Understanding Immunity: Types, Mechanisms, and Disorders

Immunology

Immune: The property of being invulnerable to a specific disease (usually surmountable). Immunology is specific (like chickenpox) and can be lifelong (like typhus), and should not be confused with disease resistance. Immunology is the science that studies immunity and the immune system.

Types of Immunity

Congenital Immunity (inherited):

  • Species: Present in all individuals of a species.
  • Race: Present in certain groups or populations of a species.
  • Individuals: Present only in a particular individual.

Acquired Immunity (during life):

  • Natural (not artificially induced):
    • Active: Acquired after having had an infectious disease.
    • Passive: Acquired during embryonic development or through maternal antibodies.
  • Artificial (caused by artificial means):
    • Active: Acquired by administering vaccines.
    • Passive: Acquired by the administration of serum.

Artificial Immunity: Vaccination

The English doctor Edward Jenner, at the end of the 17th century, discovered that some people were immune to smallpox after injecting extracts from diseased cows. The vaccine consists of intentional exposure to a killed or attenuated toxin or pathogen. Currently, there are vaccines for many infectious diseases, such as whooping cough, tuberculosis, and tetanus. With vaccination, the immune system produces specific antibodies.

Serotherapy

Serotherapy consists of injecting specific antibodies contained in serum (antiserum) obtained from an animal.

Differences Between Vaccination and Serotherapy

Vaccination:

  1. The immune system actively participates.
  2. It is a preventive measure.
  3. It involves memory cells and antibodies formed by the body itself.
  4. Its effects are long-lasting.

Serotherapy:

  1. The immune system does not actively participate.
  2. It is a curative measure.
  3. It does not involve antibodies formed by the body itself.
  4. It has transient effects.

Serums are used against infectious diseases like scarlet fever, tetanus, and botulism.

Defense Mechanisms of the Body

Primary Defensive Barriers

Skin secretions and openings are primary defense barriers. The skin of mammals is a physical barrier for microorganisms due to its thickness and the process of keratinization. Sweat determines the pH. The bacterial flora of the skin prevents the establishment and development of other microbes. Lysozyme can destroy the murein layer. In semen, spermine is present. In the respiratory mucosa, mucus traps microorganisms, which are removed by the movement of ciliary cells, coughing, and sneezing.

Secondary Barriers

When microbes overcome the primary barrier, secondary phagocytic defenses are activated. White blood cells (leukocytes) with phagocytic capabilities include monocytes (macrophages) and neutrophils.

Phagocytes

Monocytes migrate to the bloodstream, hepatic sinusoids, spleen, and lungs, transforming into macrophages. Neutrophils are part of the bloodstream but are attracted to infected tissues by chemotactic signals.

Inflammation

Inflammation is an immediate immune response that does not require prior sensitization. It is resolved with phagocytosis of infectious agents. Affected cells release inflammatory mediators, leading to an increase in circulating leukocytes, vasodilation, and increased temperature (fever).

Chemical Inflammation

Histamine: Released by mast cells, it causes vasodilation and increased capillary permeability.

Opsonins: Substances that facilitate the phagocytosis of bacteria by bridging molecules between phagocyte receptors and the bacterial cell wall.

Pyrogens: Fever-producing substances that act on the thermoregulatory center in the hypothalamus. Endotoxins from Gram-negative bacteria are exogenous pyrogens, while macrophages release endogenous interleukin 1.

Acute Phase Proteins: Serum proteins, mostly produced in the liver, that increase in response to infection. Their concentration increases due to inflammatory factors released by macrophages.

Prostaglandins: Chemical mediators that, along with histamine, serotonin, bradykinin, and leukotrienes, produce the sensation of pain by stimulating nerve endings.

Complement System: A system of twenty globulin-type proteins that aid the immune response. They bind to antigen-antibody complexes (or directly to polysaccharides of Gram-negative bacteria) and facilitate the lysis of microorganisms. The union is sequential, leading to the formation of pores in the cell membrane of the microorganism. It also participates in the release of histamines by mast cells.

Interferon: Small plasma proteins produced by T lymphocytes, leukocytes, and fibroblasts that interfere with virus replication. There are three types: α, β, and γ. Leukocytes and fibroblasts produce α and β in response to viruses. T lymphocytes and NK cells produce γ in response to foreign antigens from viruses, bacteria, and tumor cells.

Specific Defense Mechanisms: The Immune System

The immune system includes all cells, tissues, and processes involved in immunization. Any foreign molecule capable of activating the immune system is an antigen. Antigens can be toxins, foreign substances (produced by microbes or multicellular organisms), or components of the body’s own tumor formations.

Immune System Responses

The immune system can trigger two types of responses against an antigen: cellular and humoral. Lymphocytes form, transform, and mature in lymphoid organs.

Cells

Lymphocytes are blood cells involved in humoral and cellular immunity. They originate from pluripotent stem cells, which can also produce other leukocytes, erythrocytes, and platelets. Lymphocytes mature in the bone marrow or thymus, becoming B and T lymphocytes. In adults, stem cells are found in the red bone marrow.

Differences Between T and B Lymphocytes

T Lymphocytes: Originate in the thymus, are involved in cellular immunity, and their membrane receptors recognize small antigen fragments linked to membrane proteins (MHC) of normal cells. They are inactivated by hard X-rays.

B Lymphocytes: Originate in the bone marrow, produce antibodies, are not involved in cellular immunity, and their membrane receptors recognize intact antigens. They are easily inactivated by X-rays.

Antigen-Presenting Cells (MHC)

Antigen-presenting cells include blood macrophages, dendritic cells of lymphoid organs, and Langerhans cells of the skin. They activate T lymphocytes by presenting antigens bound to MHC proteins. The presentation process involves:

  1. Uptake of antigens by endocytosis.
  2. Degradation of antigens by endocytosis.
  3. Presentation of simple peptides associated with MHC proteins (Type I for tumor cells, Type II for endocytosed antigens).

The MHC Complex

The MHC complex is a set of genes encoding surface glycoproteins (autoantigens). It is highly polymorphic, located on chromosome 6, and consists of about 20 genes, each with 8-10 alleles. In humans, MHC proteins are called HLA. They present antigens to T cells and are responsible for individual immune characteristics.

Lymphoid Organs

Red Bone Marrow: In adults, it contains stem cells that are precursors of lymphocytes. B cells mature here and migrate to the thymus to become T lymphocytes.

Thymus: An organ that atrophies in adults, it is essential for the development of T lymphocytes.

Spleen: Filters blood, eliminates defective erythrocytes and leukocytes, and contains areas rich in T and B lymphocytes.

Antigens

Antigens are substances that trigger an immune response. They are usually macromolecules from other species or individuals of the same species. Antigens can also be molecules from the same organism. The specific area of an antigen that binds to cell membrane receptors or antibodies is called a determinant. Antigens can be univalent or polyvalent.

Antibodies

Antibodies have a Y-shaped structure comprising four polypeptide chains: two heavy chains (H) and two light chains, linked by disulfide bonds. Each chain has a variable and a constant domain. The C-terminal connects to membrane receptors or the complement system. The hypervariable regions are at the tips. The hinge region is flexible. Antibodies can be on the plasma membrane of T cells or secreted outside the cell.

Lymphocytes and Clonal Selection

Clonal selection includes:

  • Positive Selection: T cell receptors (TCR) that interact with MHC antigens are not eliminated.
  • Negative Selection: TCR cells that interact with the body’s own antigens are removed.

Only TCR cells that interact with MHC autoantigens, but not with the body’s own antigens, proliferate.

Reactions Triggered by Antigen-Antibody Binding

Non-covalent links between antigens and antibodies form antigen-antibody complexes. A single antigen can have different determinants, and the same determinant can form one or more antibodies. Reactions include:

  • Agglutination Reactions: Occur when incompatible blood groups are mixed.
  • Precipitation Reactions: Soluble antigens become multifunctional.
  • Neutralization Reactions: Antibodies bind to areas on pathogens used to adhere to cells, reducing their ability to infect.
  • Opsonization Reactions: Antibodies bind to membrane antigens and mark infectious agents.

Autoimmunity

Autoimmunity is the production of antibodies against the body’s own molecules (autoantigens). This can occur when confined proteins (from eye tissue, brain, or sperm) are released into the blood due to injury. Autoreactive lymphocytes (which should be removed in the thymus) can also cause autoimmunity. Molecular mimicry caused by bacteria and viruses can also trigger autoimmune responses.

Autoimmune Diseases

Multiple Sclerosis: Affects brain tissue and spinal cord.

Lupus Erythematosus: Affects various tissues, DNA, and platelets.

Psoriasis: Affects the skin.

Grave’s Disease: Affects the thyroid.

Addison’s Disease: Affects the adrenal gland.

Pernicious Anemia: Affects parietal cells of the stomach.

Autoimmune Hemolytic Anemia: Affects erythrocytes.

Rheumatoid Arthritis: Affects connective tissue.

Juvenile Diabetes: Affects pancreatic cells.

Allergies

Allergies are hypersensitivity reactions to harmless antigens (pollen, spores, proteins, food). Excessive hypersensitivity (anaphylaxis) can cause immediate death, while delayed hypersensitivity can also occur.

Immediate Hypersensitivity

First Contact: No symptoms occur, but macrophages capture allergens and present them on MHC. T lymphocytes recognize this and secrete interleukin-4, which matures B cells into plasma cells that secrete IgE. These antibodies bind to specific receptors on mast cells and basophils.

Second Contact: The allergen binds directly to IgE on mast cells and basophils, releasing chemical mediators that cause allergic reactions.

Delayed Hypersensitivity

Symptoms appear hours or days after the second exposure to the allergen. T lymphocytes secrete interleukins and interferon-γ, which activate monocytes and neutrophils, releasing hydrolytic enzymes that can destroy surrounding tissues.

Recombinant DNA

Recombinant DNA requires specific DNA fragments cut by restriction enzymes, which act as molecular scissors. These enzymes are isolated from bacteria and identified with numbers.

Granulocytes and Agranulocytes

Granulocytes: Basophils (circulating), mast cells (not circulating), eosinophils (circulating), neutrophils (circulating), NK cells (circulating).

Agranulocytes: Monocytes (circulating), macrophages (not circulating), plasmocytes (not circulating), B and T lymphocytes.

Answers to Multiple Choice Questions

T.10

37. D) Microbial disease affects many parts of the Earth.

38. e) All the above.

39. D) The nature of protein endotoxins are.

40. B) Antibiotics.

41. A) Comprises proteins of the globulin group.

42. e) All the above.

43. a) Cellular immunity is produced by B cells.

44. e) In the red bone marrow.

45. c) Malaria.

46. c) Are thermostable.

47. e) Injuries to the skin.

48. d) Cholera and amebic dysentery.

49. b) Artificial active.

50. b) Bind peptide antigen at MHC plasma membrane.

51. D) Opsonization reaction.

T.11

23. D) Are on the surface membrane of all cells.

24. C) Involving interferon g.

25. C) Use ionizing radiation for localized cancer treatment.

26. c) Hypersensitivity.

27. b) Related to the myelin sheath of axons of neurons.

28. c) Autoantigens.

29. a) Are substances produced by T cells.

30. d) Microorganisms can produce, such as the AIDS virus.

31. d) The virus can transmit through the placenta from the infected mother.

32. d) Is characterized by various diseases such as Kaposi’s sarcoma, cachexia, HIV encephalopathy, opportunistic infections, and lymphomas.

33. e) Prevent the reproduction of HIV.

34. d) Obtained from cloned hybridoma cells.

35. d) Where the donor and recipient are the same person, called autografts.