Immune Response and Adaptation Characteristics of Complement System to Aerobic Exercise

I. Introduction

Complement (C) is a group of globulin normally present in serum, which is related to immunity and has enzyme-like activity. In the 1960s, with the success of the separation and extraction of complement components, it was proved that complement is a plasma protein containing multiple components, so it is also called the complement system. This includes components involved in complement activation, as well as inhibitors that regulate various inactivation factors of the complement system.

The complement system plays a very important role in the body's immune response and immune adaptation. As one of the factors of non-specific immunity, it plays an important role in non-specific immunity. At the same time, it also plays an important role in specific immunity through immune conditioning, immune adhesion, virus neutralization, bacteriolysis and sterilization.

At present, there are few studies on exercise and complement at home and abroad. This may be related to the fact that it is recognized that the complement content is relatively stable in the blood, has nothing to do with antigen stimulation, and does not increase and increase body-specific immune establishment and enhancement. Therefore, this experiment aims to observe the response and adaptation of complement to aerobic exercise. The complement system is composed of more than 20 components. We selected the most important components, C3 and C4, which have the most prominent biological effects, play a key role in the two activation pathways of complement, and have the highest content in serum as the representative indicators of the complement system.

2. Experimental design and methods

1. Participants There were 16 second-year girls from the School of Economics and Management of Northwest University. The average age is 21.2 ± 0.9yr, the average height is 163.4 ± 3.2cm, and the average weight is 54.5 ± 4.8kg.

2. Experimental instruments and materials

(1) Quinton5500 type running platform (USA);

(2) Monark829E power bike (Sweden);

(3) CH-B14S-T biological microscope (Japan);

(4) LXJ-â…¡ type centrifugal sedimentation machine (Shanghai Medical Analysis Instrument Factory);

(5) C3 immunodiffusion plate (Beijing Kehai Medical Testing Reagent Company);

(6) C4 immunodiffusion plate (Beijing Kehai Medical Testing Reagent Company).

3. Test indicators and test methods

(1) Test indicators C3 and C4;

(2) The test method uses the one-way immunodiffusion method.

4. Experimental design

(1) Responsive response: Before the start of aerobic exercise for 8 weeks (zero week), the first exercise test (9Km * h-1, slope 0, 15min) was performed on the active treadmill. Venous blood samples were taken before exercise, immediately after exercise and 1 hour after recovery. The sera were separated by centrifugal precipitation, and C3 and C4 were determined using immunosingle diffusion method.

(2) Adaptability changes: Subjects performed aerobic exercise for 30 minutes on a power bike (90W, 60RPM, 15min) and an active treadmill (9Km · h-1, slope 0, 15min) Exercise for 8 weeks. Exercise tests were conducted on the weekend mornings of WK1, WK2, WK4, WK6 and WK8 respectively (loading methods and blood collection were the same as the first exercise test).

5. Data statistical processing Routine processing of the test data, with P <0.05 as the significance level of the difference.

3. Results

1. C3's responsive response and adaptability to aerobic exercise (Table 1)

It can be seen from Table 1 that the basic characteristics of C3's response to the initial load are: there is a certain increase after exercise, and it falls back after 1 hour of recovery. However, there was no significant difference between the value immediately after exercise and the quiet value (P> 0.05). After 1 hour of recovery, it rose instead, showing an overreaction. As aerobic exercise progresses, the overall response to exercise load is characterized by an increase after exercise, but the amplitude becomes smaller and the recovery is faster. The general rule of C3's adaptive process for aerobic exercise (Figure 1) is: Week 2 Compared with the zero week, the quiet value showed a significant downward trend (P <0.05), and there was no significant difference between the fourth week and the second week. By the 6th week, there was a transient rebound, and at the 8th week, there was a clear downward trend, which was significantly different from the 6th week value (P <0.05).

Fig.1 Time course of C3 adaptation to aerobic exercise (fig. 1 Time course of C3 adaptation to aerobic exercise)

Table 1 Changes in C3 during aerobic exercise (n = 16, unit: g / l) (table 1 C3 changes during aerobic exercise (g / l))

WK0WK1WK2WK4WK6WK8

BL0.99 ± 0.181.09 ± 0.430.78 ± 0.150.82 ± 0.160.99 ± 0.260.75 ± 0.16

JAL1.13 ± 0.371.01 ± 0.240.94 ± 0.291.03 ± 0.351.06 ± 0.280.83 ± 0.18

R1h1.04 ± 0.241.15 ± 0.450.84 ± 0.160.93 ± 0.230.93 ± 0.160.80 ± 0.21

Table 2 Changes of C4 during aerobic exercise (n = 16, unit: g / l) (table 2 C4 changes during aerobic exercise (g / l))

WK0WK1WK2WK4WK6WK8

BL0.46 ± 0.100.44 ± 0.190.36 ± 0.110.34 ± 0.090.42 ± 0.130.30 ± 0.07

JAL0.50 ± 0.210.45 ± 0.180.43 ± 0.150.39 ± 0.120.41 ± 0.170.35 ± 0.10

R1h0.43 ± 0.210.41 ± 0.150.37 ± 0.140.39 ± 0.100.42 ± 0.190.37 ± 0.14

2. Responsiveness and adaptability of C4 to aerobic exercise (Table 2)

Fig. 2 Time course of C4 adaptation to aerobic exercise (fig. 2 Time course of C4 adaptation to aerobic exercise)

It can be seen from Table 2 that the basic characteristics of C4's response to the initial load are: a slight increase after exercise but no significant difference. Recover in 1 hour. In the subsequent weeks of training, the basic response of C4 to each test was the same, indicating that C4 was less affected by the one-time load. However, it can be clearly seen from the adaptive changes that although C4 is less affected by exercise load, it shows a specific change as aerobic exercise progresses (Figure 2). In the first 4 weeks, as the training progressed, it showed a progressive decreasing trend. Compared with the quiet value, there was a significant difference at the second week, with a drop of 22% (P <0.05). By the 4th week, it dropped to the lowest point, which was significantly different from the quiet value before exercise (P <0.05, a decrease of as much as 26%). By week 6, it rebounded obviously, but then fell sharply again at week 8, showing only a transient increase. Compared with before the experiment, it showed a very significant difference (P <0.01), and the decrease was as high as about 35%.

4. Discussion and analysis

1. The possible mechanism of C3 and C4 reduction during exercise adaptation

Various immunology textbooks and monographs [1,2,3,4], when describing the physical and chemical characteristics of the complement system, think that complement has nothing to do with antigen stimulation, and has the ability to self-regulate and maintain content, so it is recognized as an immune response. The most stable immune substance. However, this experiment noticed a very significant phenomenon, that is, the changes of C3 and C4 in response to the stress of one-time exercise basically conformed to the above characteristics, but they showed a gradual downward trend during the aerobic exercise process and were quieter than before the exercise The values ​​are significantly different. The following will try to analyze its possible mechanism.

(1) The excessive consumption of complement components due to excessive activation of the complement system: under pathological conditions, there are three reasons for the decrease of complement content: the excessive consumption of complement components (such as serum disease, glomerulonephritis, etc.) Mass loss (such as trauma, blood loss, surgery, etc.) and insufficient complement synthesis (cirrhosis, severe hepatitis, etc.). Since the subjects in this experiment are all healthy young students, the decrease in complement caused by the above diseases can be ruled out. Therefore, the possible reasons are: 30 minutes of aerobic exercise every day (equivalent to running 4500 meters in 30 minutes every day) and two consecutive months. The damage and repair of muscle cells caused by exercise, the regeneration of the internal environment, etc. The immune system puts forward higher requirements. In this case, the body will inevitably mobilize the host defense with higher immune function. As an important part of the body's immune response, the complement system must also be highly activated. Because of the daily exercise, and the continuous activation of the complement system, it will inevitably consume a lot of complement components, and it will cause the body's immunity to decrease. Under normal circumstances, the excessive activation of complement and its adverse consequences can be avoided through the mechanism of complement regulation. However, due to the long daily exercise, and because the body must undergo a warning reaction period (including the shock phase and the anti-shock phase) during exercise stress, it causes a larger reaction of the body. In this case, continuing to exercise continuously will increase the burden on the complement system, so that the consumed complement components cannot be effectively supplemented, resulting in a decrease in complement content.

(2) The regulatory effects of antibodies and complement regulatory factors: There are a variety of soluble and membrane-bound complement regulatory factors in the body, which interact with different complement components in a specific manner to regulate the activation and inhibition of complement. Among the more important are C1 inhibitors, C4 binding proteins (accelerating the decay of C4b2b, assisting factor I-mediated C4b cleavage), factor H (accelerating C3bBb decay, assisting factor I-mediated C3b cleavage), factor I (cleaving C3 And inactivation of C3b, C4b), CR1 (acceleration of C3 convertase dissociation), membrane cofactor protein (auxiliary factor I mediated degradation of C3b, C4b), decay factor (acceleration of C3 convertase degradation), etc. These complement regulatory proteins can inhibit the activation of complement in the liquid phase and regulate the work of complement on substrates. Therefore, the reduction of complement components in aerobic exercise is directly related to its regulatory role. Second, activation of the complement system is mainly triggered by antigen-antibody complexes. In our simultaneous antibody (IgG, IgM, IGA) test, the change pattern has a significant correlation with the change trend of complement (C3, C4 and IgGr = 0.6683; 0.6439; IgM r = 0.5805; 0.6296; and IgA r = 0.7569; 0.9302). This indicates that changes in complement levels are directly related to changes in antibodies.

(3) Changes in physical and chemical factors in the internal environment during exercise: there are classical activation pathways and alternative activation pathways in the complement system. Once the complement is activated, the activated cleavage products will produce enzyme-like effects, which in turn activate the next complement, that is, gradually transition from the recognition stage (C1q, C1r and C1s) to the effect stage (C2, C3, C4, C5) and membrane Attack phase (C6-C9). However, due to the large amount of O2 and energy substances consumed during exercise, a large amount of metabolites (CO2, lactic acid, ketone bodies, amino groups, uremic, etc.) are produced, a lot of water is lost, minerals (K +, Na +, Ca2 +, etc.) and vitamins, and the pH drops , Resulting in large changes in the internal environment, that is, the cell's living environment. Changes in these physical and chemical factors may accelerate the activation of the complement system, resulting in a relatively large amount of complement consumption and insufficient synthesis, resulting in a relatively low complement. In addition, due to blood flow redistribution during exercise, the relative reduction of spleen blood flow, renal blood flow, and liver blood flow may also be related to the reduction of complement.

2. The possible mechanism of transient increase of complement during exercise adaptation

It can be seen from Figures 1 and 2 that no matter whether C3 or C4, a transient rebound phenomenon occurs in the sixth week, that is, the lower level suddenly rises to about the normal value in the fourth week, and this transient rebound and immunity The changes of globulin are very similar. After a transient rebound, it often plunges to a low level below the previous week. We believe that this is due to the transient regulation of the body to maintain a functional balance. During exercise, with the gradual decline of complement (and Ig, etc.), the body's immunity also decreases (this can be seen from the increased susceptibility to disease). However, when continuing to exercise, the body must make the necessary adjustments to maintain its balance and safety, including fully mobilizing the regulation of the nerve-endocrine-immune network to try to correct this imbalance. With this effort, there will be positive changes. However, because the original exercise process continues, the internal environmental factors that affect the immune function have not been fundamentally improved. Therefore, even if all the adjustment power is mobilized, it can only maintain short-term balance and cannot maintain it for a long time. Once the body is unable to maintain a highly strengthened adjustment system (causing a new imbalance), the downward trend of complementation will intensify and may fall to the lowest point. In addition, the decline of complement is related to the shock of the body in the process of stress. As the exercise continues, the body's regulatory mechanism and complement activation mechanism gradually adapt to the exercise, and as the body's function increases, the body's response decreases, and it will gradually enter the anti-shock phase until the resistance period (adaptation period), and the immune function gradually recovers.

In the body's immune response, there is a close relationship between complement and antibody. In the experiment, we found that the decrease in complement is synchronized with the decrease in antibody, and both have a transient recovery phenomenon at week 6. What is the relationship between the two phenomena? , Need to be further explored.

V. Conclusion

1. The basic characteristics of C3 and C4 responsive responses are: increased after exercise and reduced recovery period, but the amplitude is not obvious, that is, the complement content is not greatly affected by one-time exercise load.

2. The basic characteristics of the adaptive changes of C3 and C4 are: With the aerobic exercise, the content gradually decreases, and it drops to the lowest value in the second and fourth weeks. There was a transient recovery in the sixth week, but then it fell to a lower level.

3. The possible mechanisms of complement reduction include: excessive activation of the complement system due to continuous exercise, which leads to a large consumption of complement components; the regulatory effect of antibodies and complement regulators; and physical and chemical factors that may cause changes in the body's environment and changes in the body Influencing the rate of complement activation, accelerating complement consumption, affecting complement synthesis, etc.

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