Download Antigen Presenting Cells

Antigen Presenting Cells
1. CD4+ T cells only see antigen presented on MHCII
2. CD8+ T cells only see antigen presented on MCHI
General Features
1. innate system activated  cytokines + APCs  T lymphocyte differentiation
2. professional antigen presenting cells present antigen to CD4s
a. dendritic cells – most efficient during primary response
b. macrophages – most efficient during secondary response
c. B cells
3. antigen is presented on major histocompatibility complex (MHC)
4. all APCs require:
a. MHC II
b. Costimulatory molecules (B7, CD40)
5. Cells that present antigen to CD8+ T cells are called target cells because these
cells are targeted for death
6. Any nucleated cell is a potential target because all nucleated cells express MHC I
Dendritic cells
1. immature dendritic cells
a. everywhere (in skin = Langerhans cells)
b. Function: Ag capture (carry Ag from peripheral tissues to secondary
lymphoid tissue)
c. High FcR, low MHC II and costimulatory molecules
d. Express CD4, chemokine receptors CCR5, CXCR4: receptors for HIV
2. mature dendritic cells
a. secondary lymphoid tissue
b. Function: Ag presentation and cytokine secretion (IL-12)
c. High MCHII and costimulatory molecules
3. present antigen and activate T cells
Macrophages
1. Express CD4, chemokine receptors CCR5, CXCR4: receptors for HIV
B cells
1. recognize antigen via membrane antibody receptor
2. best APC when antigen is low
3. antigen is taken up with receptor into an endosome
Antigen Presenting Molecules
1. Two types:
a. class I MHC molecules
1. all nucleated cells
2. encoded by 3 loci = A, B, C
3.
b. class II MHC molecules
1. all professional APCs
2. encoded by a D locus subdivided into: DP, DQ, DR
2. In humans, MHC = human leukocyte antigen (HLA)
3. polymorphism: genes encoding each MHC locus are present in multiple forms
a. characteristic of both class I and II MCH
Antigen Presenting Molecule: Class I MHC Molecules
Role of class I MHC molecules and class I MHC restriction
1. antigen + MHC I recognized by CD8s
2. CD8s only recognize viruses or other cytosolic pathogens presented on MHC I =
class I MHC restriction
Structure of class I MHC
1. transmembrane polymorphic polypeptide heavy chain – binds antigen 10 aas long
2. nonpolymorphic 2-microglobulin – does not bind antigen
Nomenclature and codominant expression of class I MHC molecules
1. class I MHC molecules are codominantly expressed: inherit a copy from each
parent (6 class I MHC)
Antigen processing
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free microorganisms in cytoplasm are degraded by proteosome
peptide fragments bind to transporter of antigen processing (TAP)
TAP transports peptides from cytosol to ER
peptides bind MHC I
complexes released in vesicles from Golgi
vesicles fuse with plasma membrane and are displayed
Class I MHC molecules and viral evasion of immune defenses
1. Herpes simplex virus (HSV)
a. hides in neurons that have little MHC I
b. inhibits TAP in non-neuronal tissues
2. Epstein Barr virus (EBV)
a. latent infection in B cells
b. inhibits proteosome
3. Cytomegalovirus (CMV)
a. takes class I MHC from ER back into cytoplasm
b. class I MHC are degraded by proteosome
Antigen Presenting Molecules: Class II MHC Molecules
Role of class II MHC molecules and class II MHC restriction
1. MHC II present antigen to CD4s
2. class II MHC restriction
3. class II MHC activate CD4s which in turn secrete cytokines
Structure of class II MHC molecules
1. heterodimer of two transmembrane polymorphic polypeptide chains
2. binds antigen 15-10 aas in length
3. invariant chain (Ii) binds to class II MHC in ER
a. blocks binding of excess peptide
b. direct transport of MHC II through Golgi
Nomenclature and codominant expression of class II MHC molecules
1. codominant expression: one copy inherited from each parent
2. six class II MHC
Processing of microorganisms and association with class II MHC molecules
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extracellular microorganisms are endocytozed by APCs
endosome fuses with lysosomes
endosome with pathogen fuses with another endosome with class II MHC
Ii chain is degraded by lysosomal enzymes
peptide binds to class II MHC
chimeric endosome fuses with cell membrane and is displayed
recognition by CD 4s
secretion of cytokines by CD4s
Disease association with class I and class II MHC expression
1. HLA-B27  ankylosing spondylitis in Caucasian males
2. HLA-DR3, HLA-DR4  type 1 diabetes
Antigen Presenting Molecules: CD1 molecules
Nomenclature and structure
1. similar to class I – have 2-microglobulin
2. no polymorphism like class I
Tissue distribution and function
1. tissue distribution similar to MHC II
2. present lipid and/or glycolipid antigens to CD4+ and  T cells specially with
mycobacterial infection