Ch 3 - Antigen Capture and Presentation to Lymphocytes

Question 1

What causes immune responses to protein antigens of micobes?

Answer 1

a specialised system of capturing and displaying antigens for recognition by rare naive t cells specific for any antigens

Question 2

How do microbes get into the body and where do they get transported to/captured?

Answer 2

Microbe antigens enter the body through epithelia and are captured by dendritic cells in epithelia.
Transported to regional lymph nodes or captured by DCs in lymph nodes/spleen

Question 3

How are protein antigens of microbes displayed?

Answer 3

By antigen presenting cells (APCs)

Presented to naive T lymphocytes that recirculate through the lymphoid organs

Question 4

What happens to molecules encoded in MHC?

Answer 4

Can display peptides derived from protein antigens

Question 5

MHC gene are highly______?

Answer 5

polymorphic
- occurring in several different forms, in particular with reference
to species or genetic variation.

Question 6

What are the major products of MHC genes?

Answer 6

Class 1 and Class 2 MHC molecules

Question 7

MHC Class 2 binds to _____?

Answer 7

CD4+ T cells

Question 8

MHC class 1 binds to ___?

Answer 8

CD8+ T cells

Question 9

What allows MHC classes to bind to their co-receptors?

Answer 9

peptide binding clefts –> have polymorphic residuals (concentrated) and invariant regions which bind to coreceptors CD4 and CD8 respectively.

Question 10

Proteins produced in infected cytosols, tumor cells or who enter cytosol from phagosomes are degraded by what?

Answer 10

Proteasomes

Question 11

Where does CD8 bind to class 1 MHC?

Answer 11

the invariant part

Question 12

What happens when proteins are ingested by APCs (from extracellular environment)?

Answer 12

proteolytically degraded (breakdown of proteins) within the vesicles of the APC
- Peptide generated bind to clefts of newly synthesised class 2 MHC molecules

Question 13

Why does CD4 bind to MHC class 2?

Answer 13

CD4+ helper T cells can only be activated by class 2 MHC associated peptides derived mainly from proteins degraded in vesicles which are typically ingested extracellular proteins

Question 14

What is the role of MHC molecules in antigen display?

Answer 14

T cells only recognise cell-associated protein antigens and the correct type of T cell (helper or cytotoxic) responds to the type of microbe the T cell is best able to combat

Question 15

Microbes activate APCs to _______?

Answer 15

• express membrane proteins (costimulators)

- secrete cytokines –> providing signals that function in together with antigens to stimulate specific T cells

Question 16

WHat is co-stimulation?

Answer 16

Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response.

Question 17

Why do we have co stimulators to stimulate t cells?

Answer 17

ensure t cells respond to microbial antigens and not harmless, nonmicrobial substances

Question 18

Why do B lymphocytes recognise?

Answer 18

• proteins

- non-protein antigens (even in native conformations)

Question 19

Follicular dendritic cells display antigens to _____?

Answer 19

• germinal centre B cells

- select high affinity B cells during humoral immune responses

Question 20

Q - When antigens enter through the skin, in what organs are they concentrated?

Answer 20

Antigens that enter through epithelial barriers, such as skin or intestines, are captured by dendritic cells that reside in or below the epithelium, and the dendritic cells transport the antigens to the draining lymph nodes, where the antigens are displayed to lymphocytes. Free antigens also may enter secondary lymphoid organs and be captured by resident dendritic cells.

Question 21

Q - What are MHC molecules? WHat are human MHC molecules called? How were MHC molecules discovered and what is their function?

Answer 21

Major histocompatibility complex (MHC) molecules are cell surface proteins that bind antigenic peptides and display them for recognition by T cells. Human MHC proteins are called human leukocyte antigen (HLA) molecules. Their physiologic function is peptide antigen presentation to T cells. They were initially discovered as products of polymorphic genes that mediate transplant rejection..

Question 22

Q - What are the differences between antigens displayed by class 1 and class 2 MHC molecules?

Answer 22

Proteins that are produced in or enter the cytosol are digested by the proteasome and their peptides are presented by class I MHC molecules. Proteins from outside the cell that are internalized into vesicles by endocytosis are processed by lysosomal proteases and these peptides are presented by class II MHC molecules.

Question 23

Q - describe the sequence of events by which class 1 and class 2 MHC molecules aquire antigens for display.

Answer 23

Protein antigens in the cytosol are cleaved into peptides by proteasomes, and the peptides are transported into the endoplasmic reticulum by the TAP pump. Once inside the ER, these peptides bind to newly produced class I MHC molecules. The peptide–class I MHC complex is then transported to and displayed on the cell surface. MHC class II α and β chains are produced in the endoplasmic reticulum, where they assemble with each other and with an invariant chain that occludes the antigen binding cleft. The MHC class II–invariant chain complex is transported to a late endosomal/lysosomal compartment, where the invariant chain is degraded, leaving a peptide called CLIP in the cleft. Proteins internalized by the endocytic pathway are degraded in late endosomes and lysosomes into peptides. Specific peptides displace CLIP and bind tightly to the cleft of the class II MHC molecule, which is then transported to the cell surface.

Question 24

Q - Which subsets of T cells recognise antigens presented by class 1 and class 2 MHC molecules? What molecules on T cells contribute to their specificity for either class 1 or class 2 MHC-associated peptide antigens?

Answer 24

CD4+ helper T cells recognize peptide antigens bound to class II MHC molecules, and CD8+ cytotoxic T lymphocytes recognize MHC class I–peptide complexes. The CD4 coreceptor of helper T cells can bind to class II MHC molecules, and the CD8 coreceptor of cytotoxic T cells binds to class I MHC molecules.