Lecture 3: T Cells, MHC and Lymphocyte Activation

Question 1

T Cell Receptors

Answer 1

T cells do not recognize native antigen. The antigen must be proceesd by the APC and recognized in conjunction with a MHC molecule

T cells are heterodimers of mostly alpha and beta chains

Each apha chain has an antigen binding site, a variable region, a constant region, and a transmembrane region

Develops in thymic cells by somatic rearangments of TCR v, D, and J gene segments

Requires RAG 1 and RAG2 enzymes

Question 2

T_C

Answer 2

Cytotoxic T cells

CD8 is the co-receptor that also binds MHC class 1

The TCR recognizes the MHC plus the peptide of the antigen on the antigen presenting cell

TC cells recognize and kill virus infected cell by releasing perforin which forms channels in the membrane or by releaseing Fas on the target cell and activating the death pathway

Viral proteins are made endogenously

Question 3

T_H

Answer 3

T helper cells

CD4 Co-receptor binds MHC Class II

Recognize exogenous peptides presented in association with MHC class II molecules of APCs

Question 4

Interaction between T cells and antigen presenting cells that leads to T cell activation

Answer 4

Since T cells do not recognize native antibody, the native antigen protein is denatured by the antigen presenting cell and the antigen peptide complexes with the MHC molecule

Forms the tripeptide complex: T cell receptor, peptide antigen, and MHC molecule

1. Cut - bacteria enters the body
2. Antigen is taken to the lymph node in the context of an MHC receptor
3. The T cell recognizes the peptide antigen in the context of a MHC molecule
4. T cell is activated

Question 5

MHC Class I Molecules

Answer 5

Expressed on nearly all nucleated cells (except RBCs, sperm, and ovum)

Recognized by TC cells - CD8+

TC cells recognize and kill virus infected cells - recognize the endogenous viral peptide presented in the context of MHC class 1

Intracellular antigen

Question 6

MHC Class II Molecules

Answer 6

Expressed only on antigen presenting cells (APC) - Dendritic cells, macrophages, and B cells

Recognized by TH cells - CD4+

TH cells recognize exogenous proteins presented in association with MHC class II molecule of antigen presenting cells

Question 7

T cell Education

Answer 7

TCR genes rearrange in the thymus

T Cells are educated to determin self antigens in the thymus

The thymus activates a gene that produces self epitopes, and if T cells bind, they are destroyed to prevent autoimmunity from developing

Question 8

Positive Selection

Answer 8

T cells undergo positive selection in the thymus to select for T cells that recognize antigen in the context of MHC receptors

Question 9

Negative Selection

Answer 9

T cells undergo negative selection in the thymus to eliminate T cells that react with self peptides

Gets rid of self reactive t cells due to a gene in the thymus producing self epitopes om the thymus during dedevelopment. When self reactive t cells react with the epitope, the t cells are are deleted

Prevents autoimmunity from developing

Question 10

Antigens recognized by B Cell Receptors

Answer 10

B cell receptors recognize native antigen

Question 11

Antigens recognized by T Cell Receptors

Answer 11

T cell receptors recognize peptide from the antigen in the context of a MHC molecule

Question 12

How is an immune response initiated?

Answer 12

1. Antigen is collected in the lymphatics and transported tot he draining lymph node by APC (dendritic cells)
2. In the lymph node the activated dendritic cells (APC’s) interact with, and stimulate TH cells
3. TH cells interact with, and activate antigen specific B cells
4. B cells then form germinal centers and undergo germinal center reactions (isotype switch, somatic hypermutation, diffenetiation of B cells to plasma cells, and generation of memoory B-cells)

Question 13

How does viral immunity develop?

Answer 13

1. The host cell proteosome degrades viral proteins which are transported to the ER
2. Peptides bind to MHC class I molecules and transport through the golgi apperatus
3. MHC class I presents peptides at the cell surface and activates CD8 Tc Cells
4. Activated Tc cells can kill the virus infected cell through a perforin dependent killing or through a fas dependent killing mechanism

Question 14

How does immunity to extracellular pathogens develop?

Answer 14

1. The cell engulfs the extracellular antigen in an endocytic vesicle
2. Peptide is produced in a phagolysosome
3. The peptide binds MHC class II molecules through vessicle fussion
4. The MHC class II presents the peptiide at the cell surface and activates CD4+ Th cells
5. Activated Th cells can then differentiate and prolliferate and effector Th cells will develop in response to specific cytokines released

Question 15

TH Cell Activation

Answer 15

Costimulation (2 signals) is required for activation of TH cells

1. TCR recognition of the peptide in the context of MHC receptor on an APC (often dendritic cell)
2. Interaction of CD28 on T cells and B7 on APC (costimulatory molecules)

Activation of Th cells causes the release of a specific set of cytokines that stimulate proliferation and differentiation into effector T cells

Question 16

TH1

Answer 16

Activates macrophages to kill intracellular pathogens and activate cytotoxic T cells to kill virus infected cells

The antigen presenting cell releases IL12 and IFNy

The activated T cell then releases IL2 and IFNy to differentiate into Th1 cells

Question 17

TH2

Answer 17

TH2 cells help activate B cells, which are activated to differentiate into plasma cells and secrete antibody which protects the host from extracellular pathogens

Activation and differentiation of B cells occurs in the lymph nodes and germinal centers

IL-4 promotes TH2 activation

Question 18

TH17

Answer 18

Promotes the release of IL-17 and induces a neutraphill response

Early in the immune response

TH2 cells are activated by IL-6 and TGFbeta

Question 19

TReg

Answer 19

CD4+ T cells that supress T cell activity and help prevent autoimmunity

Develop in resonse to TGFbeta

Question 20

What is the importance of cytokines in the immune response?

Answer 20

Cytokines produced by the dendritic cell activae a T cell to release another set of cytokines that influence the proliferation and differentiation of a specific subset of Th cells

Question 21

3 Major effector mechanisms of the immune system

Answer 21

1. Antibody and complement can together kill extracellular bacteria
2. CD8+ CTL kills virus infected cells
3. Activated macrophages results in delayed hypersensitivity and kills intracellular organisms

Question 22

Effector T Cells

Answer 22

CD4+

1. TH1
2. TH2
3. TH17
4. T Reg

CD8+

1. CTL (cytotoxic t lymphocytes)

Question 23

Memory

Answer 23

Lymphocytes generated following enncounters with antigen that are charachteristically long lived

They are more readily stimulated than naive lymphocytes and mediate a secondary response to subsequent encounters with antigen

Question 24

Specificity

Answer 24

The capacity of an antibofy and T cell recptor to recognize and interact with a signle unique antigenic determinant or epitope

Question 25

Cytokines

Answer 25

Small secreted proteins that regulate the intensity and duration of the immune response by wxerting a variety of effects on lymphocytes and other immune cells

Question 26

APC

Answer 26

Any cell that can orocess and present antigenic peptides in the context of a MHC class 2 molecule and deliver a costimulatory signal necessary for T cell activation Dendritic cells, B Cells, Macrophages

Question 27

BCR

Answer 27

A complex comprised of a membrane bound immunoglobulin molecule

Question 28

TCR

Answer 28

Antigen binding molecule expressed on the surface of T cells Recognizes antigen in the context of a MHC molecule

Question 29

Memory B Cells

Answer 29

An antigen committed persistent B cell B cell differentiation can result in the formation of plasma cells and memory cells which are involved in the secondary response

Question 30

Primary immune response

Answer 30

Immune response after an initial exposure to antigens. Characterized by short duration and low magnitude of response when compared to subsequent exposure response

Question 31

Secondary Immune Response

Answer 31

The immune response following exposure to previously encountered antigens. The secondary response is more rapid and is greater in maggnitude and durration

Question 32

Humoral Immunity

Answer 32

Host defenses that are mediated by antibody present in the plasma, lymph, and tissue fluids. (B cell - plasma cell) It protects agains extracellular bacteria and foreign molecules Transfer of antibodies confers theis type of immunity on the recipent

Question 33

Cellular Immunity

Answer 33

Host defenses that are by antigen specific T cells and various nonspecific cells of the immune system Protects against intracellular bacteria, viruses, and cancer cells Is responsible for graft rejection Transfer of primed T cells confers this type of immunity on the recipient

Question 34

Co-Receptor

Answer 34

CD4+ - T Helper Cells CD8+ - Cytotoxic T Cells

Question 35

Costimulatory Molecule

Answer 35

Additional signal that is required to induce prolifferation of antigen-primed T cellsand is generated by the interaction of CD28 on T cells with B7 on antigen presenting cells

Question 36

What is the risk of developing a large T cell repertoire?

Answer 36

Self reactive T cells can develop, resulting in autoimmunity To get rid of self reactive T cells, there is a gene in the thymus that produces self epitopes. If the T cells bind to the self epitopes during development, the self reacting T cells are deleted

Question 37

What occurs in Germinal Centers?

Answer 37

* B cells can differentiate to form plasma cells which secrete antibody * B cells can become memory B cells which circulate looking for antigen * B cells undergo somatic hypermutation which can only occur in the germinal center, and selection for high affinity antibodies occurs

Question 38

How does the immune system respond to a protein antigen?

Answer 38

1. The system is exposed to an antigen at a distant site 2. The dendritic cell takes up the antigen and transports it to the draining lymph node via the lymphatics 3. A naïve CD4+ cell recognizes an antigen in the context of a MHC molecule on an APC 4. The activated T cell develops into a specific type of T cell based on a specific cytokines (dendritic cells are thought to stimulate the release of a certain set of cytokines to direct Th development based on the antigen) 5. The activiated Th cells release a different set of cytokines which have different functions based on the type of T cell * Th1 – releases cytokines that activate macrophages to kill intracellular bacteria * Th2 – releases cytokines that activate B cell differentiation * Th17 – release cytokines that activate the recruitment of neutrophils to the site of infection resulting in an inflammatory response * T reg – release cytokines that inhibit CD4 T cells 6. The activated B cells form germinal centers and undergo germinal center reactions