Chapter 59: Immunology and Allergy

Introduction

The Immune System

1. Distinguishes “self” from “nonself (Table 59-1).”

   1. Self: should not be target by the immune system

      1. Tolerance: The immune system is not reactive to self-particles.

   2. Non-self

      1. Microbes: Bacteria, fungi, viruses, parasites.

      2. Particles: Dust, pollen, chemicals.

      3. Make or contain proteins (antigens) that the immune system reacts to.

2. The immune system is mediated through two interactive processes.

   1. Innate immunity

      1. Immune responses are mediated through toll-like receptors (TLR) that coordinate various cytokine-generated, complement-mediated, and phagocytic responses.

      2. Targeted to anything that is deemed “non-self.”

      3. First line of defense to prevent infection.

      4. Composed of mechanisms in place prior to exposure to antigens:

         1. Physical barriers: Skin, body hair, upper and lower respiratory tracts, GI tracts

         2. Chemical barriers: Saliva, tears, mucous, bile, gastric acid

         3. Immune response

            • Inflammation

            • Complement cascade

            • Nonspecific cellular response

      5. Cells of the innate immune system

         1. Macrophages

            • Cross capillaries

            • Recruit other immune cells with cytokines

            • Antigen-presenting cell allows communication from the innate to the adaptive immune system

         2. Neutrophils

            • Toxic to bacteria and fungi

         3. Mast cells

            • Mast cell degranulation releases histamine and other cytokines triggering inflammatory cascade

              1. Vasodilation, increased blood flow, recruitment of neutrophils and macrophages.

         4. Eosinophils

            • Toxic to bacteria and parasites

         5. Basophils

            • Toxic to parasites

            • Secrete histamines

         6. Natural killer (NK) cells

            • Signaled by infected host cells to destroy the infected cells

            • Account for 10% of circulating lymphocytes

            • Rarely found in lymph nodes

            • Positive for CD16

         7. Dendritic cells

            • Specialized macrophages found in the skin, mucosa, lymph nodes, spleen, and thymus

              1. Contact with external environment

            • Antigen-presenting cells

         8. Complement cascade

            1. Works primarily with the innate immune system but can augment the adaptive system as well.

            2. Opsonization: “Non-self” particles and infected cells are marked for phagocytosis.

            3. Chemotaxis: Cytokines attract macrophages and neutrophils to the infected sites.

            4. Cell lysis: The cell membranes of “non-self” cells are penetrated to decrease their ability to proliferate and spread infection.

            5. Agglutination: Antibodies bind pathogens together.

         9. Adaptive immunity

            1. Coordinated response, with memory for prior antigen exposure and amplification in magnitude with successive antigen stimulation.

            2. Memory

               1. Exposure of the immune system to an antigen enhances its responses when again presented with that antigen and subsequent responses are more rapid.

            3. Self-regulation

               1. Normal immune responses decrease over time after antigen stimulation, and the response is self-regulatory via feedback control.

               2. Immune system returns to basal resting state (homeostasis).

            4. Nonreactivity to self

               1. Recognize and eliminate foreign materials while avoiding harmful responses to host tissues.

                  • Mediated by lymphocytes

                    1. B lymphocytes

                       • Produce antibodies.

                       • Carry endogenously produced immunoglobulins (Ig) on surface.

                         • – Act as antigen receptors

                       • Maturation occurs in the bone marrow.

                       • Naïve B cells differentiate into plasma cells or memory B cells upon encountering an antigen that matches their membrane bound antibodies.

                       • Memory B cells express identical membrane bound receptors as its naïve parent cell.

                       • Plasma cells secrete antibodies into circulation.

                       • Act collaboratively with T cells and macrophages.

                       • Account for 10% to 15% of circulating lymphocytes.

                       • Positive for CD19, CD21.

                    2. T lymphocytes

                       • Mature in the thymus

                       • Classification into subsets depends on the pattern of ...