Inflammation

Local - Red, swollen, pus, hot

Systemic – fever, high heart rate, low blood pressure

When the body is injured by invaders, it needs its homeostatic mechanisms reset to cope, and to best kill the invaders

Bacteria don’t like the heat – it inhibits their replication, but heat makes the immune system work well

Opening up the local blood vessels makes the area warm and red – allowing more inflammatory cells in

Neutrophils come in – made quickly and get there quickly. They phagocytose and kill – and then die, leaving pus.

Macrophages take up particles by phagocytosis and release cytokines

eg IL1 and TNFa is released, sending messages afar (liver and hypothalamus)

Liver responds by producing acute phase reactants – such as more complement components and activators of complement (eg MBL)

VIRUSES

Infect cells and replicate from cell to cell utilising the cells own nuclear equipment

Virally infected cells present the viral antigens on HLA Class I

The infected cell also releases cytokines, which

activate macrophages and APCs

upregulate local adhesion molecules

APCs engulf viral proteins and debris ready to present to T cells

DCs transport the antigen to present to T cells in the LN

In the LN:
Lymphocytes come in from the blood and the lymphatics, contributing to the LN swelling and enlarging. The T cells pass by the DCs, and those with the complementary TCR for the MHC/Ag connect, activating the T cell to proliferate and produce cytokines

B cells receive antigen at their surface, and after connection with the appropriate T cell, proliferate, and produce IgM antibodies. Some B cells will differentiate further and produce specific IgG antibodies.

Antigen presentation from both B cells and DCs to T cells requires two signals to work.

TCR-MHC and CD80/86 - CD28

Cytotoxic T cells are also recruited and activated by the T helper cells via cytokines, such as IFN The express virus specific TCRs which will go back to the site of the inflammation, and start killing cells infected with the virus.

Local Th cells and B cells increase the local inflammation.

Antibodies will

• neutralise form immune complexes
  
• which can then be cleared by the phagocytes help the
  
• NK cells recognise the NK cells

NK cells

Viruses will often down grade all the Class I expression of the infected cell.

NK cells survey cells for cells which don’t have Class I and are activated by that absence. (‘absence of self”)

NK cells are also activated by the presence of antibodies which recognise the virally infected cells and point them out to the NK cells, and thus activate them.

Type I Interferon

Interferon alpha and gamma are produced in response to viral infection. They upregulate Class I to increase cytotoxic T cell killing and inhibit viral RNA replication

Type I interferons have a different role to Type II interferon (Interferon gamma which is released by Th2 cells)

Bacterial Infection

The body surfaces are a good barrier for bacteria, often gets in due to a break in the normal surface.

Bacteria have various foreign elements on the surface,

eg LPS which initiates alternative complement and activates the endothelium and the neutrophils which are infiltrating

Further cells are attracted by the complement by-products which are chemotactic

Complement sticks to the outside of the bacteria (opsonises) leading to recognition and killing by the phagocytes eg neutrophils and macrophages

DCs migrate as with viruses, and present to the T cells

T helper cells activate B cells to produce more antibodies. IgM enhances complement activation and induces phagocytosis by opsonisation.

Category: Pathology Notes