W1L1 - T Cells

Question 1

Humoral Immunity

Answer 1

Mediated by antibodies produced by B cells
Primarily defence against extracellular microbes
Antibodies can bind to microbes and assist in elimination
Lead to further activation of effector mechanisms
- neutralisation of microbes
- phagocytosis
- complement activation

Question 2

Cell-Mediated Immunity

Answer 2

Mediated by T cells and their products
Defence against extracellular and intracellular microbes
Helper CD4+ T cells
- lead to activation of macrophages and inflammation
- lead to activation (proliferation and differentiation) of T and B cells
Cytotoxic CD8+ T cells
- direct killing of infected cells

Question 3

Where do T Cells come from?

Answer 3

1. Precursors travel from bone marrow through the blood to thymic cortex, where they acquire TCRs and both CD4 and CD8 co receptors
2. Positive selection promotes survival of cells whose TCRs bind MHC with low affinity
3. Differentiation into CD4+ or CD8+ T cells occurs in the medulla, and mature T cells are released into circulation
4. Differentiation into regulatory T cells and γδ T cells also occurs

Question 4

T Cell Receptor (TCR)

Answer 4

T cells express an antigen-specific receptor - the T Cell Receptor
Every clone of a T cell expresses a TCR with a unique sequence
Possibilities generated by same V(D)J gene arrangement as Ig antibodies
TCRs exist within a complex of proteins on the surface termed - CD3 complex
(TCR and CD3 often used interchangeably)

Question 5

Major Histocompatibility Protein (MHC)

Answer 5

Allows generation of an antigen-specific immune response
Allows a cell to be targeted by T cells
Antigen presenting cells (APCs) express MHC molecules carrying antigenic material on the cell surface => TCR binds the MHC:antigen complex
T cells must recognise antigen as a complex with MHC
Signal 1 for T cell activation

Question 6

Activation of T Cells by Antigen

Answer 6

APCs (such as dendritic cells) traffic antigen to lymph nodes to interact with T cells
Depending on interaction, T cells are activated to differentiation into effector CD4+ T cells or CD8+ T cells

Question 7

PAMPs and DAMPs

Answer 7

Pathogen associated molecular patterns
- recognition of molecules shared by microbes but not present on mammalian cells
- recognise microbial products essential for survival of microbes
Damage associated molecular patterns
- recognition of molecules produced/released from damaged and dying cells
- injury to cells (e.g. following infection or burn, trauma etc).

Question 8

Antigen Capture and Presentation by APCs

Answer 8

Immature dendritic cells (DCs) capture antigen and transport to lymph nodes
During migration, the DCs mature and (hopefully) become efficient APCs via up-reguation of costimulatory molecules
Signal 2 for T cell activation

Question 9

T Cell Subsets - CD4+

Answer 9

Recognise MHC class II
Mainly produce cytokines
Macrophage activation and inflammation

Question 10

T Cell Subsets - CD8+

Answer 10

Recognise MHC class I
Directly kill cells

Question 11

Interleukin-2

Answer 11

Interleukin-2 (IL-2) is a cytokine involved in promoting/controlling T cell responses
Resting naïve T cells express IL-2 receptor β and γ complex which has moderate affinity for IL-2
Activation of T cells by antigen, co-stimulation and IL-2 leads to IL-2 receptor α chain and high affinity IL-2Rαβγ

Question 12

Functions of Interleukin-2

Answer 12

Stimulates survival and proliferation = autocrine growth factor
Maintains regulatory T cells to control immune responses

Question 13

CD4+ T Helper 1 (Th1) Responses

Answer 13

Driven by IL-12 produced by APCs
Interferon-gamma (IFNγ) produced by NK cells
IL-12 and IFNγ => Th1 cells => IFNγ
IFNγ:
- inhibits Th2 and Th17 responses
- macrophages => inflammation
- stimulates B cell IgG production

Question 14

CD4+ T Helper 2 (Th2) Responses

Answer 14

Driven by IL-4 produced by activated T cells, mast cells and eosinophils => Th2 cells
Th2 cells then secretes IL-4
IL-4:
- inhibits Th1 and Th17 responses
- macrophages => tissue repair
- stimulate B cell IgE production
IL-5 activates eosinophils
- defence against parasites

Question 15

CD4+ T Helper 17 (Th17) Responses

Answer 15

Driven by IL-1 and IL-6 produced by APCs and transforming growth factor-beta (TGF-β) from macrophages and other cells
IL-23 produced by APCs stabilizes Th17
TGF-β inhibits Th1 and Th2 responses
Th17 cells then secrete IL-17
IL-17:
- local chemokine release
- recruit neutrophils
- release of anti-microbial peptides

Question 16

Regulatory CD4+ T Cells

Answer 16

Generated by self antigen recognition in the thymus and peripheral lymphoid organs
Development and survival requires IL-2 and FoxP3 transcription factor
Regulatory T cells:
- suppress self-reactive T cells
- suppress excessive inflammation

Question 17

CD8+ T Cell Functions

Answer 17

Release perforin and granzyme:

• perforin ‘drills holes’ into the cytoplasm
• granzyme enters target => apoptosis

Question 18

Memory Responses

Answer 18

Memory allows responses to subsequent exposure occur faster and larger
Memory cells are more efficient at responding and eliminating antigens
Contraction occurs after elimination of antigen stimulation
Returns the immune system to homeostasis
Memory T cells are antigen-specific
Lower threshold for activation