Cell-mediated immunity Flashcards
Why do we need cell-mediated immunity?
Designed to fight intracellular microbes
- bacteria in phagosomes (in phagocytes)
- viruses: in cellular cytoplasm
- parasites (helminths) - both intra- and extracellular
main mediators are T cells
Why are viruses largely intracellular organisms?
intracellular obligate pathogens
they require host cell machinery in order to survive and replicate
What are the main types of T cells?
Th1 (CD4+)
help phagocytes to kill ingested microbes
Th2 (CD4+)
help eosinophils/mast cells to kill helminths. (also active in IgE mediated allergy/anaphylaxis)
Th17 (CD4+)
role in defence against bacteria and fungi
CTL (CD8+)
kill cells infected by microbes that grow freely in the cytosol
How do T cells recognise antigens?
Only if digested and bound to MHC molecules on another cell (e.g. APC)
Cannot recognise Ag directly
What kind of Ag particles do T cell recognise?
CELL BOUND Ag
usually peptides via MHC
Which type of T cells recognise non-peptide antigens?
gamma- delta T cells
What kind of antigens do B cells recognise?
SOLUBLE or CELL BOUND Ag
Which MHC complexes are used in Ag presentation to T cells?
CD4+ T helper cells use MHC Class II (present on APCs)
CD8+ cytotoxic T cells use MHC class I (present on all nucleated cells)
What does Ag presentation via MHC to naive T cells cause?
Activation and production of their effector counterparts
What are the types of T cell receptor (TCR)?
alpha and beta TCR
this type of TCR present on CD4+ and CD8+ T cells
gamma/delta chains TCR present in gamma/delta T cells
What are the main structural elements of the alpha/beta T cell receptor (TCR)?
includes variable domains at Nter and constant domains towards Cter
TMEM domain is immediately upstream to Cter cytosolic (intracellular) portion
Variable regions contain hypervariable loops e.g. CDR3 (similar to Ig structure)
these regions are responsible for generating Ag specificity and binding between TCR
What is MHC restriction?
refers to type of antigen recognition in T cells
Concept that T cell will only respond to an Ag presented on a particular type of MHC molecule
e.g. CD4+ cells will only respond to Ag bound to MHC Class II molecules etc
What is the specific structure of the MHC I molecule?
alpha chain and beta 2 micro globulin chain
N.B. beta-2-microglobulin is smaller in size that the beta chain in MHC II
What is the specific structure of the MHC II molecule?
alpha chain and beta chain
Which T cells are not MHC-Ag restricted?
gamma-delta T cells
this means that it can respond to Ag bound to both MHC I and MHC II
Where are the different MHC molecules expressed?
MHC I = all nucleated cells
MHC II = APCs (mQ and DCs)
What is the generic structure of a MHC molecule?
2 peptide chains
form a groove between them that holds the Ag/peptide that is presented to T cell
What bonds hold the chains together in MHC molecules?
disulphide bonds
What regions determine the Ag binding specificity and diversity in TCR:MHC complex?
hypervariability loops
hypercomplimentarity domains
both present in TCR structure
What are dendritic cells?
type of APC
sentinel cells
present in skin, mucosa and tissues
role to capture microbes via phagocytosis
process pathogens and present Ag to T cells (via MHC class II for CD4+)
What is the main function of APCs?
capture and present Ag to T cells
provides link between innate and adaptive immune responses
What are the 3 signals needed for T cell activation via APCs?
Signal 1
MHC-peptide on APC
TCR on naive T cell
Signal 2
CD80/86 on APC
CD28 on naive T cell
regulatory signal of T cell activation
Signal 3
cytokines released from both APC and T cell
have both autocrine and paracrine effects
type of cytokine released will determine type of effector T cell produced