Adaptive Immunity

Question 1

What causes Th0 cells to become Th1 cells?

Answer 1

IL-12

Question 2

IL-12 is produced by?

Answer 2

Antigen presenting cells such as macrophages

Question 3

What causes macrophages to become classically activated?

Answer 3

Direct activation: T cell CD40L binds CD40 on the macrophage

Indirect activation: IFN-g

Question 4

Indirect classical activation of macrophages?

Answer 4

Cytokine IFN-g

Question 5

Direct classical activation of macrophages?

Answer 5

CD40L binding to macrophage CD40

Question 6

What cytokine leads to classical activation of macrophages?

Answer 6

IFN-g

Question 7

What cytokine leads to alternative activation of macrophages?

Answer 7

IL-4

Question 8

Alternative macrophage activation can also be known as?

Answer 8

Wound healing

Question 9

Which cytokine leads to deactivation of macrophages?

Answer 9

IL-10

Question 10

What causes Th0–>Th2?

Answer 10

IL-4

Question 11

What causes Th0–>Th1?

Answer 11

IL-12

Question 12

What are the roles of dendritic cells?

Answer 12

Antigen presenting cells

IL-12 producing

Question 13

CD8+ cell importance?

Answer 13

Produce IFN-g which can classically activate macrophages

Can kill infected cells directly via perforin and granzymes

Question 14

CD4+ cell importance?

Answer 14

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

Question 15

In which infections are CD8+ cells more important?

Answer 15

When cells are infected
Intracellular parasites
Can use granzymes and perforin
Can produce IFN-g

Question 16

In which infections are CD4+ cells more important?

Answer 16

Blood stage infection
When the parasites are extracellular- can be opsonised by antibodies
IFN-g is produced

Question 17

Which T cell is most important during the liver stage of Plasmodium infection and why?

Answer 17

CD8+

Can kill infected liver cells via perforin and granzymes

Question 18

Which T cell is most important during the blood stage of Plasmodium infection and why?

Answer 18

CD4+ T cells

Lead to antibody production, which can opsonise the infected RBCs or extracellular merozoites

Question 19

CD8+ cells and cerebral malaria?

Answer 19

CD8+ T cells can cause severe cerebral malaria through accumulation in the brain, destruction of the blood brain barrier and excessive inflammation

Question 20

Which T cell type is more important in Leishmania infection and why?

Answer 20

CD4+

Leishmania is present in macrophages and therefore cannot be accessed by CD8+ T cells

Question 21

Why are CD8+ T cells not important in the blood stage of malaria?

Answer 21

RBCs do not possess MHC-I

Therefore antigen cannot be expressed

Question 22

Why are CD8+ T cells not important in T.brucei infection?

Answer 22

As it is an extracellular parasite

Question 23

What is IL-10?

Answer 23

Anti-inflammatory cytokine

Question 24

When IL-10 is depleted it leads to?

Answer 24

Increased reduction in parasite load

Question 25

However, why is it not a good idea to drastically deplete IL-10?

Answer 25

As IL-10 is important in regulating the immune response, depleting IL-10 leads to increased pathology associated with the disease

Question 26

What else can regulate the immune response?

Answer 26

Tregs

Question 27

What are Tregs?

Answer 27

A subset of CD4+ T cells which can produce IL-10, prevent self-reactive T cell proliferation and can regulate the immune response

Question 28

What does IL-10 do to macrophages?

Answer 28

It deactivates them

Question 29

Removal of IL-10 and Tregs can lead to?

Answer 29

Reduced parasite load | Increased pathology associated with the disease

Question 30

How do CD4+ cells activate naive B cells?

Answer 30

CD40L on the T cell binds the CD40 on the B cells and causes them to become plasma cells

Question 31

What are the roles of antibodies?

Answer 31

- 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

Question 32

How can Leishmania interfere with interferon signalling?

Answer 32

Interferes with the JAK/STAT pathway

Question 33

Evasion of CD8+ cells?

Answer 33

- T.brucei extracellular - Giardia extracellular - Leishmania within macrophages - Blood stage Plasmodium is within erythrocytes which do not express MHC-I

Question 34

Evasion of CD4+ cells?

Answer 34

- 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

Question 35

Evasion of NK cells?

Answer 35

- T.brucei is extracellular | - Giardia is extracellular

Question 36

Evasion of complement?

Answer 36

- 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

Question 37

Evasion of interferons?

Answer 37

Leishmania can prevent interferon JAK-STAT signalling

Question 38

Evasion of innate immunity?

Answer 38

- 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