Adaptive Immunity Flashcards
What causes Th0 cells to become Th1 cells?
IL-12
IL-12 is produced by?
Antigen presenting cells such as macrophages
What causes macrophages to become classically activated?
Direct activation: T cell CD40L binds CD40 on the macrophage
Indirect activation: IFN-g
Indirect classical activation of macrophages?
Cytokine IFN-g
Direct classical activation of macrophages?
CD40L binding to macrophage CD40
What cytokine leads to classical activation of macrophages?
IFN-g
What cytokine leads to alternative activation of macrophages?
IL-4
Alternative macrophage activation can also be known as?
Wound healing
Which cytokine leads to deactivation of macrophages?
IL-10
What causes Th0–>Th2?
IL-4
What causes Th0–>Th1?
IL-12
What are the roles of dendritic cells?
Antigen presenting cells
IL-12 producing
CD8+ cell importance?
Produce IFN-g which can classically activate macrophages
Can kill infected cells directly via perforin and granzymes
CD4+ cell importance?
Produce IFN-g which can classically activate macrophages
Can activate naive B cells causing them to become antibody producing plasma cells
Treg
Produce IL-10 to regulate the immune response
In which infections are CD8+ cells more important?
When cells are infected
Intracellular parasites
Can use granzymes and perforin
Can produce IFN-g
In which infections are CD4+ cells more important?
Blood stage infection
When the parasites are extracellular- can be opsonised by antibodies
IFN-g is produced
Which T cell is most important during the liver stage of Plasmodium infection and why?
CD8+
Can kill infected liver cells via perforin and granzymes
Which T cell is most important during the blood stage of Plasmodium infection and why?
CD4+ T cells
Lead to antibody production, which can opsonise the infected RBCs or extracellular merozoites
CD8+ cells and cerebral malaria?
CD8+ T cells can cause severe cerebral malaria through accumulation in the brain, destruction of the blood brain barrier and excessive inflammation
Which T cell type is more important in Leishmania infection and why?
CD4+
Leishmania is present in macrophages and therefore cannot be accessed by CD8+ T cells
Why are CD8+ T cells not important in the blood stage of malaria?
RBCs do not possess MHC-I
Therefore antigen cannot be expressed
Why are CD8+ T cells not important in T.brucei infection?
As it is an extracellular parasite
What is IL-10?
Anti-inflammatory cytokine
When IL-10 is depleted it leads to?
Increased reduction in parasite load
However, why is it not a good idea to drastically deplete IL-10?
As IL-10 is important in regulating the immune response, depleting IL-10 leads to increased pathology associated with the disease
What else can regulate the immune response?
Tregs
What are Tregs?
A subset of CD4+ T cells which can produce IL-10, prevent self-reactive T cell proliferation and can regulate the immune response
What does IL-10 do to macrophages?
It deactivates them
Removal of IL-10 and Tregs can lead to?
Reduced parasite load
Increased pathology associated with the disease
How do CD4+ cells activate naive B cells?
CD40L on the T cell binds the CD40 on the B cells and causes them to become plasma cells
What are the roles of antibodies?
- Neutralise parasites, preventing cell entry
- Opsonise parasites for phagocytosis
- Activate classical complement
- Cause the membrane attack complex to form
- ADCC: Antibody dependent cell mediated cytotoxicity via NK cells
- Binding action alone can cause cell rupture
How can Leishmania interfere with interferon signalling?
Interferes with the JAK/STAT pathway
Evasion of CD8+ cells?
- T.brucei extracellular
- Giardia extracellular
- Leishmania within macrophages
- Blood stage Plasmodium is within erythrocytes which do not express MHC-I
Evasion of CD4+ cells?
- T.brucei antigenic variation and coat cleaning mechanism
- Plasmodium antigenic variation
- Giardia antigenic variation
- Plasmodium rosetting
- Intracellular parasites: Toxoplasma, T.cruzi, Leishmania,, Plasmodium
- VSG coat of T.cruzi hides the invariant surface receptors
- Flagellar pocket of the kinetoplastid protozoa shelters invariant receptors
Evasion of NK cells?
- T.brucei is extracellular
- Giardia is extracellular
Evasion of complement?
- LPG of Leishmania can prevent MAC
- GP63 of Leishmania converts C3b to iC3b
- Trans-sialidase of T.cruzi transfers host sialic acid to mucins on the cell surface
- Intracellular parasites
- T.brucei dense VSG coat prevents complement mediated lysis
Evasion of interferons?
Leishmania can prevent interferon JAK-STAT signalling
Evasion of innate immunity?
- Leishmania LPG can delay the fusion of the phagosome with the lysosome to allow time for the promastigotes to differentiate into amastigotes
- Leishmania can survive in the phagolysosome and can even replicate here
- Leishmania can induce the macrophage or produce its own arginase which can deplete the level of L-arginine available for use by iNOS- inducible nitric oxide synthase to produce nitric oxide
- T.cruzi escapes the acidification of the phagosome by entering the cytosol and replicating there, this is facilitated by the trans-sialidases and by haemolysins which are pore forming
- Entering a dormant state in cells can help to evade the immune response e.g. Toxoplasma bradyzoites are immunologically dormant and can go undetected
- Intracellular parasites can avoid being phagocytosed as they are intracellular
