-neural projections

-complex lineage....may be derived from myeloid, lymphoid, or distinct progenitor cells

-resident dendritic cells reside in the EPITHELIaL TISSUES where microbe entry is anticipated

[skin,GI,resp track,blood,lymph nodes]

Dendritic cells as APCs(professionals)

[image]

-in migration process naive dendr cells transfrm to mature cells & can present ANTIGENS TO naive T-CELLS in lymph nodes

-TNFalpha & IL-1B released frommicrobe activated tissue macrophages also promote dendritic cell migration & maturation

-antigenic determinant

-smaller structr. in antigen directly intrx w/ antibody T& B cell recepotrs

-usually 10 amino acids or mono sacharides long

-molecules(drugs)/fragments too small to be immunogenic but can be made so by binding to a large carrier(protein)

-binds to generate antibody against the hapten or the combo

-mature in thymus

-generated in generative lymphoid organs from stem cells in bone marrow

-w/out intrxn w/ a microb antigen >>live weeks to months before apoptose

-mature t cells circulate and encounter APCs

-from CD4- & CD8- to CD4+,CD8+(in thymus)

-become non reactive to self proteins

-2% T cells passing slection leave thymus as naive mature Tcells

-Cortical thymic epithelial cells (cTEC) as APC

-In thymus cortex CD3 complexed to TCR recognizes self protein on MHC-I/II 

-High affinity recognizing TCR cell kept

Negative clonal selection

[medulllar thymic epithelial cells(mTEC), driven by AIRE(autoimmune regulator),express a wide array of self proteins for MHC presentation]

-proliferation & additional TCR rearrangement to further inc diversity

-IN Thymus Medulla

-if TCRcell still recognizes self protein this is baddd!!!

-High affinity eliminated

Major Histocompatability Complex

[image]

T cel receptor

[image]

HLA[an MHC molecule]

[image]

-Human Leukocyte Antigen; genes located on chromosome 6

-MHC-1:classical, non-classical

-MHCII: classical, non classical

positive means that T cell has this cluster of differentiation -CD8positive T cells are CYTOTOXIC & bind MHCI

[kills bad cells]

-CD4 positive T cells bind MHCII and attracted to professional cells

-T cells then differentiate and turn to memory or effector cells

-MADE OF ALPHA CHAIN OF mhc-i MOLECULE (3DOMAINS ALPHA1,2,3)

-& A BETA-2 MICROGLOBULIN MOLECULE (BETA2M,gene on chromosome 15)

-Classical(ALL NUCLEATED CELLS)

HLA-A, HLA-B, HLA-C

-Non-classical(RESTRICTED EXPRSSN)

HLA-E, HLA-F, HLA-G,MICA,MICB

CLASSICAL: most polymorphic(hundreds of alleles vs reg 2-3)

NONCLASSICAL:10-40 alleles

BETA-2 MICROGLOBULIN: NOT polymorphic

-heterodimer of MHCII molecule w/ alphaa chain and beta chain(both have two domains)

-Pair within sub types(DQ-DQ,DP-DP,DR-DR)

-classical[exprssd on APCs]

HLA-DP, HLA-DQ, HLA-DR

-Non classical

HLA-DM,HLA-DN,HLA-DO,TAP,TAPBP

[APCs,intracellular]

-classical

beta chains [>150 alleles] 

alpha chains [10-30 alleles]

-nonclassical

less than classical[~10 alleles]

alpha chain can pair with one beta chain (beta1,3,4,or 5)

- t cell receptor

-expressed on T-cell surface

-made of 2 heterodimersof 2 peptides of 30-40 kda linked by DISULFIDE BOND

-needs to form complex w/ CD3 & CD247

-encoded by VDJ segment (c regeion by C segment)

-v=variable  c=constant

-TCR alpha gene=chromosome 14

-TCR beta gene=chromosome 7

wrk w/ B cells to produce antibodies

actiavte macrophages

-induces production n release of IL-2

[IL-2 binds to IL-2R on same tcell to differntiate to EFFCTOR n MEMORY t helper cells]

-derived from stem cells in bone marrow

-Mature but naive B cells circ blood & lymphoid org 

-survive weeks to months then apoptose

-naive B CELLS  EXPRESS A MONOMERIC IgM as their  B CELL ANTIGEN RECEPTOR(BCR)[SOME USE IgD]

-neutralizes pathogens,activate compliment,opsonize microbes for phagocytosis, prevent attahcmnt of microbes to mucosal surf

-conc of IgG in serum = up to 10mg/ml

-

Light chain=25 kda (identical for both chains Vl region,Cl region)

Heavy chain= 50-70 kda identical for both chains[Vh,Ch]

FAB=fragment fr antibody binding=antibodybinding sites

Fc region(crystallizable fragment)=binds complement proteins and Fc receptors on NK and Macrophage cells

# of heavy chains

# of light chains

5

2

10%

dimer

involved in mucosal immunity

0.004%

monomer

involved in hypersensitivity

0.2%

BCR

monomer

75% 

monomer

half life 20 days 

only one that can get into placenta and provide immunityfor fetus

10%

AS BCR on B cell surface=Monomer 

In blood as free molecules=pentamer

VDJ somatic gene Rearrangment

Somatic Hypermutation

can only produce IgM

[important for blood born e pathogens]