Chapter 22: Lymphatic System Flashcards
List the functions of the lymphatic system
- drain interstitial fluid: returns interstitial fluid leaked from blood vessels back to blood
- transport dietary fats: absorbed by the GI tract
- carry out immune responses: initiates highly specific responses against particular microbes or abnormal cells
lymph
interstitial fluid that has entered the lymphatics
lymphatic vessels (lymphatics)
carry lymph from peripheral tissues to the venous system
lymphoid tissues and lymphoid organs
- houses lymphocytes, phagocytes and other immune cells
2. structures include spleen, thymus, tonsils, lymph nodes and other lymphoid tissue
lymphatic vessels include
- lymphatic capillaries
2. larger lymphatic vessels
List the four cardinal signs of inflammation
- Redness
- Heat
- Swelling
- Pain
Pus
creamy yellow mixture of dead neutrophils + tissue/cells + living/dead pathogens
Abscess
accumulation of pus in an enclosed tissue space collagen fibers may be laid down (walling off sac of pus) may need to be surgically drained
Ulcer
superficial infection (surface of organ or tissue) outer layers of tissue sloughs off resulting in open sore
Allergy
aka Immediate Hypersensitivity or Acute (type 1) hypersensitivities
Begin in seconds after contact with allergen
Activated IgE against antigen binds to mast cells and basophils
Later encounter with the same allergen causes flood of histamine release from IgE’s resulting in induced inflammatory response
Allergen
antigen that causes allergic reaction
Two types of adaptive/specific immunity
- Humoral Immunity
2. Cellular Immunity
Stages of inflammation
- inflammatory chemical release
- vasodilation and increased vascular permeability
- phagocyte mobilization
Humoral Immunity
- Antibody-mediated immunity: antibodies, produced by lymphocytes, circulate freely in body fluids and bind temporarily to target cell, temporarily inactivate and mark for destruction by phagocytes or complement
- B Lymphocyte involvement
Cellular Immunity
Cellular-mediated immunity
T Lymphocyte involvement: act against target cell either directly or indirectly
adaptive/specific immunity
- a specific defensive system that eliminates almost any pathogen or abnormal cell in body.
- Amplifies inflammatory response and activates complement
How does cellular-mediated immunity act against target cells directly?
by killing infected cells
How does cellular-mediated immunity act against target cells indirectly?
by releasing chemicals that enhance inflammatory response; or activating other lymphocytes or macrophages
Lymphoid organs
fibrous connective tissue capsule
lymph nodes, spleen and thymus
Lymphoid cells
consist of 1) immune system cells found in lymphoid tissue and 2) supporting cells that form lymphoid tissue structures.
Immune System Cells
- Lymphocytes: T cells and B cells (protect against antigens)
- Macrophages
- Dendritic Cells
Macrophages
phagocytize foreign substances and help activate T cells
Dendritic Cells
capture antigens and deliver them to lymph nodes
help activate T cells
Supporting lymphoid Cell
-reticular cells: produce reticular fibers, called stroma, that act as scaffolding for immune cells in lymphoid organs.
Lymphoid tissue
largely composed of reticular connective tissue
- macrophages live on reticular fibers
- Spaces between fibers offer a place for lymphocytes to occupy when they return from patrolling body
diffuse lymphoid tissue
loose arrangement of lymphoid cells and some reticular fibers
found in virtually every body organ
larger collections in lamina propria of mucous membranes
lymphoid follicles (nodules)
-consisting of tightly packed lymphoid cells and reticular fibers
-contain germinal centers of proliferating B cells
may form part of larger lymphoid organs
-isolated aggregations: tonsils, peyer’s patches (intestinal wall) and appendix
Structure of a Lymph Node
- vary in shape and size but most are bean shaped: small, less than 2.5 cm
- Surrounded by external fibrous capsule
- Capsule fibers extend inwards as trabeculae
2 Main Functions of Lymph Nodes
- Cleansing the lymph: act as lymph “filters”
- macrophages remove and destroy microorganisms and debris that enters the lymph- prevents unwanted substances from being delivered to blood
- immune system activation: offer a place for lymphocytes to become activated and mount an attack against antigens
Lymph nodes have 2 histologically distinct regions:
- cortex
2. medulla
Cortex
- superficial outer cortex contains follicles with germinal centers that are dense with dividing B cells
- deep inner cortex houses T cells in transit: t cells circulate continuously among blood, lymph nodes and lymph
- abundant number of dendritic cells are closely associated with both T and B cells
Medulla
medullary cords extend inward from cortex and contain B cells, plasma cells and macrophages
lymph sinuses
- found throughout lymph node
- consist of large lymphatic capillaries spanned by crisscrossing reticular fibers
- macrophages reside on fibers, checkin for phagocytizing any foreign matter
General Structure of Antibodies
consists of four looping polypeptide chains linked by disulfide bonds
4 chains consist of:
- Two identical heavy (H) chains with hinge region at “middles”
- Two identical light (L) chains
- Variable (V) regions at one end of each arm combine to form two identical antigen-binding sites
- Stems makeup constant (C) regions
What are the 3 innate/non-specific defences of the human body?
- Nonspecific Barrier
- Nonspecific Cellular Defense
- Nonspecific Chemical Defense
What are the 2 nonspecific barriers?
- Physical Nonspecific Barrier
2. Chemical Nonspecific Barrier
Physical Nonspecific Barrier
- skin
- mucous membrane (lines the respiratory, digestive, reproductive and urinary)
- resident bacteria/normal flora that inhabit the body use available nutrients and space thus prevent pathogens from taking up a residence.
Chemical Nonspecific Barrier
- secretions of the oil and sweat glands (dermicidin)
- lysozyme (found in saliva, tear, sweat)
- acidity of stomach and vagina
- urine
- defensins (antimicrobial peptides - inhibits microbial growth)
- mucin: sticky mucus (traps microorgansim)
Nonspecific Cellular Defense
- phagocytes: white blood cells that ingest and digest (eat) foreign invaders (neutrophils and macrophages)
- natural killer cells: Kill by inducing apoptosis in cancer cells and virus-infected cells and secrete potent chemicals that enhance inflammatory response
Nonspecific Chemical Defense
- inflammation
- protective (antimicrobial) proteins: interferon and complement
- fever
What occurs in this stage of inflammation: inflammatory chemical release?
- Chemicals are released into ECF by injured tissues, immune cells, or blood proteins.
- Include Kinins, Prostaglandins (PGs), Leukotrienes (LTs) and Complement
What occurs in this stage of inflammation: vasodilation and increased vascular permeability?
- Vasodilation: hyperemia—congestion with blood—which leads to redness and heat
- Increased capillary permeability: exudate—fluid containing clotting factors, antibodies, microbes —to leak into tissue
- Results in local swelling (edema)
- Swelling also pushes on nerve endings, resulting in pain
What occurs in this stage of inflammation: phagocyte mobilization?
- Neutrophils flood area first; macrophages follow
- If inflammation is due to pathogens, complement is activated; adaptive immunity elements arrive (pus, abscess and ulcers)
Kinin stimulates
- vasodilation of local arterioles
- increase capillary permeability
- attract leukocytes to area (positive chemotactic agent)
Leukotrienes stimulate
- increase capillary permeability
- attract leukocytes to area (positive chemotactic agent)
Prostaglandins stimulate
- attract leukocytes to area (positive chemotactic agent)
- triggering pain receptors (inducing pain)
- stimulating release of more inflammatory chemicals & intensifying effects (histamine & kinins)
Complement
complements the action of antibodies
How are B cells activated?
- when antigens bind to B cell receptors, cross-linking them
- Triggers receptor-mediated endocytosis of cross-linked antigen-receptor complexes (clonal selection), leading to proliferation and differentiation of B cell into effector cells
How are B cells developed?
- Most clone cells become plasma cells, antibody-secreting effector cells
- Clone cells that do not become plasma cells become memory cells: Provide immunological memory and mount an immediate response to future exposures to same antigen
Major Histocompatibility (MHC) Proteins
- Self-antigens
- Contain groove that can hold piece of self-antigen or foreign antigen
- T lymphocytes can recognize only antigens that are presented on MHC proteins
2 classes of MHC proteins:
- Class I MHC proteins: present in plasma membrane of all nucleated cells (except RBCs)
- Class II MHC proteins: present in plasma membrane of Antigen Presenting Cells (APCs): B lymphocytes, dendritic cells, macrophages
Function of MHC molecules
bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T cells.
Actions of antibodies in human immunity
- Antibodies do not destroy antigens; they inactivate and tag them for destruction
- Form antigen-antibody (immune) complexes
Defensive mechanisms used by antibodies
- Neutralization
- Agglutination
- Precipitation
- Complement fixation
What are the five major classes of Antibodies?
IgM, IgA, IgD, IgG, and IgE
Primary immune response
- cell proliferation and differentiation upon exposure to antigen for the first time
- Lag period: 3 to 6 days
- Peak levels of plasma antibody are reached in 10 days
- Antibody levels then decline
Secondary Immune response
Re-exposure to same antigen gives faster, more prolonged, more effective response
- Sensitized memory cells provide immunological memory - Respond within hours, not days - Antibody levels peak in 2 to 3 days at much higher levels - Antibodies bind with greater affinity - Antibody level can remain high for weeks to months
How are human T cells activated?
Activation is a 2-step Process:
- Antigen binding
- Co-stimulation
Antigen binding
- T cell antigen receptors (TCRs) bind to antigen-MHC complex on APC surface
- TCR must perform double recognition by recognizing both MHC and foreign (nonself) antigen it displays
- Binding of TCR to antigen-MHC complex triggers multiple intracellular signaling pathways that start T cell activation
- Other T cell surface proteins are involved in T cell activation: CD4 and CD8 (help maintain coupling during antigen recognition)
Co-stimulation
- The release of cytokines: co-stimulatory signals
- Without co-stimulation, anergy occurs, in which T cells:
- Become tolerant to that antigen
- Are unable to divide
- Do not secrete cytokines
Development of human T Cells
- Activated TH cells enlarge and proliferate in response to cytokines
- Primary TH cell response peaks within a week
- TH cell apoptosis occurs between days 7 and 30
- Activated T cells are a hazard because they produce large amounts of inflammatory cytokines
- Could result in hyperplasia or cancer if not cleared from system
- Memory TH cells remain and mediate secondary responses
Steps involved in cell mediated immunity
…
What are the 2 populations of T Cells?
- CD4 Cells
2. CD8 Cells
CD4 Cells
-become helper T cells (TH)
- activate B cells, other T cells, and macrophages - direct adaptive immune response
• Some become regulatory T cells, which moderate immune response
• Can become memory T cells
CD8 Cells
become cytotoxic T cells (TC) - capable of destroying cells harboring foreign antigens
• Can become memory T cell
Helper T cells function
• Play central role in adaptive immune response
• Activate both humoral and cellular immunity
• Once primed by APC presentation of antigen, helper T cells:
- Help activate B cells and other T cells
- Induce T and B cell proliferation
- Secrete cytokines that recruit other immune cel
Class II MHC protein function
- Bind with longer fragments (14–17 amino acids) of exogenous (extracellular) antigens
- Recognized by helper T cells
• Signal CD4 cells that help is required
Class I MHC protein function
- Bind with short fragment (8–9 amino acids) of endogenous antigen: protein synthesized inside cell
- Crucial for CD8 cell activation
• Act as antigen holders; form “self” part that T cells recognize
• Inform cytotoxic T cells of microorganisms hiding in cells (cytotoxic T cells ignore displayed self-antige
Self-antigen
normal proteins of cell
Nonself antigen
abnormal proteins found in infected or abnormal cell
Cytotoxic T Cell Function
- Directly attack and kill other cells
- Activated TC cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize
Activated TC cells target:
- Virus-infected cells
- Cells with intracellular bacteria or parasites
- Cancer cells
- Foreign cells (transfusions or transplants)
What two mechanisms do TC cells use?
- TC cell releases perforins and granzyme by exocytosis
• Perforins create pores through which granzymes enter target cell
• Granzymes stimulate cytolysis - TC cell binds specific membrane receptor on target cell, release granulysin and stimulates apoptosis
What are the 3 types of immunodeficiencies?
- Severe combined immunodeficiency (SCID)
- Hodgkin’s Disease
- AIDS
Severe combined immunodeficiency
genetic defect with marked deficit in B and T cells
• Defective adenosine deaminase (ADA) enzyme allows accumulation of metabolites lethal to T cells; fatal if untreated
• Treatment: bone marrow transplants
Hodgkin’s Disease
- an acquired immunodeficiency that causes cancer of B cells
- depresses lymph node cells and thus leads to immunodeficieny
Immunodeficiency
Congenital or Acquired conditions that impair function or production of immune cells or molecules
Acquire Immune Deficiency Syndrome (AIDS)
- Human immunodeficiency virus (HIV) cripples immune system by interfering with activity of helper T cells
- Characterized by severe weight loss, night sweats, and swollen lymph nodes
- Opportunistic infections occur, including Pneumocystis pneumonia and Kaposi’s sarcoma
Autoimmune diseases
when immune system loses ability to distinguish self from foreign
Autoimmunity
production of autoantibodies and sensitized TC cells that destroys body tissue
List examples of autoimmune diseases
- Rheumatoid arthritis: destroys joints
- Myasthenia gravis: impairs nerve-muscle connections
- Multiple sclerosis: destroys white matter myelin
- Graves’ disease: causes hyperthyroidism
- Type 1 diabetes mellitus: destroys pancreatic cells
- Systemic lupus erythematosus (SLE): affects multiple organs
- Glomerulonephritis: damages kidney
Hypersensitivities
immune responses to perceived (otherwise harmless) threat that cause tissue damage
• Antibodies cause Immediate and Subacute Hypersensitivities
• T cells cause Delayed Hypersensitivity