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1. INTRODUCTION,
PRINCIPLES, CELLS…,
molecular and cellular principles
IMMUNE SYSTEM MUST
RECOGNIZE:
__________________________________________________
 SELF VS. FOREIGN
resp.
 „CORRECT VS. INCORRECT“
resp.
 HARMLESS VS. DANGEROUS
 IT SHOULD NOT DAMAGE THE ORGANISM (BUT
TOO OFTEN DAMAGES – „DOUBLE EDGED
SWORD“
PROBLEM:
WHAT IS „SELF“
WHAT IS „FOREIGN“
IMMUNE SYSTEM RECOGNIZES:
“SOME SELF COMPONENTS FROM SOME FOREIGN“
IMMUNE MECHANISMS
- “NONSPECIFIC” (PHAGOCYTOSIS, COMPLEMENT
LECTINS, INTERFERONS...)
- ANTIGEN-SPECIFIC
ANTIGEN SPECIFIC MECHANISMS
- HUMORAL (ANTIBODY)
- CELL-MEDIATED
BASIC TERMS
ANTIGEN
INFLAMMATION
IMMUZIZATION (PASSIVE, ACTIVE)
IMMUNODEFICIENCY
TOLERANCE
ALERGIES
MEMORY
AUTOIMMUNITY
ANTIBODIES
MHC PROTEINS
CYTOKINES
Cell type
Relative representation
(%)
Neutrophil granulocytes
60 - 70
Eosinophil granulocytes
1-3
Basophil granulocytes
<2
Monocytes
5 - 10
Lymphocytes
20 - 40
LYMPHOID TISSUES AND ORGANS

BONE MARROW – DEVELOPMENT FROM STEM CELLS

THYMUS – DEVELOPMENT OF T-LYMPHOCYTES

DIFFUSE LYMPHOID TISSUE – UNDER EPITELIAL SURFACE

LYMPHOID FOLLICLES

ORGANIZED AGGREGATES OF FOLLICLES:
- TONSILS
- PEYER PLAQUES
- APPENDIX

LYMPH NODES

SPLEEN
2. ANTIGEN NONSPECIFIC
MECHANISMS;
PHAGOCYTES, GRANULOCYTES
PHAGOCYTOSIS

NEUTROPHIL GRANULOCYTES REMOVAL OF BACTERIA; PUS

MACROPHAGES – MAINLY REMOVAL OF DAMAGED AND DYING
CELLS
MECHANISMS:

RECEPTORS OF “FOREIGN“ STRUCTURES (TLR, LECTINS)

OPSONIZATION (Ig, COMPLEMENT) – BINDING TO
Fc-RECEPTORS, COMPLEMENT RECEPTORS

ENGULFMENT

“KILLING”
- FUSION WITH LYSOSOMES (LOW pH, ENZYMES,
DEFENSINS)
- OXIDATIVE BURST
PHAGOCYTOSIS
TOLL-LIKE RECEPTORS
OXIDATIVE (RESPIRATORY) BURST
 Prodution of reactive oxygen compounds by the enzyme NADPH-oxidase
 Localized in the phagosome membrane and catalyses the reactions:
(surface)
O2 → O2- (superoxide anion-radical)
_________________________________________
(cytoplasm) NADPH → NADP+ + H+
 Superoxide reacts further to produce toxic compounds (“singlet oxygen“, H2O2,
ClO-)
3. COMPLEMENT
COMPLEMENT
A SYSTEM OF ~ 30 SERUM AND MEMBRANE PROTEINS
A PART OF „NONSPECIFIC“ MECHANISMS:
ALTERNATIVE PATHWAY OF ACTIVATION
A PART OF ANTIGEN-SPECIFIC (ANTIBODY-BASED) EFFECTOR
MECHANISMS:
„CLASSICAL“ PATHWAY OF ACTIVATION
BASIC SERUM COMPONENTS
C1 (q, r, s)
C5
C2
C6
C3
C7
C4
C8
Factor B
C9
Factor D
C1 – C4, B, D - specific proteases cleaving further components of
the complement cascade
PROTECTION OF SELF CELLS FROM
COMPLEMENT
Membrane proteins interfering with the complement cascade on
different levels:
- BREAKDOWN OF C3-CONVERTASE
- CLEAVAGE OF C3b
- BLOCKING OF C9 POLYMERIZATION (CD59)
ABSENCE OF CD59 – SPONTANEOUS ERYTHROCYTE LYSIS,
HEMOGLOBINURIA (PNH)
4. INFLAMMATION
INFLAMMATION
A set of physiological reactions to damage
of tissue integrity, leading to protection
against infection, localization and
restriction of the damaged site and finally
to healing.
MANIFESTATIONS OF
LOCAL INFLAMMATION
reddening (rubor)
swelling (tumor),
pain (dolor)
increased local temperature (calor)
acute, chronic (pathologic)
Characteristics of local inflammation
Signals - degranulated tissue mast cells and phagocytes,
molecules liberated from damaged cells
 increased blood vessel permeability
 increased endothelial adhesivity, trapping of phagocytes,
lymphocytes, penetration into tissues
 activation of coagulation, fibrinolytic and complement
systems
 effects on nerve endings (pain)
 temperature regulation changes (mediators - pyrogens)
SYSTEMIC RESPONSE TO INFLAMMATION
fever (stimulation of hypothalamic thermoregulation center by
inflammatory cytokines - TNF, IL-1 a IFN-)
 septic shock
 anaphylactic shock
 expression of heat shock proteins
 production of serum acute phase proteins (CRP, SAP, C3 a C4 opsonins).
 leukocytosis
REPARATION OF THE
DAMAGED TISSUE
 Elimination of damaged cells by phagocytes
(macrophages)
 activation of fibroplastic mechanisms
 activation of angiogenesis
 regeneration and remodeling of tissues