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THE IMMUNE RESPONSE

  • The human body can respond to antigen via innate and/or adaptive immunity (Fig. 27-1)

  • Innate immunity (nonspecific, nonclonal, no anamnestic characteristics)

    • Characteristics

      • – Immediate first-line defense against pathogens composed of 3 major components

        • Nonspecific physical and chemical barriers

        • Recruitment and activation of leukocytes

        • Release and/or activation of extracellular humoral mediators (i.e., cytokines, complement)

      • – Exists prior to exposure to a given microbe or antigen (requires no previous exposure) and is rapidly available on pathogen encounter (minutes)

    • Key components

      • – Physical and chemical barriers to pathogen invasion

        • Skin, mucous membranes, cilia, and secretions (mucous and sweat) cover body surfaces and prevent microorganisms and other potentially injurious agents from entering the tissues beneath

          • Mucus traps, dissolves, and sweeps away foreign substances

          • Sweat contains lactic acid and other substances that maintain the surface of the epidermis at an acidic pH, thereby decreasing colonization by bacteria and other organisms

          • Chemical barrier antimicrobial substances include enzymes that can directly injure or kill microbial pathogens

FIGURE 27-1

The immune response. (Reprinted with permission from Goldsmith LA et al. Fitzpatrick's Dermatology in General Medicine, 8th Ed. New York: McGraw-Hill; 2012.)

Complement

Alternate pathway of complement can be spontaneously activated by microbial surfaces in the absence of specific antibodies

Antimicrobial Peptides

  • Produced by keratinocytes; include cathelicidins and β-defensins

    • Defensins (α or β) and cathelicidins have multiple receptor-mediated effects on the immune cells

    • Defensins are secreted by resident epithelial cells or by transient leukocytes that coat and destabilize the cell membrane of pathogens

    • Beta-Defensins interact with chemokine receptor 6 (CCR6) which results in attraction of dendritic cells and memory T cells

    • Defensins may facilitate microbial antigen delivery to dendritic cells

    • Cathelicidins are secreted by neutrophils, keratinocytes, epithelial cells, mast cells, and monocytesmacrophages

Pattern Recognition Receptors (PRRs)

  • Phagocytic cell PRRs recognize highly conserved pathogen amino acid sequences and result in a variety of signals

    • Examples of PRRs:

      • Toll-like receptors (TLRs): mediate innate immune response in host defenses; expressed in peripheral blood leukocytes (monocytes, B cells, T cells, granulocytes, and dendritic cells). Modulate inflammatory responses via cytokine release. Activation of TLRs can lead to tissue injury (e.g., TLR2 activation by Propionibacterium acnes induces inflammatory responses in acne which result in tissue injury, but TLR2 activation by Staphylococcus epidermidis may also induce β-defensins that protect against infection by pathogenic bacteria.

      • – Innate transmembrane receptors that recognize different types of pathogen-associated molecular patterns (PAMPs), which are molecular patterns unique to pathogens

      • – Ligands include lipopolysaccharide, peptidoglycan, CpG DNA

      • – Humans have at least 10 different TLRs

      • – TLRs identify the nature of the pathogen and result in NFαB activation, which results in appropriate cytokine and chemokine expression, along with increased expression of additional immune system receptors

      • – Triggering receptors expressed on myeloid ...

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