Bowden- T and B cell Flashcards

1
Q

What is considered the “nursery” of cells?

A

Lymphoid tissue

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2
Q

What is the first T cell activation signal?

A

Binding of MHC/peptide complex displayed by DC to TCR on T cell

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3
Q

Explain the process of anergy in T cell activation

A

T cells recognizing antigen without binding of co-stimulatory ligands or cytokine support will not become activated. These cells become unresponsive to additional stimulus

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4
Q

What is Zap-70?

A

Tyrosine kinase that is associated with the Zeta chain in T cell activation. Necessary for all downstream signaling (can be CD4 or 8)

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5
Q

What do activated CD4+ and CD8+ cells express?

A
CD4+= Th cells express CTLA-4 and PD-1 for immune regulation
CD8+= T cells express PD-1
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6
Q

What is IL-2 (in relation to T cell activation)?

A

Autocrine survival signal for newly activated T cells. It is NOT produced until activation

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7
Q

What is IL-2RByc?

A

Constitutively expressed on mature, naive T cells as a low affinity receptor minimizing proliferation

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8
Q

What is IL-2RaByc?

A

The high affinity chain in IL-2R (CD25). It os upreg upon activation

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9
Q

In DC cytokines, what do IL-10, IL-23, and IL-12 correspond to?

A

IL-10: Tregs
IL-23: Th17
IL-12: Th1

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10
Q

What is the clinical application of inhibiting IL-2?

A

Inhibition of IL-2 used to prevent the rejection of organ transplant by suppressing the activation and differentiation of naïve T cells and all immune responses that require activated T cells

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11
Q

What is CD69’s role in sequestering?

A

S1P is in high quantity in the blood & lymphatics. Naive T cells express receptor for S1P (S1PR) that directs their migration through circulation. Newly act. T cells will transiently express CD69. CD69 binds to S1pR on T cell surface & sequesters it. Leaves T cell unable to respond to S1P migration signals. Ensures act. T cells has time to provide help to other lymphocytes

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12
Q

What are Gamma Delta T cells?

A

TCR composed of y/g chains instead of a/b. Less than 5% of Ts. Found in higher #s at epithelial boundaries especially the gut mucosa. Ag restricted (limited diversity of peptides recognized, can recognize non-protein Ag, not restricted to MHC/HLA presentation)

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13
Q

How do effector Ts enter the peripheral tissues?

A

By interacting with cytokines, chemokines and adhesion molecules on the endothelium at the site of infection

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14
Q

What are Th1 cells associated with, their role, defense, & pathology?

A

IFN-y
Role: macrophage act
Defense: intracellular paths
Path: chronic inflammation

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15
Q

What are Th2 cells associated with, their role, defense, & pathology?

A

IL-4, IL-5, IL-13
Role: eosinophil, mast cell & alternative macrophage act
Defense: Helminths
Path: allergy

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16
Q

What are Th17 cells associated with, their role, defense, & pathology?

A

IL-17, IL-22
Role: neutrophil act
Defense: extracellular bacteria & fungi
Path: autoimmunity, inflammation

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17
Q

What are Treg cells associated with, their role, defense, & pathology?

A

IL-10, TGF-beta
Role: Peripheral tolerance
Defense: regulation of T cell responses
Path: autoimmunity

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18
Q

What are Tfh cells associated with, their role, defense, & pathology?

A

IL-21, IL-4
Role: support of B cells in germinal center
Defense: extracellular pathogens
Path: antibody mediated autoimmunity

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19
Q

What is IFN-y’s role?

A

Stimulates B cells to class switch to IgG during activation (opsonization). Stimulates Class II HLA antigen presentation & B7 (CD80) expression. Inhibits Th2 & Th17. They secrete IL-2 upon activation (Autocrine survival signal)

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20
Q

How does Th2 provide protection against helminths?

A

Mast cell activation, mucus production, peristalsis, IgA production, eosinophil activation. Alternative macrophage activation

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21
Q

IL-17 and 22 are both T helper 17 cytokines. How are they different?

A

IL-17: inflammatory: recruitment of pro-inflammatory leukocytes. Increases pro-inflamm cytokine & chemokine production. Stimulates anti-microbial peptide (defensins) production
IL-22: Protective, promotes regenerative responses within epithelial barrier. Stimulates anti-microbial peptide (defensins) production

22
Q

What is the effector function of CD8+ cytotoxic T lymphocytes?

A

Killing of cells infected with intracellular pathogens or tumor-transformed cells by release of lytic enzymes or Fas/FasL induced cell death.

23
Q

What is the purpose of the Fas ligand?

A

Effectors CTLs express Fas ligand (FasL) which binds to the death receptor Fas expressed on many cell types. Act of caspases & apoptosis of Fas-expressing altered target cells

24
Q

How are NK cells and CTLs similar/different?

A

Both kill tumor cells & virus infected cells by granzymes, perforin, or Fas/FasL induction of apoptosis
CD8+ killing activated by altered peptide MHC/HLA Class I
NK killing act. by decreased display of MHC/HLA Class I (inhibitory receptor)

25
Q

What is ADCC & how is it targeted?

A

Antibody-dependent cell-mediated cytotoxicity. Targeted recognition through IgG or IgE binding

26
Q

Describe CD4+ T regulatory cells

A

Tregs/Th3. Influenced by IL-2, IL-10, TGF-b. Always express CTLA-4 & CD25 (alpha chain). Novel transcription factor FOXp3. Secrete IL-10 & TGF-b. CTLA-4 binds to B7 co-stimulatory ligand & competitively blocks APCs

27
Q

When are CTLA-4 and PD-1 inducible?

A

CTLA-4 is inducible on activated Th cells. Competitive binding to B7/CD80 for downregulation of presentation. binds w/higher affinity than CD28
PD-1 inducible on Ts, Bs & myeloid cells after activation (contains ITIM signaling domain)

28
Q

What is the purpose of follicular dendritic cells in migration of mature naive B cells?

A

They send survival signals to mature naive B cells that have migrated to primary follicles to sample antigens

29
Q

What do follicular dendritic cells express receptors for?

A

C3b (CR1) and IgG (FcyR)

30
Q

In T-dependent antigen activation of B cells, what are the 3 steps?

A

Happens in follicular space

  1. crosslinking of serveal BCRs w/signaling thru Iga and Igb ITAMs
  2. Crosslinking of BCR w/co-BCR w/signaling thru Iga & Igb ITAMs & CR2 & CD19 signaling motifs
  3. crosslinking of BCR w/TLRs w/signaling thru Iga & Igb ITAMs & TLR signaling motifs
31
Q

In B cell activation, what happens in the first signal of crosslinking BCR signaling?

A

Ag binds mIgs. Must crosslink 2 or more BCR for signaling to occur. Signaling occurs thru ITAMs on Iga & Igb cytoplasmic tails. Syk- B cell phosphorylation

32
Q

What are the Co-BCRs?

A

CR2, CD19, CD81

33
Q

What happens to newly activated B cells and Th cells?

A

B cells: downreg CXCR5 & upreg CCR7, migrate towards the paracortex, increase expression of HLA Class II & B7 (CD80)
Th cells: Downreg CCR7 & upreg CXCR5, migrate towards follicles, increased expression of CD40L & cytokine secretion

34
Q

What is constitutively expressed on T and B cells?

A

T cell: CD28 (binds to B7)

B cell: CD40 (CD40L)

35
Q

What is AID enzyme?

A

Activation-induced deaminase enzyme. Proliferates & induces clonal expansion of B cell activation in 2nd activation signal

36
Q

What happens to B cells after they receive a second signal from T cells?

A

Change their chemokine receptor expression & migrate to the follicular area & establish germinal centers in follicles. B cells begin cytokine modulated isotype (class) switching & affinity maturation (somatic hypermutation) of BCR genes. Successful re-arrangements are selected/supported by TFH & follicular dendritic cells

37
Q

What two things do Tfh cells secrete?

A

Secrete IL-21, facilitates B cell survival, clonal expansion, & differentiation to plasma cells
Secrete Th cytokines to influence isotype switching

38
Q

What two general functions do cytokines released by Th & Tfh cells promote?

A
Induce heavy (H) chain class switching. 
Augment B cell differentiation & proliferation into plasma cells
39
Q

What are plasma cells in relation to B cell activation?

A

Terminally differentiated effector B cells. Long lived: bone marrow (IgG) and mucosa (IgA). Abs: effector molecules of humoral immunity

40
Q

Define memory B cells

A

Survive for long periods of time without additional Ag stimulation. Express high levels of anti-apoptotic protein Bcl-2. Surface markersL CD27, CD45R(O). Need survival support from IL-7. Conduct secondary immune response (subsequent exposure to same Ag)

41
Q

Define T-independent B cell activation

A

Cross linking & clustering of several hundreds of BCRs. Mainly seen w/long repeating epitopes like polysaccharises. Enough BCRs engaged to trigger enough Iga & Igb intracellular signaling to stimulate cell to secrete IgM (no class switching, no affinity maturation, little to no memory). Can provide IgM antibody protection in a short amount of time.

42
Q

Which antibody is the only one that cannot bind to an antibody feedback receptor when it is unbound?

A

IgG

43
Q

Humoral immunity is principle defense against what type of pathogens?

A

Extracellular pathogens

44
Q

What triggers the functions of effector (plasma) cells?

A

The binding of antigen to the Fab’ variable region

45
Q

What 2 distinct functions does the effector region of antibody effector have?

A

Deliver antibody to inaccessible anatomical sites

Link bound antigen to molecules/cells that effect destruction- Opsonin

46
Q

What is FcRn?

A

n is for neonatal. It is specific to IgG ONLY. Important for maintaining IgG levels in the serum. Increases the half-life of IgG by protection from proteolysis. Expressed on APCs, neutros, podocytes, mucosal epithelial cells, vascular endothelium

47
Q

What is the most rapid & efficient pathway and what initiates it?

A

Complement activation classical pathway. Initiated by IgG (2) or IgM

48
Q

What do all three C’ pathways end with?

A

polymerization of many C9s for formation of the membrane attack complex (MAC). Can all 3 be occurring at same time, they are antigen-independent

49
Q

Describe the process of waste management

A

Opsonization with IgG & C3b allows for clearance of ICs from circulation in non-inflammatory manner.
CR1 on erythrocytes binds circulating immune complexes with attached C3b & C4b & transports the complexes to the liver & spleen
Organ resident phagocytes remove the immune complexes from erythrocyte surface & it continues to circulate
Phagocyte degrade ICs

50
Q

Describe Ab-dependent cell-mediated cytotoxicity (ADCC).

A

NK cells, macrophages, neutrophils, eosinophils (Only one that goes thru IgE)
Targeted recognition thru IgG or IgE binding to surface antigens. FcR on immune cells binds to antibody activating cell killing mechanisms. Killing by lytic enzymes, TNF and perforin/granzyme

51
Q

How is maternal IgG transported to a fetus?

A

By FcRN across the placental barrier into fetal circulation

52
Q

What is passive immunization?

A

Introduction of antibody or antiserum into a naive recipient. Ex: snake-bite venom, passive transfer of Ig from mother to child