The above changes represent, in a schematic manner, what happens when a noxious agent acts directly or indirectly upon blood. The same basic patterns of defense, the substances used and the processes involved can be found at various hierarchic levels. It is easy to see that, with such a complex mechanism occurring in different individuals and against a great variety of antigens, great variations in manifestations will be evidenced.

Table XI. The Immunological Defense Mechanism

Defense Stages

Character

Intervening Factor Present

Nature Of the Processes

Means Used

Moment Of Appearance

Resulting Condition

Effect Of Immune Serum

Primary Immediate

Non Specific

Antigen

Hydrolytic

Hydrolytic Enzymes

Immediate

Shock

Curative

Primary Prolonged

Lipidic Defense

Antigen (probably in lipidic frac.)

Lipidic liberation

Lipids

From minutes to days

Toxic

Curative

Allergic Immediate

Allergic Specific

Allergic complex antigen antibody

Allergic bond followed by diphasic phenomena

Lipoproteinic antibodies followed by hydrolytic enzymes

Around 6th day

Allergic Shock

Not curative but preventive

Allergic Prolonged

Allergic lipidic defense

Allergic complex

Allergic bond followed by lipidic liberation

Lipoproteinic antibodies followed by new lipidic bonds

After the 6th day

Allergic Toxic

Not curative but preventive

Immune

Healing & Protective Specific

Neutral complex antigen antibody

Neutralizing bond

Proteinic antibodies

Around 15th day and later

Healing

When an antigen enters the organism and is not fully neutralized by the intervention of immune antibodies, the mechanism of defense is set in motion. This can be limited to a group of entities, to one level, or can affect more levels and entities. According to the nature of the antigen and the capacity of the different entities to respond, the different process will proceed all the way to the stage of protective immunity or it can stop at any stage. These factors, nature of the antigen, levels and entities involved and degree of response for each of them, determine the pathogenic characteristics of the resulting condition. The manifestations for a stage and a group of entities can be so exclusive as to produce a characteristic clinical disease. The ability to respond through only a part of the defense mechanism depends on the nature of the antigen and on the conditions existing in the different entities affected. The clinical manifestations furnish important information concerning the defense processes which are occurring.

Clinical Manifestations

The first stage of the defense reaction, if highly intensive, can be manifested clinically as superacute shock. This occurs minutes after the intervention of the noxious factor. If the second phase of the diphasic phenomenon is intensive, a chill with high temperature will appear. A state of shock occurs if fatty acids remain predominant, as in the prolonged first phase. A feverish condition corresponds to a predominant anti fatty acid intervention in the prolonged second phase. While the first phase of the condition appears immediately after the intervention of the antigen, the appearance and persistence of the second phase, which corresponds to the prolonged lipidic, depends upon the nature and especially the amount of antigen present in the organism. Incubation time may vary from minutes to several days. This relatively short and variable incubation time represents an important characteristic which enables us to recognize this stage. Another characteristic of this stage is the disappearance of symptoms after administration of neutralizing immune antibodies specific for the antigen.

If the antigen by itself has no toxic effects upon the organism, its presence will not induce important manifestations. The direct response, enzymatic or prolonged lipidic, will be so limited as to have either minimal clinical manifestations or none at all.

We have seen that allergic coagulant antibodies usually appear after the 6th day following penetration of the antigen into the organism. If the antigen is still present, the appearance of the antibodies will induce an allergic condition. In cases where the antigen already has produced toxic manifestations, the appearance of the allergic stage will be marked either by new symptoms or increased intensity of existing ones. With a nontoxic antigen, the presence of which was not revealed previously by any clinical manifestations, the appearance of the allergic complex will coincide with the appearance of symptoms and, thus, with the appearance of the clinical condition. The period before the appearance of symptoms corresponds to the time before the appearance of these allergic antibodies. This incubation time, as for all allergic manifestations, will be 6 or more days, which corresponds to the time necessary for the appearance of the coagulant antibodies. An obligatory incubation time of 6 days or greater thus is an indication that the process has an allergic pathogenesis.

If the organism has previously manufactured similar coagulant antibodies against the same antigen, this incubation period could be shortened to 5 or even 4 days. Against certain antigens, some organisms need a longer time to produce coagulant antibodies and the incubation time may run as long as several weeks.