Parasite Survival Strategies Flashcards
What are the requirements for pathogen to avoid immune mechanisms to cause disease?
- For infection to establish/persist and pathogen replicate (ultimate aim), pathogen must overcome some immune mechanism (s)
- Common parasites can avoid/escape/damage host immune mechanisms: common = successful
- There is a myriad of strategies that different parasites possess to escape immune action from host –> look at some
What are some of the strategies that evades the immune system?
- Interfere with phagocytois - a major innate mechanism
- Interfere with ciliary action
- Interfere with the activation of complement –> a major innate mechanism
- Produce iron-bind-molecules –> an important nutrient for many bacteria (produce powerful iron-binding protein to sequester from host iron-binding proteins e.g. Neisseria)
- Block interferons (IFN) - produced within 24 hours of infection, limit transmission to other cells (some viruses are poor inducers e.g. Hep B virus, some others can block action of IFN e.g. HIV)
How do pathogens intefere with phaocytosis
- Release toxins (organism releases rtoxin, phagocyte killed by toxin)
- Opsonization prevented
- Conract with phagocyte prevented (organism produces a capsule which prevents contact with phagocyte)
- Phagolysosome fusion inhibited (fusion of phagosome and lysosome inhibited by organism)
- Resistance to killing (organism resists killing by producing antioxidants)
How do pathogens interfere with complement
- Outer capsule prevents complement activation
- Extended surface molecules obstruct phagocyte contact to C3b (opsonisation)
- Surface structrues divert attachment of kill complex
- Degrade or shed complement proteins
- Capture complement inhibitors
- Direct inhibition of C3 and C5 convertases
Describe concealment strategies (avoidance strategies) to evade Adaptive IS
a) remain inside a cell without their antigens being displayed on the surface prevents recognition, examples of strategies
- HSV intergrating into host DNA of sensory neurons
- HIV and coronaviruses only display antigens on the interior of vacuoles, not allowing them to fuse with cell surface
- Adenovirus protein binds to MHC class 1 molecules and prevents MHC molecule travelling to cell surface
b) concealment by colonizing immune privileged sites –> site on the body in which there are few circulating lymphocytes
- glands of skin - sweat and sebaceous glands offer non-keratinised cells directly linked to external surface
- infect external epithelial stem cells e.g. papillomaviruses
- some parasites create their own immune-priveleged environment (hydatid cyst produced by the tape worm echinococcus granulosus, present in liver, lung and brain
- Mimicry - limited value
- Taking up host proteins (the fluke) –> Schistosoma binds blood group proteins and MHC antigens on its surface –> becoming virtually invisible to IS
Describe how antigenic variation evades the Adaptive IS
>There are three mechanisms
Results from change in genes that control parasite surface proteins involved in immune recognition
- Can occur during the course of an infection or during spread of microbe to other hosts
- Common to infections of the respiratory system and intestinal epithelium where incubation period< 1 week
- For systemic infection where incubation periods are longer (e.g. measles, mumps), the secondary responses are more effective
a) Variation through mutation - antigenic drift
- Small numebr of mutations on surface proteins reduces effectiveness of activated B and T cells –> microbe looks like a new infection –> primary response again –> delaying removal of parasite
- Examples: common influenza virus causing flu –> mutation on the hemagglutinin and neuraminidase surface proteins
b) Recombination - antigenic shift
- Extensive and sudden change in genetic material
- Example: pandemic influenza (A)
- Simultaneous infection of different influenza viruses in one host can result in recombination of genetic material
- Outcome = hemmaglutinin and neuraminidase that new B and T cell have to recognise and mount primary response
c) Gene switching - most dramatic form of antigenic variation
- Example: the African trypanosomes causing sleeping sickness
- Carries 1000 different genes for different surface proteins
- Proteins cover the complete surface of the parasite
- Each is an immuno-dominant antigen recognised by B and T cells
- Typanosome can change the type of protein on a weekly basis therefore the IS constantly mounting new, primary response
Describe how immunosuppression evades the Adaptive IS
- Many microorganisms cause immunosuppresion in the host
- Often involves invasion of human tissues e.g, HIV and Helper T cells
- Host may have a depressed response to specific antigen of the parasite –> antigen specific suppression
- HIV causes destruction to helper T cells and therefore weakens the cell mediated reponses
a) Infection of immune cells - may result in impaired function by stopping cell division or blocking release of cytokines or even cell death
- T cells - HIV, measles
- B cells - Epstein Bar Virus (EBV)
- Macrophages - HIV
- Dendritic cells - HIV
b) Microbes release immunosuppressive molecules
- HIV - gp41 polypeptide temporarily blocks T cell function
- Poxvirus, herpesvirus –> release molecules that interfere with the action of complement or cytokines like IFN, TNF
c) Toxins as immunomodulators –> the release of exotoxins by some microbes cause tissue damage
- Act as super-antigens and cause massive activation of T cells which results in ineffective responses
- Exotoxins bind to class II MHC’s on antigen presenting cells and cause the following –> result in death of T cell or other immune cells
d) Interfere with local immune responses
- Production of enzyme that cleave IgA antibody in mucus
- Fc receptor molecules –> Fc is constant region of antibodies that bind to immune cells
- Protein A –> released soluble ptoein, binds to Fc portiona nd blocks opsonisation by immune cells
- Fc receptor on membrane –> causes antibodies to bind with Fc portion and hinders antigen binding site to attach to antigens
What are persistent infections?
>Failure of host immune response to completely eliminate parasite
Four main reasons why persistent infections are medically important
- They can re-activate e.g. herpes simplex virus (HSV) causing cold sore
- They are sometimes associated with chronic diseases e.g. HIV causing AIDS
- They are sometimes associated with cancers e.g. hepatocellular carcinoma by hepatitis B virus
- They enable infection to remain in the community through intermittent or continous shedding –> persistence is a microbial survival strategy
