cell mediated immunity

Question 1

what does cell-mediated immunity target?

Answer 1

• intracellular bugs
• viruses
• fungi
• parasites
• tumor cells

Question 2

subsets of T cells and their most identifying characteristics

Answer 2

CD4+ helper cells:

• MHC class II
• secrete cytokines to support other cells
• Th1, Th2, and Th17 subsets

Tregs

CD8+ cytotoxic T cells:

• MHC class I
• directly kill other cells

Question 3

Th1 cell

Answer 3

• CD4+ T helper cell
• produces IFN-g
• promotes cellular activity and macrophage activation

Question 4

Th2 cell

Answer 4

• CD4+ T helper cell
• produces IL4, IL5, IL13
• promotes humoral immunity and anti-helminth response

Question 5

Th17 cell

Answer 5

• CD4+ T helper cell
• produces IL17
• involved in host defense and autoimmune disease pathogenesis

Question 6

Treg

Answer 6

• CD4+ T helper cell

- modulates immune responses

Question 7

mechanisms of CD8+ cytotoxic T cell cellular killing

Answer 7

• release of molecules from granules: perforins form channels in cell membrane and granzymes are proteases that degrade membrane proteins
• activation of caspases => apoptosis
• express FasL => binding to Fas on cell => apoptosis

Question 8

what cells are involved in cell mediated immunity?

Answer 8

• APC’s (macrophages and dendritic cells)
• Th1 CD4+ helper T cells
• CD8+ cytotoxic T cells
• NK cells
• B cells (via ADCC)

Question 9

compare the activation of naive and effector T cells

Answer 9

naive:

• encounter antigen in secondary lymphoid organs
• requires antigen receptor + co-stimulation

effector:

• encounter antigen in other tissues
• require antigen receptor but no co-stimulation

Question 10

cell mediated immunity against intracellular bugs

Answer 10

1. APC’s ingest bugs
2. PAMP recognition => APC expression of co-stimulatory molecules (like B7) and cytokine production (IL2 and IL12)
3. IL12 drives CD4+ T helper cell => Th1 cell differentiation APC CD40 binds T cell CD40L
4. T cells secrete IFN-g => activation of CD8+ cytotoxic T cells and activation of APC’s to kill phagocytosed pathogens

B cells/antibodies help by blocking bugs from binding to receptors they use to get in to the cell

Question 11

cell mediated immunity against viruses

Answer 11

CD8+ cytotoxic T cells recognize viral peptides presented on MHC class I => kill infected cells

Question 12

humoral immunity against viruses

Answer 12

antibodies:

• neutralize virus by direct binding (and blocking cell receptor binding)
• opsonization
• bind to new antigens produced on surface of infected cells => complement activation and killing by MAC
• ADCC

Question 13

NK cell/innate immune response to virus

Answer 13

• NK cells recognize infected cells by lack of MHC class I

- kill target cell with perforins and granzymes

Question 14

macrophages and viral immunity

Answer 14

phagocytosis, antigen presentation, stimulation of immune response, IFN production

Question 15

processing of intracellular antigens through MHC class I pathway

Answer 15

1. proteasome cleaves intraceullular proteins
2. peptides associate with a TAP transporter
3. TAP transporter transports peptide to ER
4. MHC class I molecules are synthesized in the ER and associate with peptide fragments
5. Peptide binding stabilizes MHC I => transport through golgi to cell surgace

Question 16

processing of extracellular antigens through MHC class II pathway

Answer 16

1. pathogens and foreign molecules are engulfed into phagosomes or endosomes
2. phagosome/endosome fusion with protease containing lysosomes
3. MHC II is synthesized in the ER and peptide binding in the ER is blocked by invariant chain protein
4. MHC class II transported to endosomal vesicles and invariant chain is removed by a protease
5. peptide fragments associate with MHC class II in endosomal vesicles and are transported to cell surface

Question 17

antigen cross-presentation

Answer 17

1. APC’s take up extracellular pathogens or foreign material and transport peptides to cytosol and then ER
2. peptides presented on MHC class I to induce a CD8+ cytotoxic T cell response

Question 18

how do chemokines facilitate APC (under epithelial surfaces) and B/T cell (lymphoid tissue) interaction?

Answer 18

1. APC’s upregulate chemokine receptors after ingestion of a microbe
2. T cells produce chemokines
3. APC’s move along the chemokine gradient through the lymphatics to the lymphoid tissue

Question 19

cell mediated immune response to Mtb

Answer 19

delayed type hypersensitivity:
Mtb are phagocytosed but survive in phagosomes => CD4+ Th1 cell response and constant IL-2 and IFN production => stimulation of macrophages and CD8+ T cells => macrophages secrete IL-12 increasing the Th1 response

=> => granuloma formation from all of the macrophages => macrophages secrete hydrolases which leads to central necrosis

Question 20

cell mediated immunity basis of organ rejection

Answer 20

• CD8+ cytotoxic T cells damage organ
• non self MHC = target
• acute/chronic rejection (in contrast to hyperacute, which is Ab mediated)

Question 21

effect of cell mediated immunity deficiency

Answer 21

• predisposition to infection by intracellular bugs, viruses, and fungi
• increased risk of neoplasia (viral driven tumors)
• infection by opportunistic pathogens