Immunology Lecture 8 Activation of the Immune System

Co-stimulatory Molecules The most important interactions are between _______ and _______ and the interaction of the B7 protein (CD__/CD__) on the APC and _____ on the T-cell surface.

CD40 CD40L CD80 CD86 CD28

CD2 is a T-cell specific molecule that binds to what on the APC?

CD58

B-cells also have _____ receptors for the ____ that T-cells secrete.

Cytokine Cytokines

What does TLR2 recognize?

Teichoic acid

Activated B-cells The cross-linking of Igα and Igβ sends a signal to the _____ of the _____.

Nucleus B-cell

B-cells have ___ to _____ fold advantage over other APCs in activating ____ _____, especially when there is relatively little ___ around.

100-10,000 Helper T-cells Antigen

A virgin B-cell is a poor ____ due to low levels of Class ___ MHC molecules and little or no ___.

APC II B7

Experienced B-cells are able to act as ______ for _____ cells.

APC T-helper

What are the 3 types of APCs?

Activated dendritic cells Activated macrophages Activated B-cells

Macrophages are very adaptive ______ cells which can function as garbage collectors, APC's, or killer depending on the signals they receive.

Sentinel

Once the CTL has killed its target cell, it detaches and seeks out another target cell. This process is known as ______ _____ ____ ____.

Activation-induced cell death

Activation of B-cells leads to _______ production and _______ cells.

Antibody Memory

The T-cell activating cells are referred to as _____ ____ ____.

Antigen presenting cells (APCs)

Macrophages are activated either by detecting cytokines such as ______ or by having their ______ ligated by invading pathogens.

IFN- γ TLR

The same co-stimulatory and adhesion pairs necessary for APC-T-cell interaction are necessary for activation of _____.

B-cells

Activation of B Lymphocytes ______ present antigen to _____ and then receive signals from the ____ for differentiation and proliferation

B-cells T-cells T-cells

Co-stimulation involves a protein called ___ on the surface of an ____ that "plugs into" a protein called _____ on the surface of a T-cell.

B7 (CD80, CD86) APC CD28

On the surface of B-cells the ____ is the receptor for protein antigen.

BCR

APCs are WBC's that originate in the ___ _____ and migrate out to various sites in the body.

Bone marrow

Which T-cell specific molecule binds to CD58 on the APC?

CD2

The clustering of CD4 with TCR is considered the "first signal" in activation of ____ T-cells.

CD4

CD4-MHC Class II Interactions After the peptide-MHC complex binds to the TCR, ____ moves closer to the TCR. This clustering of ____ with TCR brings an enzyme into a signal transduction complex that is necessary but not sufficient for ____ activation.

CD4 CD4 T-cell

Interactions of ____ (on the T-cell) with the MHC Class ____ molecule (on the APC) enhances binding of a _____ T cell to the APC.

CD4 II CD4+

Activated _____ T-cells also up and down regulate surface molecules which allow it to migrate from the site at which it was activated (secondary lymphoid organs) to infected tissues.

CD4+

Once a B-cell is activated, the levels of Class ___ MHC molecules and ___ proteins on its surface (increase/decrease) dramatically.

II B7 Increase

What is the most important co-stimulatory interaction in T-cell - B-cell cooperation?

CD40 on B-cell binding to CD40L on T-cell

What are the 2 forms of B7?

CD80 CD86

Killing via Fas-Fas ligand interaction This results in a sequential activation of proteolytic enzymes known as _____ within the target cell. The net effect is ____ of the target cell.

Capsases Apoptosis

What do thymus-independent antigens generate?

IgM

Only certain cells are equipped to provide both class I and class II MHC molecules and _____________.

Costimulation

Activated B-cells Second, a _______ key is also required for activation. This key is usually provided by a ____ _____. It involves ___-____ ____ during which _______ on the surface of the _____ T-cell binds to the ______ proteins on the surface of a B-cell.

Costimulatory Helper T-cell cell-cell contact CD40L Helper CD40

Activated B-cells First, ___-____ and clustering of multiple ____ to signal what they have seen. This ____-______ brings the ___ and ____ molecules close together resulting in a threshold amount of enzymatic activity.

Cross-linking BCR's Cross-linking Igα Igβ

CD8+ lymphocytes also secrete _____.

Cytokines

Activation of T-cells lead to synthesis & secretion of ________ or development of _________ cells as well as memory cells.

Cytokines Cytotoxic

Which cell has Fas ligand?

Cytotoxic T cell (CD8+)

Which cells are the most important of the APCs?

Dendritic cells

Activation refers to B-cells' and T-cells' ______ functions.

Effector

As a result of antigenic stimulation, both B-cells and T-cells differentiate into _______ or ________ cells.

Effector Memory

TI antigens generate primarily _____ and elicit no _____ cells.

IgM Memory

CD8+ T-cell What granules are serine proteases that enter the target cell through the perforin caused pores and induce apoptosis?

Granzymes

When CD40 on B-cell binds to CD40L on T-cell, this promotes upregulation and proliferation, and is required for _____ switching.

Isotype

What happens if the T-cell fails to receive costimulation of B7 from APC on CD28 from T-cell?

It dies by apoptosis

_____ on the T-cell binds to iCAM-1 also known as _____ on the APC.

LFA-1 CD54

_____ on the T-cell binds to _____ also known as CD54 on the APC.

LFA-1 iCAM-1

APC always refers to special cells which provide high levels of _____ and the _____ molecules required for T-cell activation.

MHC costimulatory

Macrophages only express enough ____ and ________ molecules to function as APC's after being activated.

MHC costimulatory

The chemokines that DCs release encourage ______ to leave the blood and enter tissues. Then they develop into _____ ____.

Monocytes Dendritic Cells

Dendritic cells must be activated by 2 basic signals. The first signal comes from other immune or dying cells. Both _____ and ______ secrete ____, a cytokine.

Neutrophils Macrophages TNF

Sets of _____ interactions between the APC and T-cell surfaces are required for full T-cell activation.

Paired

CD8+ T-cell What granule punches holes and forms pores in the target cell membrane?

Perforins

Since new blood cells are made continuously, APC's are made and ________ as needed.

Replenished

Additional signals known as co-stimulatory or ____ signals are required for full T-cell activation.

Second

___ lymphocytes are the central cell of the immunologic process.

T

What is the end result of the second signal/adhesion interactions? ______ proliferation Secretion of cytokines (____, _____, ______) Differentiation into ______ cells

T-cell IL-2, IL-4, INF-γ memory

Activation of B-lymphocytes involves the interactions of ____-____.

T-cells B-cells

Most antigens encountered by the immune system are ________. These ______ antigens require help from ____ And _____ to activate B-cells.

T-dependent T-dependent T-cells Cytokines

Activation of CD4+ T-cells Contact between the ____ and ____ proteins is necessary but NOT sufficient for T-cell activation.

TCR MHC

Which TLR recognizes teichoic acid?

TLR2

Which TLR is the receptor that DC's and macrophages use to recognize LPS?

TLR4

_____ is the receptor that DC's and macrophages use to recognize _____.

TLR4 LPS

Which TLR alerts cells to attack by various viruses?

TLR7

Some antigens with repeating antigenic determinants are capable of activating B-cells to produce antibody in the absence of T-cell or cytokines. These antigens are referred to as ___-____ _____ (TI) and are generally large polymeric molecules.

Thymus-Independent antigens

Are co-stimulatory interactions more important in activating unprimed resting T-cells or primed (memory) T-cells?

Unprimed resting T-cells

Before a killer T-cell can kill or an helper T-cell can help, it must be _____.

activated

B-cells have one great advantage over other APC's in that they can concentrate ______ for presentation.

antigen

For the activation of T-cell to occur, a T-cell must recognize its cognate _____, presented by a ______ molecule. In addition, it must also receive a _____ __________ ______.

antigen MHC second costimulatory signal

Activation of CD8+ T-cells is accomplished by ___-___ contact, ______ molecules, ________ molecules, and _______.

cell-cell adhesion co-stimulatory cytokines

After activation of the DC but before it begins its travels, it produces special cytokines called ________.

chemokines

Activated macrophages mainly function to restimulate ________ T-cells at the site of infections.

experienced

There are 2 primary pathways for CTL killing: (1) release of _______ by ______ onto the target cell. (2) killing via interaction between ____ on the target cell and ____ ______ on the activated CTL.

granules exocytosis Fas Fas ligand

DCs are classified as members of the ____ immune system as they are hard wired but actually function as a _____ between the innate and adaptive system.

innate bridge

Once activated, DC leaves the tissues, migrates to the lymphoid system and goes to the nearest ___ _____.

lymph nodes

APCs degrade Ag into _____ fragments (______) which are transported to the cell surface in the groove of MHC proteins.

peptide epitopes

What do the granules that CD8+ T-cells release contain?

perforins granzymes

The second signal to activate dendritic cells involves ______ which recognize certain molecular _____. These are called ____.

receptors patterns Toll like receptors (TLRs)

The macrophages do not travel like DCs, they ____ _____ in various tissues are are one of the main weapons in the early defense against invaders.

remain fixed

Activated DCs recruit their own ____.

replacements

Co-stimulatory interactions enhance and _____ signals by the MHC-peptide complex to the TCR.

sustain

When an invader is first encountered, all the B-cells are ______ so the important APCs are activated ____. Later, activated ________ present Ag to T-cells to keep them ________. Finally, if the same invader is encountered again, experienced ____ _____ from the first attack and then become the MOST IMPORTANT APCs.

virgins DCs macrophages restimulated memory B-cells