4 - Histocompatibility complex & antigen presentation

Question 1

Professional Antigen Presenting Cells

Answer 1

Dendritic cells, macrophages and B cells

Question 2

What T cells can “see”

Answer 2

T lymphocytes can see only peptide fragments of protein antigens, when they are displayed on host cell surfaces bound to MHC molecules

Question 3

Activation of dendritic cells

Answer 3

• Upon activation, DCs lose their adhesiveness for epithelia and peripheral tissues and begin to migrate through lymphatic vessels to the lymph nodes

Question 4

What happens during migration of dendritic cells

Answer 4

Start to mature by increasing the synthesis and stable expression of MHC molecules, and other costimulatory molecules such as CD80/CD86

Question 5

Numerous cytoplasmic processes and high surface area allows intimate contact with many surrounding cells

Answer 5

only one mature DC is required to stimulate 100 - 3000 T cells

Question 6

MHC-I and MHC-II molecules

Answer 6

facilitate immune surveillance for microbes in different locations

Question 7

Class I MHC pathway

Answer 7

converts proteins in the cytosol into peptides that bind to MHC-I molecules for recognition by CD8 + T cells

Question 8

Class II pathway

Answer 8

converts protein antigens that are endocytosed into vesicles of antigen-presenting cells into peptides that bind to MHC-II molecules for recognition by CD4 + T cells

Question 9

Major Histocompatibility Complex

Answer 9

Collection of genes encoding proteins that enable the host to distinguish self and non-self

Question 10

How many genes found in MHC

Answer 10

more than 200 genes which have many possible variations

Question 11

Name for human MHC

Answer 11

Human leukocyte antigen (HLA)

Question 12

HLA

Answer 12

• Many different alleles are
  present in the population
• Different individuals are able to present and respond to different microbial peptides
• Variation is further amplified because HLA genes are codominant – both parental alleles of each MHC gene are expressed

Question 13

Features of peptide binding to MHC molecules

Answer 13

• Broad specificity
• Each MHC molecule displays one peptide at a time
• MHC molecules bind only peptides
• Stable surface expression of MHC molecule requires bound peptide
• Very slow off rate

Question 14

Class I MHC molecules

Answer 14

• Identify all nucleated cells of the body as “self”
• Bind to normal (self) peptides and antigens extracted from intracellular pathogens, signalling to the immune system that it is an infected host cell
• Smaller binding pocket
• Endogenous antigen processing

Question 15

Class II MHC molecules

Answer 15

• Expressed by professional antigen presenting cells (dendritic cells, macrophages and B cells)
• Bind to antigens degraded as a consequence of phagocytosis or receptor mediated endocytosis
• Larger and deeper pocket
• Exogenous antigen processing

Question 16

Antigen cross presentation

Answer 16

DCs transport the ingested antigens into the cytosol, where they are processed and mounted on MHC-I molecules

Question 17

3 T cell activation signals

Answer 17

• Signal 1: Antigen specific signals
• Signal 2: Costimulatory signals
• Signal 3: Cytokine

Question 18

Signals for T cell activation

Answer 18

• Signal 1: presentation of the antigen by an APC (CD4 and CD8 co-receptors on T cells stabilise interaction of TCR and MHC/peptide)
• Signal 2: Dendritic cell presents B7 (CD80/CD83) to T cells (CD28 receptor)
• Signal 3: Release of cytokines by APC and T cells themselves (IL-2), driving T cell proliferation, survival and differentiation

Question 19

CTLA-4

Answer 19

Blocks and removes B7 molecules from the surface of APCs, reducing costimulation by CD28 and preventing the activation of T cells

Question 20

PD-1

Answer 20

expressed on T cells after antigen stimulation, and acts by inhibiting kinase dependent activating signals from CD28 and the TCR complex

Question 21

what happens to T cells that recognise antigen without costimulation

Answer 21

may die or become unresponsive (tolerant) to
subsequent exposure to antigen

Question 22

Why is requirement for costimulation important

Answer 22

Ensures that naive T cells are not activated by harmless foreign substances or by self antigens

Question 23

What happens to T cells in the presence of costimulation

Answer 23

Rapidly secretion of IL-2 , and
increase expression of IL-2R

Question 24

Function of IL-2

Answer 24

Stimulate the survival and proliferation of T cells

Question 25

CD4+ cell

Answer 25

Helper T cell

Question 26

CD8+ cell

Answer 26

Cytotoxic T cell

Question 27

Helper T cell

Answer 27

Secrete cytokines that stimulate different mechanisms of immunity and inflammation

Question 28

Outcomes of helper T cells

Answer 28

• Activation of macrophages
• Inflammation
• Activation of B lymphocytes

Question 29

Cytotoxic T cell

Answer 29

Kill any type of host cells that harbour infectious microbes in the cytoplasm

Question 30

How long does it take for T lymphocytes activated by antigens and costimulation to proliferate

Answer 30

1 or 2 days

Question 31

what causes immunological memory

Answer 31

Infection or vaccination

Question 32

Memory T cells

Answer 32

Formed during a primary adaptive immune response and can persist for extended periods in the absence of the antigen that originally induced them

Question 33

Memory T cells characteristics

Answer 33

• Survive long-term
• More sensitive to restimulation by antigen than naïve T cells
• Proliferate more rapidly and robustly compared to naive precursors