This document discusses immunoregulation and the various mechanisms that regulate immune responses. It describes how regulatory mechanisms act at all phases of the immune response, including recognition, activation, and effector function. Cytokines and regulatory T cells are highlighted as key regulators that can either stimulate or inhibit immune responses. The role of genetic factors in influencing immunoregulation is also summarized, noting genes related to immunoglobulins, T-cell receptors, and MHC complexes.

1. Immunoregulation
done by :-
Karrar abdo al kareem
Ayman hameed
Abdo al salam

3. Teaching objectives
• To discuss regulation of immune responses
including regulation by antibody, Tregs, and
cytokines
• To discuss some genetic factors influencing
immunoregulation

4. 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

5. • 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 .

6. 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.

7. APC

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

9. • 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. 10
Th1
+IL-1,2 +IL-4
IL-2
IFN-g
IL-4
IL-10
inhibit
Cell mediated
immunity
Humoral
immunity
Th0
Th2
Interaction of Th1 and Th2

11. The immune response from this point
follows two paths :-

12. 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

14. • 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. 16
Th1
+IL-12 +IL-4
IL-2
IFN-g
IL-4
IL-10
inhibit
Cell mediated
immunity
Humoral
immunity
Th0
Th2
Interaction of Th1 and Th2

17. 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

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

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

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

23. • 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.

25. 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.

26. 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

27. 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.

28. • 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.

29. • 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.

30. 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.

31. 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.

32. 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

33. 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.

34. • 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.