9 Immune responses to viruses Flashcards
what are the innate defences in innate immunity
- Interferon
- NK cells
- Macrophages
- Cytokines
what are the defences in acquired immunity
- Humoral
- Cell mediated
what do the immune responses ideally do
- protect
- Irrelevant to ineffective parts of microorganism
- harmful
- counter protective
how should the immune responses protect
> sterilising (eradication)
concomitant (harmless symbiosis)
modulating (environment changed)
what is innate immunity
- “natural” /’fixed”
> non- specific
what is active adaptive immunity
- highly specific recognition
- adaptive response, learning/memory aspect
- antigen/antibody (humoral)
- T cell involvement (cell-mediated)
what is passive adaptive immunity
- (serum, colostrum)
> cross over between innate and acquired system
> cell mediated immunity
what happens in slow developing diseases
slow infection
transmissible agents ‘multiply’ without resulting in disease symptoms until cause fatal infection
what happens in chronic infection
after initial infection with or without disease symptoms infections virus released from host with no symptoms
what happens in latent infection
after initial infection, virus replicates in neurons in non-infectious state
virus activated to make new disease symptoms
what happens in acute infection
virus disappears after disease ends
what is the immune system overview for natural host resistance
- Lack of pathogen receptors
- Chemical or physical barriers
- Innate Immunity
what are the innate defences
surface barriers
internal defences
what are the surface barriers
skin
mucous membranes
what are the internal defences
phagocytosis fever NK cells antimicrobial proteins inflammation
what does early immune defence lead to
innate immunity
what leads to innate defences
barrier defences breached
what are interferons
“proteins secreted by virus infected cells”
what are interferons for
to protect non-infected
Stimulate T cell response
what are the types of IFN
type I
type II
which IFN are type I
IFNα: leucocyte IFN
IFNβ: fibroblast IFN
IFNτ/ε: trophoblast IFN
IFNλ and IFNκ (new groups)
which IFN are type II
IFNγ: Ag stimulation of NK and T cells
what does IFN-alpha and IFN-beta activate
- Antiviral mechanisms in neighbouring uninfected cells
- Intracellular defences
what triggers the antiviral state
dsRNA
what is the IFN response
- Antiviral protein
- MHC-I molecules
- NK activation
- Apoptosis (induction)
- Gene activation for Antiviral proteins
- MHC I
what does MHC I molecules do in IFN response
Present viral peptide on infected cell surface to T cell
what are NK cells known as
LGL = “large granular lymphocytes”
what are NK cells like
Like lymphocytes with more cytoplasm
what does NK cells do
Kill virus infected, and have some action against tumour cells Recognize surface structure changes of infected cell Require activation (very quick compared to the adaptive)
what happens after NK activated
- Release perforins
- Induce apoptosis
- Release IFNγ help activated acquired immune system
- ADCC (~acquired)
what is the activation of NK like
quick
what is a macrophage
Phagocytosis virus + viral infected cell
what do macrophages do
Killing (“cytotoxic”) of viral infected cell
what does antiviral enzymes do
Induce mutation affecting RT => viral “death”
what does tetherin do
Prevents budding of viruses by tethering virus and lipid membrane
what does IFN do in viral count measures - stopped
Proteins to block production or activity
General gene expression inhibition (e.g. poliovirus)
what does NK cells do in viral counter measures - stopped
- Down regulation of MHC-I expression to avoid detection
- Altering/Non-expression of activator proteins on NK surface = inhibition of NK response
what does tetherin do in viral counter measures - stopped
Vpu protein block expression/degrade of tetherin
what is the high viral count for in acquired immunity
- Ab non-neutralising
> excess Immune complex
> Immune complex deposits (tissue/fluid) Inflammatory response
what is the ADE for in acquired immunity
“antibody dependant enhancement” of virus infection
- Macrophage uptake of poor neutralising Ab replication in macrophage ADE
what is CTL’s activity in acquired immunity
- Tissue damage where CTL’s infiltrate
- Some cases disease severity/death is result of CTL
what is the auto-immune reaction in immune response damage
- Tissue damage induces inflammation followed by:
- Ag presentation of host’s own Ag (normally undetected)
Or - Viral molecular mimicry of self-protein loss of immune tolerance to own tissue
what is involved the humoral immunity - antibody structure
- Antigen binding (Fab site)
- Biological activity induction site (Fc)
- Fc domain (H chain)
what are the 5 types of antibodies
- IgG
- IgM
- IgA
- IgE
- IgD
what does IgG do
opsonisation
what does IgM do
complement, opsonisation, agglutination, virus neutralisation
what does IgA do
dimer
mucosal surface and secretion areas (sIgA)
what does IgE do
acute phase Type I hypersensitive
helminth, protozoa
what does IgD do
Relatively unknown
what is the humoral immunity
B-cell produce Ab
IgM, IgG and IgA
what does B-cell produce Ab for
anti-viral response
what does IgM, IgG and IgA do
prevent spread between cells, tissues and blood stream
Prevent re-infection (site of entry)
what is the effect of direct AB binding
- Viral neutralisation
- Complement limited effect
what are the AB mediated effects
Opsonisation viral infected cell
Complement activation
ADCC (Antibody Dependant Cell-mediated Cytotoxicity
what is the Opsonisation viral infected cell
response by immune cells to Fc –receptor
Neutrophils + macrophages, NK cells
> Results in enhanced phagocytosis
what is the complement activation in AB mediated effect
- Destroy viral infected cells
- Damage viral envelope (free virus)
- Virus opsonisation enhanced phagocytosis
what is the ADCC AB mediated effect
- by ADCC “competent cells” (Tcytoxic, macrophage, NK)
- Tcytoxic cells binds to Ab coated viral infected cell
= perforin dependant killing of cell - Better at detecting infected cell than complement activation
Note: involves both - humoral + cell-mediated response!
what are the T-cell mediated responses
CD4+ T cell (T-helper cell)
CD8+T cell (CD8+ CTLs)
what is the CD4+ T cell (T-helper cell) response
- essential for B-cell/ Ab response
- Induce CD8+
- Ab more essential to prevent re-infection
what is the CD8+T cell (CD8+ CTLs) response
- Destroy virus infected cells
- MHC-1 dependant: viral protein presentation
- Perforin cytotoxic attack
- “Clear” persistent infection through IFNγ and TNF
what do cytokines do
immune ammunition/communication
what makes IFNγ and TNFα
Produced by CD8 and CD4 Tcells
what is IFNγ
Macrophage activator
what does TNFα do
induction of
- Intracellular IFN
- Apoptosis
what are the viral counter measures
Antigenic variation
IFN disruption
Cytokine
Chemokine disruption
what does the antigenic variation do
able to rapidly change the virus particles on the surface – affect APC
