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)
16
Q
Immune modulation?
A
- 5 methods to avoid inducing immune response or inducing poor response:
1. infection during embryonic life
2. production of large quantities of microbial antigen or antigen antibody complexes
3. exploiting gaps in immune repertoire
4. upsetting balance between antibody and cell mediated immune responses
5. inducing immune responses that down regulate or suppress protective immunity
17
Q
Infections in early embryonic life? (modulation)
A
- before immune system development infection could regarded as self
- hep B in neonatal period
- results in permanent carriage of virus
- in intrauterine infections of fetus, fetus may develop IgM antibody against infection, however cell mediated responses are more impaired
- result is congenital infections that may take years to clear and severe debilitation
18
Q
Production of large quantities of antigen or antigen antibody complexes? (modulation)
A
- can result in immune tolerance
- anergy can develop where normal antibodies are made but cell mediated immunity is very depressed
- example: disseminated coccidioidomycosis and cryptococcosis, large amounts of antigen present in circulation
19
Q
gaps in host response? (modulation)
A
peptides to which host responds poorly
20
Q
Unbalanced TH1 and TH2 responses? (modulation)
A
-in active Mtb, IL4 T cells are detected, but a reduction of TH1 cytokines occurs
21
Q
Regulatory T cells? (modulation)
A
- induction of T regs by some bacteria and helminths
- result IL 10 that is anti inflammatory is made and down regulation of TH1 cytokine response
22
Q
Microbial toxins? (modulation)
A
- staph
- released toxins (super antigens) cause polyclonal activation which may kill other immune cells and result in release in irrelevant antibodies
23
Q
Many viruses code for fake molecules and fake cell receptors for host molecules? (modulation) (34)
A
- HSV glycoprotein C (example)
- receptor for C3b
- its presence with proper complement activation
- another example:
- EBV codes for IL10 homologue that down regulates the cell mediated response induced by IL12
- intracellulars like Mtb, Leishmania major, Histoplasma capsulatum inhibit IL12 production by macrophages thus no activation of T cells by IL12 so limited T cell response
24
Q
Other things that viruses do to avoid immune response?
A
- some viruses down regulate MHC 1 expression so cytotoxic T cells cannot recognize
- adenoviruses and HSV - some viruses interfere with production or action of interferons
- rotaviruses, adenoviruses - some bacteria and viruses induce apoptosis
- especially after encountering macrophages
- helps their spread
- Yersinia pestis, measles - some viruses prevent apoptosis to become persistent infections
- HSV, EBV, HIV
25
Q
Interference with immune response in tissues?
A
- protease A that cleaves IgA
- gonorrheae, strep, haemophilus influenza - production of Fc receptor molecules
- bind to IgG and inhibit phagocytosis
- HSV, CMV, VZV - production of elastase
- inactivates C3b and C5a components of complement
- pseudomonas
26
Q
Immunosuppression?
A
- temporary immunosuppression
- HIV killing of CD 4 T cells - actual infection of host immune cells
- T cells (HIV, measles)
- B cells (EBV)
- macrophages (HIV, CMV, leishmania)
- dendritic cells (HIV) - release of immunosuppression molecules
- may block complement or cytokines
