Viral Immunity I

systems that act rapidly within minutes of the initial infection of a cell and locally, within the infected cell or in nearby cells

• three stages of it
• 1) pathogen recognition
• 2) signal amplification
• 3) pathogen control

toll-like receptors

Once these proteins detect the presence of a pathogen, they set off a highly coordinated response that involves receptor-mediated signaling, activation of gene transcription, secretion of proteins, and cell-to-cell communication

This response leads to the secretion of cytokines, including interferons, and the activation of enzyme systems that inhibit replication of the infecting pathogen within cells

• innate immunity
• adaptive immunity

acts quickly

takes days to weeks to deploy its maximum effects.

However, what is beneficial about it is that, once you get exposed to it once, the second time, the response is much quicker. This is due tot he formation of memory cells

receptors  located either on the cell surface or in endosomal membranes

recognize a variety of conserved molecular structures typically found in pathogens (ex: dsRNA)

Prokaryotes and eukaryotes have different defenses

• restriction enzymes
• CRISPR bacterial immunity

• cuts specific sites on DNA
• can be used for cloning and other apps
• early form of innate immunity in pro-k cells, which have modifications on their own DNA to prevent degradation
• innate and unchanging

• kind of like adaptive immunity
• With this, bacteria can incorporate foreign DNA and recognize it as foreign when it encounters it again

Phage infects bacteria

DNA injected

Bacteria cut up the viral DNA nand put it in specific places

The cells make a complex of proteisn (revolve around CAS proteins) with the foreign RNAs

Bacteria use this to recognize the foreign DNA upon further infection to degrade it

• Starting as early as binding of a virus to a receptor, several alarms go off.
• When certain molecules that our body recognizes as viral bind to the molecules, our cells know that something is wrong. Therefore, they send out molecules

• Interleukin-1a: molecular alarm
• Interferon: virus gets into the cell and triggers interferon expression--interferes with successful replication of virus in cell and nearby cells
• TLRs get released to recognize broad groups of molecules that we don't make but pathogens do

They exist in homodimers and are in various places of the cell

it usually recycles it and releases the building blocks for reuse

The cells turn up the digestion and freedom of building blocks. An infection would also turn up the rate of self-digestion. This occurs in special compartments, known as phagosomes. It will digest the stuff in hopes of freeing up viral material for TLRs to recognize

recognizes dsRNA

plays a role in recognition of viral nucleic acids by TLRs

intrinsic cell process

involves the use of phagosomes

There is RIG-I and also MDA5. They recognize viral RNAs (ds)

Binding of viral proteins or nucleic acids to toll-like receptors leads to the recruitment of the downstream adaptor molecules MyD88 and TRIF

Most TLRs interact with MyD88

Through a series of reactions, these adaptors recruit protein kinases, which initiate the NF-kappaB signal transduction cascade

NF-kB moves into the nucleus and acts as a TF to induce expression of interferons, other cytokines, and interferon-stimulated genes

Cell can commit suicide as a result of infection. A lot of the signals inside and outside of the cell lead to apoptosis.

intrinsic: internal stress/ viral DNA replication and DNA damage can cause the pathway to be activated

extrinsic: cells know that the cell is defective. It will signal it with a bunch of molecules, such as TNF (tumor necrosis factor). The cell notices a cell is infected, releases TNF, and causes apoptosis/ binding of a molecule to receptors on cell surface

• apoptosis
• caspases

• cytokines
• intrinsic cellular defense system
• innate immune response
• innate
• adaptive immune system

• interferons: major players in host defense against most viruses; can be produced by either immune cells or normal cells
• Pro-inflammatory cytokines: activate immune cells in the circ system; can keep a pathogen localized in the inflamed area
• chemokines: recruit other immune cells to site of infection
• anti-inflammatory cytokines: suppress the pro-inflame cytokines; work to keep swelling at a level that won't cause damage

Things that the cell releases when infected to help stop the infection

The virus gets in, sets up shop, makes viral proteins. The cell responds by making viral interferons since viral infection induces its expression. The cell itself may die but it will signal other cells by sending interferons to protect the cell.

• If a cell is being hit with it, it will make 2',5'-oligo(A) synthetase and ribonuclease L.
• The 2',5'-oligo(A) synthetase is activated by binding to dsRNA and then makes an oligo(A) that activates ribonuclease L to degrade both host and viral mRNAs, stopping the infection

PKR

Expression is increased by presence of virus. It is activated by dsRNA. Two molecules bidn to the RNA, phosphorylating each other and inducing a conformational change that increases their kinase activity. They then phosphorylate a variety of cellular proteins.

• 1) eIF-2 is phosphorylated by PKR, which leads to formation of an inactive complex that involves eIF-2 bound to guanosine diphosphate and the recycling factor eIF-2B. Normally, eIF-2B catalyzes the exchange of GDP to GTP, and the regenerated eIF-2-GTP complex binds to initiator met-tRNA and forms a translation initiation complex with mRNA and a ribosomal subunit.
• 2) Since the GDP-GTP exchange reaction is blocked, insufficient met-tRNA-eIF-2-GTP complex is formed and translation initiation can't occur

have at least one mechanism for averting these processes of infection. They can prevent interferon inhibition. Some hide their RNA so as not to be found. Others inhibt TLR synthesis and RNA helicase signaling. Others inhibit functioning of IRF-3 and activation of PKR