The Lymphatic System Nonspecific Resistance and Immunity



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Zoology 141 Chapter 22 Dr. Bob Moeng

The Lymphatic System

Nonspecific Resistance and Immunity




Lymph System

  • Functions include: draining interstitial fluid, return of leaked plasma proteins, transport of dietary fats, protection or resistance (both specific and non-specific)

  • Body cells susceptible to a variety of damaging agents, chemical and biological

Lymph Circulation

  • Vessels begin as blind-ended capillaries in all but avascular, nervous, splenic, and bone marrow tissue

  • Capillaries drain interstitial fluid between endothelial cells held in place by anchoring filaments

  • Based on relative pressure in and outside

  • Lacteals are specialized lymph capillaries found in villi in small intestine

  • Lymph vessels, lymph nodes, then trunks

  • Thoracic duct or right lymphatic to subclavian veins

  • Thoracic collects from left side of head, neck, chest, left upper limb & everything below ribs; begins at cisterna chyli

  • Right collects from upper right side of body

  • Trunks are major inflow

  • About 3 liters per day

  • Lymph flows similarly to veins

Primary Lymphatic Tissue

  • Bone marrow - site of B lymphocyte proliferation and pre-T cell production from pluripotent stem cells

  • Thymus - located below the sternum, site of T cell proliferation & maturation

  • Two thymic lobes that consist of lobules

  • Each divided into a cortex and medulla

  • Cortex primarily packed, developing T lymphoctyes and some reticular epithelial cells

  • Medulla primarily reticular epithelia cells that produce thymic hormones (probably important in managing T cell maturation) and some lymphocytes

Lymph Nodes (Secondary Lymphatic Tissue)

  • Grouped in various regions particularly in mammary glands, and around axilla, and groin

  • Outer structure or cortex surrounded by connective tissue capsule with trabeculae extensions inward

  • Inter-trabeculae spaces at perimeter - cortex

  • Outer cortex - B-cells (antibody forming plasma cells), dendritic cells (APCs), and macrophages

  • Inner cortex - T-cells (cytotoxic)

  • Inner structure or medulla - lymphocytes (B-cells and plasma cells) are arranged in cords

  • One way flow through nodes (many afferent and few efferent vessels)

  • Filtering effect - foreign substances trapped by reticular fibers, and then either physically attacked by macrophages or destroyed by immune response from lymphocytes

  • T cells and plasma cells leave to provide immune response elsewhere

Spleen (Secondary Lymphatic Tissue)

  • Spleen - located below diaphragm

  • Similar capsule, trabeculae, reticular fiber structure

  • Internal structure consists of white & red pulp

  • white - largely B & T lymphocytes for immune response around central arteries

  • red - venous sinuses with projection of splenic cords (concentrations of macrophages, lymphocytes, plasma cells, & granulocytes)

  • Important for phagocytosis of pathogens and removal of aged RBCs and platelets

Diffuse Lymphatic Tissue

  • Lymph nodules or mucosa-associated lymphoid tissue (MALT)

  • Clusters of lymphocytes associated with connective tissue within mucous membranes in the GI, urinary and reproductive tracts, and respiratory passages

  • e.g. tonsils at back of oral cavity which include pharyngeal (adenoid), palatine, and lingual tonsils (the latter two commonly removed); portions of appendix

  • Their location provides protection against foreign substances inhaled or ingested

  • Not encapsulated

Nonspecific Resistance

  • General defense against a broad range of damaging agents

  • Typically the first line of defense

  • A variety of defense tactics

Skin and Mucous Membranes

  • Most exposure of all cells

  • Use mechanical & chemical protection

  • Mucous membranes line all cavities connected to exterior

  • Mechanical protection

  • Skin - tightly packed keratinized epithelial cells of epidermis that are continually shed

  • Nasal passage mucous (plus hair) entraps pathogens, dust, other particulates and drains product into acidity of stomach

  • Cilia & mucous in respiratory tract move particulates out and into stomach

  • Tears, saliva, urine, vaginal secretions, vomiting carry on similar processes

  • Chemical protection

  • Sebum (from sebaceous gland) has a pH of 3.5, poor environment bacterial and fungal growth

  • Perspiration (from sudoriferous glands) floods skin washing skin surfaces

  • Enzyme (lysozyme) in saliva, sweat, tears, etc. attack membranes of some bacteria

  • Gastric juice in stomach (pH of 1.5-3) kills bacteria and their toxins

  • Vaginal secretions are slightly acidic as well

Antimicrobial Substances

  • Act as second line of defense by inhibiting proliferation of bacteria and viruses

  • Interferons

  • Produced by virus infected cells that diffuse to surrounding cells, activating the synthesis of anti-viral proteins that inhibit viral replication

  • Also enhance activity of phagocytes, and natural killer cells, inhibit general cell growth, suppress some tumor formation

  • Complement System

  • A group of about 20 proteins, that when “activated”, complement or enhance portions of the immune, allergic, and inflammatory responses

  • Activation by either binding of antibodies and antigens (classical pathway) or microbial surface polysaccharides (alternate pathway)

  • Three general effects (overhead)

  • Reinforced activation of inflammation (arteriole dilation, histamine release, phagocyte chemotaxis)

  • Attachment to microbial surface (opsonization) to attract phagocytes

  • Formation of membrane attack complex (MAC) which cause cytolysis

Natural Killer Cells

  • Specialized lymphocytes that kill a variety of pathogens

  • 5-10% of lymphocytes in blood are NK cells, also found in lymph nodes, spleen and red bone marrow

  • Attack either by release of perforins (causing cytolysis) or binding

Phagocytosis

  • Third line of defense by identifying foreign substances or pathogens and consuming them

  • Phagocytes include granulocytes (neutrophils & eosinophils) and macrophages (wandering or fixed)

  • Mechanisms

  • Chemotaxis - phagocytes attracted to a region of infection or damage by chemical agents released by WBCs, damaged cells, or activated complement proteins

  • Adherence - phagocyte adheres to foreign material, enhanced by opsonization

  • Ingestion - by phagocytosis resulting in a phagocytic vesicle

  • Digestion - lysosomes merge with vesicle to deliver a variety of substances

  • digestive enzymes

  • oxidative chemicals - hydrogen peroxide, hypochlorite, & super oxide (O2-)

  • bactericidal substance - defensins

  • undigested parts removed by exocytosis

  • Some pathogens survive, proliferate and ultimately kill phagocyte

Inflammation

  • Series of activities of blood & tissue cells in response to damage by pathogens, physical breakage or toxins

  • Signs include redness, pain, heat, swelling, and possible loss of function

  • Three basic stages - vasodilation and increased permeability of blood vessels, phagocyte migration, and tissue repair

Vasodilation & Permeability

  • This stage primarily responsible for the signs of inflammation

  • Vasodilation causes the reddening and increased heat

  • Increased permeability enables movement of antibodies, phagocytes and clot forming chemicals to leave capillaries and general edema

  • Fibrinogen forms fibrin network around site and limits pathogen movement

  • Several chemical causes for Stage I

  • Histamines released by mast cells, basophils and platelets

  • Kinins formed from precursor in blood (kininogens) - also enhance chemotaxis of phagocytes

  • Kinins, along with foreign substances, may stimulate pain

  • Prostaglandins released by damaged cells enhance histamine & kinin effects; and increased emigration of phagocytes

  • Leukotrienes released by basophils & mast cells

  • Complement components

Phagocyte Migration

  • Neutrophils are first to arrive at site due to chemotaxis along with the nearby fixed macrophages - phagocytosis begins

  • Wandering macrophages are hours later to clean up dying neutrophils, damaged tissue and pathogens

  • Dying cells accumulate (pus)

  • If pus cannot drain out, an abscess forms

  • Prolonged inflammation may cause ulcers

Fever

  • Not a bad thing, unless too high

  • Found to enhance some of the non-specific responses including: effect of interferons and tissue repair

Immunity

  • Also known as specific resistance

  • Involves production of specific lymphocyte or antibody that acts on antigens from strains of bacteria, viruses, cancer cells or toxins

  • Prolonged “memory” of antigens from previous exposure enhances a rapid second response

  • Dependent on B & T cells, during maturation, cells acquire distinctive surface proteins (antigen receptors and self-receptors)

  • T cells with different proteins on membrane (CD4+ or CD8+)

Types of Immunity

  • Cell-mediated immunity (CMI) - destruction of antigen by T cells or their derivatives (killer T cells)

  • Effective against intracellular pathogens

  • Antibody-mediated immunity (AMI) - destruction of antigens by antibodies produced by plasma cells (activated B cells)

  • Effective against extracellular pathogens

  • CD4+ T cells (helper) aid in both

Antigens

  • Two characteristics

  • Immunogenic - stimulates proliferation of specific T and/or B cells or antibodies

  • Reactive - interacts with receptors on T and/or B cells or antibodies

  • An antigen with both characteristics - complete antigen or immunogen

  • Microbial vs. non-microbial (pollen, egg white, incompatible blood or tissue)

  • Antigens find their way to several lymphatic tissues - blood/spleen, skin/lymph nodes, mucus membranes/MALT)

  • Major histocompatibility complex antigens - recognition of self

  • Class I MHC found on all cells except RBCs

  • Class II MHC found on antigen-presenting cells, thymus cells and activated T cells

Structural Nature of Antigens

  • On your own

Antigen Processing

  • Antigen-presenting cells - typically macrophages, B cells and dendritic cells (in epithelial tissue or lymph nodes)

  • Exogenous (antigen outside cell) - ingestion, digestion, binding with MHC-II, display

  • Endogenous (antigen inside cell - viral) - binding with MHC-I, display

Cell-Mediated Immunity

  • Antigen is recognized (T cell receptors)

  • Small group of specific T cells are activated and proliferate

  • Activation requires costimulator (20 currently known including some cytokines)

  • Differentiate into a clone of effector cells (each derived from single activated T cell)

  • Antigen is eliminated

Types of T Cells

  • Helper T cells (TH or T4) - respond to MHC II and release interleukin-2 (a cytokine) which helps stimulate activation and/or proliferation of TC, B and more TH cells)

  • Cytotoxic T cells (TC, T8 or killer T cells) - respond to MHC I or locate foreign cells and secrete substance to kill them (perforin, lymphotoxin)

  • Memory T cells (TM) - recognize the original antigen

Antibody-Mediated Immunity

  • Cells strictly limited to lymphoid tissue (unlike CMI)

  • In presence of foreign antigens, specific B cells process and display MHC II, activate and differentiate into plasma cells (helper T cells are involved)

  • Plasma cells produce the antibodies which circulate in lymph and blood

Structure of Antibodies

  • A glycoprotein with four polypeptide chains, 2 identical heavy, and 2 identical light chains

  • Disulfide bonds hold all chains together in constant portions

  • Variable portions are presented at tips of Y or T shape and form the antigen binding sites

  • The two receptor cites enable two antigen attachments

  • Five classes of antibodies dependent on complexity

Antibody Action

  • Neutralization - blanketing antigens

  • Immobilization - binding on or near cilia or flagella

  • Agglutination - two binding sites can assemble groups of antigens

  • Activation of complement

  • Enhancement of phagocytosis

Immunological Memory

  • Presence of long-lived antibodies or lymphocytes (memory B and T cells)

  • Fundamental concept to immunization

  • Memory B and/or T cells formed during first exposure (primary response)

  • See Table 22.4

Disorders

  • Pay particular attention to AIDS


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