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Immunomodulation in
Homotoxicology
Juan Carlos Herrera Correa, MD
Immunological tolerance
Hyporeactivity or nonreactivity of the immune
system to an antigen,
induced by previous contact
with this antigen
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
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IL 10
β-TGF
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MALT
MALT
NALT
LALT
BALT
GALT
SALT
Czerkinsky, Cecil; Anjuere, Fabienne; McGhee, Jerry R.; George-Chandy, Annie; Holmgren, Jan; Kieny,
Marie-Paule; Fujiyashi, Kohtaro; Mestecky, Jiri F.; Pierrefite-Carle, Valérie; Rask, Carola; Sun, Jia-Bin.
Mucosal immunity and tolerance: relevance to vaccine development. Immunological Reviews. Volume
170 August 1999 pp 197-222.
Mucosa-Associated Lymphoid Tissues
Brandtzaeg, P. Homing of mucosal immune cells-a possible connection between intestinal and articular
inflammation. Alimentary pharmacology & Therapeutics, Supplement. Volume 11 Supplement 3
December 1997 pp 24-39.
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Patients who are allergic to cow’s milk
show increased intestinal permeability.
Van Elburg RM, Heymans HS, De Monchy JG. Effect
of disodium cromoglycate on intestinal permeability
changes and clinical response during cow’s milk
challenge. Pediatr Allergy Immunol 1993; 4:79–85.
Schrander JJ, Unsalan-Hooyen RW, Forget PP, et al.
[51Cr] EDTA intestinal permeability in children with
cow’s milk intolerance. J Pediatr Gastroenterol Nutr
1990; 10:189–92.
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Immunological tolerance and
intestinal mucosa
Barrier mechanism:
secretion of mucus
Intestinal flora
Mucosal integrity
IgA
MALT regulation mechanisms
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Antigen presentation
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Antigen presentation
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Antigen
APC
M. Rosales Sdme de
Inflamación de las
Mucosas. 2nd edition
CD8
MHC
PROCESSED
ANTIGEN
TCR
Th0
Th1
Macrophage
Th2
IL-10
Th3
TGF-B
IL-10
IL2, IFN-G, TNF-A
IL4, IL5, IL6 IL9, IL10, IL13
Cell-mediated
immunity
IGM,
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
B
B
IgE, IgG
IGA
Th1
How does the body react to the
entry of an antigen?
1. Production of antibodies
2. Anergy or apoptosis
3. Immunological tolerance
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Normal response in CD 4 +
T lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Types of response
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Immunological tolerance
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Schmidt-Weber, C. B.; Blaser, K. T-cell tolerance in allergic response. Allergy: European
Journal of Allergy and Clinical Immunology. Volume 57(9) September 2002 pp 762–768
Swiss Institute for Allergy and Asthma Research, Switzerland
Tolerance mechanisms
1. Insufficient co-stimulation
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Without co-adjuvants
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Tolerance mechanisms
1. Insufficient co-stimulation
2. Abundant soluble antigen
without adjuvants
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Tolerance mechanisms
1. Insufficient co-stimulation
2. Abundant soluble antigen
without adjuvants
3. CTLA4 receptors
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
“Cytolytic T lymphocytes”
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Tolerance mechanisms
1. Insufficient co-stimulation
2. Abundant soluble antigen
without adjuvants
3. CTLA4 receptors
4. Slight mutation of antigen
structure
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Tolerance mechanisms
1. Insufficient co-stimulation
2. Abundant soluble antigen
without adjuvants
3. CTLA4 receptors
4. Slight mutation of antigen
structure
5. APC-mediated suppression
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IL 10
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Tolerance mechanisms
1. Insufficient co-stimulation
2. Abundant soluble antigen without
adjuvants
3. CTLA4 receptors
4. Slight mutation of antigen structure
5. APC-mediated suppression
6. Bystander suppression
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Bystander suppression
Immunological bystander reaction
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Immunological bystander
reaction
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Immunological
bystander reaction
(IBR)
Special kind of
“low dose antigen reaction”
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Entry
Oral
Mucosa-associated
lymphoid tissue MALT
Other
routes
Immunological cells of
the matrix
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
The potentized
proteins of the
medicines are
immunologically
challenged by
antigen presenting
cells
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Antigen presenting cells
APC
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Phagocytosis
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
D1-D14
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Processing in proteasomes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Digestion by lysosomes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Short sequences of amino acids
(9-15)
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Coupling to MHC class II
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Transport via vacuoles
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
To the cell membrane
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Anchorage in glycocalyx
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Expression of epitopes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Patrolling lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
CD4 T lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
APC-lymphocyte complex
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Epitope – Paratope
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
B7 – CD28
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
As many epitopes as there are
compounds
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
D3
D8
D5
D5
D12
As many epitopes as there are compounds
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Cytokine activating co-stimulants
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
IL2
Activated T lymphocyte
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Regulatory lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
TH3 lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Homing
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Cloning of TH3 lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Cloning of TH3 lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Cloning of TH3 lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Cloning of TH3 lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Cloning of TH3 lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Bloodstream and lymph system
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Chemotaxis
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Entry into tissues
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Antigenic similarity
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Antigenic similarity
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
TGF-β
Antigenic similarity
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
IL4
Antigenic similarity
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
IL4
IL10
Antigenic similarity
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Modulation of proinflammatory
lymphocytes
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
TGF-β
IL10
IL4
Differentiation to IgA producing cells
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IBR
Inhibits the
activation of
macrophages
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
IL10
Antigen
APC
MHC
PROCESSED
ANTIGEN
TCR
Th0
Th1
IFN-G
IL2, IFN-G, TNF-A
Th2
Thr
TGF-B
IL4, IL5, IL6 IL9, IL10, IL
IL1313
IL4
Cell-mediated
immunity
IGM,
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
B
B
IgE, IgG
IGA
Macrophages
Monocytes
M cells
Epitopes
TH3
LT
TGFB
TH2
TH1
T4
IL4 IL10
Cytokines
IL4 - IL 10 - TGFb
Fibrogenesis
SERPINs
Inhibitors of
metalloproteinases of
the extracellular
matrix
Dr. Juan Carlos Herrera Correa_Immunomodulation_Speakers' Training 2006
Fibrolysis
TNFa - IFNg – IL1
SERPS
Metalloproteinases
of the extracellular
matrix