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Lecture: Infection and Immunity
Date: Friday 16th February
Time: 1pm – 2pm
Cell – Cell Communication
Today we are going to concentrate on how cells communicate with one another, and how
cytokines and receptors are involved. At the end we will look at the process starting from an
innate immune response and how pathogens can interfere with antigens.
Reading: A paper has been uploaded onto Moodle regarding smoking and its effect on your
immune system.
Learning objectives:
- Many receptors found on immune cells belong to immunoglobin supergene family.
- The t cell receptor resembles an antibody Fab fragment.
- T cell signalling via CD3 co receptors.
- The role of CD4 and CD8, coreceptors found in T cells.
- Costimulatory and cell adhesion molecules.
- Cytokines in activation and regulation.
- TH1 and TH2 cells produce different sets of cytokines, these cross regulate and
support different subsets of the immune system.
- TNF a cytokine and inflammation.
- Superantigens.
- Summary of immune response.
- The immune system interacts widely with nerve and endocrine systems of the body.
The immunoglobin supergene family
These are horseshoe shaped genes, with DNA sharing sequences encoding immunoglobin-
like domains on the surface of the antibody, each have signalling tails.
Examples:
CD3- long plasmid tails that signal to the t cell receptor.
CD4 – helper t cells.
CD8 – cytotoxic t cells.
IgA – binds in dimer form and passes through the lumen to the gut.
The rest of the molecules are adhesion molecules, holding the structure together.
Antigen binding site and the t cell receptors have similar structures. Looking at the t cell in
more detail, there are carbohydrates which are added through the Golgi to increase activity.
Schematic representation of T cell receptor
1
, Epsilon CD3
Delta chain
Gamma chain
Immunoreceptor Tyrosine based Activation Motif (ITAMS) -
important for signalling.
Zeta chains with 3 IITAMS on each chain – involved in signalling
to the interior of the cell through ITAMS.
CD4
This structure is found on all helper T cells. For example, the HIV virus locks on to helper t
cells through the immune structure which is why the cells become supressed. CD4 cells help
to produce antibodies. D1 domain of CD4 binds to HIV-1 gp120.
CD8
Classic marker of cytotoxic t cells.
Interactions Taking Place Between T Cell and Antigen Presenting Cell.
Antigen presenting cell with MHC class 2 and MHC 1. It contains B7, a co stimulatory
molecule which binds to CD28 on antigen presenting cell. If it has a naïve t cell, they require
cytokines help, the helper cell produces cytokines, so they respond.
Immature helper t cell
Receptor, MHC class 2, CD28 binds to class B7.
Cell adhesion molecules
ICAM is a cell adhesion molecule which binds to leukocyte function-associated antigen (LFA-
1) or macrophage-1 antigen (Mac-1). These are the glue that stick around the outside of the
interactions (the pSMAC). For example, LFA1 binds to ICAM1, both are members of the
supergene family.
(Image showing the central area of interactions with MHC, t cells and adhesion molecules).
Peripheral SMAC – Cell adhesion molecules with LFA1, ICAM-1 and talin. Talin makes sure
the t cell can produce cytokines to help relocate the antigen presenting cell into the correct
orientation.
Central SMAC – t cell receptor, CD2, CD4 CD8 CD28 PKC0.
T cell receives signals from B cell secretary componenets produce cytokines (IL2) help
the B cell.
Kuby immunology book: Three signals required for the activation of a naïve t cell by an
antigen presenting cell.
1) TCR signalling – binds to antigen and MHC.
2
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