Intracellular Immunity Flashcards
How do interferons prevent viral infection of host tissues?
They are secreted quickly and are antiviral (bind and block viral receptors)
What is the difference between type 1 and 2 interferons and how do they work?
Type 1- (IFN alpha and beta)- from tissue cells, stimulate NK activity against viral cells and secretion of IFN gamma
Type 2- IFN gamma- from activated T and NK cells, prevent viral growth by induction of nitric oxide secretion and more intracellular IFN production and activate macrophages
How does Th1 activate macrophages and CD8 cells?
CD4 cells bind to infected cell with TCR and MHC I and from the microenvironment produce IFN gamma which primes macrophages and activates CD8 cells
How do CD8 cells destroy bacteria and viruses?
Virus/bacteria within a cell can be targeted for killing
Cytotoxic granules contain granzyme or perforin leading to loss of membrane integrity
Alternatively programmed cell death can be triggered by CD8 using FasL on their surface to bind with Fas on the target cell
How do macrophages activated from Th1 cells destroy pathogens?
Macrophages receiving activation signals from Th1 cells express nitric oxide and other radicals, the can cause host cell death
Not very specific though
How do natural killer cells become activated and how does it kill intracellular infections?
NK cells become activated from IFN gamma from Th1 cells
NK cells recognise MHC I on health cells and don’t kill, infected cells decrease MHC I on surface so NK cells destroy it
Why are Th1 and Th2 both needed for protozoal infections?
Th1 is needed for stimulation of Th2, macrophages, NK cells and neutrophils
Th2 is needed for cytotoxic T cells
What are the 4 pathogenic mechanisms of viruses?
1) Lytic infections- destruction of host cells
2) Persistent infection- no cell lysis, release viral particles over long period
3) Latent infections- delay between the infection and appearance of smptoms
4) Transformation- to tumour cells
What are the adverse consequences to viral immunity?
Inappropriate or excessive immune responses
Leads to damage of infected/neighbouring cells:
Distemper (demylination)
Canine adenovirus (blue eye)- immune complexes deposited in cornea, neutrophils respond and damage opacity of eye
What are the normal pathways of humeral and cell mediated immunity responses?
Humoral- Antibodies control parasite numbers Th2 driven
CMI- intracellular parasites, Th1
Both needed
How can protozoa evade immunity with examples?
Resistance to complement- Trypanasoma- not lysed, Leishmania- blocks C5-9
T.gondii- survives inside phagocytes, manipulates dendritic cells
Leishmania poor PAMP expression
What secretes exotoxins?
Bacteria
What is an endotoxin?
Toxin attached to bacteria- LPS and Lipid A
What are LPS and Lipid A?
LPS is outer leaflet of gram -ve bacteria and is an endotoxin (activates macrophages which causes tissue degradation)
Lipid A part of outer leaf and is endotoxin (activation of coagulation)
What is endotoxic shock?
Excessive release of cytokines, often triggered by LPS , leads to intravascular coagulation causing defective clotting, increased vascular permeability, loss of fluid to tissues, fall in blood pressure, circulatory collapse, particularly in gut
