The Immune System: Components and Function

Basic Components of the Immune System

• Organs are divided into primary and secondary lymphoid organs.
• Primary lymphoid organs include bone marrow and the thymus.
• Secondary lymphoid organs consist of tonsils, adenoids, lymph nodes, lymphatic vessels, spleen, and appendix.
• Cells are categorized into lymphocytes, granulocytes, and others.
• Lymphocytes include B cells and T cells.
• Granulocytes consist of neutrophils, eosinophils, and basophils.
• Other cells include monocytes, macrophages, dendritic cells, and natural killer cells.

Function of the Immune System

• The main role is to prevent or limit infections, fungi, and parasites like protozoa and worms.
• The first line of defense is the intact skin and mucous membranes.
• The second line of defense involves innate immunity, which is nonspecific.
• The third line of defense is adaptive immunity, which is specific and acquired.

Immunology

• The two fundamental branches of the immune system are innate and adaptive.

Innate Immunity

• Innate immunity is present before exposure to a microbe and does not improve post-exposure.
• Components include physical barriers like skin and mucous membranes.
• Additional components include chemical barriers such as stomach acid and the complement complex.
• Cells involved are white blood cells (neutrophils, eosinophils, monocytes), and tissue cells (macrophages).
• It is nonspecific.
• Key functions are to kill invading microbes and activate adaptive immune processes.
• Includes; Phagocytosis, destruction of swallowed organisms and resistance of the skin
• Also the presence of certain chemical compounds (lysozyme, basic polypeptides, the complement complex and natural killer lymphocytes)

Major Leukocytes of Innate Immunity

• Neutrophils function through phagocytosis, reactive oxygen/nitrogen species, and antimicrobial peptides.
• Macrophages utilize phagocytosis, inflammatory mediators, antigen presentation, reactive oxygen/nitrogen species, cytokines, and complement proteins.
• Dendritic cells present antigens, use costimulatory signals, reactive oxygen/nitrogen species, and produce interferon and cytokines.
• Natural killer cells lyse viral-infected cells, produce interferon, and activate macrophages.

Characteristics of Granulocytic Cells

• Neutrophils have a multilobed nucleus and granulated cytoplasm that stains with both acid and basic dyes.
• Eosinophils have a bilobed nucleus and granulated cytoplasm that stains with the acid dye eosin red.
• Basophils feature a lobed nucleus and heavily granulated cytoplasm that stains with the basic dye methylene blue.

Phagocytosis

• Phagocytosis is the cellular ingestion of offending agents.
• Phagocytic cells are neutrophils and macrophages.

Recognition of Microbes by Innate Immunity

• Detecting carbohydrates or lipids on the surface of microorganisms.
• The innate immune system uses pattern-recognition receptors to identify pathogen-associated molecular patterns (PAMPs) found on microbes but not on human cells.
• Toll-like receptors (TLR) are the most important pattern-recognition receptors.
• TLR's are mainly found on macrophages, dendritic cells, and mast cells.

Acquired (Adaptive) Immunity

• The component includes lymphocytes (T and B cells).
• It occurs after exposure to an agent and improves with repeated exposure.
• It is specific and mediated by antibodies and T cells.
• Long-term memory for specific antigens is a characteristic.

Origin and Differentiation of T and B Cells

• B cells originate in the fetus liver and differentiate in the bone marrow.
• T cells originate in the bone marrow and differentiate in the thymus.

Origin of T Cells

• Immature T cells are neither CD4 nor CD8 (double negatives), then become both CD4 and CD8 (double positives).
• A double-positive cell differentiates into a CD4-positive cell if it contacts a cell bearing class II MHC proteins.
• A double-positive cell differentiates into a CD8-positive cell if it contacts a cell bearing class I MHC proteins.

Modes of Acquired Immunity

• Active immunity involves making one's own antibodies, either naturally through recovery from disease or artificially through vaccination.
• Passive immunity involves receiving antibodies from an external source, either naturally through placental transfer or artificially through antitoxin administration.

Active and Passive Immunity

• Active immunity provides long-term memory but no immediate large amounts of antibody.
• Passive immunity offers prompt antibody availability but has a short lifespan and potential hypersensitivity reactions.

Types of Adaptive Immunity

• Humoral immunity (B-cell immunity) involves developing circulating antibodies in the blood plasma.
• Cell-mediated immunity (T-cell immunity) involves activated T lymphocytes crafted in lymph nodes.

Both Types of Adaptive Immunity Are Initiated by Antigens

• Antigens initiate adaptive immunity.
• They are proteins or polysaccharides (parts of bacteria, viruses, and other microorganisms).
• Molecular weight: ≥ 8000 Dalton

Epitopes (Antigenic Determinants)

• Epitopes are small chemical groups on the antigen molecule that can elicit and react with antibodies.
• Each antigen can have one or more epitopes (multivalent)
• The overall three-dimensional structure, antigenic specificity is the main criterion.

Haptens

• A hapten is a molecule is not immunogenic because they cannot activate helper T cells.
• Haptens are usually small, and many drugs (e.g., penicillin) are haptens.
• Although they cannot stimulate a primary or secondary response, they can do so when covalently bound to a "carrier" protein.

Antigen Presenting Cells

• Macrophages, dendritic cells, and B cells are antigen-presenting cells.

Antibodies

• Consist of identical H chains and identical L chains.
• Antibodies have variable regions for antigen-binding and constant regions for biologic functions.
  • Hypervariable regions form the antigen-binding site on both L and H chains.
• The constant region carries out complement activation and binding to cell surface receptors.
• The two main fragments of the antibody are:
• Fab fragments carry antigen-binding sites and consist of 1 variable domain + 1 constant domain.
• Fc fragments (constant portion) are involved in placental transfer, complement fixation, attachment to various cells, and other biologic activities.

Classes of Antibodies

• Produced by plasma cells.
• The five classes are IgG, IgA, IgM, IgD, and IgE.
• These classes are subdivided based on differences in their heavy chains.

IgG

• IgG is the smallest and most numerous antibody.
• Increases in second exposure to an antigen.
• It crosses the placenta, fixes complement, opsonizes bacteria, and neutralizes bacterial toxins and viruses.

IgA

• Secretory IgA (mucosal Ig), prevents attachment of bacteria and viruses to mucous membranes.
• Found in breast milk.

IgM

• IgM is the largest and heaviest antibody.
• It is the first to increase in a first exposure to an antigen.
• This antibody also fixes complement.

IgD

• IgD is found on the surface of many B cells as well as in serum, but its function is uncertain.

IgE

• IgE responds to parasitic infections and is present in allergic reactions.

Properties of Human Immunoglobulins

Action of Antibodies

• Antibodies protect the body against invading agents through direct attack, agglutination, precipitation, neutralization, lysis, and activation of the "complement system."

Three Major Types of T Cells and Their Different Functions

• Helper T cells (CD4) are the most numerous and regulate immune functions.
• They form a series of protein mediators or lymphokines (IL-2, 4,5, and gamma interferon)
• Functions of helper T cells include:
• Stimulation of B cell growth and differentiation (IL4 and 5)
• Activation of the macrophage system (gamma interferon)
• Positive feedback effect on the helper cells
• Help in the functioning of Cytotoxic T – cells (IL 2)
• Cytotoxic T cells (CD8+) kill multiple cells, including cancer cells and heart transplant cells.
• Suppressor T cells suppress the functions of both cytotoxic and helper T cells.
• This function is the limit the immune system's ability to attack self (immune tolerance)

Important Functions T Cells

• Regulatory includes helper (CD4-positive) T cells, which create interleukins.
  • Regulatory activates CD4 and CD8 cells
  • Activates B cells to produce antibodies, especially IgE
  • Interferon enhances killing by macrophages
• Effector functions are carried out primarily by cytotoxic (CD8-positive) T cells.
  • Killer activates virus infected cells, tumor cells, and allografts

Role of Macrophages in the Activation Process

• Macrophages orchestrate phagocytosis, antigen presentation, and cytokine production.

Major Histocompatibility Complex (MHC)