Immunoregulation

done by :-

Karrar abdo al kareem

Ayman hameed

Abdo al salam

Teaching objectives

• To discuss regulation of immune responses including regulation by antibody, Tregs, and cytokines

• To discuss some genetic factors influencing immunoregulation

What is immunoregulation?

• The ability of the immune system to control and regulate its own responses is called immunoregulation.

• Magnitude of immune response determined by:

– Ag-driven activation of lymphocytes

– Negative regulatory influences that prevent or dampen response

• Regulatory mechanisms act at all phases of immune response

– Recognition

– Activation

– Effector function

• Once the foreign body enter the body is recognized as non self .

Activation

• The activation of the immune response typically begins when the pathogen enters the body

• Macrophages ingest ,process and display the Ag fragments on their surface

• Macrophages with the Ags on their surfaces are called APCs.

APC

APC interact with a T-helper cell that recognize the same Ag

• During interaction the microphage releases a chemical alarm signals called IL-1 which stimulate the T-helper cell to release IL-2.

• IL-2 causes the proliferation of certain cytotoxic T-cells & B-cells

10

Th1

+IL-1,2 +IL-4

IL-2

IFN-gIL-4

IL-10

inhibit

Cell mediated

immunity

Humoral

immunity

Th0

Th2

Interaction of Th1 and Th2

The immune response from this point follows two paths :-

Action of T cells

• Normal cells of the body can also be infected by ingesting the pathogen & display Ag fragments on their cell surfaces

• The body makes millions of cytotoxic T cells each type is able to recognize aparticular type of Ag

• The cytotoxic T cell that are capable to recognizing the Ag displayed on the surfaces of infected cells bind to the infected cell and produce chemicals that kill the infected cell

• Death of the infected cells result in the destruction of the pathogen .

16

Th1

+IL-12 +IL-4

IL-2

IFN-gIL-4

IL-10

inhibit

Cell mediated

immunity

Humoral

immunity

Th0

Th2

Interaction of Th1 and Th2

Action of B cell

• B cell also contain millions of types each able to recognize a particular Ag

• When B cells become activated by T helper cells they differentiate into plasma cells

• These plasma cells become Ab producing factories fludding the blood stream with Abs that can bind to the Ag envolved in this infection

• Abs bind to the Ag on the surfaces of the pathogens marking the for destruction by macrophages

• Some of the B cells do not turn to Ab factories but instead become memory B cells that may survive for several decades .

• Because of these memory B cells , the secondary immune response to a future infection by the same pathogen is stronger.

• This act of immune response is what gives immunity to some diseases after you had them once or after you have bean vaccinated.

Regulation by cytokines

a) Cytokines are positive or negative regulators. They act at many stages of the immune

response, but their activity is dependent upon the other cytokines present in the

microenvironment as well as receptor expression on effector cells. Cytokines regulate

the type and extent of the immune response generated.

IMMUNE RESPONSE:

STIMULATORY AND INHIBITORY

CYTOKINES

• Interleukin-2 (IL-2)

• IL-1

• IL-4

• IL-5

• IL-6

• IL-12

• IL-18

• Interferon gamma

(IFN- g)

• IL-4

• IL-10

• IL-11

• IL-13

• Transforming growth

factor beta (TGF-)

• IFN-/

• IFN-g

Regulation by regulatory T cells (Tregs)

formerly known as suppressor T cells, are a subpopulation of T cells which modulate the immune system, maintain tolerance to self-antigens, and abrogate autoimmune disease.

These cells generally suppress or downregulate induction and proliferation of effector T cells. Additional regulatory T cells known as Treg17 cells have recently been identified.

• Regulatory T cells (Tregs) are recently described populations of cells that can regulate immune responses. They do not prevent initial T cell activation; rather, they inhibit a sustained response and prevent chronic and potentially damaging responses. They do not have characteristics of Th1, Th2 cells but they can suppress both Th1 and Th2 responses.

• a) Naturally occurring Tregs – The thymus gives rise to CD4+/CD25+/Foxp3+ cells that function as Tregs. These Tregs suppress immune responses in a cell contact-dependent manner but the mechanism of suppression has not been established.

• b) Induced Tregs – In the periphery some T cells are induced to become Tregs by antigen and either IL-10 or TGF-β. Tregs induced by IL-10 are CD4+/CD25+/Foxp3- and are referred to as Tr1 cells. These cells suppress immune responses by secretion of IL10. Tregs induced by TGF-β are CD4+/CD25+/Foxp3+ and are referred to as induced Tregs. These cells suppress by secretion of TGF-β.

c) CD8+ Tregs – Some CD8+ cells can also be induced by antigen and IL-10 to become a Treg cell. These cells are CD8+/Foxp3+ and they suppress by a cell contact-dependent mechanism or by secretion of cytokines. These cells

have been demonstrated in vitro but it is not known whether they exist in

vivo.

Genetic factors influencing immunoregulation

• Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility is associated with multiple genes plus other risk factors. Genetically predisposed individuals do not always develop autoimmune diseases.

Three main sets of genes are suspected in many autoimmune diseases. These genes are related to:

1 ) Immunoglobulins

2 ) T-cell receptors

3 ) The major histocompatibility complexes (MHC).

• The first two, which are involved in the recognition of antigens, are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocytes capable of self-reactivity

Also devided into :-

• a) MHC-linked genes help control response to infection. Certain HLA haplotypes are associated with individuals who are responders or nonresponder, those who are susceptible or resistant.

• b) Non-MHC genes are also involved in immunoregulation. An example is a gene related to macrophage activity encoding a transporter protein involved in transport of nitrite (NO2-) into the phagolysosome, natural resistance-associated macrophage protein-1 (Nramp1). Polymorphisms in this gene could change the activity of macrophages.

• c) Cytokine, chemokine, and their receptors are involved in immunoregulation . Polymorphisms in the genes encoding these, in particular the receptors, have been shown to correlate to susceptibility to infection or generation of autoimmune disease.