The immune system
The immune system is a physiological function of the human body that recognizes “self” and “non-self” components and destroys and rejects antigenic substances that enter the body, or damage cells and tumor cells produced by the body itself, in order to maintain the health of the body. It is a state of resistance or prevention of infection by microorganisms, parasites or other “non-self” organisms.
The skin and mucous membranes are the first line of defense of the human immune system, and under normal conditions, the main functions of the immune system are as follows.
I. Immune defense
Under normal conditions, it can defend or destroy pathogenic microorganisms and their toxic products or other foreign substances, in order to protect the body from infection. Under abnormal conditions, if the defense response is too low (or defective), the body is prone to recurrent infections or immunodeficiency disease; conversely, when the function is too hyperactive and the defense response is too strong, it can cause hypersensitivity reactions.
Second, immune self-stabilization
Human tissue cells are constantly metabolizing, and a large number of new cells are available at any time to replace aging and damaged cells. Under normal circumstances, the immune system can identify and remove damaged, aging or dead cells or antigen-antibody complexes from the body in a timely manner, but does not respond to its own tissue components, and is in a state of immune tolerance, thus maintaining the stability of the human body. If this function is dysfunctional, autoimmune diseases can occur.
III. Immune surveillance
The immune system has the function of identifying, killing and removing mutated cells and abnormal harmful cells in the body in time to prevent the occurrence of tumors, which is called immune surveillance. Immunosurveillance is one of the most basic functions of the immune system. If this function is reduced or dysregulated, tumor or persistent infection may occur.
Immune regulation
It is a neuro-endocrine-immune network regulation system composed of immune system, nervous system and endocrine system of the body. It not only regulates the overall function of the body, but also regulates the function of the immune system itself.
Vaccination stimulates the body with antigens to produce antibodies and improve the body’s ability to defend itself. It removes mutated or aberrant cells, removes tumor cells, and destroys cells that have been infected by viruses. When this function is abnormal, cellular carcinogenesis will not be contained in time and persistent infections will not be cleared in time.
Immunological basis of dermatological diseases
I. Skin constituents can be antigenic
Keratin-forming cells are involved in the structural integrity of the epidermis and play a central role in epidermal immunology. They express MHC class II molecules and ICAM-1 on their surface and release cytokines. The “own” antibodies (IgG) to keratinous material are found in the serum of normal healthy individuals, but healthy individuals have a barrier that prevents the “own” antibodies from invading the stratum corneum. In psoriasis, this barrier is broken and the anti-keratin “self” antibodies invade the stratum corneum where they cause an immune response, complement is activated, and neutrophilic white blood cells move over.
The epidermal intercellular substance is a glycoprotein secreted by the epidermal cells, and IgG-type “self” antibodies appear against this substance in cases of pemphigus. The antigens that react with these self antibodies are not only found in intercellular and cellular membranes, but also in the epithelial cells of the oral and esophageal mucosa. This antigen is sometimes found in a wide range of drug rashes on a transient basis.
Subepidermal basement membrane substances are substances and glycoproteins secreted from basal cells, and “self” antibodies against these substances can be produced in herpes pemphigoid and gestational herpes.
In collagen diseases, vitiligo, and malignancies, “self” antibodies against cytoplasm of epidermal cells, especially against mitochondria and microsomes, have been reported, but these antibodies lack disease specificity. “The nuclear antigens include n-DNa single-stranded DNA, RNA, ENA, RNP, etc. These nuclear antigens also lack organ-specific and species-specific properties.
In malignant melanoma, antibodies against melanocytes can be produced, and the issue of tumor-specific antigens is an important topic for the future and is of clinical interest. Patients with herpes-like dermatitis have been shown to produce antibodies (IgG) to the dermal component reticulin.
All of these skin components are antigenic to themselves and can produce their own antibodies, but these “own” antigens cannot react directly with antibodies when they are present in the cells, and if these antibodies react with antigens, the cell membrane must be damaged and the internal antigenic components exposed to the outside in order for the reaction to occur. UV irradiation, infection, trauma, inflammation, etc. are often the triggers.
If the skin component itself can not directly become antigen, foreign antigen substances invade the skin, the invasion site can also produce antibodies and cause an immune response, and various external contacts, infection, trauma, insect stings and injections of various antigenic substances (bacteria, viruses, mold, foreign bodies, insect toxins, etc.) into the skin that cause an immune response.
Second, the skin is also the site of the movement of antibodies
It can remove the invading antigenic substances after catching them quickly and accurately. Tissue cells, fibroblasts, and vascular endothelial cells in connective tissue have receptors for complement (C3) and immunoglobulin (Fc) on their cell surfaces, and they can capture antigen-antibody complexes when an immune response occurs. Langerhans cells in the epidermis have the same function. Mast cells have Fc receptors for IgE on their cell membranes (40,000-90,000 on a single cell), so they bind easily to IgE antibodies and degranulate in response to antigen invasion, releasing histamine, pentazocine, slow reactive substances, and bioactive substances of the ECF-A series.
III. Immunodeficiency
Various diseases caused by congenital and acquired decreases in the body’s ability to produce antibodies and the inability to effectively prevent the invasion of antigens are called immune deficiencies.
Lack of T lymphocytes or B lymphocytes or decreased function, white blood cell foreign body phagocytosis, bactericidal function will cause immune response insufficiency; general T lymphocyte function decline is prone to viral and mycobacterial infections, B lymphocyte function decline is prone to bacterial infections.
The causes of acquired immune deficiency include anticancer drugs, paracorticosteroids, immunosuppressants, long-term exposure to large amounts of X-rays and long-term invasion of antigenic substances.
Fourth, the relationship between complement abnormalities and skin diseases
The main cause of hereditary angioneurotic edema is the congenital lack of C1 inhibitor, an esterase inhibitor of the complement system. there are two forms of C1 inhibitor deficiency: the inhibitor is completely or nearly completely absent (60%); the inhibitor structure and content is the same as normal. However, it is inactive (40%). The disease can be treated by inputting healthy human serum containing C1 inhibitor or by giving androgens to stimulate C1 inhibitor synthesis.
2.Systemic lupus erythematosus Defects in C1q, C2.C4 cause blocked activation of the classical pathway, and circulating immune complexes formed by autoantibodies cannot be effectively cleared, while reduced expression of CR1, the complement receptor on the surface of erythrocytes, can also heterogeneously cause impaired clearance of circulating immune complexes, thus causing their deposition in the vessel wall, which can cause or aggravate autoimmune diseases, such as systemic lupus erythematosus.
3, skin infections Defects in Clr, Cls, C2.C3.preparatins, and D-factor can cause membrane attack complexes to fail to form. Cannot effectively lyse foreign microorganisms, C3 deficiency can lead to phagocytosis and bactericidal effect of phagocytes is significantly weakened. The result can lead to serious infection.
4, neutrophil fragmentation vasculitis Most cases have lower than normal serum total complement levels and decreased C1.C2.C3.C4 levels during the active phase of the lesion. In addition, direct immunofluorescence examination of early lesions reveals deposits of C3 and immunoglobulins on the vessel wall. The immune complexes deposited in the terminal skin vessels and small vessels activate the classical pathway of complement, producing C3a and C5a. They have a chemotactic effect on neutrophils, causing inflammatory infiltrates.
5. psoriasis The levels of C3a and C4a in the serum of patients with psoriasis are significantly higher than normal, and the increase in C4a concentration is more significant than C3a. In psoriasis patients, the presence of C3a, C4a and C5a was also found in large amounts in the scales and horny layer.
6, AIDS HIV infection is accompanied by a significant increase in C3.C4 levels, and C3 promotes HIV infection through its regulatory effect. Complement plays a role in the pathogenesis of AIDS.
V. Immunoglobulin abnormalities
The presence of abnormal immunoproteins or abnormal increase of immunoglobulins from specific strains (Clone) in blood is called immunoglobulinemia. Cryoglobulin (Cryoglobulin) is a protein that precipitates below 37°C. The presence of cryoglobulin in blood is called cryoglobulinemia. It is positive in SLE, PSS, Sjgren’s syndrome, aspergillosis, sarcoidosis-like tumors, and leprosy. Although the antigenic antibodies vary, the common skin changes in cryoglobulinemia are basically cyanosis, purpura, and necrotizing Raynaud’s phenomenon in the uncircumscribed extremities.
1, polyclonal hyperimmunoglobulinemia skin manifestations
Polyclonal immunoglobulinemia, skin symptoms are less, but connective tissue diseases, especially systemic lupus erythematosus, primary dry syndrome, dry syndrome, rheumatoid arthritis, because of the simultaneous appearance of cryoglobulinemia, causing blood viscosity, resulting in vascular obstruction and the corresponding skin symptoms.
2, monoclonal immunoglobulinemia (M proteinemia) skin manifestations
Due to benign plasma cell disease or malignant plasma cell disease caused by abnormal proliferation of monoclonal plasma cells, synthesis and secretion of chemical structure and immune specificity of identical monoclonal immunoglobulin or its polypeptide chain units, clinically known as M components or M protein.
3.Primary monoclonal immunoglobulinopathy
Including multiple myeloma, monogenic myeloma, extramedullary plasmacytoma, macroglobulinemia, primary amyloidosis, heavy chain disease. Due to the presence of large amounts of M protein, serum viscosity rises, which can cause vascular occlusion with superficial mucosal oozing and cutaneous purpura, and nodular erythema can occur when myeloma cells infiltrate skin tissue. The lack of immune activity of M protein and the significant reduction of normal polyclonal immunoglobulins predispose to viral diseases such as herpes zoster or varicella. light chains of M protein and polysaccharide complexes deposited in tissues and organs can cause amyloidosis, including giant tongue and skin mossy or nodular lesions.
4.Other tumors of lymphoreticular system, metastatic carcinoma of hematopoietic system, autoimmune diseases (systemic lupus erythematosus, dermatomyositis, scleroderma, nodular polyarteritis, aspergillosis, etc.), nodular disease, liver disease, drug reactions, etc. may have monoclonal plasma cell reactive elevation, and may also have a limited amount of M protein, but do not directly cause clinical symptoms.
Sixth, the classification of allergic reactions
After the body is stimulated by antigen (including semi-antigen), the corresponding antibodies or sensitized lymphocytes are produced, which cause humoral or cellular immune reactions in the body when exposed to the same antigen again, resulting in tissue damage or physiological dysfunction of the body is called allergic reactions, also called allergic reactions.
Allergic reactions can be divided into six types.
(a) Type I allergic reactions, i.e. tachyphylaxis. These reactions are caused by the interaction of antigen and IgGE-based antibodies. It can lead to the shedding of basophilic granules in mast cells and the release of chemical mediators in the granules, such as histamine and the slow-reacting substance eosinophil chemotactic factor, which act on target organs and cause local smooth muscle spasm, increased vascular permeability, microvascular dilation and congestion, plasma extravasation, edema, glandular hypersecretion and eosinophilia.
Common skin diseases belonging to this type include urticaria, angioedema, etc.
(B) Type II metaplasia, also known as cytotoxic type or cytolytic type. The body produces antibodies against the cell itself or the antigen (semi-antigen) fixed in the cell, and when an antigen-antibody reaction occurs with the corresponding antigen, cell lysis or tissue damage occurs with the participation of complement.
Skin diseases belonging to this type include: anemia and thrombocytopenic purpura caused by drug allergy; pemphigus and pemphigoid in autoimmune diseases.
(C) Type III allergic reaction, i.e. immune complex reaction type. The antigen-antibody complex formed by the sinking antibody to a certain antigen is called immune complex. They are deposited in and around the basement membrane of the blood vessel wall and undergo changes centered on the wall of small blood vessels, resulting in organ and tissue damage.
This type of allergic skin disease includes: serum sickness-like syndrome caused by certain drugs, vasculitis, SLE glomerulonephritis, etc.
(d) Type IV allergic reaction, i.e., delayed allergic reaction, is an immune reaction caused by sensitized lymphocytes and is not related to serum antibodies. After the body is stimulated by antigen, T lymphocytes differentiate and proliferate in large numbers, and finally form effector lymphocytes, which often react violently after 1 to 2 days when they encounter antigen again. It can cause macrophages to wander and gather locally and activate macrophages. Therefore, the infiltrating cells at the site of delayed metaplasia are important macrophages and lymphocytes.
Skin diseases of this type include: tuberculin skin reactions, contact dermatitis and eczema-like skin diseases.
Seven, skin disease and human leukocyte antigen (HLA)
Human leukocyte antigen (HLA) is actually the main human histocompatibility antigen system in the human body, which is not only closely related to organ transplantation, but also has a certain influence on the occurrence of certain diseases. Numerous studies have shown that HLA is a genetic susceptibility factor for some skin diseases, and the detection of specific types of HLA is closely related to the incidence of certain skin diseases. Therefore. Analysis of the correlation between HLA) and diseases. It not only helps to understand the role of genetic factors in the pathogenesis, but also has some significance for the diagnosis and differential diagnosis of diseases and eugenics.