Lymphatic and Immune systems
natural active immunity
- - production of one's own antibodies or T cells as a result of infection or natural exposure to antigen - produces memory cells
IgM
- 10% in plasma - 1st immune response - agglutination - complete fixation - pentamer
IgG
- 80% circulating - crosses placenta to fetus - 2nd immune response - complement fixation
CD4 and CD8
- additional surface proteins on T cells that interact with the Ag-MHC to maintain the TCR-MHC coupling - called coreceptors
thymic hormones
- aid in maturation of T cells - only about 2% of developing T cells survive - die via apoptosis and are clearing by macrophages
lymphandenopathy lymphadenitis
- all lymph node diseases - common site for metastatic cancers (usually swollen, firm, and painless) - lymphadenitis: swollen, painful node responding to a foreign antigen
type I (acute) hypersensitivity
- antibody mediated (IgE), acute - anaphylaxis, asthma, anaphylactic shock
type II hypersensitivity
- antibody mediated (IgG or IgM), subacute - binds to antigens on cells, complement activation and lyses or opsonization - may bind to cell surface receptors and either interferes with function or over-stimulate - blood transfusions
type III hypersensitivity
- antibody mediated (IgG, IgM), subacute - form widespread antigen-antibody complexes - complexes precipitate and trigger intense inflammation, involved in acute glomerulonephritis in systemic lupus erythematosus
T-cell receptors (TCRs)
- antigen receptors on the surface of T cells that recognize and bind to specific antigen fragments - millions of different T cells with unique can recognize specific Ag-MHC complex
stimulants of adaptive immunity
- antigens: large molecules that trigger an immune response, foreign and self-antigens - haptens: small molecules, combine w/ large proteins and producing an adaptive immune response - epitopes: stimulate immune response - autoimmune disorders: failure to distinguish friend from foe
immunocompetent T cells must be able
- bind to MHC on cell - not react to self antigens - positive selection if they can - negative selection if they cannot
in order for B or T cells to produce a response, there must be
- binding of the MHC-II - costimulation
tissue repair
- blood platelets and endothelial cells in injured area secrete a cytokine, platelet drive growth facto (PDGF), stimulating fibroblasts to multiply and synthesize collagen - facilitated by hyperemia that provides materials needed and heat that increases metabolism - fibrin clot may provide a scaffold for repair - pain limits use of body part allowing repair
nonspecific defenses (innate)
- broadly effective, no prior exposure - first line of defense are the external barriers: skin, tears, saliva, mucous, acid mantle, chemical mediators, cells involved in phagocytosis - second line of defense is more specific and includes phagocytic cells, antimicrobial proteins, inflammation and fever
cytotoxic T cells (Tc cells)
- carry out the attack - also known as killer T cells - ex. T8, CD8
type IV hypersensitivity
- cell mediated - 12-72 hr delay - APCs in lymph nodes display antigens to helper T cells, which secrete interferon and cytokines that activate cytotoxic T cells and macrophages - cosmetic and poison icy allergies (happens) - TB skin test
cytotoxic T cells recognize antigen fragments associated with MHC-I molecules:
- cells infected with virus - tumor cells - tissue transplants
interleukins
- chemical messengers between leukocytes - used by lymphocytes and APCs to communicate - cytokines, macrophage, T cell
lymphatic capillaries
- closed at one end - tethered to surrounding tissue by protein filaments - endothelial cells loosely overlapped (allow bacteria and cells entrance to lymphatic capillary, creates valve-like flaps that open when interstitial fluid pressure is high and close when it is low) - more permeable than blood capillaires - several one-way valves - found in nervous system, bone marrow, and tissues w/o blood vessels
complement system
- complement (C) proteins in blood must be activated by pathogens - classical pathway: requires antibodies, specific immunity - alternate pathway: nonspecific immunity - lectin pathway: nonspecific immunity
elimination of invaders: perforin and granulysin
- cytotoxic T cells bind to infected target cell and 2 proteins are released from granules - perforin creates channels in membrane and ECF rushes in causing cytolysis - granulysin enters through the channels and destroys microbes by causing holes in their membranes
elimination of invaders: granzymes
- cytotoxic T cells bind to infected target cells (microbial antigens on surface) - release these, protein digesting enzymes that trigger apoptosis - infected cell is destroyed and released microbes are killed by phagocytes
fever
- defense mechanism that does more good than harm - promotes interferon activity - accelerating metabolic rate and tissue repair - inhibits pathogen reproduction
inflammation overview
- defensive response to injury - limit spread of pathogens and then destroy them - removes debris - initiates tissue repair - cytokines: small proteins that regulate inflammation and immunity including interferons, interleukins, tumor necrosis factor, and chemotactic factors
medulla of thymus
- defined, concentric layers filled w/ granulo - surviving T cells enter here - consist of more mature T cells, epithelial cells, dendritic cells, and macrophages
lymphatic nodules
- dense oval masses of lymphocytes, congregate in response to pathogens - peyer patches: more permanent congregation, clusters found at junction of small to large intestine
lymphatic tissue
- diffuse lymphatic tissue: lymphocytes in mucous membranes and CT of many organs; MALT - lymphatic nodules
lymph nodes all the things
- distributed along vessels and filter lymph - encapsulated oval structures located along lymphatic vessels - contains T cells, macrophages, follicular dendritic cells, and B cells - lymph enters through afferent lymphatic vessels, filtered to remove damaged cells and microorganisms and exits through efferent lymphatic vessels - foreign substances filtered here are trapped by nodal reticular fibers - macrophages then destroy some foreign substances by phagocytosis and lymphocytes bring about the destruction of others by immune responses - site of proliferation of plasma and T cells - about 600 in the human body - covered by a capsule w/ trabeculae extensions
lethal hit mechanism
- docks on cell with antigen-MHC-I protein complex - releases perforin and granzymes to kill target cell - interferons: decrease viral replication and activates macrophages - tumor necrosis factor: kills cancer cells
lymphatic ducts
- drain tissues of body and move lymph into major veins - right lymphatic duct drains to the right side of the head, right upper limb, and right thoracic - thoracic duct drains the remainder of the body
blood flowing into the spleen
- enter central arteries of white pulp - B and T cells carry out immune functions similar to lymph nodes - macrophages destroy blood-borne pathogens - enters red pulp which has 3 functions 1. removal of ruptured, worn out, or defective blood cells and platelets w/ macrophages 2. storage of platelets (up to 1/3 supply) 3. production of PCs during fetal life
autoimmune disease
- failure of self tolerance (core-reactivity, abnormal exposure of self-antigens, changes in structure of self-antigens) - production of autoantibodies
containment and destruction of pathogens: fibrinogen heparin chemotaxis neutrophils
- fibrinogen: tissue clots trapping pathogens - heparin: prevents clotting at site of injury so that the pathogen are in a fluid pocket surrounded by clot - chemotaxis: leukocytes are attracted to chemotactic chemicals - neutrophils: phagocytosis, respiratory burst, secrete cytokines for recruitment of macrophages and neutrophils, macrophages and T cells secrete colony-stimulating factor to stimulate leukopoiesis
wandering macrophages
- found in most tissues - during migration, monocytes enlarge and develop into macrophages
helper T cells
- help promote Tc cell and B cell action and nonspecific defense mechanisms - display CD4 on surface - recognize antigen fragments associated with MHC-II molecules and activated by APCs - function: costimulate all other lymphocytes (secrete cytokines)
immunodeficiency disease
- hereditary lack of T and B cells - vulnerability to opportunistic infections
functions of lymphatic system
- immunity: fluids from all capillary beds are filtered, immune cells standby ready to respond to foreign cells or chemicals encountered - lipid absorption: lacteals in small intestine absorb dietary lipids, fluid called chyme - fluid recovery (fluid balance): absorbs plasma proteins and fluid (2-4L/day) from tissues and returns it to the bloodstream, interference w/ lymphatic drainage leads to severe edema
secondary lymphatic organs
- immunocompetent cells populate these tissues - lymph nodes, tonsils, spleen
the complement system ends with
- inflammation - phagocytosis - cytolysis - immune clearance
mobilization of defenses
- kinins, histamine, and leukotrienes are secreted by damaged cells, basophils, and mast cells - stimulates vasodilation, leading to hyperemia (causes redness, heat, increase in metabolic rate, cell multiplication, healing, dilution of toxins, provides O2, nutrients, waste removal) - stimulates an increase in permeability of blood capillaries (allows blood cells and plasma proteins into tissue, clotting sequesters bacteria, forms scaffold for tissue repair)
tonsils
- large groups of lymphatic nodules in nasopharynx and oral cavity - provide protection against bacteria and other harmful material, form a ring around the border between the oral cavity and the phayrnx - 3 groups
cortex of thymus
- large number of T cells, dendritic cells, epithelial, and macrophages - immature T cells migrate from red bone marrow to cortex - proliferate and begin to mature - dendritic cells assist in maturation process - epithelial cells: serve as framework for as many as 50 T cells, educated the pre-T cells in in positive section, produce thymus hormones
thymus gland
- large organ infants but atrophied as an adult - 2 lobed organ located in the mediastinum - capsule and trabeculae divide it into lobules - each lobule has a cortex and medulla (cortex: tightly packed lymphocytes and macrophages; medulla: reticular epithelial cells produces thymus hormones, hassall's corpuscles)
macrophages
- large phagocytic cells - monocytes that leave blood and enter tissues - longer-lived than neutrophils - can ingest larger particles - found beneath free surfaces within sinuses (spleen, bone marrow, liver, lymph nodes
lymphatic vessels
- large vessels with valves - carry lymph away from tissues
spleen
- largest single mass of lymphatic tissue in the body - 5in organ between stomach and diaphragm
eosinophils
- leave blood and enter tissues - reduce inflammation by breaking down chemicals produced by basophils and mast cells - secrete enzymes that kill parasites
mechanisms of lymph flow
- lymph flows at low pressure and speed -moved along by rhythmic contractions of lymphatic vessels - flow aided by skeletal muscle pump - thoracic pump aids flow from abdominal to thoracic cavity - valves prevent backflow - rapidly flowing blood in subclavian veins, draw lymph into it - exercise significantly increases lymphatic return
lymphatic cells types and explanation
- lymphatic organs contain lymphatic tissue - natural killer cells: responsible for immune surveillance - T lymphocytes: mature in thymus - B lymphocytes: activation causes proliferation and differentiation into plasma cells that produce antibodies - antigen presenting cells: macrophages, dendritic cells, reticular cells
leukocyte development
- margination: selectins cause leukocytes to adhere to blood vessel walls - diapedesis (emigration): leukocytes squeeze between endothelial cells into tissue space
MHC-I
- molecules built into cell membrane of all cells expect RBCs - function: cells infected with viruses are labeled bad by this so that T cells recognize there is a problem - displays the "kill me!" flag
tissue cleanup
- monocytes are the primary agents, arriving in 8-12 hours and then become macrophages - edema decreases venous flow, increases lymphatic flow that factors removal of bacteria and debris - formation of pus: mixture of tissue fluid, cellular debris, dying neutrophils, and microbes
IgA
- monomer in plasma - dimer in mucus, saliva, tears, milk, intestinal secretions - prevents adherence to epithelia
white blood cell immunity
- most important cellular components of immune system - must be able to move into infected tissues and destroy infection - chemotaxis: movement toward the source of chemotactic factors - phagocytosis: endocytosis by neutrophils and macrophages
neutralization complement fixation agglutination precipitation
- neutralization: antibodies mask pathogenic region of antigen - complement fixation: antigen binds to IgM or IgG, antibody changes shapes, initiates complement binding; primary defense abasing foreign cells and bacteria - agglutination: antibody has 2-10 binding sites; binds to multiple enemy cells immobilizing them - precipitation: antibody binds antigen molecules; creates antigen-antibody complex that precipitates, phagocytized by eosinophil
phagocytes
- neutrophils and macrophages - ingest microbes o particulate matter - macrophages develop from monocytes
IgE
- on mast cells - stimulates release of histamines, attracts eosinophils - immediate hypersensitivity reactions
attack phase: cytotoxic T cells
- only T cells directly attach enemy cells - lethal hit mechanism - do the dirty work
3 groups of tonsils and their descriptions
- palatine: "the tonsils", pair at posterior margin of oral cavity, most often infected - pharyngeal: "the adenoids", single tonsil on wall of pharynx - lingual: pair at the root of the tongue
neutrophils
- phagocytic and first cells to enter infected tissue - last only a few hours - create a killing zone primarily against bacteria - degranulation: lysosomes discharge into tissue fluid - respiratory burst: toxic chemicals are created - regularly cross wall of gastrointestinal tract, providing protection - 126 billion/day
artificial active immunity
- production of one's own antibodies or T cells as a result of vaccination - produces memory cells
basophils and mast cells
- promote inflammation when activated by innate or adaptive system - basophils are motile and mast cells are non-motile - dont directly attack the foreign cells
activation of helper T cells
- receptor on CD4 cell binds to foreign antigen fragment associated with MHC-II - inactive these recognize exogenous antigen fragments associated with MHC-II on surface of APC - costimulation occurs and this becomes activated - within hours of activation, secrete cytokines (IL-2), needed for almost all immune responses and prime trigger for T-cell proliferation, acts as costimulator for other T cells and some B cells, positive feedback cycle
activation of cytotoxic T cells
- receptor on CD8 cell binds to foreign antigen fragment part of MHC-I (body cells infected by microbes, some tumor cells, cells of tissue transplant - recognition requires TCR and CD8 cell to maintain coupling with MHC-I - costimulation from helper T cell - occurs in secondary lymphatic organs (such as lymph node)
humoral immunity
- recognition: B cell receptors bind antigen, take in, and digest to then display epitopes on its MHC-II protein; aster costimulation of helper T cell, divide repeatedly and differentiate into plasma cells, producing antibodies specific to that antigen - attack: antibodies bind to antigen, render it harmless, tag it for destruction - memory: some B cells differentiate into memory cells
lymphatic system
- resistance is the ability to ward off disease - nonspecific resistance to disease (general defensive mechanisms effective on a wide range of pathogens) - specific resistance or immunity (the ability to fight a specific pathogen; cell mediated immunity and antibody-mediated immunity)
specific defense (adaptive)
- results from prior exposure, protects against onto a particular pathogen - third line of defense contains the immune system, specificity, and memory
attack phase: helper T cells
- secrete interleukins (attract neutrophils, NK cells, macrophages, stimulate phagocytosis, stimulate T and B cell mitosis and maturation) - coordinate humoral and cellular immunity
interfons
- secreted by certain cells invaded by viruses - generalized protection - diffuse to neighboring cells and stimulate them to produce antiviral proteins - activate natural killer cells and macrophages - destroy host infected host cells - stimulate destruction of cancer cells - interferes w/ viral production
MHC-II
- seen only on membrane of antigen presenting cells (macrophages, B cells, thymus cells) - function: if antigen presenting cells ingest foreign proteins, they display this surface marker - "rally around the flag" stimulates other immune system cells to respond to an antigen
primary lymphatic organs
- site where T and B cells become immunocompetent - red bone marrow and thymus
external barriers involved in immunity
- skin: toughness of keratin, dry and nutrient-poor, defensins (peptides, from neutrophils attack on microbes), lactic acid (acid mantle) - mucous membranes: stickiness if mucous, lysozyme (enzyme destroys bacterial cell walls) - subepithelial areolar tissue: tissue gel (viscous barrier of hyaluronic acid; hyaluronidase: enzyme used by pathogens to spread)
specific immunity
- specificity and memory - cellular immunity: sell-mediated (T cells), direct attack against foreign/diseased host cells, can attack intracellular stages - humoral immunity: antibody mediated (B cells), indirect attack on pathogen, only works against extracellular stages of infectious microorganisms
fixed macrophages
- stand guard in specific tissues - skin, liver, lungs, brain, spleen, red marrow, and lymph nodes
storm of a lymph node
- supports the node - is the capsule, trabeculae, and reticular fibers
natural passive immunity
- temporary, fetus acquires antibodies from mother - through placenta and milk
artificial passive immunity
- temporary, injections of immune serum (antibodies) - snakebite, rabies, tetanus
natural killer cells
- type of lymphocytes - lyse tumor and virus-infected cells - recognize whole classes of cells, not a specific kind of cell - found in blood, spleen, lymph nodes, and red marrow - about 5-10% of lymphocytes are these - attack any cell displaying abnormal or unusual plasma membrane proteins - binding causes release of granules containing toxic substances
suffix for inflammation cardinal signs 3 major processes
-itis redness, swelling, heat, pain mobilization of body defenses, containment and destruction of pathogens, tissue clean-up and repai
IgD
B cell membrane antigen receptor
somatic hypermutation
B cells in lymph nodules rapidly mutate creating new sequences
the three pathways of the complement system leads to
C3 dissociates into C3a and C3b
somatic recombination
DNA segments shuffled and form new combinations of base sequences to produce antibody genes
_____ attack foreign cells and diseased host cells; memory of antigens
T cells
pyrogen
a cytokine, IL-1 that is secreted by macrophages, stimulates anterior hypothalamus to secrete PGE to make body temp go higher
complement proteins from _____ in plasma membrane of target cells causing ______
a ring ; cytolysis
immunity
ability to resist damage from foreign substance and chemicals
if costimulation does not take place, cells exhibit
anergy - usually occurs when T cell encounters a self antigen
costimulation by surface markers
binding of two molecules (B7 and CD28) on the macrophage and helper T cell - helps to hold the cells together
hilus of spleen contains
blood and lymphatic vessels
stroma of spleen contains
capsule, trabeculae, fibers, and fibroblasts
lymph
clear, colorless fluid, like plasma, but w/ much less protein - similar to interstitial fluid w/ the difference being location
hassall's corpuscles
concentric layers of flat cells that degenerate and are filled w/ keratohyalin granules
perforin
creates channels in membrane and ECF rushes in and cells burst
immunization
deliberate exposure to antigen or antibody
analogy for activation of T cell
driving a car - insert correct key (the antigen) into ignition (TCR), turn and the car starts (recognition) but cant move until shifted into gear (costimulation)
negative selection
eliminated clones of lymphocytes that each against self-antigens - occurs more frequently - clonal deletion - alive but unresponsive (anergy, inactive state)
positive selection
ensures survival of lymphocytes that react against antigens - proliferate and form clones with identical. receptors for a specific antigen
sites of development of B cells
fetal stem cells in liver, bone marrow, junction of small and large intestine and appendix
antigen recognition by a TCR w/ CD4 or CD8 protein is
first signal in activation of T cell - becomes active only if it binds to foreign antigen - at same time receives a second signal (costimulation) - different costimulators have different effects
adaptive immunity
involves the ability to recognize, respond to, and remember a particular response - types: humoral or antibody-mediated (B cells) and cell-mediated (T cells)
lymphatic trunks
jugular, subclavian, bronchomediastinal, intestinal, lumbar
major histocompatibility complex (MHC)
molecules attached to plasma membrane - have variable region that can bind to foreign and self antigens - cell ID tag - unique (unless you are an identical twin) - normal function is to help T cells recognize that an antigen is forming and not self
stages of fever
onset, stadium, defervescence
origin and development of lymphocytes (B and T cells)
originate in red bone marrow, move to primary lymphatic organs where they mature into functional cells (B cells in bone marrow, T cells in thymus)
mucosa-associated lymphatic tissue (MALT)
prevalent in passages open to exterior
swollen nodes/tonsils is caused by
proliferation of lymphocytes during immune response
granzymes
protein digesting enzymes to induce apoptosis, kills infected cell but not necessarily the microbe
member T cells
provide immunity from future exposure to antigen
costimulation by cytokines
released by the macrophages of a cytokine that binds to a receptor on the helper T cell
B cells (should/should not) react to self antigens or suffer. clonal deletion/anergy
should not
antigenic determinants
specific regions of a given antigen recognized by a lymphocyte
antigenic receptors (T-cell receptors and B-cell receptors)
surface of lymphocyte that combines directly with antigenic determinant
self-tolerant B cells form B cell clones to
synthesize antigen receptors, divide rapidly, produce immunocompetent clones
T cell recall response
upon re-exposure to same pathogen, memory cells launch a quick attack
parenchyma of spleen contains
white pulp and red pulp - white is lymphatic tissue (lymphocytes and macrophages) - red is venous sinuses filled with blood and splenic tissues