Immunology Final Exam

Comprehensive set of Units 1-4

Dendritic Cells

What cells alert T cells of an infection?

Stop Phagocytosis, upregulate MHC expression, migrate to T cell zone of LN

When DCs take up pathogens, what three things are done?

Following Chemokines

How do DCs know how to get to T cell zone of LN?

It becomes more compact

When searching in tissue, DCs have long limbs, but when they take up an antigen, how does their morphology change?

To increase SA to meet with more T cells

In the LN, the DCs morphology changes from compact to flattened. Why does this occur?

Ebola and HIV

What viruses specifically target DCs?

In the lymph nodes

Where do naive T cells encounter antigens presented by the DCs?

High Endothelial Venules (HEV) and Lymph

How do naive T cells get to the LN?

1-3 days

How long does it take for a T cell to pass through all LNs in the body?

It is trapped in the LN

In relation to the LN, what happens to a naive T cell after it is presented an antigen by a DC?

GlyCAM-1 and CD34

To allow a rolling interaction in the HEV, L-selectin on the circulating T cell binds to what?

ICAM-1

Activated LFA-1 on circulating T cell binds to what on the HEV wall?

conformational change induced by cytokines

What allows ICAM-1 on circulating T cells to be able to tight bind?

TNFa

What cytokine binds to HEV cells activating expression of ICAM-1?

DC and T cell

In order for signaling to occur, what two cells must be held together for a time?

low-affinity LFA-1 : ICAM-1 interactions

How does a naive T cell initially bind to a DC?

Subsequent binding of TCR

What causes conformational change in LFA-1 that increases affinity and prolongs DC-T cell contact?

Antigen recognition and Costimulation

In words, what two signals are required to activate naive T cells?

MHC:TCR and B7:CD28

Specifically, what bindings represent two signals are required to activate naive T cells?

T cells

CD28 is always expressed on what cell?

DCs during innate immune response

What cell (and during what response) turns on expression of B7?

Phagocytosis and breakdown of bacteria

When specifically does an APC begin to express B7?

Anergy of T cell

T cell recognition of an antigen without costimulation results in what?

T cell activates and proliferates

When a naive T cell is exposed to a specific antigen and co-stimulator, what happens?

Immunological synapse

The region of contact between T cell and APC is called what?

cytoplasmic tails of CD3

The signal that an antigen has been bound by TCR is transmitted inside the cell via what?

Gene expression

What is altered by T cell activation?

Protein tyrosine kinases

Sequences on CD3 tails, ITAMs, are associated with what enzymes?

CD4/8 binds to MHC interacting with TCR, CD4/8 intracellular tails bring associated protein tyrosine kinase (Lck) along, Lck phosphorylates ITAMs of CD3 and zeta chains, ZAP-70 (kinase) binds to phosphorylated zeta chains, Lck phosphorylates ZAP-70

From MHC interacting with TCR to Lck phosphorylating ZAP-70, what are the steps in the T cell (signal 1) activation pathway?

ITAMs of CD3 then zeta chains then ZAP-70

After being brought over by CD4/8, Lck phosphorylates in what order?

Lck phosphorylation of ZAP-70

What is the point of no return for signal 1 in T cell activation?

they are easily phosphorylated by kinases

Why are tyrosines special?

NF🇰B, NFAT, and AP-1

What three transcription factors are released because of T cell activation?

Calcineurin

What is a common drug target in the T cell activation pathway?

NFAT

Calcineurin activates what transcription factor in T cell activation pathway?

No clonal expansion

To suppress T cell activation, say after a transplant, calcineurin could be targeted, resulting in NFAT not being activated and thus what not occurring?

Protein Kinase C

What enzyme activates NF🇰B in T cell signal transduction pathway?

Cell division, proliferation, and differentiation into effector T cells

The combined efforts of NF🇰B, NFAT, and AP-1 lead to what?

IL-2

What is one of the most important/first activated genes turned on from the three transcription factors after T cell activation?

NFAT

What transcription factor directly induces IL-2 express and turns on high affinity IL-2 receptor in activated T cell?

Autocrine

By what type of cell communication does T cells receive IL-2’s signal?

Clonal Expansion

The first cellular response in activated T cells, the binding of IL-2 to the high affinity receptor leads to what?

Cyclosporin A

What drug inhibits calcineurin?

Cyclosporin A, Tacrolimus (FK506), rapamycin (siroliums)

What three drugs target IL-2 (or the activation pathway)?

Differentiation

Towards the end of proliferation, activated T cells acquire the ability to make the proteins they need to perform specialized functions of effector T cells.

Helper T cells (TH1 and TH2)

What do activated CD4 cells become?

Cytotoxic T lymphocytes (CTLs)

What do activated CD8 cells become?

TH1, TH17, T_reg, TH2

What are four classes of CD4 T cells?

IFNγ and IL-12

What cytokines from innate immune response (NK/macrophages) drive immature but activated Helper T cells to become TH1?

T-bet and STAT 4

What transcription factors are activated and drive TH1 development?

IFNγ

Activated by T-bet/STAT4 in activated but immature T cells, this cytokine inhibits TH2 cell development

IFNγ autocrine signalling

What reinforces the TH1 pathway signals?

Helps by releasing cytokines!

Generally, what is the role of TH1 cells?

CXCL2, IL-3/GM-CSF, TNFa, IFNγ

At the SOI, what cytokines do TH1 cells secrete?

CXCL2

Secreted by TH1 cells, this cytokine attracts macrophages to SOI

IL-3/GM-CSF

Secreted by TH1 cells at SOI, this cytokine produces more macrophages from monocytes

TNFa

Secreted by TH1 cells at SOI, this cytokine recruits more macrophages and neutrophils along with activating adhesion proteins and increasing vascular permeability

IFNγ

Secreted by TH1 cells at SOI, this cytokine activates/stimulates the activity of macrophages

IFNγ

Secreted by TH1 cells in LN, this cytokine activates B cells and directs isotype switching to IgG (opsonizing).

TH17

This T cell type protects against some fungal and bacterial infections, contributes to inflammation and autoimmunity.

T_reg

T cell type that inhibits inflammation and maintains homeostasis of the immune response

IL-4 and IL-2

What cytokines drive the activated but immature T cell to become TH2?

Intracellular pathogens

Generally, what kind of pathogens do TH1 cells protect against?

TH2 cells

What type of T cell protects against extracellular pathogens (esp IgE) and are involved in allergies?

Mast cells

Where is IL-4 secreted from?

GATA-3 and STAT6

What transcription factors are activated in TH2 cells to drive TH2 development?

IL-4

What cytokine is released from TH2 in response to GATA-3 and STAT6 to inhibit TH1 development?

IL-5 activates eosinophils which degranulate and help kill parasites

What is an effector function of TH2 cells at the SOI?

IL-4/IL-13 help activate B cells and direct isotype switching to IgE

What is an effector function of TH2 in the LN?

they release histamine, causing flushing of parasitic infections

When mast cells primed with IgE degranulate, what occurs?

higher than conventional T cell self-reactivity

What is an interesting property of T_reg cells?

Foxp3

What transcription factor do T_reg cells activate to exhibit self reactivity?

TGF-β

What cytokine can conventional CD4 cell receive to gear them toward becoming a T_reg cell?

Maintaining peripheral (outside of thymus) tolerance to self

What important function does T_reg cells perform?

T_reg

What T cell suppress and lyse self-reactive T cells, cause APCs to stop making MHC, provide anti-inflammatory cytokines, and soak up IL-2 to prevent clonal expansion in self-reactive T cells?

TGF-β and IL-10

What anti-inflammatory cytokines do T_reg produce?

Antigen recognition and costimulation

Like CD4 cells, CD8 cells are activated by what two signals?

IL-2 is needed from a helper T cell

Though some viruses allow CD8 to produce their own IL-2 for clonal expansion, other viruses need help stimulating CD8 cells how?

Downregulation of let-7 microRNAs (which suppress translation of cytotoxins)

How do CD8 T cells differentiate?

increase in temperature

Differentiation in CD8 T cells is slightly increased by what?

Cytotoxins: perforin, granzymes, granulysin, serglycin; Cytokines: IFNγ, LT, IL-12

List the Cytotoxins and Cytokines used by Effector CD8 Cells

Inducing apoptosis through cytotoxins and cytokines

How do CD8 cells kill virus infected cells?

cytokine signalling

Effector CD8 Cell responses rely on what?

co-stimulatory molecules, they need only recognize the Ag

Once CD8 cell becomes an effector T cell, they no longer rely on what?

One specific cell

How many cells do Effector CD8 cells direct their killing response to?

BCR cross-linking, B cell co-receptor, Helper T Cell (most need)

What are the three signals (in most cases) needed to activate a B cell?

Cluster of antigen receptors

How should BCRs be brought together to allow the signal transduction pathway for BCR cross-linking?

NFAT, NFkB, AP-1

Same as T cell activation, what three transcription factors are made in B cells after signal transduction for activation?

CR2 (CD21), CD19, CD81

What makes up the co-receptor complex in B cells?

Binding of CR1

What membrane component (not on co-receptor) of B cells causes C3b bound to a pathogen to be cleaved by factor I to iC3b and C3d?

CR2

What component of the B cell co-receptor can bind to C3d?

Complement Pathway

What pathway is necessary for B cell activation?

pathogen or soluble antigen

BCR and co-receptor cooperate in B-cell activation, activated by what?

cytokine help from activated CD4 cells

Most B cells require what third signal to activate?

boundary region between B cell zone and T cell zone in LN

Where can activated CD4 cells help activate B cells?

directs full B cell activation and isotype switching

How do T helper cells help B cells?

Strong activation from signals 1 and 2

Why do a minority of B cells not need Helper T cell assistance to activate?

Highly repetitive epitopes or antigen

What causes signals 1 and 2 in B cell activation to be so strong that signal 3 isn’t needed?

Become plasma cells and secrete antibodies, somatic hypermutation, isotype switching

What three things can activated B cells do?

IgA

TH1 secretes TGF-β which activates B cells and directs isotype switching to what isotype?