L10 - Immunity against infection Flashcards
What are viruses?
Obligate intracellular parasites, but may also be extracellular at some stage in infection
Innate defences against viruses
Interferons
Natural killer cells
How do viruses infect host cells?
1) Virus infects the host cell & takes over machinery
2) Upregulation of interferons alpha & beta – type 1 interferons
3) Prevents viral nucleic acid production/replication
4) They activate NK cells & dendritic cells
5) Produces lots pf cytokines – induce chemokines
6) Switches on the adaptive response
Types of interferons & what they do
Synthesis of IFN-alpha & IFN-beta (type I) induced in virus-infected cells is the early response to infection
Type II interferon – IFN-gamma secreted by activated T cells & NK cells
• Inhibits TH2 response (antiboides) & promotes TH1 (cell killing)
• Recruits macrophages
What are type I interferons?
IFN-alpha & IFN-beta
What are type II interferons?
IFN-gamma
Therapeutic uses of interferons
rIFN-alpha (recombinant) can be used to treat hepatitis B & C
Some cancers – kidney & melanoma
Side effects – can be very severe
• Cytokine storm – massive fever, flu like symptoms
What are natural killer (NK) cells?
- Type of innate lymphoid cells
- Large granular lymphocytes
- Recognise structures on viral infected cells
- Can recognise stressed cells in absence of Igs and MHC
- Kill by extracellular mechanism- perforin and granzyme
- FAST
Role of NK cell receptors
Needs to distinguish between infected & uninfected host cells
Types of NK cell receptors
Activating receptors: recognise carbohydrate ligands, triggers killing
Inhibiting receptors: recognise MHC class I molecules (no binding – only TCR can do this)
Cell mediated specific immunity against viruses
Cytotoxic T cells (CTL) • Recognise viral peptide + MHC class I
Cytokines with anti-viral activity • Eg. IFN-gamma (class II) – activates macrophages to produce cytokines to induce cell response
Mechanisms of killing by cytotoxic T cells
2 mechanisms: both induce apoptosis in the target cell
1) Secretion of cytotoxic granules
– Perforin – polymerises in membrane
– Granzymes (proteases) enter cell
2) Fas ligand on T cell interacts with Fas on target –> RIP
What does the release of granules do?
- Can kill several host cells
- Need recognition & fusion
- Controlled release – cytoskeleton migrates to be in the vicinity of the cell – polarised
- Releases through close contact
How do CTLs work?
Limits the infection by limiting the amount of virus particles
No inflammatory response – still contained & no inflammation
What cytokines do CTLs secrete?
Secrete IFN-gamma
- Inhibits viral replication
- Upregulates MHC class I & II expression & antigen presentation
- Increases macrophage phagocytosis of dead cells
- Promotes NK cell killing activity
Specific immunity against viruses
ANTIBODIES
Neutralise free virus (prevent entry into and spread between cells)
• Can prevent spread within the body (e.g. poliovirus) or protect mucosal surfaces against reinfection (e.g. ‘flu’)
Opsonise to increase phagocytosis
Activate complement leading to lysis (enveloped viruses)
Antibody & cell mediated immunity in influenza
Infection induces antibody and cytotoxic T cell (CTL) response
Antibody recognises viral haemagglutinin and neuraminidase
High levels of CTL activity correlate with reduced viral shedding
Epidemics arise due to new strains not recognised by antibody
HIV
Can develop to AIDS
Attacks specific immune system
Targets CD4 T cell, macrophages and dendritic cells
Progressive development of AIDS leads to opportunistic infections
Opportunistic infections of AIDS
Kaposi’s sarcoma: herpes virus B
TB
Fungal infections
How is HIV infection controlled?
Antibodies to HIV do not seem to protect
Infection may be controlled by cytotoxic T cell responses
• Patients with higher levels of CTL activity show slower disease progression
• Virus mutations that escape CTL recognition may lead to progression to AIDS
What are parasites?
Where one organism, the parasite, lives on or in another organism, the host, causing it some harm
A diverse range of organisms: unicellular or multicellular
Often multiple complex stages in life cycle
How do antibodies protect against parasites?
Opsonisation
Complement lysis
ADCC – antibody-dependent cell-mediated cytotoxicity
Cell mediated immunity against parasites
Important for protozoa that can survive in macrophages (e.g. Leishmania – not in the UK but in southern Europe – sandfly vector) hidden from Igs
Cytokines important in inducing macrophage activation (eg IL1)
What is cell mediated immunity?
Cell-mediated immunity is an immune response that does not involve antibodies
Rather, cell mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to antigen
Malaria
Has a complex life cycle
Different effector mechanisms active at different stages
- Sporozoite and merozoite may be susceptible to antibody
- Antibody may also kill infected red blood cells
- Cytotoxic T cells active against infected liver cells
