Antigen Processing & Presentation Flashcards
Describe what antigen processing & presentation is.
APCs (macrophage, dendritic, B cells) digest antigen from outside/inside the cell & display the antigenic fragments on cell surface of MHC for recognition by T lymphocytes to initiate a immune response.
*without APC there would be no T cell response.
Describe the 3 professional APCs.
- Dendritic
-present antigen to naive CD4 & CD8 T lymphocyte - Macrophage
-present antigen to differentiated (effector) CD4 T lymphocytes cell mediated immunity - B lymphocytes
-present antigen to helper CD4 T lymphocytes humoral immune response
Describe non professional APCs.
all other nucleated cells that when they become infected with a virus can act as APCs (not main function)
Describe the distribution & properties of APCs.
Describe the 2 functions of APCs.
- Convert protein antigens to peptides within APCs = antigen processing
- APCs provide stimulus to T cells = co stimulation
Describe how antigen presentation begins with antigen processing.
-convert protein antigens from extracellular or cytosol into peptides & onto MHC to display to lymphocytes
>protein antigens in acidic vesicular areas of APCs = MHC class II associated peptides
>antigens in cytosol = MHC class I associated peptides
Describe the process of endocytosed antigens for MHC class II. (UPTAKE)
*uptake of extracellular protein into vesicular compartment of APC
>receptor mediated macrophages & dendritic cells on surface to bind microbes
>B lymphocytes use BCR to internalize antigen & localized in endosomes that have proteolytic enzymes that communicate w lysosomes to make phagolysosome to degrade engulfed material
Describe the process of endocytosed antigens for MHC class II. (PROCESSING)
*processing of internalized proteins in endosomal or lysosomal vesicles
-14-20aa peptides made that bind to peptide binding cleft of MHC II
*cathepsins are most imp proteolytic enzymes involved in degradation
Describe the process of endocytosed antigens for MHC class II. (BIOSYNTHESIS)
*biosynthesis & transport of MHC II to endosomes
-a & B chain of MHC II synthesized in ER & transport to GA & then to endosomes with an invariant chain (Ii)
Describe the process of endocytosed antigens for MHC class II. (ASSOCIATION)
*association of processed peptides with MHC II in endocytic vesicles
-in endosomes the invariant chain dissociates & the antigenic peptides are associated with MHC II
Describe the process of endocytosed antigens for MHC class II. (EXPRESSION)
*expression of peptide class II complex on APC surface
-displayed for recog by CD4 T lymphocytes
Describe the processing of cytosolic antigens for MHC class I. (CYTOSOL SOURCE + PROCESSING)
Source:
-proteins in cytosol endogenously synthesized in nucleated cells
-may originate from viruses or other intracellular microbes
-endocytosed antigens may be presented through MHC I
Processing:
-cytosolic proteins antigens are ubiquitinated -> proteosomal degradation (protein to peptide) ‘proteolysis in proteasome’
>proteasome = multi enzyme complex in cytoplasm
Describe the processing of cytosolic antigens for MHC class I. (TRANSPORT)
*transport of peptides from cytosol to ER via transporter associated w antigen presentation (TAP)
-TAP located in ER
Describe the processing of cytosolic antigens for MHC class I. (ASSEMBLY)
*assembly of peptide MHC I complex in ER
Describe the processing of cytosolic antigens for MHC class I. (SURFACE EXPRESSION)
*surface expression of peptide MHC I complex
-MHC I peptide complex move thru golgi complex & delivered to cell surface
-once expressed the complex may be recognized by peptide antigen specific CD 8 T lymphocytes
Describe the alternatives to antigen presentation through MHC.
*another pathway to present lipid antigens
-lipid antigens presented by class I-like non polymorphic molecules = CD1
-CD1 on APCs & some epithelial cells
-CD1 presents lipid antigens to T cells that arent MHC restricted like NKT cells
Describe T cell responses.
*presentation of vesicular/cytosolic proteins by MHCII/I = determines which subsets of T cells will respond to antigens
-exogenously = acquired proteins make peptides activate CD4 T cells
-endogenously = acquired proteins make peptides activate CD8 T cells
Describe the TCR.
-surface molecule on T cells
>each T cell has a TCR of only one specificity
-recognizes antigen presented in correct MHC
-similar to Ig structure & part of superfamily
-recog antigen by the aB TCR is MHC dependent
-γδ TCR recognize antigen in MHC independent
Describe the 2 types of TCR.
- aB TCR
-predominant
-on T lymphocytes in lymphoid tissue - γδ TCR
-on T lymphocytes at mucosal surface
Describe the TCR & CD3 complex.
-TCR with 4 proteins = CD3 complex
-CD3 complex = 1γ, 1δ, 2 ε, 2 ξ chains
>proteins of CD3 complex are invariant & dont contribute to TCR specificity
>necessary for cell surface expression of TCR during T cell development
>transduces activation signals to cell nucleus following antigen interaction w/ TCR
Describe the properties of antigens recognized by T lymphocytes.
-most T lymphocytes recognize only peptides
-T cells specific for amino acid seq of peptides
-recognize few anchor residues in peptide seq
-T cells recog & respond to foreign peptide antigen when attached to surface of APCs in MHC
-some T cells specific for haptens conjugates (dinitrophenol, urushiol of poison ivy, beta lactams of penicillin derived antibiotics)
Describe self MHC restriction.
-T cells from one individual recog foreign peptides only when these peptides are bound to & displayed by MHC molecule of that individual = self MHC restriction
1. MHC II restricted CD4 T cells
2. MHC I restricted CD8 T cells
Describe the BCR.
-doesnt interact w MHC
-B cells recog soluble antigens & antigens on cell surface
-B cells recog peptides, proteins, nucleic acids, polysaccharides, & lipids
Describe the role of costimulatory molecules.
-required for full T cell activation
-signal 1 generated by interaction of antigenic peptide bound in MHC w TCR-CD3 complex
-signal 2 via interaction w CD28 on T cells & B7 (CD80/CD86) family on APC = co stimulatory signal
Describe clonal anergy.
-when T lymphocytes are stimulated without co-stim signal = no response
Describe APCs & TLRs.
-antigen presenting function of APCs enhanced by exposure to microbial products
-APCs express TLRs that respond to microbes
*detection of microbes through TLRs:
>induce expression of MHC & co-stims
>improve efficiency of antigen presentation
>activate APCs to make cytokines that stim T cells
>stim production of chemokines that promote their migration to sites of infection
Describe antigen presentation to naive T cells.
-role of dendritic cells in initiating T cell responses
-T cell response initiated in peripheral lymphoid organs = protein antigens transported after being collected from portal of entry
-dendritic cells (resident in epi & tissue) = capture protein antigens & transport to draining LN
Describe the properties of DC that make them effective APCs for initiating primary T cell responses.
-located at sites of entry of microbes & in tissue that may be colonized by microbes
-express receptors that allow them to capture microbes & respond to them
-migrate to T cell rich zones of LN where naive T cells circulate
-mature DCs express high levels of co stim molecules (needed to activate naive T cells)
Describe cross presentation/priming.
-DCs can ingest infected cells & tumor cells & present antigens from these cells to CD8 T cells
-ingested antigen is presented through MHC II
-presentation of antigen through class I
