immune response to infectious agents Flashcards
innate vs adaptive immunity
in innate, thereis inhibition of infection by type 1 interferons and killing of infected cells by NK cells
in adaptive, there is killing of infected cells by CD8 CTLs(cytotoxic t lymphocytes) and neutralizing antibodies block virus binding and entry to host cells.
PAMPs
(pathogen associated molecular patterns) are microbe molecules that are recognized by TLRs the innate immune system (toll like receptors) and PRRs(pattern recognition receptors)
o PAMPs activate type 1 interferons (IFN-alpha and IFN-beta)
Viral PAMPs = ssRNA, dsRNA, and uncapped RNA
PRRs
pattern recognition receptors
receptors on host cells that recognize viral PAMPs
TLRs 3, 7, and 8
how do type 1 interferons work in innate immune response?
PAMPs activate type 1 interferons (IFN-alpha and IFN-beta)
Viral PAMPs = ssRNA, dsRNA, and uncapped RNA
Type 1 interferons then:
Induce enzymes that inhibit viral replication
Increase expression of ligands for receptors on NK cells
Activate NK cells to proliferate and kill virus-infected cells (apoptosis)
how do NK cells function in innate immune response?
type 1 interferon causes differentiation of cytotoxic NK cells (they kill infected cells by inducing apoptosis)
o Healthy cells express MHC1 which connects with NK cell inhibitory receptor(no apoptosis) o Virus-infected cells do not express MHC class 1 (inhibited by virus) connects with the NK cell activating receptor
NK cell killing is done via
Perforin and granzymes = granzymes enter through perforin holes activation of caspases and apoptosis of cell
which immune response uses NK cells?
what do NK cells use to kill?
innate
NK cell killing is done via
Perforin and granzymes = granzymes enter through perforin holes activation of caspases and apoptosis of cell
innate immune system response to viruses vs intracellular organisms vs extracellular organisms
viruses –> type 1 IFN and NK cells
intra –> phagocytes and NK cells
extra –> complement and phagocytes
adaptive immune system response to viruses vs intracellular organisms vs extracellular organisms
viruses –> CD8 (CTLs) and B cells/CD4
intra –> CD8 and CD4(TH1)
extra –> B cells/Ig and CD4
what activates NK cells?
TYPE 1 interferons
IFNalpha, IFNbeta, TNFalpha, and IL12
CTLs
cytolytic (cytotoxic) T lymphocytes (CTLs) = CD8+ T cells
part of adaptive immunity
CTLs can kill using
Perforin and granzymes
Or
FasL (Fas ligand) – Fas receptor is on the virus-infected cell Fas + FasL induces apoptosis
how do CTLs sense virus?
o Viral proteins are presented on MHC class 1 to TCR on CD8+ Tcells
do CTLs affect healthy normal cells?
no, target specific
Thelper and neutralizing antibodies in adaptive immunity
Neutralizing antibodies block virus binding and entry into host cells – virus cant bind to host cell receptors!
o CD4+ T helper cells also needed for immunity; IgG aids in neutralization, opsonization, and sensitization for NK killing, mast cells, and complement system
common intracellular pathogens
Mycobacterium tuberculosis
M. leprae
Listeria monocytogenes
Leishmania spp.
what causes the damage with intracellular pathogens?
host response!
3 components of innate immunity to intracellular pathogens
Phagocytes (neutrophils and macrophages)
NK cells
cytokines (IL-12 and IFN-gamma)
once PRR is bound, 2 things happen…
o Phagocytosis and Cytokine production
phagolysosome mechanism for killing
Macrophage receptors that recognize microbial surface (PRRs on the macrophage) bind microbes
microbes are internalized by receptor-mediated endocytosis
fusion of the endosome with a lysosome forms a phagolysosome which degrades the microbe
cytokine feedback loop
Activated macrophages secrete cytokines that stimulate NK cells
NK cell and macrophage form a synapse in which IL-12 and IL-15 activate the NK cell
NK cells proliferate and differentiate into effector NK cells that secrete IFN-gamma
IFN-gamma binds to its receptor on macrophages and activates them to increase phagocytosis and secretion of inflammatory cytokines
adaptive immunity to intracellular bacteria consists of 3 components
T cells (TH1/TH2/CD40L)
IFN-gamma
macrophages
TH1 (CD4) vs Nk cells
• CD4+ T cells that develop into TH1 effectors = are more effective producers of IFN-gamma; they take over from NK cells
development of TH1 response in adaptive immunity
Naïve CD4+ T cell is activated by dendritic cell with co-stimulation by CD28 + B7
clonal expansion and differentiation into TH1 and TH2 effector cells + production of IFN-gamma, IL-4, and IL-5
The antigen presenting cell (dendritic or macrophage) produces IL-12 when its receptors for microbe products are activated
the IL-12 activated naïve CD4+ T cell and causes differentiation of TH1 effector cells
TH1 then produce IFN-gamma
activation of macrophages microbes killed
damage in etracellular pathogen immune response
due to their exo and endo toxins
3 pathways of complement activation
order of activation?
classical
lectin pathway
alternative pathway
A –> L –> C
