anti-viral immunity Flashcards
what is the innate immune system
everything from your skin, bone marrow, spleen, liver, lymph nodes, tears, pH, micro-organisms that live on and in body
2 parts of the immune system
Natural- what you are born with
educated - what has to be developed and taught how to fight
parts of the innate immune system
Barriers (epithelial barriers)
Phagocytes
macrophages
NK cells
the initial attempt to stop the bacteria from getting in and establishing an infection
Innate immunity
what cell appears first in a bacterial infection
a neutrophil
what cell appears first in a viral infection
NK cell
how does Innate and Adpative immunity work together
Innate sets up the stage and then adaptive goes in and destroys shit
what T cells are absolutely criticial for fighting Viral infections
CD8+
what cell is needed to active CD8+ cells so they can fight viral infections
Helper t cells (CD4)
what part of adaptive immunity is needed to fight viral infections
all parts
what do CD4 (helper T cells) make
make cytokines
importance of cytokines
without, you cannot effectively fight viral infection
what type of Immunity protects agianst infection
both innate and adaptive
what type of immunity eradicates an established infection
both Innate and adaptive
what is essential for the innate immune system to begin work
the cytokines made by the NK cells in addition partly to the T cells cytokines
Roll of Type I interferon (IFN)
directly neutralize a virus by coating and binding to the Virus
bind to cell and turn on machinery that makes that cell resist the virus
how does an interferon block viruses from infecting
keep cells from taking up the virus in the first place
how does adaptive immunity protect from infection
B cells make antibodys that bind to the virus and neurtralize it
what antibody isotype is important for antibody neutralization
IgG and IgA( IgA is in mucal secretions)
how does innate immunity eradicate an established infection
NK cells induce appoptosis of infected cells
how does adaptive immunity eradicate established infection
CD8+ CTL induce apoptosis of infected cells
what must the body do in order to fight infection
it must be able to realize that it has been infected
why must a virus replicate within cells
they cannot generate energy or synthesize proteins on their own
what kind of parasite are viruses
can only reproduce within cells: Obligate intracellular parasites
where in the Cell does it detect most bacterial infections
on the outside of the cell
where are receptors that sense viruses located
inside of the cell
Toll like receptors sense
pathogen associated molecular patterns
what do toll like recptors do when the sense a pathogen
tell the cell to start doing shit
what cytokine is important for fighting viral infections
interferon
what is a PAMP for a virus
Viral DS RNA
VIral single stranded RNA
Viral and bacterial unmethylated CpG DNA
what happens to the TLR when it binds to a PAMP
it becomes phosphoralated leading to a signal transduction pathway and recruitment of transcription factors
what would a cell make if something binds to a TLR and it heads down the signal transduction pathway
inflammatory cytokines Chemokines Endothelial Adhesion molecules Costimulatory molecules Antiviral cytokines
Cytokine that makes a chemical gradient telling cells to come here
Chemokines
what parts of the innate immune resposne are common to all pathogens
Phagocytosis and kiling of microbes
Antigen presentation
Cytokine production to induce inflammation and reactive endothelium
does the innate immune system repond the same to all intracellular pathogens
No (especillay viruses)- regulation of genes to turn on interferon alpha and beta
what comprises a large group of IFN proteins
Human type I interferons
what does the name interferon come from
Interfering with a virion
the two important types of anti-viral type I interferons
Interferon-alpha and Interferon-beta
Types of IFN-alpha proteins
13 subtypes called (IFNA 1, IFNA 2…)
types of functionally active IFN-beta proteins
1 functionally active type
what is the most potent stimulus for IFNs
Viral nucleic acids as detected by pattern recognition receptors (dsRNA, ssRNA, unmethylated CpG DNA)- internal toll like receptors
where are Homologous molecules to IFN-alpha/beta
in many specifies (most mammals) also birds, reptiles, amphibians, and fish
functions of Type I INF
inhibits viral replication and inhibits viral protein synthesis
how does INF stop viruses from infecting new cells
induces the synthesis of proteins that are able to inhibit protein sysnthesis and also degrade viral mRNA
what must the immune system kill to kill an intracellular pathogen
must kill host cell infected with intracellular pathogens
what cells are involved in killing infected host cells
Cytotoxic T cell
Natural KIller Cell
what does a Natural Killer Cell kill
Kills a stressed cell(going to become a tumor) and Infected cell
what percentage of Leukocytes are NK cells
5-15%
Primary job of NK cells
Kill Virally infected (or tumor) cells)
Produce cytokines important for infection
are NK cell MHC restricted
no
What part of the immune system are NK cells because they are not MHC restricted
they are part of the innate immune response
can NK cells develop a memory response
No, because they are innate immunity
Big difference between NK and T cells
NK is non-specific( has non-specific receptors)
What does a T cell need in order to see an antigen
It need the antigen presented via MHC by an antigen presenting cell
what on cells deals with tissue compatability
MHC
How can NK cells kill target cell
the death receptor
Granule-dependent pathways (Perforin and GRanzymes)
why would a target cell have a death receptors
if it knows its infected or is about to become tumor if will up-regulate the receptors
ligands from NK cells binding to the Death receptor leads to
apoptosis in the target cell
when does the NK or T cell release Granules
contact dependent to the Target cell
what does the Granul perferin do
pokes holes in the target cell
difference between Apoptosis and Necrosis
Apoptosis is planned cell death (ordered)
Necrosis is unplanned cell death (unordered)
Death Receptor
FasL on NK cell binds to FasR(death Domaine) on Target cell.
This initiates the phosphorylation that tells the cell to die
Cytotoxic Granuoules Pathway
Cytoxic GRanules are made and released because of sensing a problem.
Vescicles containing Cytotoxic Granules release contents due to contact with Target cell.
Perforin creates a hole in the Target cell
Release of Granzymes
Granzymes cause phorsphoylation pathway turning on Caspase pathway leading to cell death via the death receptors
what is Immmunologic memory a property of
B and T lymphocytes
when is Immunologic memory acquired
after Primary (initial) exposure to a given Ag
what does Immunologic memory hep with
faster and more robust secondary response after a subsequent exposure
why do vaccines work
Immunologic memory
why do individuals rarely suffer from the same disease twice
Immunologic memory
Can you transfer a primary response
can be transferred by a small lymphocytes
How do All T cell recognize Ag
via the T cell receptor (TCR)
Begore TCR can recognize an Ag it must be
Processed by the antigen presenting cell
Presented by the Antigen presenting cell
What is done in processing an Ag by an Antigen presenting cell
Ag is broken down into short fragments (peptides)
how can an antigen presenting cell present and Ag
MHC I - viral
MHC II - bacterial
Do B cells require an Ag to be presented to them
no, they do not, since B cells have membrane bound Ig that can recognize the Ag in its native form
what cells have MHC I
Constitutively present on virtually all nucleated cells in the body
what do MHC I cell present
endogenous Ag ( critical for immunity to viruses)
who does MHC I cells normally present to
to cytotoxic T cell
what cells have MHC II
Constitutively expressed on professional APC’s (Macrophages, Dendritic Cells, B cells)
what is MHC II critcal for activation of
Naive T cells
regulation of MHC II
up-regulated on infected cells
what does MHC II present
exogenous Ag ( critical for immunity to bacterial)
who does MHC II present Ag to
Helper T cells
Effector function (what happens) if Th Cells are activated
Cytokine Secretion
Importance of Cytokine secretions from Th cells
Activation of macrophages
Activation and enhanced Ab production by B cells
Activation and enhanced kill of Cytotoxic T cells
what cytokine does Th cells secrete to activate macrophages
Th Cells make IFN-gamma
what cytokine does Th cells secrete to activate and enhance Ab production by B cells
Th cells makes IL-4 and other cytokines
what cytokine does Th cells secrete to activate and enhance killing of cytotoxic T cells
Th cells make IFN- gamma
Effector function of cytotoxic T cells
Killing of Infected or Tumor Transformed cells
Cytokine Secretion
how does A Cytotixic T cell kill infected or tumor transformed cells
Perforin
Granzmes
What cytokines do Cytotoxic T cells secrete
IFN-gamma
Tumor Necrosis Factor- TNF-alph
action of TNF-alpha
Aids in th cytolytic process
what is needed for a Cytotoxic T cell to release Granules for killing a target cell
TCR binding to MHC I on target
how can virally infected cells be killed
Specific T cell cytotoxicity
Killer activated recetpor-mediated cytotoxicity
downregulation of Killer inhibitory receptor (located on tissue)
Antibody Dependent cellular Cytotixicity
how does something die via a Killer inhibitory receptor
NK cell sees a cell presenting a Killer inhibiotry receptor, it will inhibit the killing pathways
Antigbody dependent Cellular Cytotoxicity
Antibody bonds to the antigen of a virus infected cell.
FcR from a NK cells binds to the Fc portion of an antibody that is bond to the antigen of a virus infected cell
Immune Responses Against Viruses over time
IFN-alpha and beta peak NK cells peak Virus Titer Peaks Virus specific CTLs peak and plateau then fall Antibody peak
