Lecture 3: Innate Immune System Flashcards
Innate immunity is _____
The first line of defense and what people are born with
Innate immunity is _____
The first line of defense and what people are born with
How long does immediate innate immunity last?
0-4 hours
What are the steps
Infection > Recognition by preformed, non-specific and broadly specific effectors > removal of infectious agent
How long is early induced innate response?
4-96 hours
What are the steps of early induced innate response?
Infection > recruitment of effector cells > recognition of PAMPS, activation of effector cells, and inflammation > removal of infectious agent
When does adaptive immunity kick in?
After 96 hours
What are the lines of defense for adaptive response?
Infection > transport of antigen to lymphoid organs > recognition by naiive B and T cells > clonal expansion and differentiation to effector cells > removal of infectious agent
What does innate immunity constitute?
The first two phases of the response (tissues like the skin and mucosal surfaces
What kind of receptors does the innate immune system use?
Germ-line encoded receptors
What type of surfaces provide the first line of defense against infection?
Epithelial surfaces
What do keratinocytes produce?
beta-defensins and other microbicidal compounds in lamellar bodies and are secreted into extracellular spaces
What does the lung have that moves a stream of mucus up?
Cilia
What are intestinal cells called and what do they produce?
Paneth cells that produce alpha-defensins and other antimicrobial proteins
What do dendritic cells do along with macrophages?
they form a bridge between innate and adaptive immune responses
What are the granulocytes in the innate immunity?
neutrophil, eosinphils, basophils, and monocytes
What is in the adaptive immunity?
B cells and T cells
What do innate mechanisms defend against?
extra and intracellular pathogens
For interstitial spaces, blood, lymph, what are the protective immunity components?
Complement, Phagocytosis, Antibodies
For epithelial surfaces what are the protective immunity components?
Antimicrobial peptides, antibodies especially IgA
What are the two intracellular areas of pathogens?
Cytoplasmic and vesicular
What protective immunity is in the cytoplasmic area?
NK cells, cytotoxic T cells
What kind of protective immunity is in the vesicular area?
T-cell and NK-cell dependent macrophage activation
How do the extracellular areas clear up the pathogens?
They promote uptake and destruction by phagocytes
How are the intracellular pathogens killed?
- infected cell is attacked by NK cells (innate) or cytotoxic T cells (adaptive)
- Activation of macrophages by NK cells or T helper cells can induce macrophages to kill pathogens living within vesicles
What is an example of an autocrine effect?
The IFN producing cell depicts a cell induced to synthesize IFN in response to either virus infection or antigen or mitogen stimulation
What is an example of a paracrine effect?
IFN-regulated proteins that collectively constitute the antiviral response that is responsible for the inhibition of virus multiplication
Interferons induced by _________ make several contributions to _______
viral infection, host defense
What are the IFN induced proteins believed to affect virus multiplication within single cells:
PKR kinase, OAS synthetase, Mx protein, ADAR, and IFN-induced expression of MHC class 1 and 2 antigens and NOS.
PKR kinase inhibits ______ through the phosphorylation of __________
translation, protein synthesis initation factor elf2
OAS synthetase family and RNase L nuclease mediate _______
RNA degradation
What is the family of MX protein GTPases?
They appear to target viral nucleocapsids and inhibit RNA synthesis
IFN-induced expresssion of MHC class 1 and class II antigens and NOS may contribute to ______
the antiviral responses observed within whole animals
What is ADAR?
Edits double-stranded RNA by deamination of adenosine to yield inosine
IFN A and IFN B chart Step 1:
induce resistance to viral replication in all cells by inducing Mx proteins, 2 -5 linked adenosine oligmers, and the kinase PKR
IFN A and IFN B chart Step 2:
Increase MHC class 1 expression and antigen presentation in all cells
IFN A and IFN B chart Step 3:
Activate dendritic cells and macrophages
IFN A and IFN B chart Step 4:
Activate NK cells to kill virus-infected cells
IFN A and IFN B chart Step 5:
induce chemokines to recruit lymphocytes
What are the direct mechanisms of pathogenesis?
Exotoxin production, endotoxin, direct cytopathic effect
What are the indirect mechanisms of pathogenesis?
immune complexes, anti-host antibody, cell-mediated immunity
What are the most abundant cells in early infection that release many proteins and small-molecules inflammatory mediators that both control infection and cause tissue damage?
Neutrophils
What activates several types of receptors that evolved to detect pathogens and initiate an immune response?
macrophages and dendritic cells
T/F: Specificity inherited in the genome is in innate immunity
yes
Each receptor is devoted to recognizing a distinct set of molecular pattern are not found in healthy cells which is called _____
Pattern recognition receptors
Patterns are characteristics of components of pathogenic microorganisms and are called ___________
Pathogen-associated molecular patterns or PAMP
Where are TLRs?
On surface dendritic macrophages, and other cells - detect extracellular pathogens
TLRs located ____
Intracellularly
Where are TLR3 and TLR9
In the wall of endosomes - they recognize microbial components such as DNA and RNA that are accessible only after the microbe has been broken down or when microbe enters cell via endosomes
Cytokines and chemokines are involved in ______
Innate responses
Where do cytokines and chemokines act on?
Different families of receptors and are responsible to mediate cellular activation and trafficking
How are macrophages and dendritic cells activated?
By pathogens that secrete a range of cytokines that have a variety of local and distant effects (autocrine, paracrine, and endocrine)
What are the 5 different important families of cytokines and chemokines
IL-1B
TNF alpha
IL6
CXCL8
IL-12
What does IL1B do?
Activates vascular endothelium
Activates lymphocytes
Local tissue destruction increases access of effector cells
What are systematic effects of IL1B
Fever production of IL6
What does TNFAlpha do?
Activates vascular endothelium and increases vascular permeability which leads to increased entry of IG, complement, and cells to tissue and increased fluid drainage to lymph nodes
What are the systemic effects of TNF alpha
Fever mobilization of metabolites shock
What does IL6 do?
Lymphocyte activation increased antibody production
What are the systematic effects of IL6?
Fever, induced acute phase protein production
What does CXCL8 do?
Chemolactic factor recruits neutrophils, basophils, and T cells to the site of infection
What does IL12 do?
Activates NK cells induces the differentiation of CD4 T cells in TH1 cells
What do chemokines released by dendritic cells do?
Recruit effector cells to sites of infection
What can the chemokines be specific for?
Different cell types and tissues
Chemokines act on
G protein coupled receptors
Cell-adhesion molecules control interactions between ________ and _____ during an inflammatory response
Leukocytes and endothelial cells
Different cytokines have different effects on cells to express ________
Adhesion molecules on their surface
Infectious agents must overcome _______ to establish a focus of infection
Innate host defenses
First step of infectious agent: adherence to ______
Epithelium ; normal flora, local chemical factors, phagocyte (especially in lung)
Second step of infectious agent: local infection ______ of epithelium
Wound healing antimicrobial proteins and peptides, phagocytes and complement destroy invading microorganisms
Third step of infectious agent: local infection
Complement, cytokines, chemokines, phagocytes, NK cells,
Activation of macrophages, dendritic cells migrate to lymph nodes to initiate adaptive immunity
Blood clotting helps limit spread of infection
What is the fourth step of the infectious agent?
Adaptive immunity: infection cleared by specific antibody, T-cell dependent macrophage activation and cytotoxic t cells
What are the four distinct steps in cell migration from the blood into the tissues?
Rolling adhesion, tight binding, diapedesis, migration
What makes up the first wave of cells that cross the blood vessel wall to enter an inflamed tissue?
Neutrophils
What reduces the blood pressure and the speed of blood flow?
Vasodilation
What activates secretion of innate cytokines and chemokines and expression of adhesion molecules?
Pattern recognition receptors
What is Selectin mediated adhesion?
They bind to leukocytes and allow leukocytes to roll along the vascular endothelial surface
What does the innate immune response generally result in?
Inflammation
What does activation of innate cells lead to production of?
Cytokines and chemokines that convey important signals to other immune cells
What is a cytokine?
Any protein that is secreted by a cell and affects the behavior of nearby cells expressing appropriate receptors
What are chemokines?
They are secreted proteins that act as attractants, bringing cells out of the bloodstream and into infected tissues
What activate cytokines and chemokines?
Macrophages which initiate a process called inflammation
What is inflammation described as (4)
Heat, pain, redness, and sewlling
What does inflammation involved that directly kill the pathogen
Recruitment of cells
What does inflammation to the lymphatic system?
Increases lymph flow to draining lymph nodes, where microbes and associated cells will initiate
After entering the tissues, the pathogens are recognized, ingested, and killed by what?
Phagocytes
What expresses receptors that enable them to take up microbes by phagocytosis?
Macrophages and dendritic cells
Which two receptors are proteins that bind sugar residues?
Destin 1 and mannose
Which receptors recognize polyanionic sequences of many types?
Class A scavenger receptors
What types recognizes and internalizes lipids?
CD36
Which receptors internalize complement coated bacteria?
Complement receptors
What leads to fusion with lysosomes forming acidified phagolysosomes where ingested material is broken down by acid hydrolases?
Internalization in phagosomes
What engulfs and kills the microbes to which they bind?
Neutrophils
What is microbicidal respiratory burst in phagocytes?
Induced by activation-induced assembly of the phagocyte NADPH oxidase
What does NADPH oxidase do?
Activation leads to a respiratory burst with transient increase in oxygen consumption by the cell
