Lecture 7 - Cell-Mediated Immunity

Question 1

How is Self-Reactivity Prevented?

(2 Points)

Answer 1

• T-cells under selection in thymus during their development, with strongly reactive cells being eliminated via apoptosis
• T-cells require Co-stimulation from receptors expressed exclusively on APCs to become activated

Question 2

What is the fate of Thymocytes?

(2 Points)

Answer 2

• Mature into CD4/CD8 Naive T-cells, which leave the Thymus to re-circulate until the encounter their specific antigen
• Naive T-cells - divide infrequently, and can live for many years

Question 3

What is Naive T-cell Priming?

Answer 3

Peripheral Naive T-cells may encounter their specific antigen, being induced to proliferate and differentiate into armed effector cells (Clonal Expansion)

Question 4

What is the Zone of Contact between the APC and T-cell known as?

How does Synapse formation differ between CD4 and CD8 T-cells?

Answer 4

• Immunological Synapse
• CD4 T-cells - synapse formation is enduring (hours)
• CD8 T-cells - synapse formation is rapid (minutes)

Question 5

What is the Effect of Successful Immunological Synapse formation on:
(i) Naive T-cell
(ii) APC

Answer 5

(i) Induce T-cell to express a high affinity IL-2 Receptor and IL-2, which is a t-cell proliferation and survival factor

(ii) Increases expression of Co-stimulatory molecules on surface e.g., B7.2

Question 6

Compare the Differentiation of (i) Naive CD8 T-cells and (ii) Naive CD4 T-cells?

(2 Points)

Answer 6

(i) Naive CD8 T-cells differentiation into effector cells produces Cytotoxic T-cells only, and only requires 2 activation signals

(ii)Naive CD4 T-cells differentiation into effector cells has several outcomes (TH1, TH2, TH17, TREG), and requires 3 signals (3rd signal determines subtype)

Question 7

What are the General Properties of Armed Effector Cells?

(2 Points)

Answer 7

• Produce/Release Cytokines and related membrane-associated proteins
• Act by binding to specific receptors on target cell

Question 8

Define the two Mechanisms by which Armed CD8 T-cells can perform their function.

Answer 8

1. Release of Cytotoxins from Lytic Granules such as:
   * Perforin (produces pore in bacterial membrane)
   * Granzymes (Activates Caspase 3)
   * Granulysin (Antimicrobial Activity)
2. Release of Cytokines (e.g., IFNy) to generate antiviral responses and facilitate antigen presentation

Question 9

What happens to Naive T-cells if they do not recieve their activation signals simultaneously? Why is this Important?

(3 Points)

Answer 9

• Signal 1 Only - triggers anergy (no IL-2 produced) and clonal deletion
• Signal 2 Only - no effect
• Requirement of both signals simultaneously prevents self-immunity, as if T-cell recognises antigen on a normal cell it will not recieve sufficient co-stimulation and will become anergic

Question 10

How do the Cytokines (Signal 3) released by the APC vary?

Answer 10

Depends on Environmental Conditions (e.g., Stage of Infection, Pathogen Type), which may favour a particular subtype of Helper T-cells

Question 11

What is the Role of CD4 TH1 cells?

How do they perform this role?

(3 Points)

Answer 11

• Help to Activate Macrophages to Kill intracellular bacteria
• CD4 TH1 cells synthesise membrane-associated proteins (CD40L) and soluble cytokines (IFNy), which activate the macrophage to produce toxic agents to kill the pathogens
• TH1 cells bind to macrophages for several hours (time taken to produce effector molecules)

Question 12

What is the role of CD4 TH2 Cells?

How do they perform this role?

Answer 12

• CD4 TH2 Cells help B-cells to produce antibodies, as well as stimulating switching to certain isotypes (IgA and IgE)
• Produce IL-4, which activates naive antigen-specific B-cells to produce IgM antibodies

Question 13

What are CD4 TH17 Cells?

What is their role in an Immune response?

Answer 13

• Produced early in the adaptive immune response to Extracellular bacteria
• Secrete IL-17 which induces epithelial cells/fibroblasts to produce chemokines (CXCL9/10) that attract neutrophils to site of infection

Question 14

What is the role of Treg cells?

(Give One Example)

Answer 14

Release IL-10, which suppresses T-cell responses in order to limit the Immune Response
* E.g., Can Inhibit Maturation of Monocytes into mature forms

Question 15

What are Memory T-cells? How do they provide Immunological Memory?

(3 Points)

Answer 15

• Long-lived Cells which retain many characteristics of armed effector T-cells, but also expression novel proteins
• Number of Memory/Effector Cells remain 100-1000 fold higher than pre-immune levels
• Following re-infection, the memory T-cells are reactivated following interaction with APC, once again achieving armed effector T-cell status