Download Слайд 1 - sechenov.ru

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.
2014-2015 education year
GENERAL ORGANIZATION OF THE IMMUNE-SURVEILANCE SYSTEM
IMMUNE –SURVEILLANCE SYSTEM
FACTORS OF THE INNATE
IMMUNITY
Nonspecific defense
reactions
FACTORS OF THE ADAPTIVE
IMMUNITY
Specific defense
reactions (immune
response)
TYPICAL FORMS OF DISORDER OF THE
IMMUNE SURVEILLANCE SYSTEM
■ Immune deficiency states
■ Pathologic tolerance
■ Graft-versus-host disease
■ Allergies
Immune deficiency state
is the result of a decrease of
the immune response to
various antigens or
deficiency of factors of the
innate immunity
CLASSIFICATION OF THE IMMUNE DEFICIENCY STATES
I. 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)
Manifestations of the immune
deficiency states
► High frequency of infectious diseases
► Unusual severity of infection
► Prolonged duration of infection
► Infection with unusual complications
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
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
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)
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
TYPES OF ALLERGENES
Heterologous
(pollen, horse serum)
Homologous
(erythrocyte mass)
Autologous
(self-antigens)
Exogenous
Endogenous
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.
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
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)
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