2 Immuno: Adaptive Immunity: Apcs, Mhc

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dendritic cells gen

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dendritics:
- key/ professional: only fx APC
>100x more effective APC than macs and B cells
- produced from bone marrow stem cells
- dendrites: long, thin cytoplasmic processes
1. mature: best at processing and presenting Ag
2. immature: good at Ag capture

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dendritic cell locations

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dedritic cells:
1. found in all organs except brain, parts of the eye and testes
2. prominent in lymph nodes, skin and all mucosal surfaces where invading microbes likely to be encountered

Front 3

dendritic cells: Ag

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dendritic cells can take up:
1. dead microbes
2. soluble Ag
3. Ag released by dying cells
- after capture, immature DCs migrate to lymph nodes where they mature and process Ag to present to lymphocytes

Front 4

dendritic cells and naive T cells

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dendritic cells are the only APC that can present to and activate naive T cells
- therefore essential to initiating the primary immune response

Front 5

langerhans cells

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langerhans cells:
- immature dendritic cells that reside in the skin
- origin of histiocytoma in dogs

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interdigitating dendritic cells

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interdigitating dendritic cells:
- mature dendritic cells that interact wit T cells in the lymph node

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thymic dendritic cells

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thymic dendritic cells:
- reside in thymus
- important for negative selection of T cells that recognize self Ag
- recognize and kill self-reacting T cells in thymus

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macrophages

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macrophages:
- semi-professional APC
- also phagocytic
- can only present Ag to T cells that have been activated by dendritic cells

Front 9

B cells gen

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B cells:
- semi-professional APC
- main fx: make Ab
- BCR (Ab) binds:
1. whole Ag molecules: proteins, polysaccharides and lipis
2. small, soluble molecules: eg toxins

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B cells as APCs

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B cells as APCs:
1. bind Ag with BCR
2. ingest and process Ag
3. present Ag via MHC II to Th cells
- main, secondary response: B cells increase in numbers and present to memory T cells

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B cells and Ab production

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B cells: main fx Ab production:
1. bind Ag with BCR
2. signal to B cell to differentiate into Ab secreting cell, plasma cell, often with Th help
3. Ab made: identical to membrane-bound Ab making up BCR, specific for Ag that triggered the signal

Front 12

non-professional APCs

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non-professional APCs:
- most nucleated cells can express MHC I and present endogenous Ag to CTLs
- eg endothelial cells, astrocytes, fibroblasts

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MHC gen

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MHC:
- T cell can only see an Ag on APC if bound to these Ag-presenting molecules
- glycoproteins codes located in a gene cluster called MHC

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MHC restriction

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MHC restriction:
- Ag can only trigger an immune response if bound to self MHC
when interacting with TCR
- T cells can only recognize Ag in context of self MHC
- eg Bovine leukemia virus only infects those whose MHC cannot bind= no immune response

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MHC Ag presentation

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MHC is an organized cluster of genes that control Ag presentation:
- determines which Ag can be presented to the immune system

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MHC polymorphism

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MHC polymorphism:
- variable region: binds Ag
- MHC gene region highly polymorphic: large number of alleles code variable region (eg humans size of MHC= genome of E coli)
- each animal expresses a number of different MHCs: able to present a wide variety of Ag
- only identical twins have the same MHC repertoire

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MHC broad specificity

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MHC broad specificity:
- an MHC can bind a number of different Ag peptides
- only present one Ag at a time

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MHC- Ag binding

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MHC- Ag binding:
- anchor residues: critical aa's of Ag fit into binding pocket of MHC
- structure of binding groove determines what Ag can bind
- MHC can bind an array of peptides

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TCR unique specificity

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- a given TCR can only interact with self MHC presenting a particular peptide complex

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MHC I location

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MHC I:
- expressed by most nucleated cells
- not found on RBCs, gametes, neurons, or placental trophoblacts cells

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MHC I

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MHC:
- present endogenous antigenic fragments from to cytotoxic T cells

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MHC II

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MHC II:
- only expressed by professional and semi-professional APCs
- present exogenous Ag fragments to Th cells
- Ag from engulfed extracellular organisms or engulfed infected cells

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MHC and infectious disease

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- MHC associated with the following infectious diseases:
1. bovine lymphoma and bovine leukemia virus (BLV)
2. marek's disease: virus that causes nerve paralysis in chickens

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MHC and autoimmune diseases

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MHC is linked to the following autoimmune diseases:
- almost all ai diseases in humans
1. MHC recognition of self: eg rheumatoid arthritis, MHC class II bind and present self collagen Ag
2. diabetes: insulin recognized as foreign, dog MHC alleles DLA-A3, A7 and A10
3. thyroiditis in dogs, Grave's disease

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heterogenous MHC

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heterogenous MHC:
- MHC that can bind a variety of Ag
- evolutionary advantage of population
- social animals have more diversity than solitary (felids)

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MHC diversity

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MHC diversity:
- within population: MHC alleles expressed at about same frequency
- diversity will allow at least a few animals to mount an immune response and survive

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lack of MHC diversity: examples

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lack of MHC diversity:
1. some cheetah populations: genetic erosin by MHC homozygosity
2. Tasmanian Devil facial tumor disease: started in one animal and spread through the rest of the population by biting