Innate Immunity Flashcards
describe the timeframe and the sequence of events in the innate response
immediate: 0-4 hours
infection –> recognition by preformed, nonspecific effectors –> removal of pathogen
describe the timeframe and sequence of events in the early induced innate response
early: 4-96 hours
infection –> recruitment of effector cells –> recognition of PAMPs, activation of effector cells and inflammation–> removal of pathogen
describe the timeframe and sequence of events in the adaptive response
late: >96 hours
infection –> transport of antigen to lymphoid organs –> recognition by naive B and T cells –> clonal expansion and differentiation to effector cells–> removal of pathogen
What is the protective immunity against pathogen in the interstitial spaces, blood, and lymph?
Complement
Phagocytosis
Antibodies
What is the protective immunity against pathogen on epithelial surfaces?
Antimicrobial peptides
Antibodies, especially IgA
What is the protective immunity against pathogen in the cytoplasm?
NK cells
Cytotoxic cells
What is the protective immunity against pathogen in vesicles?
T cell and NK cell dependent macrophage activation
What is released by epithelial cells and what does it do?
Defensin - highly charged, will infiltrate the cell membrane and form a pore
what are the general characteristics of inflammation?
triggered by innate cells that generate inflammatory mediators
tries to destroy or contain pathogen
orchestrates repair of damaged tissue
What are the effects of inflammation?
calor, dolor, tumor, rubor
alteration of blood flow
increased vascular permeability
infiltration of white cells into reaction area
Discuss the main functions and locations of Macrophages/Monocytes
monocytes: blood
macrophages: tissue
first responder, long lived
discuss the main functions and locations of neutrophils
most common circulating white blood cell
short lived
rapid responder
rarely found in normal tissue
How do macrophages and neutrophils counter threats?
phagocytosis and mediator production
discuss phagocytosis
uptake of particles via receptors that can bind PAMPS, antibody, or complement
what are the mediators that are release by macrophages and neutrophils?
cytokines, chemokines, hydrolases, reactive oxygen and nitrogen species
differentiate between cytokines and chemokines
cytokines: can promote differentiation, proliferation, or recruitment of other cells
chemokines: only recruit other cells
What is the detector of the “danger” signal in the immune response?
Pattern recognition receptor (PRR)
What are the danger signals that PRRs recognize?
PAMPS (pathogen associated molecular pattern) - foreign
DAMPS (damage associated molecular pattern) - endogenous
What occurs with binding of PAMPS/DAMPS?
expression of proinflammatory cytokines and antimicrobial proteins
What are the four classes of PRRs and where are they expressed?
Toll-like receptors (TRRs) - cell surface
NOD-like receptors - intracellular
C-type lectin receptors - cell surface
Rig-I-like receptors - intracellular
How are TLRs activated?
TLRs can bind multiple targets (not like Ab), diversity is preset
what are the differences between PRRs and Ab?
Diversity: TLRs have preset binding capabilities against general epitopes (flagella, etc.), and we only have ~100s of them –> PRR recognize unique repeated structures
Ab are specific for a very specific epitope and we can generate millions of different specificities via ecombination
Explain what happens after activation of a PRR in the context of the inflammasome
activation of PAMPS or DAMPS activate cascades that lead to the activation of the inflammasome, which activates caspase-1 to cleave pro-IL-1Beta and pro-IL-18 to IL-1Beta and IL-18 which are cytokines that are released to stimulate the inflammatory response
What does C-type lectin recognize on pathogen?
The PRR C-type lectin on phagocytic cells recognize terminal mannose on pathogen glycoprotein
What else can bind pathogen mannose?
Mannose binding lectin (MBL)
How does MBL activate complement?
Binding to mannose results in a conformational change, leading to activation of c3 convertase which cleaves c3 leaving c3 bound to the microbial surface and the release of c3a
What is the function of c3a?
c3a and c5a recruit phagocytic cells to the site of infection and promote inflammation
what is the function of c3b?
c3b is recognized by phagocytes with that specific receptor, which phagocytize and destroy the pathogen
what is the ultimate result of complement?
formation of the MAC (membrane-attack complex (c5b, c6, c7, c8, c9)) which forms a pore resulting in cell lysis
What is an important general function of c3b?
It is a bridge to adaptive immunity (phagocytosis)
how does the phagolysosome kill ingested material?
release of superoxide via NADPH
What are the general functions of dendritic cells?
Very good APCs –> present Ag to T cells
multiple PRRs
roam freely
high phagocytic activity
do not promote inflammation
what kind of antigen does MHC class I primarily present?
present peptide generated within the cell
what kind of antigen does MHC class II primarily present?
exogenous antigen
What are innate lymphoid cells and how are they different from T/B cells?
there are 3 groups of ILCs: they use PRR and produce cytokines
- have no RAG gene
- lack of myeloid cells/don’t have DC marker
- lymphoid morphology
