Immunology

The immune system is broadly categorized into two branches: the innate and the adaptive, with interaction and overlap between the two (Fig. 1.48).

• The innate system is primitive, nonspecific, the first line of defense using complement and leukocytes.

  • Is antigen independent and involves NK cells, mast cells, basophils, eosinophils, macrophages, neutrophils, and dendritic cells

  • Barriers—physical and chemical components (e.g., enzymes, pH)

    • Skin—sebum, sweat (lysozyme, RNases and DNases, defensins, cathelicidins)

    • Mucous membranes (IgA is most common immunoglobulin)

    • Respiratory epithelium

    • Urinary tract

  • Recognition of pathogens by innate system

    • Pathogen-associated molecular patterns (PAMPs) on microbes are recognized by TLRs on innate immune system cells (e.g., macrophages and dendritic cells).

    • Example of a PAMP is bacterial lipopolysaccharide (LPS), which is recognized by TLR-4.

    • There is an upregulation of NF-κB transcription factor, resulting in release of immune mediators (e.g., IL-1, IL-6, TNF-α).

      • IL-6 causes the liver to release inflammatory mediators such as CRP.

    • Arachidonic acid released from cell membranes is acted on by COX and 5-lipoxygenase to make prostaglandins and leukotrienes that mediate exudation, chemotaxis, and bronchospasm.

      • Ibuprofen inhibits COX and reduces

        prostaglandin production, preventing renal efferent arteriolar relaxation and increasing GFR.

    • Factor (XII)—inflammatory protein made in the liver

      • When exposed to collagen under damaged endothelium, activates coagulation

      • Acute production of coagulation factors elevates ESR.

  • Complement

    • Activated by IgM or IgG antigen (Ag) complexes, microbial products, or mannose on microorganisms

    • Mediates chemotaxis of PMNs, opsonization (tagging of evasive bacteria for elimination in the spleen), and membrane attack complex lysis of microbes, among other functions

• The adaptive system is more complex, is antigen dependent, and works through antigen presentation with B and T lymphocytes and antibodies.

  • Response to a pathogen generates an immunologic memory in the adaptive system.

    • Antigens are ligands recognized by the immune system. The smallest part of an antigen “seen” by a T- or B-cell receptor is an epitope.

  • Cell mediated—T lymphocytes (helper, CD4+; cytotoxic, CD8+), macrophages

    • Targets intracellular bacteria, virus, fungi, parasites, tumors, and transplanted organs/orthopaedic hardware

    • Antigen-presenting cells (APCs— macrophages, dendritic cells, certain B cells, and Langerhans cells) process antigens.

  • Humoral—B lymphocytes and their matured counterparts, plasma cells. Both produce antibodies.

    • Targets exotoxin-mediated disease, encapsulated bacterial infection, other viral infections

    • Each B cell makes antibodies specific to one single epitope (antigen). B cells use immunoglobulins (IgM and IgD) as cell membrane receptors.

    • Terminally differentiated B cells are called plasma cells. The difference is that they secrete immunoglobulins into fluid.

    • Immunoglobulins (Fig. 1.49) (mnemonic: MADGE)

      • IgM: heaviest, first in the adaptive response

      • IgA: in mucosal surfaces (e.g., MALT [mucosa-associated lymphoid tissue]) and secretions

      • IgD: only on B-cell surfaces

      • IgG: also on B-cell surface but also secreted.

        • Mediates opsonization; later in the adaptive response

      • IgE: on the surface of mast cells (allergic reactions), basophils, and eosinophils (response to parasite).

         

         

        FIG. 1.49 Basic subunit structure of the immunoglobulin molecule. C H and C L , Constant regions; Fab, antigen-binding fragment; Fc, crystallizable fragment; V H and V L , variable regions.

        From Katz VL et al: Comprehensive gynecology,

        ed 5, Philadelphia, 2007, Mosby.

         

    • Once secreted, antibodies can defend by a variety of mechanisms.

      • Neutralization of viruses and toxins

      • Opsonization

      • Complement activation (IgG and IgM)

      • Antibody cellular cytotoxicity

      • Prevention of adherence and colonization (IgA)

  • Cellular response in inflammation

    • Neutrophil response—first cells recruited to sites of tissue injury

      • Margination, rolling, adhesion, chemotaxis, and phagocytosis