Intracellular Bacteria Infections

Front 1

What are intracellular bacterial infections?

Back 1

Some bacteria are intracellular pathogens that can replicate inside macrophages

Front 2

Why are intracellular bacterial infections so deadly?

Back 2

For these type of pathogens they are able to shut down the innate immune responses and prevent the macrophage from klling them
-They also are able to modify the phagosome so that it cannot fuse with the lysosome
-Eventually the macrophage lyse and the bacteria released from the dead macrophage can invade other macrophages and spread the infection

Front 3

So how would we deal with bacteria that replicate inside macrophages?

Back 3

Antibodies would not be useful in the infection
-Cell mediated immune responses are needed to combat this type of infection
-Goal of the immune system is to activate the macrophages so that they can kill the bacteria that are inside of them

Front 4

Why is it called cell mediated immune response?

Back 4

Because it involves T cells and macrophages and is not carried out by soluble proteins in the blood such as antibodies

Front 5

How does the bacteria end up inside the macrophage? And what does it do to it?

Back 5

They enter the macrophage by phagocytosis but most of the phagosomes do not fuse with lysosomes.
-INstead bacteria modify phagosome so that it becomes a specialized organelle in which they can replicate
-Small number of phagosomes do fuse with lysosomes before the bacteria can modify them
-This results in some of the bacteria being killed and degradation of their proteins by lysosomal proteases
-Antigenic peptides derived from bacteria are displayed on MHC class II proteins

Front 6

What happens next?

Back 6

T helper cells with correctly shaped TCR bind to these peptide/MHC II complexes and the CD3 complex sends a signal to nucleus (signal 1 of T cell activation)
-CD28 molecule on the T cell interacts with B7-co-stimulatory molecule on the macrophage (signal 2 of T cell activation)
-T helper cell recieve cytokines IL-12 and IFN-gamma from infected macrophage that instruuts it to develop into a TH1 type of T helper cell
-TH1 cell starts to express CD40L on its cell surface

Front 7

What happens next?

Back 7

Activated TH1 cell divides
-Some of the cells will differenitate into memory T cells and some will differentiate into effector cells (activated Th1 cells which secrete cytokines)
-These TH1 cells can migrate to the infected site and secrete interferon-gamma (IFN-gamma)
-Macrophages can be activated by two signals
-Secretion of IFN-gamma and other cytokines by the Th1 cell mediates one signal
-Second signal is binding of CD40L on the Th1 cell to CD40 on the macrophage

Front 8

What happens next?

Back 8

Activated macrophages fuse their lysosomes more efficiently to the phagosomes and kill intracellular bacteria and recently ingested pathogens
-TH1 cells provide activating signals for macrophages that result in the induction of antimicrobial mechanisms such as the reactive nitrogen metabolite nitric oxide (NO) oxygen radicals and proteases
-These compounds can also kill extracellular pathogens and unfortunately damage the healthy cells and tissues of the host

Front 9

What happens next?

Back 9

Th1 cells also secrete substances that cause an inflammatory response
-Cytokines made by the Th1 cells increase blood flow to area and also attract neutrophils and macrophages that release bactericidal substances and phagocytose baceria that have escaped from lysed cells

Front 10

How strong is the primary response and secondary responses?

Back 10

It is usually quite weak and there is little or no inflammation
-This is because there are very few T cells specific for the bacterial antigens and they can only activate a small number of macrophages
-In the secondary response, there is more memory T cells specific for bacterial antgiens
-These can activate many macrophages resulting in substantial inflammation

Front 11

What is delayed-type-hypersensitivity?

Back 11

Because T cells specific for bacterial antigens must find the infected macrophages and become activated, divide and then differentiate into Th1 cells, this inflammatory response takes 1-2 days to develop

Front 12

What are inflammatory T cells?

Back 12

Th1 cells or sometimes called Tdth or TD cells