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GBA Immunology > Week 6 - Complement and T cells > Flashcards

Week 6 - Complement and T cells Flashcards

1
Q

What is the basic type of cascade function taking place in the Complement system Activation? Similar example

A

limited Proteolysis - taking place in the Blood plasma.

Like in the coagulation cascade.

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2
Q

What is the initial binding site for each kind of pathway in the complement system?

A

Classical - Antibody+Antigen complex
Mannose binding Lectin - Lectin+Pathogen
Alternative - Directly to Pathogen

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3
Q

Parameters for checking the complement system activity?

Rarely measured

A
  • Concentration of regulatory factors (like C1-Inhibitor)
  • Concentration of Individual complement factors
  • Functional Tests - CH50, RBCs lysis
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4
Q

How does the measurement of complement activity with RBC lysis work? Which Pathway?

A

Anti-RBCs are used - Classical Pathway activated - MAC causes lysis

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5
Q

What is the Heat inactivation for the RBC Lysis test in complement sys measurement?

A

56C for 30 min

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6
Q

CH50 test

A

Similar to Titer, Checking for the denominator of the serum dilution that lysed 50% of Sheep RBCs in the test tube.
Value reference 142-279.

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7
Q

Will the complement system work in case of 80% shortage ?

Will the CH50 be Normal?

A

Yes! It creates a very Robust response in general and can be active in these state as well. Normal CH50

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8
Q

Deficiency of Complement - Kinds and reasons

A

Primary - Mutation

Secondary - Overconsumption autoimmune, Hepatic Dysfunction or starvation

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9
Q

Complications of Complement dysfunction

A

Early components - Accumulation of IC
C3b - Recurrent bacterial Infections
Late Components - Recurrent Neisseria Infection

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10
Q

General clinical signs for complement system problems

A

Family History
Rheumatological disorder
Impaired Kidney function
Edema

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11
Q

After detection of dysfunction of Complement system, How would it be possible to Isolate which C is responsible for the problem?

A

Radial Immune assay
Nephelometry
ELISA

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12
Q

HAE - What is it?

Cause and Treatment?

A

Hereditary AngioEdema - Robust caused by Hereditary C1INH Deficiency - Bradykinin over activation is the cause (Not the problem with Complement)
Adrenaline needs to administered a few times and quickly to eliminate the possibility of Allergy, then if not allergy Steroids and C1INH.

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13
Q

Tryptase

A

Released by Mast cells

Stable levels allow measurement for allergy detection

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14
Q

What are the basic communication methods possible between cells?

A

Contact - Adhesion molecules
Soluble messengers - Hormones, Chemokines, Cytokines
Extracellular Vesicles

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15
Q

What is the Aim of cell communication?

A

Meeting of the cells
Homing of cells
Activation/Inhibition/Differentiation/Proliferation/Injury

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16
Q

Homing of cells

Example

A

Naive B cells use contact receptors in order to “understand” they need to stay in the Lymph node

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17
Q

Kinds of extracellular vesicles

A

Apoptic Bodies
MVB
Exosome

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18
Q

Types of cell Taxis

A

Chemotaxis - Chemokine soluble concentration
Haptotaxis - Chemokine surface solid concentration
Necrotaxis - Necrotic substances
(Chemorepelent also exists)

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19
Q

Chemoattractants types

A 
CC and CXC family
C3a and C5a
Formal Peptide (Bacterial)
Arachidonic Acid
Pheromones
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20
Q

What is the main phase of Extraversion that granulocytes are located in? (Most common position)

A

Rolling

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21
Q

In which phase of Lymphocyte extravasation the interaction between CD34 and L-selection begins?

A

Rolling

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22
Q

In which phase of Lymphocyte extravasation the interaction between LFA-1 and ICAM-1 begins?

A

Adhesion

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23
Q 
Immunological Synapse - Name the counterparts for the T cell proteins on the APC.
CD28
CTLA4
CD2
LFA1
TCR and C3
A 
CD28 - CD80/CD86
CTLA4 - CD80/CD86
CD2 - CD48/CD59
LFA1 - ICAM1
TCR and C3 - MHCII+Peptide
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24
Q 
Proteins are presented on GAMMA-DELTA T Cell:
NKG2D 
TCR
TLR
Detectin-1
what are they for?
A

NKG2D - Cytotoxicity
GAMMA-DELTA-TCR - Proliferation, Cytokines release, Immune-regulation and Cell protection.
TLR - Inflammation: IL17 and IFN-gamma
Detectin-1 - IL17 and IFN-gamma

25
Q

What us the protein iNKT cell TCR binds to?

General Function of it?

A

CD1d

Presentation of Lipid antigens

26
Q

What are the different kinds of the Double negative T cells?

A

DN1,DN2,DN3,DN4

27
Q

What are the 2 processes DN-T cells go through in the Thymic Cortex?

A
  • Decision on α: β- or γ: δ T-cell line

- Gene rearrangement of the receptor chain

28
Q

What are the Possible outcomes of a DN2 cell?

A

γ𝛿-T cells or DN3-T cells

29
Q

What are the DN T cells surface factors that keep changing in expression while they progress from DN1 to DN4? (3)

A

CD44+/-
CD25+/-
c-Kit+/-

30
Q

What is the Outcome of a DN4 T cell?

A

Double Positive T cell (DP) - CD4+ and CD8+

31
Q

γ𝛿-T cells (with γ𝛿 chains in TCR) - What is the next step after formation from DN2-T cells?

A

Leave the Thymus to the bloodstream WITHOUT any more selection

32
Q

αβ-T cells (with αβ chains in TCR) formation:

What is the next step after formation from DN4-T cells?

A

Positive Selection: Dendritic Cells
If interacts with MHC-1 - CD8+ Selection
If interacts with MHC-2 - CD4+ Selection
if no interaction - no growth - Apoptosis

33
Q

αβ-T cells (with αβ chains in TCR) formation:

After Positive Selection of a CD8+/CD4+ T cell, what is the next step in maturation?

A

Negative Selection: Thymic Medullary Epithelial cells

If this cell shows recognition of self antigens - Apoptosis

34
Q

What controls the presentation of self antigens on Thymic Medullary Epithelial cells in Negative selection?

A

AIRE (autoimmune regulator)

35
Q

After Co-stimulation (with B7-CD28 and MHC-II-CD4+CD3 interaction) what is the molecule expressed by the maturing T cell? What is its function?

A

IL-2

It activates proliferation in the same T cell by Autocrine secretion and Reception.

36
Q

What is the Purpose of a B7 and CTLA-4 interaction between the B and the T cells?

A

Inhibition of the B7-CD28 signal that causes the expression and release of IL-2 (Negative Feedback)

37
Q

What are the kinds of Memory T cells that are possible to form out of an effector T cell?

A

T central memory cells and T effector memory cells

38
Q

Where are effector memory T cells located and How long does it takes for them to differentiate? What are their life span?

A

Along antigen entry points: lungs, intestines…

Shorter lifespan; Upon activation: differentiate to an effector within hours.

39
Q

Where are central memory T cells located and To which cells would they differentiate? What are their life span?

A

In secondary immune organs;
IL-2 production: self-renewers; ( + CD40L expression: costimulation) Upon activation: Differentiate to Tem or Effector T-cell

40
Q

What is the main suppressor molecule for the CD4+ T cells?

A

CTLA-4

41
Q

What is the main suppressor molecule for the CD8+ T cells?

A

PD-1

42
Q

What enters the target cell following Fas-ligand reception from CD8+ T cell? What is the consequence?

A

Perforins and Granzyme B

Induction of Apoptosis

43
Q

What cells are stimulated by the Th1 cells? How?

A

NK cells and Macrophages

by IFN-γ

44
Q

What cells are stimulated by the Th17 cells? How?

A

Inflammatory PMNs

by IL-17

45
Q

What cells are stimulated by the Th2 cells? How?

A

B-cells (to become plasma), Eosinophils and Basophils

by IL-4

46
Q

What are the main cytokine released by the Treg, Tr1 and Th3 cells?

A

IL-10

TGF-β

47
Q

What is the advantage of the γ𝛿-T cells?

A

Antigen recognition is NOT MHC-RESTRICTED

Quick attack on Damaged or Tumor cells.

48
Q

What is the advantage of the NKT cells?

A

Have an Invariant αβTCR limited diversity that allows quick Stimulates cellular response by other CD8+ / NK cells = Direct and indirect killing of virally infected and tumor cells .

49
Q

What is the interaction of the NKT cells with DCs?

A

CD1: presentation of lipids

50
Q

What is the common job of the γ𝛿-T cells and Tregs?

A

to protect self structures, tolerance, to inhibit autoimmunity
(Besides γ𝛿-T Cytotoxicity)

51
Q

PD-1 Vs. CTLA-4

T Cell type suppressed

A

PD-1 Vs. CTLA-4 - T Cell type suppressed
PD-1 : CD8+>CD4+
CTLA-4: CD4+>CD8+

52
Q

PD-1 Vs. CTLA-4

Signal inhibited

A

PD-1 Vs. CTLA-4 - Signal inhibited
PD-1: Inhibiting Chronic Antigen Stimulus
CTLA-4: Inhibiting B7-CD28 Interaction

53
Q

PD-1 Vs. CTLA-4

Major site of action

A

PD-1 Vs. CTLA-4 - Major site of action
PD-1: Peripheral
CTLA-4: Lymphoid (Central)

54
Q

PD-1 Vs. CTLA-4

Immune stage suppressed

A

PD-1 Vs. CTLA-4 - Immune stage suppressed
PD-1: Effector Phase
CTLA-4: Induction Phase

55
Q

What is the precursor of NKT cells?

A

Double Positive Pro - T cell

56
Q

What does it suggest if the C3 level is reduced, while the C4 level falls into the normal range?

A

Alternative Pathway Activation.

57
Q

What does the simultaneous reduction of C3 and C4 suggest?

A

Classical complement or/and MBL pathway activation.

58
Q

Where are the Positive and Negative selection processes occur exactly?

A

pOsitive - Thymic cOrtex

nEgative - Thymic mEdulla

GBA Immunology (15 decks)

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