lecture 10

Question 1

Give 4 examples of evasion mechanisms

Answer 1

1) Concealment of antigens
2) Antigenic variation
3) Immunosuppression
4) Interference with effector mechanisms

Question 2

How does concealment of antigens allow evasion of immune defence?

Answer 2

Some viruses inhibit antigen presentation by MHC class I
“Privileged sites”
Uptake of host molecules (cloak effect)

Question 3

How does antigenic variation cause evasion of immune defences?

Answer 3

A) large number of antigenic types
B) mutation (antigenic drift)
C) recombination (antigenic shift)
D) gene switching

Question 4

What is streptococcus pneumoniae?

Answer 4

Cause of serious bacterial infection
Causes: otitis media, sinusitis, bronchitis, pneumonia, bacteremia and meningitis
Gram positive; surrounded by a thick polysaccharide capsule which protects it from phagocytosis
Antibodies to the capsule opsonise the bacteria and protect
Large number of different capsular types = 91

Question 5

What are the streptococcus pneumoniae vaccines?

Answer 5

Vaccine has 23 subunits of capsular polysaccharides
Pneumovax:
polysaccharide vaccine with antigens to all 23 capsules, not effective in children <2 or those with poor immune functions - low level response - just B cell IgM response
Prevnar 13:
conjugate vaccine with only 13 antigens but bound to diphtheria toxoid which is highly immunogenic but non-toxic - T and B cells have all Ig response, coverts T1-2 polysaccharide antigen to a TD so children can respond

Question 6

How does Influenza virus show antigenic variation as evasion of immune defences?

Answer 6

Mutation and recombination
An RNA virus with a negative sense segmented genome
Can infect humans, birds and other animals
Causes epidemics and pandemics
Major surface antigens are haemagglutinin and neuraminidase
Can undergo antigenic drift (mild epidemic) and antigenic shift (major pandemic)

Question 7

What is antigenic drift?

Answer 7

Antigens change over time due to gradual accumulation of mutations (antibodies not as effective)

Question 8

How does Trypanosoma brucei evade immune defences by gene-switching?

Answer 8

Protozoal parasite that causes African sleeping sickness
Spread by Tsetse fly
Patients undergo bouts of parasitaemia
Correlates with changes in the major surface antigen of the trypanosome brought about by genetic rearrangement
There are many inactive trypanosome variant-specific glycoprotein (VSG) genes but only one site for expression - inactive genes are copied into the expression site by gene conversion with many rounds occuring allowing the trypanosome to vary the VSG gene expressed

Question 9

How does immunosuppression cause evasion of human defences?

Answer 9

A) infection of immune cells
B) induction of regulatory T cells

Question 10

What is the role of regulatory T cells?

Answer 10

Type of CD4+ celll
Regulate the immune system - suppress differentiation and proliferation of Th1 and Th2 cells
Immunosuppressive
Maintain tolerance to self-antigens
Help prevent autoimmune disease
Express the biomarkers CD4 and CD25 on the surface
FoxP3 transcriptional factor expressed

Question 11

What is Helicobacter pylori?

Answer 11

Gram negative bacterium that causes gastric and duodenal ulcers (also gastric adenocarcinomas)
Found in about 1 in 3 people but only causes disease in 10% of people infected
Treg cells may be involved in allowing it to establish a persistent infection

Question 12

What is the reason for inducing regulatory T cells Leishmania?

Answer 12

Parasite - genus of trypanosomes
Vector - sandfly
Can hide and survive in macrophages
Can increase expression of Treg cells
Decrease immune response

Question 13

What is the measles virus?

Answer 13

An RNA virus; disease is associated with a rash commonly accompanied by profound malaise and respiratory symptoms
Complication include: secondary bacterial respiratory infections
Causes: immunosuppression which can lead to secondary infections
Shown to infect dendritic cells causing dendritic cells to show: increased apoptosis, decreased stimulation of T cells, decreased IL-12 production (NK cells and Th1 affected)

Question 14

What is a dendritic cell?

Answer 14

Antigen presenting cell (MHC I and II)
Acts as messengers between the innate and adaptive immune systems

Question 15

How does interference with effector mechanisms cause evasion of immune defences?

Answer 15

A) Molecules interfering with antibody function - eg:IgA proteases, Fc-binding molecules
B) Molecules interfering with complement - enzymes that break down C3a/C5a or molecules that inhibit complement activation
C) Molecules binding cytokines
D) Subvert responses by producing molecules with cytokine activity
E) Inhibition of phagocytic killing

Question 16

How does Mycobacterium tuberculosis persist in macrophages?

Answer 16

On reaching the host’s lungs, cells of Mycobacterium tuberculosis bind to the TLR-2 receptor on the surface of a macrophage
Can persist in macrophages

Question 17

What is immunopathology?

Answer 17

In infectious disease pathology may result from:
direct effects of pathogen
host responses

Question 18

What are the innate pathological consequences of immune responses?

Answer 18

LPS induces macrophage cytokine secretion (IL1, TNFα via TLR4)
Systemic effects: fever, endotoxic shock cytokine storms

Question 19

What are the specific pathological consequences of immune responses?

Answer 19

Antibodies and/or T cell reactions may contribute to pathology
Microbes may play a role in initiating autoimmune responses

Question 20

What is Ebola?

Answer 20

Filovirus: enveloped, non-segmented negative stranded RNA with filamentous particles
Causes haemorrhagic fever
High fatality rate: around 70% reported

Question 21

How does Ebola cause evasion of immune responses?

Answer 21

Infects immune cells including dendritic cells and macrophages
Inhibits maturation of infected dendritic cells so they do not present antigen effectively
Causes apoptosis leading to reduced numbers of circulating T lymphocytes and NK cells and weakened immune responses
Interferes with the production of type I interferon
Also interferes with the cellular responses to interferon

Question 22

What is the immunopathogenesis of Ebola?

Answer 22

shed gylcoprotein from virus binds macrophages and dendritic cells leading to cytokine release and increased vascular permeability
Infected macrophages express abundant tissue factor which initiates coagulation cascade, disseminated intravascular coagulation -> death