L12 - Effector responses against infection II

Question 1

CD4+ T-cells: what recognition results in their activation, what do they do, and what types of cells are they activated by?

Answer 1

• MHCII expressed by antigen-presenting cells
• Co-stimulation - dendritic cell for naive CD4+ T-cells, i.e. CD28-CD80/86
• Cytokines

Activated CD4+ T-cells become T-helper cells and facilitate activation of other immune responses (CD8+ T-cells) - don’t directly kill things

Intracellular pathogens - viruses and some bacteria

Question 2

CD8+ T-cells: what recognition results in their activation, what other stimulation do they require, and what do they do?

Answer 2

• MHCI expressed by ALL nucleated cells (initial priming by DCs)
• Co-stimulation - dendritic cell for naive CD8+ T-cells, i.e. CD28-CD80/86
• Cytokines

Activated CD8+ T-cells become cytotoxic T-lymphocytes (CTLs), directly killing cells infected with intracellular pathogens

Question 3

Rewacth leccy for two above

Question 4

Types of T-cells

Answer 4

Th1
Th2
Th17
Tfh
Treg

Question 5

Th1 cells: what do they do?

Answer 5

Central activator of macrophages by secreting interferon beta (IFN-β) and by the CD40 ligand-CD40 interaction

• Uses IgG1 to stimulate low levels of antibodies
• Can opsonise pathogens in extracellular phase

Occurs more slowly - over hours, requires prolonged attachment of Th1 cell to macrophage)

Question 6

What is the slow, prolonged attachment of Th1 cells to macrophages for activation called?

Answer 6

Delayed-type hypersensitivity (DTH)

Question 7

Th2 cells: what do they do?

Answer 7

Generally generated to deal with large extracellular pathogens - ie parasitic worms (helminths) - as they are too big to be phagocytosed and may potentially cause major damage if a massive response is mounted

• Induces b-cell antibody production
• Induce eosinophils, basophils, and mast cells either directly (Th2 cytokines) or indirectly (through b-cell IgE antibody induction)

Question 8

Th17 cells: what do they do?

Answer 8

Generally generated to deal with extracellular bacteria and fungi

• Secretes IL-22 which induces antimicrobial peptide production
• Secretes IL-17 which acts on several cell types to induce cytokine/chemokine secretion, neutrophil recruitment, stimulation of macrophage and neutrophil production in bone marrow

Question 9

CD8 T cells: how do they become activated?

Answer 9

APCs activate them - converting them into a cytotoxic T lymphocytes (CTL)

CTL does not require co-stimulation

Question 10

CTLs: how do they kill infected cells, what granules do they contain, and what other parts of the body do they affect?

Answer 10

• CTL binds to target cell loosely to target cell
• CTL recognises antigen (presented by MHCI) and T-cell cytoskeleton reorganises to place granules at site of contact
• CTL releases cytotoxic granules at the cell-cell contact - allows very quick (within minutes) specific killing by apoptosis

CTL cytotoxic granules contain:
* Granzymes - serine proteases that induce apoptosis in target cell
* Granulysin - antimicrobial and can induce apoptosis
* Perforin - helps deliver granule contents to target cell

Immune system by secreting cytokines:
* IFN-γ - activates macrophages, directly inhibits viral replication, and increases MHC I expression in infected cells
* TNF-(?)aplha?) - helps IFN-γ activate macrophages and may also directly kill some infected cells
* LT-(?) - helps IFN-γ activate macrophages and may also directly kill some infected cells

Question 11

Apoptosis vs necrosis: which is more damaging?

Answer 11

Apoptosis produces less damage than necrosis - less inflammation induced

Question 12

Antibody effector mechanisms

Answer 12

Generally not directly toxic - facilitate destruction of antigens by enhancing innate immune mechanisms:
* Neutralisation - bind to directly to pathogen or toxin to prevent attachment and entry into cell
* Agglutination - lattice clump formed, easier to be phagocytosed/complement pathway
* Opsonisation - tag cells for phagocytosis
* Antibody-dependent cell-mediated cytotoxicity (ADCC) - Using Fc cells/cell receptors, a bridge is used between immune cells and the larger-than-phagocytosable pathogen which mediates death
* Activation of complement - complement cascade occurs, lysis of pathogen
* Specialised responses - ie cytokines, mast cells, granules, lipid mediators released - inflammatory response