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

Define a ‘privileged site’.

Answer 3

An area of the body where the immune response is limited or altered to protect tissues from potentially damaging inflammation

Question 4

Give an example of a pathogen using a privileged site to its advantage.

Answer 4

Latency of Herpes zoster virus in CNS (chicken pox -> shingles)
Hydatid cysts in Echinococcus infection (dog tapeworm)

Question 5

Give 2 kinds of antigenic variation.

Answer 5

Mutation - antigenic drift
Recombination - antigenic shift
Gene switching

Question 6

Give 2 pathologies caused by Streptococcus pneumoniae.

Answer 6

Otitis media
Sinusitis
Bronchitis
Pneumonia
Bacteremia
Meningitis

Question 7

Describe the structure of Streptococcus pneumoniae. (3)

Answer 7

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

Question 8

Give 2 vaccines for Streptococcus pneumoniae.

Answer 8

Pneumovax
Prevnar 13

Question 9

Describe the Pneumovax vaccine for S. pneumoniae.

Answer 9

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

Question 10

Describe the Prevnar 13 vaccine for S. pneumoniae.

Answer 10

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

Question 11

Explain how antibodies are produced in response to tetanus toxoid protein. (4)

Answer 11

B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein
Ag internalised and processed
Peptides presented to T cell
Activated B cell produces Ab against polysaccharide antigen on surface of bacterium

Question 12

Describe influenza virus.

Answer 12

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

Question 13

Describe antigenic drift in influenza. (2)

Answer 13

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

Question 14

Describe antigenic shift in influenza. (2)

Answer 14

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

Question 15

Describe Trypanosoma brucei.

Answer 15

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

Question 16

Describe the clinical course of trypanosome infection. (3)

Answer 16

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 17

Describe immunosuppression by pathogens. (2)

Answer 17

Infection of immune cells
Induction of regulatory cells

Question 18

Describe regulatory T cells (Treg).

Answer 18

CD4+ cell
Regulate and suppress differentiation and proliferation of TH1 and TH2 cells
Maintain tolerance to self-antigens
Help prevent autoimmune disease
Express biomarkers CD4 and CD25 on surface and FoxP3 (transcriptional factor)

Question 19

Describe how Helicobacter pylori interferes with immune response.

Answer 19

Boosts level of Treg suppressing immune response

Question 20

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

Answer 20

Gastric and duodenal ulcers
Gastric adenocarcinomas

Question 21

Describe Leimania.

Answer 21

Parasite transferred by sand flies
Increase expression of Treg cells
Decrease immune response

Question 22

Describe measles virus.

Answer 22

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

Question 23

Give 3 signs of infected dendritic cells.

Answer 23

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

Question 24

Define a dendritic cell.

Answer 24

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

Question 25

Give 3 methods of interference with effector mechanisms.

Answer 25

Molecules interfering with Ab function
Molecules interfering with complement
Molecules binding cytokines
Subvert responses by producing molecules with cytokine activity
Inhibition of phagocytic killing

Question 26

Give an example of interference with antibody function.

Answer 26

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

Question 27

Give an example of molecules interfering with complement.

Answer 27

Enzymes that break down C3a/C5a - pseudomonas
Molecules that inhibit complement activation - vaccinia/smallpox virus

Question 28

Give an example of molecules binding cytokines.

Answer 28

Vaccinia (smallpox) binds IFNy

Question 29

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

Answer 29

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

Question 30

Give an example of an organism that inhibits phagocytic killing.

Answer 30

M. tuberculosis

Question 31

Describe how M. tuberculosis persists in macrophages.

Answer 31

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 32

Give 2 innate pathological consequences of immune responses.

Answer 32

LPS induces macrophage cytokine secretion
Fever
Endotoxic shock
Cytokine storm

Question 33

What is the role of TNF-a?

Answer 33

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 34

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

Answer 34

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 35

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

Answer 35

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 36

Describe Ebola. (2)

Answer 36

Filovirus - non-segmented -ve RNA with filamentous particles
Causes haemorrhagic fever
Outbreak in West Africa largest in history
70% fatality rate

Question 37

Describe how Ebola evades the immune responses. (3)

Answer 37

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 38

Describe the immunopathogenesis of Ebola.

Answer 38

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