CSIM 1.26 Role of T Cells in Bacterial and Viral Immunity

Question 1

Koplik’s spots are indicative of what?

Answer 1

Measles

Question 2

What is often indicative of chickenpox?

Answer 2

Vesicles/scabs at different stages

Question 3

We have already established the three criteria for activation of T cells. However, there are differences in requirements of T-cytotoxic cells for activation, depending on which type of cell if doing the activating. Describe this.

Answer 3

Dendritic Cells
• Can directly activate CD8 T cells
• This is because they naturally express very high levels of co-stimulatory molecules CD80 and CD86

Macrophages (and B cells occasionally)
• CD4 T-helper cells are required to ‘help’
• CD4 is stimulated by the APC, which also activates the APC
• This results in up-regulation of co-stimulatory molecules on the APC
• IL-2 secretion now occurs, which is enough to ‘help’ the T-cytotoxic cell become activated

Question 4

Describe how anergy helps with the prevention of autoimmunity

Answer 4

• Self-antigen is not expressed with co-stimulatory (CD80/CD86) molecules in normal cells.
  
  • APCs with self-antigen from normal apoptosis are not activated (due to lack of inflammation), and so do not express co-stimulatory molecules
  • T-cells coming into contact with either of these without the co-stimulatory molecules will become anergic, and will no longer respond to that antigen
  • That’s fine though, because even if it does happen to be a pathogenic antigen, there are many different antigens that can come from any one pathogen

Question 5

Describe the role of non-specific adhesion molecules, and name them.

Answer 5

The initial interaction between T-cells and target cells is made between these molecules, which stabilise the interaction between the two cells so the antigens from MHC I can be sampled

Target cell:
• ICAM
T cell:
• LFA-1

Question 6

Describe briefly what happens when T-cytotoxic cells ‘kill’ a cell

Answer 6

The area of contact forms an immunological synapse:
• The specific recognition redistributes the cell contents of the T cell to optimise the release of granules towards the target cell
• The target cell is then perforated by these granules

Question 7

What is the immune synapse between a T cell and a target cell also called? What are the components of this?

Answer 7

Supramolecular Adhesion Complex (SMAC):
• c-SMAC (central) made up of TCR, MHC and CD4/8
• p-SMAC (peripheral) made up of non-sepecific adhesion molecules LFA-1:ICAM-1

Question 8

What 3 components are found in the cytotoxic granules released into immune synapses by T-cytotoxic cells? What does each do?

Answer 8

Perforin
• Polymerises to form pores in membranes which allows granzymes and granulysin to enter for the induction of apoptosis

Granzymes and Granulysin
• Induce apoptosis

Question 9

Which cytokines are released by T-cytotoxic cells upon activation, and what does each do?

Recall those:

1) Released by macrophages and dendritic cells
3) Pro-inflammatory
4) Anti-inflammatory

Answer 9

IL-2

IFNƔ
• Blocks viral replication
• Prevents lots of virus being released after cell apoptosis

TNFβ
• Activates macrophages

TNFα
• Induces NO production

1) IL-1, IL-6, IL-8, IL-12 (T cell activator), TNF-α
3) IL-1, IL-2, IL-6, IL-17, TNF-α
4) IL-4, IL-10, IL-11, IL-13, TGF-β

Question 10

In early infection, describe how differentiation of CD4 T cells changes what cytokines cause this?

What does each differentiation type of CD4 helper T cells do?

Describe the differences in action of antibodies between immune responses instigated by Th1 and Th2 cells

Answer 10

In the absence of infection, naive (Th0) CD4 T cells show a regulatory phenotype, which inhibits Th1 and Th2

In EARLY infections, IL-6 is increased, stimulating a Th17 pattern to amplify inflammation and attract neutrophils:

Th17 cells
  •  Activated by: IL-6
  •  Releases: IL-17
  •  Functions: 
          > Attract neutrophils
          > Amplify inflammation

Then there is a differentiation. Viruses and bacteria cause dendritic cells to secrete IL-12 and NK cells to produce IFN-Ɣ, causing CD4 cells to differentiate into Th1 cells. Alternatively, worms cause the synthesis of IL-4 which causes CD4 T cells to differentiate into Th2 cells.

Th1 cells
• Activated by: IL-12 (monocyte release), IFN-Ɣ (NK release)
• Releases: IL-2, IFN-Ɣ, TNF-β
• Immune responses involve opsonisation antibodies
• Functions:
> Cell mediated immunity - kills infected cells to release bacteria for macrophages
> Activates macrophages

Th2 cells
• Activated by: IL-4
• Releases: IL-4, IL-5, IL-13
• Immune responses involve Neutralisation antibodies
• Functions:
> Humoral immunity (activation of B cells)

Question 11

Why does infection with leprosy (mycobacterium leprae) cause different clinical manifestations?

Answer 11

This infection if very dichotomising between different patients, some of whom react with a Th1 reaction, and others with a Th2 reaction. This produces different clinical manifestations:

Tuberculoid leprosy
• Creates a Th1 response, which is appropriate at dealing with the intracellular pathogen

Lepromatous leprosy
• Creates a Th2 response, which is ineffective because the bacteria hide out intracellularly
• This manifestation is more disseminated, infective and aggressive

Question 12

Describe the receptors expressed by natural killer cells. Describe how these are able to identify virus-infected cells

Answer 12

FcƔRIII, a receptor for IgG

Antibodies bind to the antigen presented by MHC I, which then bind to FcƔRIII, signalling for the destruction of the cell

The Fc receptors cluster during this binding, causing the NK cell to kill the target cell (IMG 70) by forming an immune synapse

IMG 69

Question 13

What is a superantigen?

Answer 13

An antigen that binds to the outside of a cleft of an MHC molecule, and activates many of the variable regions of the beta chain of the TCR

There are only 20 families of beta chain, therefore this causes activation of 5-10% of T cells, and toxic shock

Question 14

(25) What is Chronic Granulomatous disease?

Answer 14

X-linked deficiency of NADPH oxidase – failure to create super oxide, thus affecting neutrophil oxidative burst. Causes:

• Liver abscesses
• Aspergillus pneumonia
• Inflammatory bowel disease

Question 15

(25) What is paroxysmal nocturnal haemoglobinuria?

Answer 15

Block in transfer of N-acetylglucosamine to phosphadylinosol.

glucosylphosphadylinosol anchors cannot be produced

these are essential for a expression of a number of surface molecules

Red cells lack CD55 (DAF), CD59 (protectin) and CD46 (MCP)

Red cells susceptible to complement lysis via alternate pathway because CD59 usually prevents C9 being added to MAC

Results in:
• Haemoglobinuria
• Iron deficiency anaemia

Question 16

(25) Name the membrane regulatory molecules for complement and their CD number

What is the main function of these?

Answer 16

CD55: Decay accelerating factor (DAF)
CD59: Homologous restriction factor-20 (HRF-20) ‘protectin’
CD46: Membrane co-factor protein (MCP)

Major role in preventing lytic damage of ‘self’ cells

Question 17

(25) Name the soluble inhibitory regulators of complement

Answer 17

C1 inhibitor
Factor I
Factor H [Factor I co-factor]

Question 18

(25) What are the complement receptors and where are they found?

Answer 18

Erythrocytes:
• CR1 -Bind immune complexes for transport to spleen

B cells:
• CR1, CR2- Recognise complement in association with antigen

Question 19

(25) What is systemic lupus erythematosus?

Answer 19

C2 and C4 deficiency with inappropriate immune complex formation and poor clearance of immune complexes

Causes glomerulonephritis due to immune complex deposition in glomeruli

Question 20

(25) What condition causes Factor H and Factor I deficiency (regulators)?

Answer 20

Haemolytic-uraemic syndrome