Week 6 - Complement and T cells Flashcards by Guy Ben Arie

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

limited Proteolysis - taking place in the Blood plasma.

Like in the coagulation cascade.

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

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

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Parameters for checking the complement system activity?

Rarely measured

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

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

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

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

56C for 30 min

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CH50 test

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

Will the CH50 be Normal?

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

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Deficiency of Complement - Kinds and reasons

Primary - Mutation

Secondary - Overconsumption autoimmune, Hepatic Dysfunction or starvation

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Complications of Complement dysfunction

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

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General clinical signs for complement system problems

Family History
Rheumatological disorder
Impaired Kidney function
Edema

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

Radial Immune assay
Nephelometry
ELISA

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HAE - What is it?

Cause and Treatment?

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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Tryptase

Released by Mast cells

Stable levels allow measurement for allergy detection

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What are the basic communication methods possible between cells?

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

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What is the Aim of cell communication?

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

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Homing of cells

Example

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

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Kinds of extracellular vesicles

Apoptic Bodies
MVB
Exosome

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Types of cell Taxis

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

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Chemoattractants types

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

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

Rolling

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

Rolling

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

Adhesion

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Immunological Synapse - Name the counterparts for the T cell proteins on the APC.
CD28
CTLA4
CD2
LFA1
TCR and C3

CD28 - CD80/CD86
CTLA4 - CD80/CD86
CD2 - CD48/CD59
LFA1 - ICAM1
TCR and C3 - MHCII+Peptide

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Proteins are presented on GAMMA-DELTA T Cell:
NKG2D 
TCR
TLR
Detectin-1
what are they for?

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

What us the protein iNKT cell TCR binds to? | General Function of it?

CD1d | Presentation of Lipid antigens

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

DN1,DN2,DN3,DN4

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

- Decision on α: β- or γ: δ T-cell line | - Gene rearrangement of the receptor chain

What are the Possible outcomes of a DN2 cell?

γ𝛿-T cells or DN3-T cells

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

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

What is the Outcome of a DN4 T cell?

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

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

Leave the Thymus to the bloodstream WITHOUT any more selection

αβ-T cells (with αβ chains in TCR) formation: | What is the next step after formation from DN4-T cells?

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

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?

Negative Selection: Thymic Medullary Epithelial cells | If this cell shows recognition of self antigens - Apoptosis

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

AIRE (autoimmune regulator)

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?

IL-2 | It activates proliferation in the same T cell by Autocrine secretion and Reception.

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

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

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

T central memory cells and T effector memory cells

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

Along antigen entry points: lungs, intestines… | Shorter lifespan; Upon activation: differentiate to an effector within hours.

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

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

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

CTLA-4

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

PD-1

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

Perforins and Granzyme B | Induction of Apoptosis

What cells are stimulated by the Th1 cells? How?

NK cells and Macrophages | by IFN-γ

What cells are stimulated by the Th17 cells? How?

Inflammatory PMNs | by IL-17

What cells are stimulated by the Th2 cells? How?

B-cells (to become plasma), Eosinophils and Basophils | by IL-4

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

IL-10 | TGF-β

What is the advantage of the γ𝛿-T cells?

Antigen recognition is NOT MHC-RESTRICTED | Quick attack on Damaged or Tumor cells.

What is the advantage of the NKT cells?

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 .

What is the interaction of the NKT cells with DCs?

CD1: presentation of lipids

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

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

PD-1 Vs. CTLA-4 | T Cell type suppressed

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

PD-1 Vs. CTLA-4 | Signal inhibited

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

PD-1 Vs. CTLA-4 | Major site of action

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

PD-1 Vs. CTLA-4 | Immune stage suppressed

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

What is the precursor of NKT cells?

Double Positive Pro - T cell

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

Alternative Pathway Activation.

What does the simultaneous reduction of C3 and C4 suggest?

Classical complement or/and MBL pathway activation.

Where are the Positive and Negative selection processes occur exactly?

pOsitive - Thymic cOrtex | nEgative - Thymic mEdulla