Definitions (1) Flashcards
pattern recognition receptors (PRR)
receptors on cells of the innate immune system capable of recognizing broad molecular patterns on molecules expressed by pathogens
expressed by macrophages, dendritic cells, neutrophils, & epithelial cells
pathogen associated molecular patterns (PAMPs)
broad molecular patterns on molecules expressed by pathogens and recognized by PRRs
absent or shielded in host cells
complement system
made up of a series of pro-proteins made by the liver
activation of these proteins can occur via PAMPs, antibody-antigen complexes, or mannose binding lectin
this leads to a cascade of cleavages of the pro-proteins into the active form
net result: formation of the membrane attack complex (MAC) that forms pores in the target cell membrane leading to death
PRRs:
mannose binding lectin
&
surfactant proteins
recognizes mannose on pathogens
oligomeric structure to bind w/ high affinity to mannose & fucose residues w/ correct spacing
crucial for PAMP recognition
SPs: similar to MBLs
both: secreted from cells
both: involved in phagocytosis & complement release
PRRs:
macrophage mannose receptor (MMR)
similar to mannose binding lectin (MBL)
cell surface receptor (not secreted from cells)
phagocytic receptor
PRRs:
scavenger receptors
recognize anionic polymers & acetylated LDL
shielded in host cells
cell surface receptor
phagocytic receptor
PRRs:
fMLP receptors
recognize fMet-Leu-Phe (start of many bacterial polypeptides)
cell surface receptor
not a phagocytic receptor
binding of PAMPs leads to production of cytokines
PRRs:
Toll-Like receptors (TLRs)
present on the cell surface or in endosomes
recognize viral & bacterial PAMPs
transduce intracellular signals & release cytokines in response to PAMP binding
PRRs:
NOD proteins
contain a nucleotide binding oligomerization domain
recognize following PAMPs:
- NOD1: most bacteria
- NOD2: gram-negative bacteria
located in the cytosol of epithelial cells
activate caspases
inflammation roles:
neutrophils (3)
phagocytosis
reactive oxygen & nitrogen species
antimicrobial
inflammation roles:
macrophages (6)
phagocytosis
inflammatory mediators
antigen presentation
reactive oxygen & nitrogen species
cytokines
complement proteins
inflammation roles: dendritic cells (5)
antigen presentation
costimulatory signals
reactive oxygen species
interferon
cytokines
inflammation roles:
natural killer cells (3)
lysis of viral-infected cells
interferon
macrophage activation
(adhesion molecule)-(innate immune cell receptor) interactions mediate rolling
chemokines/chemoattractants induce change in (innate immune cell receptor)
(innate immune cell receptors) adhere firmly to (adhesion molecules)
selectin-mucin interactions mediate rolling
chemokines/chemoattractants induce change in integrins
integrins adhere firmly to ICAMs
cross-presentation
antigen-presenting cells take up, process, & present extracellular antigens w/ MHC class I molecules to CD8 T cells (cytotoxic T cells)
co-stimulation
accessory signals provided by the antigen presenting cells required for priming T cells
usually a combination of surface molecules & cytokines
aka signal 2
MHC restriction
T lymphocytes recognize peptide antigens bound to an individual’s own MHC proteins on antigen presenting cells (APCs)
Langerhans cells
immature dendritic cells in the skin
specialized for antigen capture
genes that encode class I MHC molecules
genes that encode class II MHC molecules
HLA-A, B, & C
HLA-DR, DQ, & DP
class I MHC protein structure
class II MHC protein structure
heavy chain (alpha 1, 2, & 3) + beta-2-microglobulin
alpha (1 & 2) & beta (1 & 2) chains
class I MHC-expressing cell types
class II MHC-expressing cell types
all nucleated cells
professional APCs, macrophages, & B cells
peptide binding motif
interaction of peptides w/ MHC molecules is constrained by the peptide binding cleft
pockets in the floor of the cleft accommodate residues of the peptide & anchor it
dif MHC proteins have dif shaped binding clefts & bind peptide w/ dif anchor residues
peptides w/ dif primary structures can bind to the same type of MHC protein as long as they contain the proper anchor residues
enzyme responsible for generating class I peptides
enzyme responsible for generating class II peptides
proteasome
cathepsins
site of class I peptide loading & accessory molecule
site of class II peptide loading & accessory molecule
ER
TAP
MIIC vesicle
invariant chain, DM
T cell priming
naive T cells must first be activated by MHC-restricted interaction w/ professional APC (usually a DC) before the effector functions of macrophages, B cells, & CD8+ cytolytic T cells are gained
direct vs indirect MHC recognition
direct: TCR of recipient T cell recognizes foreign MHC (regardless of the peptide presented) & destroys the target cell
indirect: foreign MHC (as a protein) is acquired by the host APC, processed, & presented on recipient MHC to recipient T cells
HLA typing & 2 methods
determining the MHC type (haplotype) of the recipient & donor prior to transplantation
methods: lymphocytotoxicity assay & molecular typing
dendritic cells:
morphology
tissue distribution
origins
large, long dendrite-like extensions that mediate antigen uptake & cell-cell contact
all tissues except immune-privileged CNS, eye, & testes
bone marrow hematopoietic CD34+ progenitors or myeloid (CMP) or lymphoid (CLP) progenitors
functions of dendritic cells (6)
detect danger signals capture antigen migrate stimulate naive T & B cells secrete cytokines bridge innate & adaptive immune responses
preventative vs. therapeutic vaccines
preventative: used against infections, stimulate a primary immune response to infectious agents, leads to memory response developments; antigens are given w/ adjuvants to target, activate, & bias specific DC responses
therapeutic: harder to develop, required to modulate or reprogram an established memory response, treat chronic infections & cancer
