Pathophysiology_FULL
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The main effects of IL-6
Responsible for end-staged differentiation of T- and B-lymphocytes,
Possesses by strong antiviral properties via expression of MHC class I on the surface of cells invaded by the viruses; the last makes them more recognizable by the immune system
Strong mitogen for actively proliferating cells, including the granulocytes and monocytes
Strong mitogen for the tumor cells, and for this reason it is found in a large quantity in some growing malignant tumors, for example, plasmacytoma, osteosarcoma, glioblastoma, and carcinoma of the bladder
Early marker of disease severity, because its level in the blood increases too early, in 4-6 hours after start of a disease
Aggravates inflammation of the bones due to osteoclasts activation and destruction of bones, but its major effect is the acute phase response proteins synthesis in the liver
(80% of IL-6 receptors are in the liver), moreover, the complex of IL-6 with its receptor enhances its possibility to amplificate the effect of IL-6 on the target cells
Acute phase response and hemostasis
Increased coagulability of the blood and thrombogeinc properties of the blood vessels wall are very characteristic of an acute phase response. Last may result in thrombi formation in the small and large vessels. may complicate severe form of an APR. Such activation of hemostasis can be explained by the next events:
Under IL-1 ,TNF-alpha thromboxane A-2, and PAF synthesis become increased, however, these substances not only increase a vessels permeability which influence viscosity of the blood, but can aggregate the platelets, predisposing to slowdown of the blood flow and, finally, to stasis and thrombi formation
At the same time, IL-1 and TNF increase not only procoagulant activity of plasma, but provoke synthesis of procoagulants by the endotheliocytes
Eventually, IL-6 stimulates fibrinogen synthesis by the liver
11.The proteins of an acute phase response and their role in this condition.
Synthesis of these proteins, conducting by IL-6 in the liver is cortisol-dependent process. Acute phase response, accompanying by CNS activation, evokes increase the ACTH production by pituitary gland and, in turn, cortisol secretion by the adrenal cortex
Active fractions of complement system play role of pro-inflammatory mediators. Mostly, these proteins are the positive reactants of an acute phase response, but transferrin and albumens are the negative reactants, that means decreasing in their concentration in the blood during an acute phase response. Drop of transferring during APR may lead to iron-deficiency anemia, that isn’t rare in the patient with severe disease, moreover, sometimes, together with significant loss of weight it may be the first manifestation of the disease.
12. Fever as a basic sign of an acute phase response. Classification, causes and clinical description of three steps of fever. The mechanism of elevation of body temperature. Positive and negative features of fever.
Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response.
The hypothalamic thermoregulatory center accomplishes heat production by inducing shivering and heat conservation through vasoconstriction. At an established degree, fever is regulated
(even at a temperature of over 41.0 °C) and heat production approximates loss, as in health, though at a higher level of the set point. Therefore, fever does not climb up relentlessly.
In addition to the function as an endogenous pyrogen, IL-1 activates T-lymphocytes to produce various factors, such as INF and IL-2, which are vital for immune response. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever.
The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the host’s survival during infection.
Fever has a double meaning, positive and negative. Positive sites may be explained by bacteriostatic influences due to an activation of blood circulation, metabolism, and increasing in desintoxication function of the liver and kidneys. Negative ones, in form of the cramps in little children and heat shock; serious disturbances in cardiovascular system in old people
13. Primary immunodeficiencies. Classification and clinical variants. Bruton’s type of agammaglobulinemia and Di George syndrome. Immunopathogenesis and clinical symptoms.
14. Acquired immunodeficiency syndrome (AIDS). The causes, clinical stages and the symptoms. Pathogenesis and the most important causes of the death.
15. Classification of hypersensitivity reactions. Role of the mast cells and basophils in type I of hypersensitivity reactions.
The role of mast cells and basophils: Pathochemical stage of type I hypersensitivity
When antigen (allergen) interacts with the IgE-antibodies, attached previously to the mast cells membrane, multivalent antigen binds to more than one IgE molecule and cause cross-linkage of adjacent IgE antibodies. The bridging of IgE molecules with antigen-antibody formation activates the multiple phospholipases, imbedded in cell membrane and initiates some independent processes in the mast cells:
1.Degranulation with release of preformed mediators
2.Synthesizing of the mediators “de novo”
3.Synthesizing and release some cytokines
16. Classification of hypersensitivity reactions. Atopic disorders. The clinical examples and
common pathways of pathogenesis.
17. The clinical examples and common pathogenesis of hypersensitivity type II.
These reactions are named cytopenic or cytotoxic due to the cell population death or injury. Very often its type of immunopathology is accompanied by whole organ injury which is manifested by its hypofunction or hyperfunction. Nowadays, as an example of organ hyperfunction is only the Graves disease may be called. All reactions of type II hypersensitivity named disregulatory, because in both cases, hypo-or hyperfunction the disturbances in organ arrangement are observed.