1. Pathophysiology of the immune-surveillance system
The State Education Institution of Higher Professional Training
The First Sechenov Moscow State Medical University
under Ministry of Health of the Russian Federation
 Department of Pathophysiology
Pathophysiology of the immune-surveillance system
Lecture presentation
Professor Pirozhkov S.V.
education year

2. Nonspecific defense reactions
GENERAL ORGANIZATION OF THE IMMUNE-SURVEILANCE SYSTEM
IMMUNE –SURVEILLANCE SYSTEM
FACTORS OF THE INNATE IMMUNITY
FACTORS OF THE ADAPTIVE IMMUNITY
Nonspecific defense reactions
Specific defense reactions (immune response)

3. ■ Immune deficiency states ■ Pathologic tolerance
TYPICAL FORMS OF DISORDER OF THE IMMUNE SURVEILLANCE SYSTEM
■ Immune deficiency states
■ Pathologic tolerance
■ Graft-versus-host disease
■ Allergies

4. Immune deficiency state is the result of a decrease of the immune response to various antigens or deficiency of factors of the innate immunity

5. CLASSIFICATION OF THE IMMUNE DEFICIENCY STATES
Based on the subset of the immune surveillance system that is mainly affected:
● T-system-dependent
● B-system-dependent
● A-system-dependent
● complement-dependent
● due to deficiency of innate immunity (e.g. neutropenia)
II. Based on the origin of disorder:
■ Primary (congenital)
■ Secondary (acquired)
III. Based on the mechanism of disorder:
► Hyporegenetory
► Disfunctional
► Destructive (cytolytic)

6. Manifestations of the immune deficiency states
► High frequency of infectious diseases
► Unusual severity of infection
► Prolonged duration of infection
► Infection with unusual complications

7. DiGeorge syndrome (thymic hypoplasia)
T-dependent immunodeficiency state
DiGeorge syndrome (thymic hypoplasia)
Cause: deletion in chromosome 22q11 (or 10p in some patients)
Mechanism: hypoplasia of the thymus and parathyroid gland
Manifestations: ● peripheral blood T-cell levels are reduced; B-cell levels - normal
● paracortical areas of the lymph nodes, periarteriolar sheaths of the spleen are depleted
● serum immunoglobulin concentrations are frequently normal, but Ab responses, particularly of IgG and IgA isotypes, are impaired
● hypocalcemic tetany
● facial abnormalities – abnormal ears, micrognathia (short maxilla), hypertelorism (e.g. increased distance between eyes)
● congenital cardiac defects

8. X-linked agammaglobulinemia of Bruton
B-dependent immunodeficiency state
X-linked agammaglobulinemia of Bruton
Cause: mutation of gene for cytoplasmic tyrosine kinase in the long arm of the X-chromosome
Mechanism: block of maturation of B lymphocytes at the pre-B stage
Manifestations: ● B-cells are absent or remarkably reduced
● in the circulation levels of all classes of Ig are depressed
● plasma cells are absent throughout the body
● precursors of B cells (CD19+, Ig-) are found in normal numbers in the bone marrow
● germinal centers of lymph nodes, Peyer’s patches, the appendix and tonsils are underdeveloped
● T-cell-mediated reactions are normal
● Recurrent bacterial infections of the respiratory tract, high susceptibility to enteroviruses and Giardia lamblia

9. Manifestations of the acute graft-versus-host disease
► Immune deficiency state
(cytomegalovirus pneumonitis particularly important)
► Generalized rash leading to desquamation
► Jaundice
► Mucosal ulceration of the gut (bloody diarrhea)

10. ALLERGY is a pathologic process characterized by a specific increase in reactivity (hypersensitivity) to repeatedly administered allergen and manifested by more or less pronounced damage to the tissues of the body

11. Exogenous Endogenous TYPES OF ALLERGENES Heterologous
(pollen, horse serum)
Homologous
(erythrocyte mass)
Autologous
(self-antigens)
Exogenous
Endogenous

12. TYPES OF ALLERGIES (P.Gell, R.Coombs, 1963)
TYPE I : the immune response releases vasoactive and spasmogenic substances that act on vessels and smooth muscle and proinflammatory cytokins that recruit inflammatory cells
TYPE II : humoral antibodies participate directly in injuring cells by predisposing them to phagocytosis or lysis.
TYPE III : immune complex diseases in which humoral antibodies bind antigen and activate complement; the fractions of complement then attract neutrophils, which produce tissue damage.
TYPE IV : sensitized T-lymphocytes are the cause of the cellular and tissue injury.

13. - present on the surface of cells or other tissue components
Type II allergy (cytotoxic)
Features of antigen:
- present on the surface of cells or other tissue components
- may be intrinsic to the cell membrane, or may take the form of an exogenous antigen
Features of reaction:
- results from the binding of antibodies to (IgG or IgM) to normal or altered cell-surface antigens

14. TYPE III ALLERGY (IMMUNE COMPLEX MEDIATED)
● Features of antigen
- exogenous: foreign protein, bacterium, virus
- endogenous: antigenic component in cells and tissues
● Features of reaction:
- it is initiated when Ag combines with Ab or at extravascular sites where Ag may have been deposited
- complexes formed in the circulation produce damage when they are localize within blood vessel walls or when they are trapped in filtering structures (renal glomerulus)

15. TYPE IV ALLERGY (T-CELL MEDIATED)
● Features of antigen
- intracellular microbiologic agents: Mycobacterium tuberculosum, viruses, fungi, protozoa, parasites
- chemical agents
- graft antigens
● Features of reaction:
- delayed-type hypersensitivity
- it is initiated by CD4 T-cells and involves the direct cell cytotoxicity mediated by CD8 T-cells