ability of an antigen to induce an immune response
- some antigens more immunogenic due to
1. molecular
2. chemical properties
3. stability
4. foreigness

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molecular size and immunogenicity

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needs to be > 1kDa to be immunogenic

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simple chemical composition and immunogenicity

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- simple repeating units are poor immunogens
- eg polymers such as carbs and plastics

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proteins and immunogenicity

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- proteins and glycoproteins are complex molecules and usually good immunogens

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nucleic acids and immunogenicity

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- generally poor immunogens
1. mammalian nucleic acids are simple, readily degraded and therefore poor immunogens
2. prokaryotic nucleic acids can stimulate a potent immune response in a mammal: CpG motifs of bacterial DNA

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lipds and immunogenicity

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- generally poor immunogens
1. bacterial LPS (unlike most lipid-carb molecules) are good immunogens
2. some bacterial have polymer capsular coatings that are poorly immunogenic, protecting bacteria from an immune response
eg Bacillus anthracis

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stability and immunogenicity

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- easily degraded and inert molecules (plastics) are poor immunogens
- some proteins that are easily degraded can first be fixed with heat or formaldehyde which slows down degradation and improves immunogenicity
- fixing will also inactivate a toxin that one might want to use as an immunogen

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foreigness and immunogenicity

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- foreign proteins make the best Ag
- acquire IS develops in a way to prevent it from responding to self Ag
- genetic relatedness b/w 2 individuals plays an important role in foreigness of tissue grafts
eg identical twins will accept grafts from each other

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Epitope definition

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epitope:
- small portion of the immunogenic molecule which actually binds with Ab or TCR
- only portion of immunogenic molecule reconized by Ab or TCR
- single immunogenic molecule may have several different epitopes that will be recognized by different Ab and TCRs

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protein epitopes

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protein epitopes may:
- have primary (aa), secondary ( alpha helix, beta sheet), tertiary, or quartenary structure (multi-subunit)
- be conformational: immune responses are dependent on recognizing them in native or conformation state, will not be recognized if changed by denaturing, etc

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epitope cross-reactivity

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- identical or similar epitopes may be found on unrelated molecules
- Ab against one Ag may react unexpectedly with an unrelated Ag
- eg similar viruses or bacteria:
all RV variants share a similar glycoprotein epitope

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blood type cross-reactivity

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- bacteria posess cell wall glycoproteins with carb side chains that are similar to mammalian RBC
- bacterial gps absorbed through the intestinal wall into the bloodstream, triggering an Ab response
- therefore: type O pigs develop anti-A as a result of bacteria, not blood exposure

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Brucella and Yersnia cross-reactivity

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- Brucella abortus and some strains of Yersinia enterocolitica share a similar epitope:
1. Y.e. may provoke Ab against B.a
2. Y.e infected animal may be falsely thought to have been exposed to B.a

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autoimmune cross-reactivity

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- some microbial epitopes may be similar to the animal's own tissue epitopes
- immune response to microbial epitopes may therefore trigger Ab or T cells to attack the animal's own tissue (autoimmune)

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Haptens

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haptens:
- small molecules that are antigenic (can bind to Ab in vitro) but are not immunogenic in vivo
- cannot elicit an immune response unless bound to a carrier protein

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Penicillin as a hapten

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- penicillin (hapten) bound to albumin (carrier protein can ellicit an immune response in some animals
- pen alone is too small to elicit an immune response

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urushiol as a hapten

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when uroshiol (poison ivy toxin) binds to skin proteins (carrier proteins), skin proteins become modified and "look foreign" to the immune system

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microbial Ag

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microbial Ag:
- most are protein molecules
- can be carbs or lipids

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Eukaryotes

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eukaryotes:
- nucleus, mitochondria, metabolic enzymes
- protozoa, fungi, other parasites

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Prokaryotes

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prokaryotes:
- lack a distinct nucleus: genetic material in cytoplasm
- bacteria

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viruses

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viruses:
- very small
- nucleic acids: DNA or RNA surrounded by protein layer (capsid)
- no organelles
- obligate intracellular: require host cell to replicate and express their genes
- may carry genes for enzymes

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extracellular pathogens

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extracellular pathogens:
- most bacteria and parasites
- replicate outside the host cell

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intracellular pathogens

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intracellular pathogens:
- viruses and some bacteria
- viruses and obligate intracellular bacteria exist outside a host cell prior to infection
- need to be in cell in order to replicate

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intracellular bacteria

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pathogenic bacteria:
1. Mycobacterium
2. Rhodococcus equi
3. Listeria monocytogenes
4. Brucella abortus
- make endogenous Ag
- replicate inside macrophages: facultative intracellular

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RV

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RV is extracellular and suseptable until intracellular in nervous tissue

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exogenous Ag

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exogenous Ag; usually protein molecules, made by pathogen outside any host cell
- eg the replicating extracellular microbe itself
- may be engulfed inside a phagocytic cell

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example exogenous Ag

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extracellular bacteria live outside of cells:
- internalized into membrane-bound vacoloes (phagosome) of phagocytic cells
- digested by enzymes or respiratory burst
- no replication or microbial molecules made inside phagocytic cell so still EXOGENOUS

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endogenous Ag

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endogenous antigen:
- usually protein molecules, made by the intracellular pathogen inside a host cell

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viral endogenous Ag

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viral endogenous Ag:
- proteins made by the virus inside the cell it infects
- virus replicates and makes viral protein inside the cell
- eg Parvovirus

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Mycobacterium bovis endogenous Ag

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Mycobacterium bovis endogenous Ag:
- phagocytic cell engulfs M. bovis which has the ability to replicate inside
- bacterium is NOT killed, but makes bacterial proteins and other molecules (Ag) inside

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Bacterial Ag

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bacterial Ag:
- most bacteria live and replicate outside the mammalian cell
1. cell wall
2. pili and flagellum
3. Capsules: some bacteria poorly immunogenic as the capsule covers the immunogenic proteins and Ab can't bind

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Bacillus anthracis

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Bacillus anthracis:
- capsule protexts against bactericidal components of serum and phagocytes
- killed Bacillus vaccine or capsular Ag: no immunity
- livestock vaccine: non-encapsulated toxigenic strain
- human vaccine: Ag of avirulent, non-encapsulated strain

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non-phagocyte intracellular bacteria

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non-phagocyte intracellular bacteria:
- make endogenous Ag
- can be destroyed before infecting cell or by phagocytic cell engulfing infected cell
- eg Salmonella: intestinal epithelial cell

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viral envelope

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viral envelope:
- lipoproteins and glycoproteins
- often derived from host membrane as virus leaves the cell, less effective Ag than other viral proteins
- can vary envelope antigenicity: eg HIV, newly made viruses fail to stimulate an immune response, survive and replicate

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cell entry of virus

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viruses:
- transiently found extracellularly prior to infecting host cell
- enter cell via surface molecules
- viral contents go into the cytosol (not phagosome)
- immune cells can kill virally infected host cells

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extracellular virus killing

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extracellular virus:
- Ab can target
- RV: extracellular for some time until infecting nervous tissue

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Obligate intracellular organisms

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obligate intracellular organisms:
- viruses, some bacteria, certain stages of protozoa
- transient extracellular phase: when release from host cell, suseptible to humoral (Ab) and CMI (cytotoxic T cells) responses

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cell surface Ag

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non-microbial Ag:
cell surface Ag:
- molecules expressed on the surface of normal cells that could stimulate an immune response in another animal
1. blood group
2. MHC
3. CD

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blood group Ag

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blood group Ag:
- cell surface Ag
- glycoproteins and glycolipids on the surface of RBCs

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MHC

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MHC: major histocompatibility complex:
- protein cell surface Ag of most nucleated cells
- important in:
1. recognition and signaling events in adaptive immune response
2. tissue recognition, transplant medicine

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CD

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CD: cluster differentiation molecule:
- cell surface Ag of immune cells
- defines lymphocyte subsets
- identification: use monoclonal Ab (MoAb) made against CD
- eg fluorescent tagging of CD

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CD4

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CD4:
- expressed by a T helper cells

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CD8

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CD8:
- expressed by killer T cells

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CD25

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CD25:
- expressed on a number of different types of cells
- fx: bind IL-2