Lec 20-Immunity To Viral Infection Flashcards
(40 cards)
Layers of response to viral infection:
INNATE:
- Structural protection
- Induceable protection
- Cell-mediated protection
ADAPTIVE:
- CTL (cytotoxic T cell)-mediated protection
- Antibody-mediated protection
When is adaptive immunity activated?
Adaptive immunity relies on the innate immune sys. It is activated after innate immune sys has given fast and effective response to mitigate infection
Structural protection to viral infection
- Barrier immunity (first line of defence)
- Skin protects us from pathogens. Sweat also makes skin surface unfavourable to pathogens
- GI tract has mucosal barrier to trap bacteria, cilia move pathogens, peristalsis to cause vomiting, acids and enzymes to degrade
- Vaginal tract has mucous to trap pathogen, urine washes pathogen out of bladder and urinary tract
- Stomach acid/low pH in stomach is not liked by viruses bc it degrades proteins
- Respiratory airway has specialized cells to trap pathogens, have cilia that can cause vomiting
- Eye responds with tears to try to chop lyse virus that may enter thru eye
Innate immunity to viral infection
- Second layer of defense if first is overcome
- Virus enters epithelial cell membrane and starts to reproduce inside cell. Cell detects virus using PRRs. Detection of virus activates interferon responsive factor (IRF), which are the transcription factors that make IFN. mRNA becomes protein and is secreted, is received by IFN receptors on neighbouring cells so they can start making antiviral proteins before virus tries to infect it
What are interferons?
Interferons (IFN): Small cytokine secreted by virally infected cells as soon as they are infected (very quick). IFNs tell other cells that there is a virus!
Examples of ways can we block virus? (3)
- PKR can feel dsRNA virus, and prepares cell to stop translation so virus doesn’t reproduce
- Oligo-A-synthase can also feel dsRNA virus, promotes degradation of transcript to ensure mRNA from viral genome doesn’t do anything
- Mx proteins inhibit transcription and virus assembly even if transcription does occur
Overall point of IFN signal…what does it do
Overall point: IFN signal mounts response that preps the cell itself to block transcription, translation, and assembly of viral protein
What are NK cells?
- Cytotoxic lymphocytes
- 5-10% of circulating lymphocytes
- Part of innate immunity to viral infection
- Help to eliminate infected host cells or tumour cells
- Are activated by cytokines and also secrete cytokines
When do NK cells come into play? How fast do they proliferate?
- Comes into play approx 4 days after infection, after IFN response
- Proliferate fast
Phenotypic characteristics of NK cells
- Don’t come from myeloid progenitor, come from lymphoid progenitor but have no BCR/TCR
- Thymus is not required for development
- Do not undergo receptor gene arrangements
- Have a lot of receptors that can determine whether or not they kill target cell
How do NK cells decide what to kill?
- NK cells decide by looking for MHC1
- If MHC1 is exposed and empty, NK cells know that they dont have to kill this cell
- If cell has been infected w/ virus, 2 things could happen: 1. MHC1 is exposing viral antigen, CD8 T-cell will intervene or 2. MHC1 is hidden inside cell, NK cell activates stress protein receptors to promote release of granules from NK cell that contain perforin and granzymes which allow NK cells to kill
What is the NK cell receptor that recognizes MHC1?
KIR receptors (killer cell immunoglobulin-like receptors)
- They have an Ig domain
- Many kinds of KIR receptors
KIR receptor map on chromosomes
- KIR receptors sit on chromosome in the same area, meaning that variability of receptors increases with genetic evolution
- Do not have somatic recomb, so their variability is in their gene copy number
- Allows us to have a large range of KIR receptors to recognize diff signalling
- Humans have more possible KIR receptors than less evolved animals i.e. fish bc our immune systems are more sophisticated
How do NK cells kill?
- Via apoptosis
- Release perforin and granzymes at the junction of the 2 cells once signalling molecs are activated
Granzyme/perforin mediated cytolysis
- Granzyme and perforin are small proteins
- Perforin forms pore on target cell, granzyme can enter thru pore and degrade protein/initiate apoptosis of target cell
Cytotoxic T-cell mediated protection
- For cell-mediated adaptive immune response
- Cytotoxic T-cells AKA CD8
- Virus specific CTLs
- Most important pathway to fight viral infection
- Response begins on day 5/6, reaches peak 10 days post-infection. After 10 days is when you usually feel the worst
What if patient has T-cell deficiency?
Patients with T cell deficiency will always have overwhelming viral infection
Steps of Tc cell activation and killing
- Virus is killed and taken up/phagocytosed by dendritic cell
- Dendritic cell processes antigen and takes it to lymph node
- Dendritic cell presents antigen to Tc cells on MHC1
- Tc become activated, leave the node, travel to site of infection and recognize infected cells
- Tc kills virally infected cells
**this all happens in lymph nodes
How does a vaccine cause CD8 memory?
Dendritic cells can uptake, present, and build strong clonal response to pathogen
What are cytotoxic T-cells also called?
CD8
How does dendritic cell know if to do MHC1 or 2?
Depends on how DC uptakes pathogenic material:
- Bacteria: uptake by phagocytosis—MHC2—presents to CD4
- Virus: uptake by endocytosis—MHC1—presents to CD8
CD8 vs CD4 activation
CD8 activation:
- Same mechanism of CD4 activation
- TCR feels viral particle on MHC1, starts intracellular signalling, divides T-cell into effector and memory cells
- Virus is inside cytoplasm, therefore can be on MHC1 on ER
CD4 activation:
- Need larger antigen bc it needs to be engulfed by phagocytosis to be exposed on MHC2
What is cross-presentation?
- DCs can also uptake antigens from outside the cell, and present them on MHC1
- ONLY DCs do this
- Cross-pres is mechanism by which vaccines work
When do CD4 and CD8 interact?
CD4 and CD8 interact when there is immunological synapses for antigen presentation
