L8&9 : Immune responses against bacterial infections

Question 1

What factors affect the type of effector mechanism required in an immune response?

Answer 1

Type of pathogen, localisation, challenge and site of infection

Question 2

Compare innate and adaptive immune mechanism

Answer 2

• innate are non specfic and fast acting, while adaptive are specific and take longer to develop
• adaptive exhxibits memory but innnate doesn’t
• innate uses physical barriers, component system, phagocytes and NK cells, while adaptive uses Abs and cell mediated immunty

Question 3

What role do innate defence mechanisms have?

Answer 3

Act as first line of defence but are ineffective against many pathogen

Question 4

What role do adaptive defence mechanisms have?

Answer 4

They enhance and focus innate defences, and are less easily evaded by pathogens

Question 5

Name the types of specific response CD4+ cells

Answer 5

Th1,2 & 17

Question 6

What is the function of Th1 cells?

Answer 6

Active against intracellular pathogens

- activates macrophages and stimulates CD8+ cells

Question 7

What is the function of Th2 cells?

Answer 7

Active against extracellular pathogens

• supports Ab production, particularly class switching to IgE
• activates esinophils, basophils and mast cells

Question 8

What is the function of Th17 cells?

Answer 8

Active against extracellular bacteria& fungi

• important in attracting inflammatory cells e.g. neutrophils
• induced early in infection

Question 9

What innate responses can cell wall components (e.g. LPs, peptidoglycan) induce?

Answer 9

The binding to Toll-like receptors (TLR) on macrophages

• there are 10 TLR genes in humans: receptors recognise distinct molecular patterns on microbes, located on plasma membrane & endocytic vesicles
• NOD like receptors

Question 10

The binding of PAMPs to TLRs can cause what responses?

Answer 10

• promotion of inflamaation
• promotion of dendritic maturation
• influence differentiation of T cells
• activation of B cells (TI-1 Ags)

Question 11

Why is phagocytosis often effective against bacteria?

Answer 11

Bacteria may have protective capsules but can be opsonised by Ab/ componenet

Question 12

What is the role of Abs in bacterial infection

Answer 12

• opsonisation: binds Fc receptors on phagocytes
• componenet activation: promotes inflammation via C3a + C5a, opsonise by binding C3b receptors on phagocytes & lysis of gram -ve organisms
• bind and neutralise toxins e.g. tetanus, diphtheria
• bind to surface structures to prevent mucosal adherance

Question 13

What is a conseqeunce of defects in terminal complement componenets?

Answer 13

Can lead to susceptibility to Neisseria spp. and bacterial cell division becomes more vulnerable (can lead to cell death)

Question 14

Gram +ve bacteria can be killed by lysis. True or false

Answer 14

False, gram -ve bacteria are killed by lysis

Question 15

Some bacteria survive within phagocytes. True or false?

Answer 15

True

Question 16

Give an example of how outcome of infection depends on the type of response

Answer 16

e. g. Myobacterium leprae
- tuberculoid leprosy: strong Th1 repsonse, few live bacteria, slow progessino, granuloma formation
- lepromatous leprosy: strong Th2 and Ab response, large no bacteria in macrophages, disseminated infection and can be fatal

Question 17

What mechanisms are uesd to protect against extrcalleular pathogens and intracellular organisms respectively?

Answer 17

• Abs are imporant for extracellular pathogens e.g. s. pneumoniae
• T cell effector mechanisms are important for intracellular organisms e.g. mycobacterium

Question 18

How do virus infected host cells use type-1 interferons (IFN alpha & beta)?

Answer 18

1- induces resistance to viral replication in all cells, by inducing Mx proteins, 2’-5’ linked adenosine ogliomer and the kinase PKR
2- increase MHC class I expression and Ag presentation in all cells
3- activates dendritic cells and macrophages and NK cells to kill virus infected cells
4- induces chemokines to recruit lymphocytes

Question 19

IFN can induce the synthesis of what 2 molecules?

Answer 19

Protein kinase and 2’5’- oglioadrenylate synthetase

Question 20

How can IFN lead to the degradation of viral mRNA?

Answer 20

IFN induces the synthesis of 2’5’ oglioadenylate synthetase

• leads to adenine trinucleotide being synthesised
• this activatees endonuclease
• viral mRNA degraded

Question 21

How can IFN lead to the inhibition of protein synthesis?

Answer 21

IFN induces protein kinase

• leads to phosphorylation and inactivation of eIF-2
• this inhibits protein synthesis

Question 22

At which point of infection can type I interferons be seen?

Answer 22

In early responses

Question 23

What are type II interferons (IFN gamma) secreted by?

Answer 23

Activated T and NK cells

Question 24

How do type II intereferons respond to infection?

Answer 24

• inhibit Th2 response (Ab)
• promotes Th1 (cell killing)
• recruits macrophaages (driving Th1 response)

Question 25

rIFN alpha can be used to treat what diseases?

Answer 25

Hep B and C, and some cancers but side effects can be very severe

Question 26

What is the function of NK cells in the immune response

Answer 26

- recognise structures on viral infected cellls & stressed in absence of Igs and MHC - kills by extracellular mechanism: perforin and granzyme (potent) so work fast

Question 27

How do NK cells distinguish between infected and uninfected cells?

Answer 27

- Activating receptors: recognise carbohydrate ligands, triggers killing - Inhibitory receptors: recognises MHC class I molecules (no binding, only TCR can do this) and inhibits the activities & activation of these NK cells

Question 28

How do some viruses make cells more susceptible to NK killing?

Answer 28

By reducing MHC expression

Question 29

Explain methods of cell mediated specific immunity

Answer 29

- CD8+ cells (CTL): recognises viral peptide and MHC class I | - cytokines with anti viral activity: e.g. IFN gamma (class II, helps activate macrophages)

Question 30

Explain the mechanisms by which CD8+ cells kill

Answer 30

- secretion of cytotoxic granulese e.g. perforin which polymerises in membrane, grnazymes (proteases) which enter cell - Fas ligand on T cell interacts with Fas on target

Question 31

What 2 processes/ interactinos lead to specific recognition?

Answer 31

Collision+ non specific adhesion

Question 32

How does collision and non specific adhesion lead to specific recognition?

Answer 32

- redistributes cytoskeleton and cytoplasmic components of T cells - leads to release of granules (vesicles) at site of cell contact - this method is powerful and targeted, causing the polarised release of granules

Question 33

How to CTLs kills cells?

Answer 33

- recognise and bind virus infected cell - programs target for death, including DNA fragmentatino - CTL migrates to new target - target cell dies by apoptosis

Question 34

How do CTLs secrete cytokines?

Answer 34

- inhibit viral replication - upregulate MHC class I and II expression & Ag presentation - increases macrophage phagocytosis of dead cells - promotes NK cell killing activity

Question 35

How do Abs respond to viral infections?

Answer 35

- Neutralises free virus (prevent entry into and spread between cells can prevent spread within body (e.g. poliovirus) or protect mucosal surfaces against reinfection (e.g. flu) - Opsonise to increase phagocytosis - Activate complement leading to lysis (enveloped virus)

Question 36

Explain the role of Abs in cell mediated immunity of influenza

Answer 36

- infection induces Ab and CTL response - Ab recognises viral haemagglutinin and neruaminidase - high levels of CTL activity correlates with reduced viral stability - epidemics arise due to new strains not recognised by Ab

Question 37

How does HIV affect the immune system?

Answer 37

- attacks specific immune system - targets CD4 T cells, macrophages and dendritic cells - progressive developments of AIDS leads to opportunistic infections

Question 38

How do Abs protect against parasites?

Answer 38

By opsonisation, complement lysis and ADCC (antibody dependent cell mediated cytotoxicity)

Question 39

What response can some helminths (worms) evoke?

Answer 39

Can induce strong IgE Ab response which leads to the activation of mast cells (mediated inflammation), eosinophils and ADCC

Question 40

What effector mechanisms are used for the malaria?

Answer 40

Different effector mechanisms are active at different stages - sporozoite and merozoite may be susceptible at Ab - Ab may also kill infected RBC - CTL active against infected liver cells