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MBBS II HIS > L15 - Cell mediated immune reactions > Flashcards

L15 - Cell mediated immune reactions Flashcards

1
Q

Which immune cells are involved in cell-mediated immunity?

A

T cells: Th and CTLs

Phagocytes (e.g. macrophages, neutrophils)

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2
Q

List the 3 main effector mechanisms of Cell-mediated immunity?

A

– Cell-mediated cytotoxicity (CLT, NK)

– Chemotaxis & phagocytosis (MQ)

– Cytokine-mediated direct target cell killing (TH1)

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3
Q

Classify cell-mediated immunity?

A

T cell dependency:

– T-dependent (specific): CLT, TH

– T-independent (early phase/ non-specific): NK, MQ

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4
Q

What are the 3 subtypes of cell-mediated cytotoxicity?

A
  • Cytotoxic T Lymphocyte (CTL)-mediated Killing
  • Antibody-dependent Cell-mediated Cytotoxicity (ADCC)
  • Natural Killer (NK) Cell-mediated Killing
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5
Q

Which cells are targeted by CTL-mediated killing??

A
  • Altered self cells (virus infected or tumour cells)

- Intracellular bacteria and parasites

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6
Q

What antagonizes CTL-mediated killing?

A

antibody-binding blocks CTL recognition

Ab bind to peptide antigen directly on MHC-I of APCs

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7
Q

Describe the 5 steps of CTL mediated killing?

A

1) Attachment – CD8+ CTL’s TCR binds to antigen presented by MHC-I on target cells

2) 2 signals:
a) TCR + MHC + CD8
b) ) Co-activators: CD80/CD86 on CTL bind CD28 on APC

3) IL-2 from T helper cells cause degranulation of CTL&raquo_space; release Perforins, Lymphotoxins and Granzymes to target cell
4) IFN-γ activates macrophages
5) Recycle CTLs for additional attacks, target cell dies when CTL detaches

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8
Q

Describe the MoA of perforins?

A

–Released from cytoplasmic granules of CTLs

–Forms pores in the target cell membrane

–Allows granzymes, water to enter target cell

–May cause osmotic lysis

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9
Q

Which cytotoxic factors induce apoptosis of target cells?

A

 Lymphotoxin

 Granzymes

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10
Q

Describe the MoA of granzymes?

A

activate caspase pathway, endonuclease&raquo_space; apoptosis

  • toxic to actual intracellular pathogens
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11
Q

Which cytokine is critical for CTL killing ?

A

IL-2 from Th

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12
Q

Describe the process of ADCC?

A

Antibody-dependent Cell-mediated Cytotoxicity:

  • Fc Receptor on Large granular lymphocytes/ cytotoxic cells bind to Ab on target cells/ pathogens not using TCR

> > Release cytotoxic factors to directly kill

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13
Q

What provides the specificity in ADCC?

A

Ab binding to target cell and Fc recognized by Large Granular Lymphocytes (LGL)

Ab gives Ag specificity

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14
Q

Which type of cell-mediated toxicity is not specific?

A

Natural Killer (NK) Cell-mediated Killing

no antigen specificity

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15
Q

Compare the 2 signals in NK cell mediated killing?

A

Signal 1 = Killer activatory receptor (KAR / lectin) on NK cell + Carbohydrate on target cell

Signal 2 = Killer inhibitory receptor (KIR / Ly49) + Self MHC-I presenting own antigen

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16
Q

Describe how NK cells target abnormal cells but not own cells?

A
  • Normal cell = equal activation of Killer activatory receptor (KAR / lectin) and Killer inhibitory receptor (KIR / Ly49)
    » no killing
  • Abnormal cell with no MHC-I or abnormal antigen&raquo_space; only activate KAR
    » activate NK cell cytotoxicity
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17
Q

Define which cells can activate NK cell killing?

A

Cells with altered MHC-I or presenting abnormal/ non-self Ag

  • Tumor cells (no MHC-I)
  • Grafts (non-self MHC-1)
  • Virus-infected cells (foreign Ag)
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18
Q

What is the action of Fas ligand in cell-mediated killing?

A

Fas ligand binds to Fas on target cell&raquo_space; activate caspase, endonuclease&raquo_space; apoptosis

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19
Q

List all phagocytes

A

– Neutrophils
– Monocytes
– Macrophages

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20
Q

Describe the action of chemotatic factors in T-Independent Macrophage Activation?

A

Ab- Ag complex activate complement system

> > concentration gradient of chemotactic components / fragments

> > attract phagocytes to target cells (e.g. infected) / invading pathogenic microorganisms

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21
Q

List 3 chemotactic molecules for T-Independent Macrophage Activation?

A

Bacterial components (e.g. fMLP = polysaccharide from bacterial cell wall)

Complement products (e.g. C5a)

Locally released chemokines and cytokines

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22
Q

Define the 5 steps of T-Independent Macrophage Activation?

A
  1. Chemotaxis
  2. Attachment/ adherence
  3. Uptake by phagocytosis
  4. Destruction
  5. Release degradation products
  6. T-independent chemotaxis activation of other macrophages (release TNFa and IL-12) granulocytes
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23
Q

Define 3 ways for phagocytes to recognize and attach to target cells/pathogens?

A

1) Fc receptor on phagocyte bind to Ab on pathogen
2) Complement receptor on macrophage bind to opsonized pathogen
3) Mannose receptor bind to mannose-, fucose-containing oligosaccharides on pathogen (e.g. bacteria)

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24
Q

List 3 complement receptors on phagocytes?

A

C3b, C3bi or C1q

25
Q

Describe effector mechanisms of phagocytes to kill engulfed pathogens?

A

Inside phagolysozymes:
1) Reactive oxygen intermediates (ROIs) e.g. superoxide anion

2) Reactive nitrogen intermediates (RNIs), e.g. nitric oxide
3) Others: e.g. complements, defensins, lysozyme, cytokines, proteases

26
Q

Define the 2 reactive oxygen intermediate pathways in phagocytes?

A

Peroxidase-independent: generate H2O2 and anions from O2 for direct effect

Peroxidase-dependent: Phagosome fuses
with lysosome to generate toxic oxidants for killing

27
Q

Describe the signalling event that generates Reactive nitrogen intermediates in phagocytes?

A

1) IFNγ&raquo_space; nitric oxide synthetase (NOS)&raquo_space; NOS with tetrahydrobiopterin&raquo_space; NO
2) TNF&raquo_space; NOS with tetrahydrobiopterin&raquo_space; NO

28
Q

Describe the processing of degradation products in phagocytes?

A

Release degradation products (with free radicals)

> > antigens associate with MHC-II molecule

> > present MHC-Ag complex to activate naïve T helper cells

> > produce cytokines for other processes

29
Q

Describe how activated macrophages signal other cells?

A

Type 1 cytokines (e.g. TNFα) = further recruit and activate other macrophages/ granulocytes

IL-12, TNFα to NK
» NK releases IFNγ to activate MORE macrophages/ granulocytes

30
Q

Describe the process of TH1-dependent macrophage activation?

A

1) TCR binds to MHC-II on primed macrophage with inactivated pathogens / exogenous peptide
2) CD40L (CD154) binds to CD40 on macrophage

3) Cytokine release:
i) IL-2 to self-stimulate Th clonal proliferation
ii) IFN-γ to activate macrophage to completely kill inactivate pathogens

3) Macrophage increase MHC, IL-12 expression to attract more Th
4) Macrophage increase lysosome formation, Phago-lysosomal fusion, Inducible NO synthase

31
Q

Which process precedes Th1- dependent macrophage activation?

A

T cell independent activation&raquo_space; unable to kill pathogen completely&raquo_space; need Th1 for more enhancement of killing

32
Q

List examples of cytokines with autocrine and endocrine function?

A

Autocrine = IL-2

Endocrine = IL-8

33
Q

Define the difference between lymphokines and monokines?

A

Lymphokines: cytokines produced by lymphocytes

•Monokines: cytokines produced by monocytes/phagocytes

34
Q

List examples of interleukins and chemokines?

A

Interleukins: interleukin 1 -39 (IL-1– IL-39) interferons (IFN), TNF etc

Chemokines: CXC (IL-8), CC (MDC), CX3C (Fractalkine)

35
Q

Cytokines can activate over-lapping receptors. T or F?

A

False

Unique receptor for each cytokine

36
Q

One regulatory effect can be regulated by one cytokine only. T or F

A

False

Pleiotropic & redundant (have multiple, overlapping cell regulatory actions)

37
Q

List the source and function of IL-1?

A

Macrophages

  1. Activate T, B cell 2. Mobilize PMNs 3. Induce acute phase proteins
38
Q

List the source and function of IL-2?

A 
T cells (Th1 self prolif.)
Proliferation of T, NK cells
39
Q

List the source and function of IL-4?

A

Mast cells&raquo_space; IgE response

Th2 to suppress Th1&raquo_space; Th2 dominant response&raquo_space; Activate B cells

40
Q

List the source and function of IL-8?

A

 Macrophages  T cells  Fibroblasts  Keratinocytes

Chemotaxis of PMNs

41
Q

List the source and function of IL-10?

A

Th2 cells =Activate B cell, suppress Th1

Macrophages = Suppress macrophages

42
Q

List the source and function of IL-12?

A

 B cells = Stimulate TH1

Macrophages
= Inhibit TH2

43
Q

List the source and function of TGFβ ?

A

T cells

Inhibits other cytokines

44
Q

List the source and function of TNFα?

A

Macrophages

Inflammation

45
Q

Define the Th cell type for intra and extracellular pathogen?

A 
Intracellular pathogens (e.g. virus, mycobacteria, some protozoa)
= Th1 >> Cell-mediated immunity

Extracellular pathogens (e.g. bacteria, parasitic worms) = Th2&raquo_space; Ab production/ Humoral response

46
Q

Which cytokines direct Th0 cells to differentiate into Th1?

A

IL-12(MQ, DC)

IL-18 (MQ, DC, Kupffer cell)

IFN-γ (T cells, NK, DC) ***

47
Q

Which cytokines direct Th0 cells to differentiate into Th2?

A

IL-4 (mast cell, NK-T, DC)

IL-6 (T, MQ)

IL-10 (T, MQ, DC)

48
Q

Th1 and Th2 differentation can occur simultaneously. T or F?

A

False

Reciprocal control: Th1 and Th2 mutaully inhibit each other:

49
Q

Define the cytokines involved in the reciprocal activation of Th1 and Th2?

A

Th1&raquo_space; IFN-γ&raquo_space; inhibit TH2 proliferation

Th2&raquo_space; IL-4, IL-10&raquo_space; inhibit Th1 proliferation

50
Q

Which Th cell is vital for activation of cell-mediated immunity?

A

Th1&raquo_space; because IFN-γ has widespread effect on many effector cells

51
Q

What is the role of B cells in cell-mediated immunity?

A

Produce antibodies&raquo_space; mediate ADCC

52
Q

Define the 4 phases of delayed type hypersensitivity reaction?

A

1) Induction phase: sensitized Th1 release cytokines after 2nd contact with same Ag
2) Inflammatory phase
3) Effector phase: activated MQ kill intracellular pathogen
4) Chronic DTH reaction: can’t kill persistent pathogen (e.g. MTB), granuloatous inflammation ensues

53
Q

Define the cytokines and reactions involved in the inflammatory phase of DTH?

A

 IFN-γ activates local macrophages

 Chemokines attract / recruit more macrophages, TH1 cells

54
Q

What causes chronic DTH reactions?

A

Persistent source of Ag (e.g. mycobacteria TB)

55
Q

Define the type of inflammation that occurs in DTH?

A

Granulomatous inflammation&raquo_space; Granuloma formation to contain persistent pathogen

56
Q

Describe the composition of granulomas?

A

large mass of macrophages, TH1 cells

+ Multinucleated giant cell (Langhans type) + Epitheloid cell + Fibroblasts (producing fibrous tissue) + Peripheral lymphocytes

57
Q

Compare the type of immune response mediated by Th1 and Th2?

A 
Th1 = CMI
Th2 = Humoral response
58
Q

Define the 4 key characteristics of cytokines?

A

– Local & systemic effects
– Unique receptor for each cytokine
– Pleiotropic, synergistic & autocrine
– Complex network

59
Q

Which type of immunity defends against tumours and cause transplant rejection?

A

Both cell-mediated immunity
• Immunity against tumors (CTLs, NKs)

• Transplantation graft rejection (CTLs, NKs) – Delayed hypersensitivity reactions (DTH) – Cell-mediated cytotoxicity

MBBS II HIS (30 decks)

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