Pathophysiology - 08 Lymphatic and Immune Disorders

PATHOPHYSIOLOGY LECTURE 8 - THE LYMPHATIC AND IMMUNE SYSTEM INTRODUCTION • Any substance or microorganism that causes disease or damage to the tissues of the body is considered a pathogen. Not surprisingly, the body has ways to resist or destroy pathogens through the lymphatic system. The lymphatic system includes lymph, lymphocytes, lymphatic vessels, lymph nodes, tonsils, spleen, and thymus. o MISCELLANEOUS SYSTEMIC AUTOIMMUNE DISEASES • AUTOIMMUNE DISEASE SYSTEMIC AUTOIMMUNE DISEASES • • • Systemic Lupus Erythematosus (SLE) o disease of the connective tissue o expresses itself as a vasculitis o it is an immune complex disease characterized by overproduction of autoantibodies (DNA-antiDNA complexes - most important of immune complex formed) o Arthritis - most common manifestation o Also manifests itself by skin lesions, “butterfly rash”/RED WOLF (red rash across nose and cheeks) o Laboratory Observations: ▪ Most Striking Feature: Presence of Anti-Nuclear Antibodies (ANA) [although not diagnostic of SLE] ▪ LE Cell - PMN leukocyte with ingested LE body (a homogenous cytoplasmic mass that often fills the cytoplasm of the phagocyte) • often, LE bodies are not engulfed neutrophils producing “rosette formation” • LE Factor - a 7s IgG Antibody which reacts with DNP (deoxyribonucleoprotein) complement o Hypocomplementemia o Hypergammaglobulinemia o Depletion of suppressor T cells (w/c allows overproduction of autoantibodies) Rheumatoid Arthritis o is an autoimmune disease causing chronic inflammation of the joints and periarticular tissue o Rheumatoid Factor (RF) ▪ group of immunoglobulins that interact specifically with the Fc portion of IgG molecules (anti-antibodies) ▪ primarily, are of the IgM class o However, the presence of RF alone is not enough for a diagnosis of RA. Although RF are not consistent with RA, the presence of polymorphonucleocytes (neutrophils or PMN) in inflamed joints is observed in all stages of the disease. These cells, as well as macrophages and other immune cells, compose the cellular infiltrate resulting in release of cytokines radicals, and enzymes which participate in the destruction of a joint Ankylosing Spondylitis o is a form of chronic inflammation of the spine and the sacroiliac joints. o Chronic inflammation in these areas causes pain and stiffness in and around the spine. Over time, chronic spinal inflammation (spondylitis) can lead to a complete cementing together (fusion) of the vertebrae, a process referred to as ankylosis. Ankylosis leads to loss of mobility of the spine. the autoimmune disease with the highest criteria for HLA-disease relationship; associated w/ HLA Ag B-27 • Progressive Systemic Sclerosis (Scleroderma) o chronic dse of the connective tissue characterized by diffused fibrosis involving the skin and several internal organs o Raynaud’s phenomenon ▪ pain in the extremities when exposed to cold ▪ most common symptom of Scleroderma. Sjoren’s Syndrome o most often occurs secondary to RA, scleroderma, SLE o manifestations: dry eyes (keratoconjunctivitis sica), dry mouth (xerostomia) ORGAN-SPECIFIC AUTOIMMUNE DISEASES, THE AUTO DISEASE Goodpasture’s syndrome Pernicious Anemia Multiple Sclerosis Insulin dependent DM Grave's Disease Hashimotos’s thyroiditis Wegener’s granulomatosus Myasthenia gravis AUTOANTIBODY INVOLVED Anti-glomerular basement membrane Anti-intrinsic factor, Anti-parietal cells Anti-myelin sheath Anti beta cells (Islet cells) Anti Thyroglobulin Anti LATS (LongActing Thyroid Stimulating cells) ANCA (antineutrophil cytoplasmic antibody Anti Acetylcholine receptors ORGAN AFFECTED Kidneys Stomach Nervous system cells Pancreas Thyroid gland Thyroid gland Kidneys Muscles HIV AND AIDS • • • Human Immunodeficiency Virus (HIV) o the causative agent of HIV infection o Family: Retroviridae o Subfamily: Lentivirinae o Has a marked preference for T-helper/inducer lymphocytes (CD4+) which serves as the receptor sites for the virus Modes of Transmission o sexual contact o blood transfusion o parenteral injection o transplacental o breastfeeding o passage through infected birth canal CLINICAL MANIFESTATIONS: o Primary Stage ▪ px is either asymptomatic or may show lymphadenopathy o o • • Intermediate stage ▪ this state is known as the ARC (Aids-Related Complex) ▪ quantitative T cell deficiencies with inverted CD4:CD8 ratio o ***When HIV replication occurs, the CD4 cell is killed. This results in a severe depletion of helper-inducer T lymphocytes. (Normal CD4:CD8 ratio = 2:1, in AIDS pxs = 0.5:1) o Final Stage o - 2-10 yrs after initial infection o - a syndrome of CD4 depletion resulting in opportunistic Infections and cancers suggestive of cell-mediated immunity defects. *** Opportunistic Pathogens : Pneumocystis carinii o avium-intracellulare complex ▪ Candida albicans ▪ Cryptosporidium parvum ▪ Toxoplasma gondii ▪ Cryptococcus neoformans ▪ Herpes Simplex (I and II) ▪ Legionella spp. Kaposi’s sarcoma o tumors in skin and linings of internal organs, lymphomas and cancers of rectum & lung o most frequent malignancy observed