Dendritic cells and macrophages are the
antigen-processers in this response
ACRs of APCs present antigen fragments bound to
class II MHC molecules and B7 on their
surfaces
Th cell
TCRs bind antigen fragments and MHC-II alpha1- and
beta1-chain contact residues, while CD4 binds beta2-domain
of MHC-II
Th cells proliferate and differentiate to form large
numbers of Th and Th memory (Thm) cells
Th cellssecreteinterferon-gamma
(IFN-gamma) and interleukin 2 (IL-2) which trigger
activation of macrophages
Thm cells formed are very long-lived Th cells
(half-life of ~40 years in humans) that can respond to
processed antigen to help provide a much quicker secondary
CTL response
Macrophages express high-affinity receptorsfor
IFN-gamma and IL-2 and are activated when they bind
these cytokines produced by Th cells
respiration . . . referred to as metabolic or
respiratory burst and results in increased production of
reactive oxygen intermediates: superoxide anion, hydrogen
peroxide and hydroxyl radical
myeloperoxidase
lysosomal digestive enzyme content and
activity (selective)
Lactoferrin
Vitamin B12 binding protein
synthesis of proinflammatory cytokines, including
TNF-alpha (tumor necrosis factor alpha), IL-6,
IL-8 and IL-10
IDO (indoleamine dioxygenase)
iNOS (nitric oxide synthase)
Activated macrophages kill intracellular pathogens by a
combination of mechanisms generally referred to as cellular
immunity
Prevention of microbial escape from
phagolysosomes
Enhanced phagolysosomal killing and digestion
reactive oxygen intermediates: superoxide anion,
hydrogen peroxide and hydroxyl radical
myeloperoxidase, which is activated by hydrogen
peroxide to transfer Cl ions to various functional groups on
amino acid sidechains of proteins
Restriction of microbial growth via iron, vitamin
and/or amino acid competition
Lactoferrin, which binds iron so intracellular
microbes cannot get it
Vitamin B12 binding protein competes with
pathogens for B12
IDO destroys tryptophan, an essential amino acid,
thus restricting growth of intracellular pathogens that
require it
iNOS destroys arginine, an essential amino acid,
thus restricting growth of intracellular pathogens that
require it and, in the process, produces nitric
oxide, which is toxic
Secondary Response
Thm(emory) cells, whose numbers have also increased as
a result of the primary response, are again stimulated by
binding processed exogenous antigen on APCs
Macrophage activation is much faster (on the order of
~2-4 days) than in the primary response, but (unlike the secondary
antibody response) does not seem to be qualitatively different
from the primary response
Macrophages kill infectious agents in the same manner
as they did in the primary response
