L10 Flashcards
what are the evasion mechanisms done by the pathogens to avoid the immune system
1) Concealment of antigens
2) Antigenic variation
3) Immunosuppression
4) Interference with effector mechanisms
what does Concealment of antigens mean
inhibition of Ag presentation by MHC 1
what are the 2 ways for pathogen concealment of antigens
privileged sites
Uptake of host molecules (cloak effect)
what is a privileged site
a site with very low immune defense
give examples for a pathogens that apply the concealment of antigen via privileged site
latency of Herpes zoster virus in CNS (chicken pox -> shingles)
hydatid cysts in Echinococcus infection (dog tapeworm)
give examples for a pathogens that apply the concealment of antigen Uptake of host molecules (cloak effect).
e.g. Schistosomes (bilharzia)
how is Antigenic variation achieved
A) large number of antigenic types
B) Mutation (antigenic drift)
e.g. ‘flu’, polio, HIV (RNA viruses)
C) Recombination (antigenic shift)
e.g. ‘flu’
D) Gene switching
e.g. trypanosomes
what are the features of Streptococcus pneumoniae
an example for a pathogen with big antigenic variation
Gram positive; surrounded by a thick polysaccharide capsule which protects it from phagocytosis
Antibodies to the capsule opsonise the bacteria and protect us
Large number of different capsular types (91)
how many major disease causing polysaccharide capsule does Streptococcus pneumoniae
23
what are the vaccines for Streptococcus pneumoniae
Pneumovax
Prevnar 13
what are the features of pneumovax
-polysaccharide vaccine (contains antigens to all 23 capsules)
-not effective in children under two or those with poor immune function (eg. HIV)
-low level response – just B cell IgM
what are the features of Prevnar 13
-conjugate vaccine.
-Only 13 capsule antigens but bound to the diphtheria toxoidwhich is highly immunogenic but non-toxic.
-T cell and B cell (all Ig) response
what are the features of the Influenza virus
An RNA virus with a negative sense segmented genome
Can undergo antigenic drift and antigenic shift
what are the major surface antigens for the influenza virus
haemagglutinin
neuraminidase
what would an antigenic drift in the influenza virus result in
mild epidemics
what would an antigenic shifts in the influenza virus result in
major shifts
what is an antigenic shift
occurs when when RNA segments are exchanged between viral strains in a secondary host
what is antigenic drift
mutations that alter epitopes in hemagglutinin so that neutralizing antibodies no longer bind
what is an example for gene switching
Trypanosoma brucei
what are the features of Trypanosoma brucei
-Protozoal parasite that causes African sleeping sickness
-Spread by the Tsetse fly
-Patients undergo bouts of parasitaemia
-Correlates with changes in the major surface antigen of the trypanosome, brought about by genetic rearrangement
-Variant-specific glycoprotein (VSG)
what is Variant-specific glycoprotein (VSG)
the area that gets genetically recombined in Trypanosoma brucei
how many VSG genes are expressed at one time
1
how is immunosuppression achieved
1- infection of immune cells
2- Induction of regulatory T cells
give an example for pathogens that cause infection of immune cells
HIV -T cells (CD4+) /macrophage/dendritic cells
give an example for pathogens that cause Induction of regulatory T cells
chronic infection with Helicobacter pylori
leishmania
measles virus
what are the features of Helicobacter pylori
Gram negative bacterium that causes gastric and duodenal ulcers (also gastric adenocarcinomas)
Found in about one in three people, but causes disease in only about 10% of people who are infected
Regulatory T cells may be involved in allowing it to establish a persistent infection
what markers do T reg cells express
CD4 and CD25
what are the features of leishmania
Parasite - genus of trypanosomes
Vector – sand fly
Can hide and survive in macrophages
Can increase expression of TREG cells
Decrease immune response
what are the features of measles virus
An RNA virus; disease is associated with a rash commonly accompanied by profound malaise and respiratory symptoms
Complications include secondary bacterial respiratory infections
Causes immunosuppression which can lead to secondary infections
Shown to infect dendritic cells
Infected dendritic cells show
- increased apoptosis
- decreased stimulation of T cells
- decreased IL-12 production (NK cells and TH1 affected)
what effector mechanisms are affected in the evasion of immune defenses
A) Molecules interfering with antibody function
B) Molecules interfering with complement
C) Molecules binding cytokines
D) Subvert responses by producing molecules with cytokine activity
give examples for Molecules interfering with antibody function
e.g IgA proteases (Streptococcus pneumoniae, Neisseria spp.)
Fc-binding molecules (Staphylococcal protein A; Herpes simplex virus)
give examples for molecules interfering with compliment
Enzymes that break down C3a/C5a (Pseudomonas)
Molecules that inhibit complement activation (Vaccinia/smallpox virus)
give an example for a molecule interfereing with cytokines and what pathogen makes it
IFN - gamma, small pox
give an example of subvert responses by producing molecules with cytokine activity
epstein barr virus - vIL-10 (downregulates Th1 response)
How can TB inhibit phagocytic lysis?
Inhibiting fusion with the phagosomes
What is immunopathology?
An infectious disease pathology that may result from direct effects of a pathogen or host responses
What are the pathalogical consequences of immune responses and how can it be induced by a pathogen
LPS = induces Mq cytokine secretion (Il1 TNF alpha via TLR 4) = fever, endotoxic shock, cytokine storm.
What is the role of TNF alpha
Acvtivates vascular endotheliuim and increases vascular permeasibility - leads to increased entry of IgG, complement & cells to tissues and increased fluid drainage to lymph nodes = fever mobilisation of metabolites shock
What happens during sepsis?
Systemic infection, mass cytokine release = multiple organ failure = death
Can Ab/T cell reactions contirbute to pathology? Provide an example
Yes, skin rashes in measles due to T cells & granula formation in TB due to chronic Mq activation
Can microbes play a role in initiating autoimmune responses - provide an example
Yes. Ab to certain proteins can cross-react with heart muscle
What’s the fatality rate for ebola?
70%
What is ebola?
folivirus: enveloped, non-segmented negative stranded RNA with filamentous particles
What can ebola cause?
haemorrhagic fever
Where is the largest outbreak of ebola in history?
West Africa
What cells of the immune defence does ebola impact?
dendritic and mq
What impact can ebola have on cells?
inhibits maturation of infected dendritic cells = ineffective Ag presentation
What does ebola lead to?
Apoptosis = reduced numbers of T lymph. and NK cells & weakened immune responses
Does ebola interfere with the production of IFN Type 1?
Yes, and cellular response to IFN as well
How does ebola contribute to immunopathogenesis via infection of Mq?
induction of cytokine storm (glycoprotein from virus binds to Mq & dendritic cells = cytokine release = increased vascular permeability)
infected Mq express abundant tissue factor = coagulation cascade - disseminated IV coagulation = death
