4 - Histocompatibility complex & antigen presentation Flashcards
Professional Antigen Presenting Cells
Dendritic cells, macrophages and B cells
What T cells can “see”
T lymphocytes can see only peptide fragments of protein antigens, when they are displayed on host cell surfaces bound to MHC molecules
Activation of dendritic cells
- Upon activation, DCs lose their adhesiveness for epithelia and peripheral tissues and begin to migrate through lymphatic vessels to the lymph nodes
What happens during migration of dendritic cells
Start to mature by increasing the synthesis and stable expression of MHC molecules, and other costimulatory molecules such as CD80/CD86
Numerous cytoplasmic processes and high surface area allows intimate contact with many surrounding cells
only one mature DC is required to stimulate 100 - 3000 T cells
MHC-I and MHC-II molecules
facilitate immune surveillance for microbes in different locations
Class I MHC pathway
converts proteins in the cytosol into peptides that bind to MHC-I molecules for recognition by CD8 + T cells
Class II pathway
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
Major Histocompatibility Complex
Collection of genes encoding proteins that enable the host to distinguish self and non-self
How many genes found in MHC
more than 200 genes which have many possible variations
Name for human MHC
Human leukocyte antigen (HLA)
HLA
- 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
Features of peptide binding to MHC molecules
- 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
Class I MHC molecules
- 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
Class II MHC molecules
- 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
Antigen cross presentation
DCs transport the ingested antigens into the cytosol, where they are processed and mounted on MHC-I molecules
3 T cell activation signals
- Signal 1: Antigen specific signals
- Signal 2: Costimulatory signals
- Signal 3: Cytokine
Signals for T cell activation
- 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
CTLA-4
Blocks and removes B7 molecules from the surface of APCs, reducing costimulation by CD28 and preventing the activation of T cells
PD-1
expressed on T cells after antigen stimulation, and acts by inhibiting kinase dependent activating signals from CD28 and the TCR complex
what happens to T cells that recognise antigen without costimulation
may die or become unresponsive (tolerant) to
subsequent exposure to antigen
Why is requirement for costimulation important
Ensures that naive T cells are not activated by harmless foreign substances or by self antigens
What happens to T cells in the presence of costimulation
Rapidly secretion of IL-2 , and
increase expression of IL-2R
Function of IL-2
Stimulate the survival and proliferation of T cells
CD4+ cell
Helper T cell
CD8+ cell
Cytotoxic T cell
Helper T cell
Secrete cytokines that stimulate different mechanisms of immunity and inflammation
Outcomes of helper T cells
- Activation of macrophages
- Inflammation
- Activation of B lymphocytes
Cytotoxic T cell
Kill any type of host cells that harbour infectious microbes in the cytoplasm
How long does it take for T lymphocytes activated by antigens and costimulation to proliferate
1 or 2 days
what causes immunological memory
Infection or vaccination
Memory T cells
Formed during a primary adaptive immune response and can persist for extended periods in the absence of the antigen that originally induced them
Memory T cells characteristics
- Survive long-term
- More sensitive to restimulation by antigen than naïve T cells
- Proliferate more rapidly and robustly compared to naive precursors
