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Cellular responses CMI and AMI
Cell-mediated immunity (CMI) and Antibody-mediated immunity (AMI)
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Innate Immunity
- Immediate, initial defense, no memory
- Includes: cells, non-specific humoral factors, physical barriers
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Adaptive Immunity
Slow, antigen-specific, memory, cellular components
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Cell-mediated immunity (CMI)
- Host cells recognize PAMPs (innate)
- B/T cells recognize antigens (adaptive)
- Response to Pathogen Recognition:
- -Phagocyte activation, increase anti-microbe
- -Lymphocyte activation, proliferation
- -Cytokine production
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Humoral Immunity
- Innate: non-specific soluble blood components
- Specific: Antibodies produced by B cells
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Aspects of Immunity EFFECTIVE against fungi
Innate immunity, cell mediated-responses
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Aspects of Immunity NOT EFFECTIVE against fungi
Complement attack, Antibodies (although a strong response IS elicited)
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Fungal PAMPS can elicit:
- Cytokines, TNF's, IL's, Interferons
- Alter the expression of genes that cover antimicrobial traits
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Development of antigen-CMI to fungi
- Macrophage processes/presents antigen
- MHCII presents to T lymphocyte
- T cell expressing CD4/TCR
- T cell proliferate, activate pro-inflammatory cytokines
- Cytokines stimulate macrophage antimicrobial activity
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Defects that can make hosts more susceptible to fungal infection.
- Compromised skin barrier
- Reduction/alteration of microbiota
- Inherited immunodeficiency
- Cancer
- Radiation therapy and cytotoxic chemotherapy
- Immunosuppressive chemotherapy
- Hospitalization
- Diabetes
- Extremes of age
- Other infections
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How does skin barrier breach allow susceptibility
- Barrier compromised, reduced blood (WBC) count.
- Fungus can land, be inserted in, or skin-borne can enter.
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Can can reduction/alteration of microbiota
Normal bio fungus can over-grow, anti-biotics can remove competition.
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How can inherited immunodeficiency allow increase fungal susceptibility
- Syndromes affecting phagocytes or T lymphocytes are most relevant
- e.g: chronic granulomatous disease (CGD), severe combined immunodeficiency (SCID)
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How can cancer increase fungal susceptibility
- Cancer may disturb cytokine networks
- Can reduce function of normal immune system
- Cancer treatments can weaken immune system
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Cancer treatments that weaken immune system
- Radiation and cytotoxic chemotherapy:
- Mechanism: kills rapidly dividing cells
- kills bone marrow in process (loss of WBCs)
- widespread immunosuppressive and anti-inflammatory effects
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The longer one has granulocytopenia the more likely they are to have:
invasive pulmonary aspergillis
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Forms of Immunosuppressive chemotherapy
- Corticosteroids, TNFalpha antagonists, Calcineurin inhibitors
- All suppress various forms of immune response: inflammation, phagocytes, TNFs, T cells
Used in various autoimmune responses
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How can hospitalization effect fungal susceptibility
- Immunosupression by procedures, invasive procedures, antibiotics, illness
- Hospitals are a great place for opportunistic diseases, nosocomial infections
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How does diabetes affect fungal susceptibility
Diminished phagocytes, nutritional effects,
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Affects of age on fungal susceptibility
Very young/old are susceptible. Both have weaker immune systems
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Other infections that can affect fungal susceptibility
Herpes, HIV
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