L10 - Immunity against infection

Question 1

What are viruses?

Answer 1

Obligate intracellular parasites, but may also be extracellular at some stage in infection

Question 2

Innate defences against viruses

Answer 2

Interferons

Natural killer cells

Question 3

How do viruses infect host cells?

Answer 3

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

Question 4

Types of interferons & what they do

Answer 4

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

Question 5

What are type I interferons?

Answer 5

IFN-alpha & IFN-beta

Question 6

What are type II interferons?

Answer 6

IFN-gamma

Question 7

Therapeutic uses of interferons

Answer 7

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

Question 8

What are natural killer (NK) cells?

Answer 8

• 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

Question 9

Role of NK cell receptors

Answer 9

Needs to distinguish between infected & uninfected host cells

Question 10

Types of NK cell receptors

Answer 10

Activating receptors: recognise carbohydrate ligands, triggers killing

Inhibiting receptors: recognise MHC class I molecules (no binding – only TCR can do this)

Question 11

Cell mediated specific immunity against viruses

Answer 11

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

Question 12

Mechanisms of killing by cytotoxic T cells

Answer 12

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

Question 13

What does the release of granules do?

Answer 13

• 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

Question 14

How do CTLs work?

Answer 14

Limits the infection by limiting the amount of virus particles

No inflammatory response – still contained & no inflammation

Question 15

What cytokines do CTLs secrete?

Answer 15

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

Question 16

Specific immunity against viruses

Answer 16

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)

Question 17

Antibody & cell mediated immunity in influenza

Answer 17

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

Question 18

HIV

Answer 18

Can develop to AIDS

Attacks specific immune system

Targets CD4 T cell, macrophages and dendritic cells

Progressive development of AIDS leads to opportunistic infections

Question 19

Opportunistic infections of AIDS

Answer 19

Kaposi’s sarcoma: herpes virus B

TB

Fungal infections

Question 20

How is HIV infection controlled?

Answer 20

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

Question 21

What are parasites?

Answer 21

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

Question 22

How do antibodies protect against parasites?

Answer 22

Opsonisation

Complement lysis

ADCC – antibody-dependent cell-mediated cytotoxicity

Question 23

Cell mediated immunity against parasites

Answer 23

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)

Question 24

What is cell mediated immunity?

Answer 24

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

Question 25

Malaria

Answer 25

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