Microbial Immune Evasion Mechanisms

Question 1

What do virulence factors do?

Answer 1

1. promote colonisation and adhesion
2. evade host defences
3. promote tissue damage

pathogens have virulence factors

Question 2

What is the complement system?

Answer 2

cascade of soluble proteins that recognise mainly pathogenic antigens that lead to cascade of activating various components eg C3a and c5a that are pro-inflammatory and produce components that produce phagocytes

there are different pathways ie classical, lectin and alternative pathways

classical pathway- bacteria is recognised by an antibody, forming an antigen-antibody complex. If the antibody is IgG or IgM, it binds to C1q which then leads to cascade involving C3 convertase/c5 convertase and eventually leads to the membrane-attack complex (which all pathways eventually lead to)- cell lysis

lectin pathway- bacteria presents its pathogen recognition receptors (PRR) (normally like mannose capsules etc) and bacteria binds to a mannose-binding-lectin (MBL) that activate pathway and then leads on to c3/c5 convertase and finally membrane attack complex

alternative pathway- when bacteria are coated with C3b

Question 3

In what ways can pathogens overcome complement?

Answer 3

Some pathogens contain lipopolysaccharides or capsular polysaccharides on their surface which fail to be recognised by complement, therefore failing to trigger the complement cascade.
Other pathogens inhibit the binding of complement to their surfaces, one way they do this is by the pathogens coating themselves with non- complement- fixing antibody like IgA. Therefore, complement cascade is not triggered.
Pathogens can be bound by the opsonin Cb3 and some capsules block this from happening and also some prevent C3b receptor access.
Complement cannot be activated if there is Factor H on the surface of the bacteria.
Some pathogens secrete proteases that can digest eg C5a, preventing the complement cascade being triggered.

Question 4

What are the roles of complement?

Answer 4

induces inflammatory response
	promotes chemotaxis
	increase phagocytosis by opsonisation
	increase vascular permeability
	mast cell degranulation
	lysis of cell membranes

Question 5

What do we know about the 2 most important proteins of influenza viruses?

Answer 5

The 2 most important proteins of influenza viruses are haemagglutinin and neuraminidase. These molecules will be expressed on the surface to be recognised by antibodies.
The virus is neutralised and prevented from entering the host when the antibodies are recognised and bound to. The proteins can also be processed to bind to an MHC complex via the peptide binding groove. On the MHC I of all cells containing a nucleus, the processed protein can be recognised by CD8 T cells, activating them. On cells such as macrophage cells, which are specialised phagocytes, processed proteins bind to the MHC II and CD4 T cells recognise them which consequently leads to their activation. Depending on which type of T cell is activated, there is a different outcome. If CD4 T cells are activated, this leads to clonal selection and expansion whereas if CD8 T cells are activated, apoptosis occurs in the bound host cell.
These 2 proteins are always undergoing rapid mutation, because when the virus replicates, it has no proof-reading ability in its RNA polymerases so there will always be production of errors. This molecular process is known as antigenic drift and is what leads to epidemics. When viruses re-assort their genome, this molecular process is known as antigenic shift, so you get a new assortment of the 2 proteins.

Question 6

What is antigenic shift and drift in the context of influenza viruses?

Answer 6

Influenza Virus are remarkable because of the frequent antigenic change that occurs in HA (hemagglutinin) or NA (neuraminidase). The two surface antigens of influenza undergo antigenic variation independent of each other. They are Antigenic Shift and Antigenic Drift.

Antigenic Shift:
Occurs as a results of genome assortment between difference subtypes.
An antigenic change which results in drastic or dramatic alternation in HA (hemagglutinin) or NA (neuraminidase) subtypes.
Large change in nucleotides of RNA
Forming new sub-type (Subtype A + Subtype B –> New Subtype)

Antigenic drift:
Occurs as a result of the accumulation of point mutations in the gene.
An antigenic change can alter antigenic sites on the molecule such that a virion can escape recognition by the host’s immune system.
Small mutation of RNA
Forming new strain of virus