CMB2004/L10 Immunity Against Infection III

Question 1

Give 3 evasion mechanisms of pathogens.

Answer 1

Concealment of antigens
Antigenic variation
Immunosuppression
Interference with effector mechanisms

Question 2

Describe concealment of antigens using an example.

Answer 2

Viruses inhibit antigen presentation by MHC class I
HSV
Uptake of host molecules (cloak effect)

Question 3

Give 2 kinds of antigenic variation.

Answer 3

Mutation - antigenic drift
Recombination - antigenic shift
Gene switching

Question 4

Give 2 pathologies caused by Streptococcus pneumoniae.

Answer 4

Otitis media
Sinusitis
Bronchitis
Pneumonia
Bacteremia
Meningitis

Question 5

Describe the structure of Streptococcus pneumoniae. (3)

Answer 5

Surrounded by thick polysaccharide capsule protecting from phagocytosis
Ab to capsule opsonise bacteria and protect
91 capsular types

Question 6

Give 2 vaccines for Streptococcus pneumoniae.

Answer 6

Pneumovax
Prevnar 13

Question 7

Describe the Pneumovax vaccine for S. pneumoniae.

Answer 7

Polysaccharide vaccine (ag to all 23 capsules)
Not effective in children u2 or poor immune function
Low level B cell IgM response

Question 8

Describe the Prevnar 13 vaccine for S. pneumoniae.

Answer 8

Conjugate (weak + strong Ag)
13 capsule Ag bound to diphtheria toxoid - highly immunogenic & non-toxic
B and T cell response

Question 9

Describe influenza virus.

Answer 9

-ve sense segmented genome
Can infect humans, birds, other animals
Major surface Ag. haemagglutanin and neuraminidase
Can undergo antigenic drift and shift

Question 10

Describe antigenic drift in influenza. (2)

Answer 10

Neutralising Ab against haemagglutanin block binding to cells
Mutations after epitopes in haemagglutanin so that neutralising Ab no longer binds

Question 11

Describe antigenic shift in influenza. (2)

Answer 11

RNA segments exchanged between viral strains in secondary host
No cross-protective immunity to virus expressing novel haemagglutanin

Question 12

Describe Trypanosoma brucei.

Answer 12

Protozoal parasite causing African sleeping sickness
Spread by Tsetse fly
Patients undergo bouts of parasitaemia
Genetic rearrangement
Variant-specific glycoprotein (VSG)

Question 13

Describe the clinical course of trypanosome infection. (3)

Answer 13

Many inactive trypanosome VSG genes but only one site for expression
Inactive genes copied into expression site by gene conversion
Many rounds of gene conversion allowing trypanosome to vary VSG gene expressed

Question 14

Describe immunosuppression by pathogens. (2)

Answer 14

Infection of immune cells
Induction of regulatory cells

Question 15

Describe regulatory T cells (Treg).

Answer 15

Regulate and suppress differentiation and proliferation of TH1 and TH2 cells
surface and FoxP3 (transcriptional factor)

Question 16

Describe how Helicobacter pylori interferes with immune response.

Answer 16

Boosts level of Treg suppressing immune response

Question 17

What does the Gram -ve bacterium Helicobacter pylori cause in humans?

Answer 17

Gastric and duodenal ulcers
Gastric adenocarcinomas

Question 18

Describe Leimania.

Answer 18

Increase expression of Treg cells
Decrease immune response

Question 19

Describe measles virus.

Answer 19

RNA virus
Complications - secondary bacterial respiratory infections
Causes immunosuppression
Infects dendritic cells

Question 20

Give 3 signs of infected dendritic cells.

Answer 20

Increased apoptosis
Decreased stimulation of T cells
Decreased IL-12 production (NK cells and TH1 affected)

Question 21

Define a dendritic cell.

Answer 21

APC (MHC I and MHC II)
Act as messengers between innate and adaptive immune systems

Question 22

Give an example of interference with antibody function.

Answer 22

IgA proteases by S pneumoniae, Neisseria
Fc-binding molecules by Staphylococcal protein A, HSV

Question 23

Give an example of molecules binding cytokines.

Answer 23

Vaccinia (smallpox) binds IFNy

Question 24

Give an example of subverting responses by producing molecules with cytokine activity.

Answer 24

Epstein Barr Virus produces vIL-10 (downregulates TH1 response)

Question 25

Give an example of an organism that inhibits phagocytic killing.

Answer 25

M. tuberculosis

Question 26

Describe how M. tuberculosis persists in macrophages.

Answer 26

When reaching host's lungs, cells bind to TLR-2 receptor on macrophage surface Prevent fusion of phagosomes with lysosomes so allow bacteria survival

Question 27

Give 2 innate pathological consequences of immune responses.

Answer 27

LPS induces macrophage cytokine secretion Fever Endotoxic shock Cytokine storm

Question 28

What is the role of TNF-a?

Answer 28

Activates vascular endothelium Increases vascular permeability Leads to increased entry of IgG, complement and cells to tissues and increased fluid drainage to lymph nodes Fever Mobilisation of metabolites Shock

Question 29

Describe local infection with Gram -ve bacteria. (6)

Answer 29

Macrophages activated to secrete TNF-a in tissues Increased release of plasma proteins into tissue Increased phagocyte and lymphocyte migration to tissue Increased platelet adhesion to blood vessel wall Phagocytosis of bacteria, local vessel occlusion Plasma and cells drain to lymph node

Question 30

Describe systemic infection with Gram -ve bacteria. (4)

Answer 30

Macrophages activated in liver and spleen secrete TNF-a into bloodstream Systemic edema causing decreased blood volume, hypoproteinemia and neutropenia, followed by neutrophils Decreased blood volume causes collapse of vessels Disseminated intravascular coagulation leading to wasting and multiple organ failure

Question 31

Describe Ebola. (2)

Answer 31

Filovirus - non-segmented -ve RNA with filamentous particles Causes haemorrhagic fever 70% fatality rate

Question 32

Describe how Ebola evades the immune responses. (3)

Answer 32

Infects immune cells including dendritic cells and macrophages Inhibits maturation of dendritic cells so no APC Causes apoptosis (low T lymphocytes and NK cells) Interferes with T1 interferons production & cellular response to interferon

Question 33

Describe the immunopathogenesis of Ebola.

Answer 33

Induction of cytokine secretion ('storm') by macrophages plays central role Shed glycoprotein from virus binds macrophages and dendritic cells - cytokine release and increased vascular permeability Infected macrophages express more tissue factor = coagulation cascade & disseminated intravascular coagulation & death