Microbial Evasion of Immune Response Flashcards
1
Q
Colonization of privileged sites? (3)
A
- skin, intestinal lumen, external secretions- avoid circulating lymphocytes
- are exposed to secretory antibodies that bind to the microbe and render less infectious but do not kill microbe
- may result in local inflammatory response - certain sites safer for microbes than others
- CNS, joints, testes, placenta (hide here)
- reasons: less lymphocyte surveillance and lower access of antibodies and complement
- in inflammation is induced, lymphocytes, macrophages and antibodies can be delivered
- site loses privilege - sites created by infection itself
- hyatid cyst in liver, lung, brain from tapeworm
- Echinococcus granulosa
- worms survive within even though antibodies may be in blood - Host DNA occupied by retroviruses
- following integration, in no cell damage and no viral products expressed on cell surface, virus not recognized (HIV) - most privileged is egg or sperm DNA
- seen with endogenous retroviruses
- become part of inheritance
- does not happen with HIV or HTLV 1/2
2
Q
Strategies to evade phagocyte? (8)
A
- kill or avoid killing phagocyte
- elude contact
- protection against intracellular killing - interfering with ciliary action
- interfering with complement activation
- acquire or mimic complement regulators
- inhibit components
- enzyatically destroy complement components - produce iron binding molecules
- block interferons
3
Q
Examples of evasion and representative bacteria?
A
- no triggering of oxidative outburst (Legionella)
- modify or abort normal route of phagosome maturation (M. tuberculosis)
- diversion of phagosome to another pathway and resist phagolysosomal fusion, to Golig or ER (Chlamydia, Legionella)
- resist lysosomal degradation (coxiella burnettii, salmonella)
- cannot survive in activated macrophage - escape from phagosome (listeria monocytogenes, shigellae, rickettsiae)
- pathogen now subjected to MHC 1 of antigen processing and presentation
4
Q
Survival strategies?
A
- viruses, invasion of tissues often silent, do not form toxins
- if cells are not destroyed then no sign of illness until immune or inflammatory response, may take weeks
- hepatitis B, EBV - some viruses can infect cells for very long periods without affecting cell viability
- rubella (measles), hepatitis B, EBV
5
Q
Persistence in the host? (15)
A
- infection may be for years or life
- persistence effective only if shedding occurs periodically, maybe stays dormant, latent - persistent microbes:
- those shedding more or less continuously (EBV into saliva, hepatitis B in blood, eggs of helminths worms into feces)
- those shedding intermittently (HSV, polyomaviruses, typhoid bacilli, tubercle bacilli, malaria parasites)
6
Q
Persistent infections? (16)
A
- may persist in blood or intestinal tissues (Hep B or schistomes)
- may persist in low infectious form in tonsils or adenoids like adenoviruses
- may persist in metabolically altered states (MtB)
- may persist in non infectious form such as latent virus (HSV)
- viral genome is not integrated into host DNA, remains circular and episomal
7
Q
Strategies for host defense evasion?
A
- hit and run
- invasion followed by rapid shedding (few days after infection)
- adaptive immune defense not yet active
- body surface infection (rhinoviruses, rotaviruses) - if hit and run does not occur, strategies for evasion of lymphocytes:
- concealment of antigens
- antigenic variation
- immunosuppression
8
Q
Concealment of antigens?
A
- following intracellular infection, no antigen presentation on cell surface
- persistent latent viruses like HSV in sensory neurons - alternatively, viruses may display their proteins on the membranes of intracellular vacuoles and bud into vacuoles
- HIV on macrophages and coronaviruses - combine viral protein with MHC1 and prevent passage to cell surface
- no recognition by cytotoxic T cells in this way
9
Q
Listeria monocytogenes?
A
- ingest dairy sometimes meat, bacteria goes into gut
- infects epithelial cells in vacuoles
- leaves vacuole and binds actin in cytoplasm
- uses actin as motor to move through cell
- leave epithelium and enter portal circulation
- infects other cells, such as nervous system (meningitis)
- problem in pregnancy, death of fetus
10
Q
Concealment using host molecules? (22)
A
- blood fluke schistoma
- acquires surface coat of host glycolipids and HLA 1 and HLA 2
- only happens with worms - many viruses and bacteria produce Fc receptors
- bind all classes of immunoglobulins in an upside down position rendering them useless thus preventing access of specific antibodies or T cells
11
Q
Antigenic mimicry? (24)
A
- mimicking host antigens (heat shock protein 60)
- not recognized as foreign although not protective for microbe - best example:
- cross reaction between group A beta hemolytic streptococci and human myocardium
- causes rheumatic heart disease
- repeated strep infections leads to antibodies against cross reacting meromyosin, theses autoantibodies result in autoimmune response as well as an antimicrobial response
12
Q
Antigenic variation?
A
- occurs during the course of infection in an individual and also during spread of microbe in host community
- three main mechanisms of antigenic variation:
1. mutation
2. recombination and reassortment
3. gene switching
13
Q
Mutation (antigenic variation)?
A
- influenza virus
- repeated episodes of mutations in genes encoding hemagglutinin and neuraminidase
- small changes reduce effectiveness of B and T cell memory from earlier infections
- antigenic drift
- drift observed with other viruses such as HIV and polio with bacteria such as strep, staph, and pneumococci
14
Q
Recombination and reassortment (antigenic variation)? (28)
A
- exchange of genetic info between microbes
- influenza A virus
- human and avian strains reassort to form new strain not previously seen
15
Q
Gene switching (antigenic variation)? (29)
A
- Trypanosome Gambiense
- have genes for 1000 different surface glycoprotein molecules
- expression changes with immune response to constantly keep immune system at bay
- also may be responsible for relapsing persistent infections
- relapsing fever (borrelia recurrentis), brucellosis, gonorrheoae (with pilin expression changes)