L10 Flashcards by Hafsa Niaz

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

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what does Concealment of antigens mean

inhibition of Ag presentation by MHC 1

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what are the 2 ways for pathogen concealment of antigens

privileged sites

Uptake of host molecules (cloak effect)

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what is a privileged site

a site with very low immune defense

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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)

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give examples for a pathogens that apply the concealment of antigen Uptake of host molecules (cloak effect).

e.g. Schistosomes (bilharzia)

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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

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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)

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how many major disease causing polysaccharide capsule does Streptococcus pneumoniae

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what are the vaccines for Streptococcus pneumoniae

Pneumovax

Prevnar 13

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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

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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

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what are the features of the Influenza virus

An RNA virus with a negative sense segmented genome

Can undergo antigenic drift and antigenic shift

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what are the major surface antigens for the influenza virus

haemagglutinin

neuraminidase

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what would an antigenic drift in the influenza virus result in

mild epidemics

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what would an antigenic shifts in the influenza virus result in

major shifts

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what is an antigenic shift

occurs when when RNA segments are exchanged between viral strains in a secondary host

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what is antigenic drift

mutations that alter epitopes in hemagglutinin so that neutralizing antibodies no longer bind

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what is an example for gene switching

Trypanosoma brucei

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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)

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what is Variant-specific glycoprotein (VSG)

the area that gets genetically recombined in Trypanosoma brucei

how many VSG genes are expressed at one time

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