Lymphatic System Flashcards
intro
lines of defense
F: IMMUNITY+DEFENSE of if infectious agents by using leukocyte in CT and lymphoid organs interconnected by blood and lymphatic circulation
lymphatic system consist of lymphatic vessels+ organs
- vessels- empty into bloodstream by large veins in neck: right lymphatic duct or thoracic duct
- organs divided into PRIMARY: red bone marrow+ thymus; SECONDARY: spleen, MALT, l.n + diffuse lymphoid tissue in mucosa of GIT
classifications
- Acc to stromal tissue: LYMPHORETICULAR organs (l.n, bone marrow and spleen). LYMPHOEPITHELIAL organs-wehre immune cells infiltrate epi in embryonic dev (tonsil+ thymus)
- acc to how organs separated from surrounding tissue: NON-CAPSULATED organs (MALT), PARTIALLY capsulated (tonsils). ENCAPSULATED (thymus, spleen, l.n). Red bone marrow is in spongy bone
two lines of defence:
INNATE - fast, non-specific. Physical barriers to prevent prenetration: skin, mucous membrane in GIt, resp and urogenital tract. if penetrate machophage+ leukocyte remove it. has toll-like receptors (TLR) on leukocytes to recognize+ bind to surface components of invaders;non catalytic receptors in sentineal cells:dendritic+ macrophage. NK destroy infected host cell
- produce antimicrobial chemical which forms
HCl +organic acids (to kill entering organism +stop growh). DEFENSIN (F: kill bact by entering cell wall) + LYSOSOMES (F: hydrolyze cell wall of bact) = cationic polypeptide from neutrophils, epithelial cells
Complement system of proteins in blood plasma, mucous, macrophage. F: react w bact surface to aid removal
Interfeurons paracrine factors from leukocytes +virus infected cells F: signal NK to kill infected host+adj cells to prevent infection
ADAPTIVE- slow, specific to antigen. Acquired immunity over exposure to microorganism. B+T lymphocytes (activated against specific invaders when APC present MHC 1). MEMORY cells (similar response in case invaded again).
cytokines
Antigen+antibody
structure of antibody
Cytokines are diverse group of PEPTIDES+ GLYCOPROTEINS w low molecular weight +PARACRINE mode of action
F: COORDINATE the measure of defence and allow for COOMUNICATION between IMMUNE cells at the site of infection
- in innate+ adaptive immunity
- response to target: CHEMOTAXIS aggregation of cells+ directed cell mov. during diapedesis (leukocytes send extensions through opening of endothelial cells-> CT) =called chemokines
interleukin: stimulate/suppress lymphatic activity in adaptive immunity
increases mitotic activity in leukocytes
stimulate phagocytosis +directed cell killing
also affects endothelial cells, endocrine and certain autonomic neurons
antigen
recognized as adaptive immunity causing response. PROTEINS+POLYSACCHARIDES in foreign particle. immune cells recognize epitope and response: humeral (b cells creating antibody) or cellular (T cells)
antibody
immunoglobulin, is glycoprotein of immunoglobulin family. secreted by plasma cells (from b cells) whose receptors bind to epitopes.
antibody location: blood plasma, interstitial fluid + membrane proteins on surface B cells; transported into secretion of glands
structure
- 2 light and 2 HEAVY CHAINS held by DISULFIDE bond,
Fc region is an isolated carboxyl terminal portion of heavy chain mol; recognized by receptors on basophils+ mast cells.
variable region: first 110 aa near terminal ends of light+dark chain
antigen binding site: variable portion of heavy and light chain
classes of antibodies
actions of antibodies
classes of antibodies (IgG+D+E monomers)
IgG: MONOMERS most ABUNDANT 75-85%, highly soluble+stable; for FETAL circulation providing passive immunity. increases during infections, activate phagocytosis, neutralizes antigens
IgA: 10-15% DIMER w J CHAIN connecting both heavy chains +secretory component. produced by plasma cells in mucosa of digestive, resp and urogenital cells. in exocrine cells as secretory component undergo transcytosis. product=RESISTANT TO PROTEOLYSIS +reacts w microorganism (milk, tears, mucous). F: PROTECT MUCOSA
IgM: 5-10% PENTAMENAR. on B lymphocytes (as monomer). F: FIRST antibody produced initial immune resp activating COMPLEMENT SYSTEM (proteins that react w bacteria to remove)
IgE: MONOMER, 0.002% + bound to surface of BASOPHILS+ MAST cells. F: destroys worms+ when encountered to antigen, trigger liberation of active substance= HISTAMINE, HERAPIN =allergic reactions
IgD: MONOMER 0.001%, surface of B lymphocytes. F: antigen receptor trigger initial B CFELL ACTIVATION
actions of antibodies
- NEUTRALIZATION: IgA, IgG= antibody COVER biologically active part of virus
- AGGLUTINATOIN: form CLUMP by antibody CROSS LINKING bact cells
- PRECIPITATE: antibody CROSS LINK circulating particles (toxins) forms INSOLUBLE ANTIGEN-ANTIBODY COMPLEX
exposed Fc:
- COMPLEMENT FIXATION: Fc binds to complement proteins (complex w IgM+ IgG) and activates ENZYNATIC REACTIONS that BIND+RUPTURE c.m, clump the antigen on bact+ illicit arrival leukocytes
- OPSONIZATION: Fc binds to receptor of MACROPHAGE, neutrophils and eosinophiles. Triggering/ increasing efficiency of phagocytosis
- activate NK cells: Fc binds to NK, triggering release of cytotoxic cells= PERFORIN+ GRANZYMES for apoptosis
antigen representation
antigens recognized by lymphocytes are bound to specialized internal C.M proteins. Major histocompatibility complex are a part of this
MHC 1: to ID cell. presents self antigens cells that tell T cells to ignore/attack. synthesis: before leaving ER, binds to protease derived peptide fragments represent all protein synthesized. (present fragments that cell created)
MHC 2: for phagocytotic active leukocytes presenting fragment of cells INGESTED. synthesis: b4 joining plasmolemma, Ga vesicles w MHC 2 fuse ENDOLYSOSOMAL VESICLES-has antigens ingested by receptive mediated endocytosis, pino, or phagocytosis
B lymphocytes
T lymphocytes
lymphocyte- adult stem cells is in red bone marrow
matures into central+ primary lymphoid organs which after maturation migrate to secondary lymphoid organs. basophilic nuclei, little cyto. CD markers allow for distinguishing b cells while t cells for immunocytochemical methods
T cells
75%
CD4+ (cluster of differentiation) or CD3+ cells react to antigen on MHC
TCR: 2 BETA CHAINS made of glycoproteins w variable regions
T HELPER cells = CD4+ and produce cytokines that help different b lymphocytes-> plasma cells and activates macrophage +cytotoxic T lymphocyte (2)
has CTL’s= CD8+ binds to MHC I on foreign particles. IL-2 (interleukin 2 from CD4+) release cytotoxic t cells which bind to antigens and are removed by perforins+ granzymes
recognizes + activates +proliferate. perforins+ granzymes trigger apoptosis why its called cell-mediated immunity. (similar to NK)
memory cells formed from cytotoxic t cells
REGULATORY T cells =suppressor (CD4+ and CD25+) INHIBIT responses, identified by Foxp 3 transcription factor. Has immune tolerance, UNRESPONSIVE TO SELF ANTIGENS + suppress excessive immune response =peripheral tolerance (supplement central tolerance in thymus)
B cells-originate+ mature in red bone marrow
150,000 receptors are monomers of (IgG+ IgM) +bind to antigen directly, RECOGNIZE free soluble ANTIGENS or antigens on surface binds to antibody -> endocytosis +peptides from antigens present on MHC II -> helper T cells binds B cells and activates w cytokine which stimulate cell proliferation
Fc part of antibody (has FDC cells- mesenchymal origin, long dendritic filaments- antigen-antibody complexes that help to bind receptors to Fc (complement system or for b cells) bind MHC II causes B cells to ATTACH + become activated and aggregate as PRIMARY LYMPHATIC NODULE. T helper cells help form SECONDARY lymphoid nodule/follicle (larger, more prominent, spherical masses, lightly stained germinal layer, w CENTROBLAST (large lymphocytes, helps w immunoglobulin gene recombination, rapid proliferation and quality control). the growth of cells are exuberant+ rapid causes non proliferating b cells to be pushed aside and produce darkly stained peripheral MANTLE after 2 WEEKS cells of germinal centre + mantle DISPERESED+structure of secondary lymphoid organs LOST
gamma+ delta lymphocytes : smaller population of gamma and delta CHAINS. migrate to EPIDERMIS+ mucosal epi= INTRAEPITHELIUM. DON’T circulate 2 lymphoid organs.F: also to INVADE
lymphoid tissue
RETICULAR CT+ collagen III
w high # lymphocytes, surround capsule of 2 lymphoidal organs
stains dark blue HE
APC+ PLASMA cells
scattered w FDC (follicular dendritic cells)- mesenchymal in. origin, scattered w b lymphocytes, long filamentous processes. has ANTIGEN-ANTIBODY complexes that help receptors to bind to complement system or Fc or immunoglobulins
MALT
mucosa assoc lymphoid tissue
part of secondary lymphoidal tissue 70%
RETICULAR epi
consists of large+diffuse collections of lymphocytes, IgA secreting plasma cells, APC, lymphoidal NODULES/follicles also in epithelial lining of mucosa
conc in resp, digest, genitourinary tract bc common site of infection bc lumen open to ext environment (pathogens)
MALT is dispersed in CT+ aggregates to form tonsils, peyers patch in ileum+appendix
tonsils: waldeyers ring
are irreg masses of lymphoid tissue in mucosa of posterior oral cavity+ nasopharynx
F: protects against antigen from nasal+oral cavity. antibodies produced IgA+ IgM. biggest activity 8y-10y
- Palatine tonsil junction of oropharynx and oral cavity
ovoid dense accum of lymphatic tissue in tunica mucosa. STRAT SQ epi, increase SA due to 10-20 invaginations forms TONSILLAR CRYPS where epi lining has densely infiltrated LEUKOCYTES+ LYMPHOCYTE (where transforms to desquamatic sq-> RETICULAR epi). lymphoidal tissue filled w lymphocytes w secondary lymphoidal nodules around crypts w DENSE CT as PARTIAL CAPSULE (incomplete) - Lingual tonsil base of tongue
lymphoidal tissue in LP at root of tongue, domed elevation. also STRAT SQ epi penetrates into tonsil, w simple UNBRANCHED CRYPTS (one for each domed elev ; NO distinct CAPSULE; WEBERS glands (mucous) open to crypts - pharyngeal tonsil : post wall of nasopharynx
pseudostratified ciliated columnar epi w thin underlying capsule. mucosa w lymphoid tissue+nodules invaginated w SHALLOW INFOLDINGS. NO CRYPTS
tubal tonsil- lat wal of nasopharynx post to eustachian tube opening
MALT aggregate as lymphoidal follicles =peyers patches w 10-200 nodules +bulge to gut lumen w out CT capsule. ileum lined w absorptive SIMPLE COLUMNAR epi.+ intraepi lymphocytes between them
- nodules have M cells (F: uptake of foreign particles)
w distinct short APICAL MICROFOLDS rather than brushborder typical of neighbouring enterocytes ; basal has unique large INTRAEPI POCKETS w lymphocytes and APC dendritic cells which pass through porous basement mem
lumenal antigens bound to M cells-> binds T-helper and B cells -> dendritic cells process antigen and present to lymphocyte to induce adaptive response
- B cells differentiate to plasma cells secrete IgA which couple w secretory proteins and transport to intestinal lumen by *ENTEROCYTES (have brush border w GLYCOCALYX). IgA binds to antigen (neutralize foreign particles in lumen and binds apical surface IgA to promote antigen uptake and induces immune resp)
appendix projection of cecum:
- mucosa has lymphoidal tissue effacing glands of large intestinal wall
- lumen has bact flora of large intestine +serves to retain beneficial bact during diarrheal illness
l.n
lymph vessels: dense CT capsule surrounds l.n extends trabeculae to where blood vessels branch. VALVE allow for unidirectional flow. convex surface where afferent lymphatics enter and concave depress where hilum is where efferent lymphatics + a+n. lymph. Lymph capillary under epi (skin)+epi mucosa of git. lymph capillary wall more permeable to large mol (bact+antigens+ lipids). lymph capillaries anchored to anchoring FILAMENTS to basal lamina
process
lymphocyte from lymph: afferent LV-> subscapular sinus -> trabecular/intermediate sinus-> perforate from sinus to superficial+deep cortex -> medullary sinus-> efferent LV
lymphocyte from blood -> enter deep cortex through HEV-> superficial cortex-> efferent LV
l.n: bean shaped+ENCAPSULATED, 1-mm by 25mm. 400-450 l.n in axilla, groin, along major vessels, thorax, and visceral mesenteries. embedded in LOOSE CT. on line FILTER of lymph defend against spread of microorganism+tumour cells. provide enclosed environ for antigen representation +develop of plasma cells. most abundant cells in stroma w RETICULAR fibers (APC+ MACRIPHAGES+ FDC)
3 regions
1) cortex: SUBSCAPULAR sinus (receive lymph from afferent lymphocyte right after capsule). cortical/TRABECULAE SINUS branch internally along trabeculae. THIN DISCONTINOUS ENDOTHELIA penetrated by RETICULAR fibers +processes of DENDRITIC cells. (lymph pass through sinus+ lymphoid tissue). lymphoidal NODULES w or w out germinal center w B+ T-herlper cells+long interdigitating process of FDC+macrophage (to remove defective b cells undergoing apoptosis).
2) paracortex: no precise boundaries, differentiated from cortex by LACK B lymphoidal nodule. lymphoid tissue RICH in T-HERLPER cells. specialised epi venules= HEV high endothelial venules : represent entry point for 90% circulating lymphoid-> l.n+ endothelial cells become enlarged/CUBOIDAL and apical glycoproteins assist in DIAPEDESIS of B+T cells from blood-> paracortex
3) medulla: medullary CORDS and sinus
cords: BRANCHES cordlike MASSES of LYMPHOIDAL tissue extend to paracortex. has B +T+ plasma cells
sinus: dilated space lined w DISCONTINOUS ENDOTHELIUM separating cords. lumen of MESHWORK or RETICULAR fibers =final lymph FILTER. has MACROPHAGE+NEUTROPHILS. medullary sinus is continuous w cortical sinus + converse at hilum as EFFERENT lymphoidal vessel.
function of l.n
- filtration of lymph within sinus (foreign particles/tumour cells TRAPPED +PHAGOCYTOSED
- immune response:
a) initiated by ANTIGEN covered in lymph =immune resp
b)antigen trapped on FDC, processed by MACROPHAGE (phagocytosis), or dendritic cellls+ b cells
c) activated b lymphocytes divide (in germinal layer of lymph nodules) and differentiate to plasma cells
d) plasma cells migrate to medullary cords and release ANTIBODY (IgA)
*metastatic cancer: cells form primary tumour enter lymphatic -> sentinel l.n-> 2 tumour in l.n (l.n key to states of cancer)
Spleen
2 parts
blood circulation
- LARGEST accumulation of lymphoidal tissue
- only lymphoid organ involved in FILTRATION of blood (important for defense against blood-borne antigens).
- main site of RBC+ THROMBOCYTE destruction.
- production site of ANTIBODIES and activated lymphocyte
- left upper quadrant of abdominal cavity 12 x 7 x 3 cm (V DECREASE after puberty)
- DENSE CT capsule covered in MESOTHELIUM (single layer of sq epi). Where TRABECULAE emerge to penetrate parenchyma or splenic pulp
- LYMPHORETICULAR organ: stroma RETICULAR CT, reticular cells+fibers
- large trabeculae at hilum carry branches of a,n, v and lymphatics into spelinc pulp
***White pulp 20%
- lymphatic tissue, mostly lymphocytes
- CENTRAL A + PALS periarterial lymphatic sheath. (*THYMUS DEPENDED zone, mostly T lymphocytes needed for b cell antibody prod, DENDRITIC cells, PLASMA cells)
- lymphatic NODULES: lightly stained germinal layer, MALPHIGIAN CORPUSCLE; in course of central a (surrounded by PALS); MARGINAL ZONE = sinuses
- B cells within PALS activated by TRAPPED antigen to form a TEMPORARY lymph nodule: *arteriole PUSHED eccentric position-> send capillary throughout white pulp+ to small sinuses in peripheral marginal zone of developing B cells around each nodule.
***red pulp
- central a enter red pulp+ LOSES SHEATH of lymphocytes + branches as PENICILLAR ARTERIOLES that continue as capillaries (sheathed w APC)
- made of mostly SPLENIC CORDS (of Billroth) and are separated by splenic SINUISOIDS (where rbc removed)
- RETICULAR tissue w lymphocytes, MACROPHAGE, rbc, GRANULOCYTE and PLASMA cells
- sinusoids lined w STAVE cells (rod shaped, elongated endothelial cells w reticular fibers perpendicular to long axis of sinus) create intercellular spaces =DISCONTINOUS BASAL LAMINA to allow in/out mov of rbc. F: filter of defected rbc.
blood circulation through splenic red pulp
1) CLOSED : capillaries branch from penicillar arteriole connect directly to SINUISOIDS. covered in ENDOTHELUM
2) open: capillaries from half of penincillar arterioles are OPEN ENDED (blood goes to stroma of splenic cords). all blood must go through STAVE cells into sinusoids. SWOLLEN rbc cant pass and are removed by MACROPHAGE which stores the Fe in ferritin proteins/transferrin. iron free Hb bound to HEMOPEXIN (transport protein), * metabolised to BILIRUBIN, and excreted in BILE by liver cells.
sinuisoids-> blood goes to small red pulp converge as TRABECULAR v-> SPLENIC v
- trabecular v- NO SMOOTH m and resemble endothelium-lined channels hollowed out in trabecular CT
F: blood filtration- lymph nodes filter lymph spleen filters blood using macrophages
immune resp: APC of antigen-> initiate response
proliferate + activate w B+T lymphocyte
antibodies production against circulating in blood
antigens removed from blood
removal+destruction of rbc- (macrophage), transport Fe into bone marrow (ferritin+ transferrin)
Thymus
CENTRAL lymphoid organ +LYMPHOEPITHELIAL organ where T cells produce+mature in thymus. BILOBED in SUPERIOR MEDIASTINUM. F: *central tolerance PREVENTS AUTOIMMUNITY by removing T cells that attack self antigens
embryo: THIRD pair of PARYNGEAL POUCH (endoderm), precursor LYMPHOBLAST circulate from bone marrow to invade + proliferate thymic epi. active T cells production until puberty where INVOLUTION (Decreasing in size+activity+ filled w ADIPOSE tissue-more prominent than HASSAL corpuscle).
vasc CT CAPSULE extends septa into parenchyma dividing into incomplete lobules (cortex has lobules, medulla continuous). cortex darkly BASOPHHILIC cyto; medulla is lightly stained.
cortex basophilic due to increased density ni lymphoblast (THYMOCYTES) and small LYMPHOCYTES. Some thymocytes arrive via VENULE (among MACROPHAGE assoc w TEC thymic epithelial cells= feature of epi+RETICULAR cells). TEC large euchromatic nuclei 3 types
- 1) SQUAMOUS TEC form layer joined by DESMOSOMES+ OCCLUDING junctions. LINE CT of capsule, septa and surround microvasc. Created isolated cortical compartment + together w vasc ENDOTHELIAL cell+PERICYTES forms BLOOD-THYMUS barrier to prevent UNREG exposure of THYMOCYTE to antigens.
- 2) STELLATE TEC w KERATIN TONOFILAMENTS joined by DESMOSOME+ form CYTORETICULUM where macrophage+ lymphocyte attach instead of reticulin fibers. these cells are APC w MHC I,II. Secrete CYTOKINES for t reg cell development +other= justify occlusion to endocrine gland.
- 3) SQ CORTICAL TEC express MHC II but form sheet-like CORTICOMEDULLARY BARRIER between two regions of each lobule.
lightly stained thymic medulla, fewer, larger + more lymphocytes. MICROVASC NOT SURROUNDED by TEC and mature T lymphocytes EXIT thymus by passing through walls of venules + efferent lymphatics in region. 3 related types of medullary TEC forms: - 1) second layer of boundary between cortex+ medulla - 2) cytoreticulum supports less densely packed T lymphocytes, dendritic cells, macrophages+ express many specialised proteins specific to cells+other organs - 3) large aggregated TEC concentrically arranged = HASSAL corpuscles (100 um in d+ secrete CYTOKINES control activity of local DC (dendritic cells)+development of REG T cells for peripheral tolerance.
role of thymus in T cell maturation
- thymus site of T lymphocyte differentiation and selective removal (reactive against self antigens=key for inducing central self tolerance). T lymphocyte arriving to thymus don’t have CD4, CD8 or TCR. cells populate cortex and proliferate recombining variable regions of alpha and beta chains genes allowing for expression of all three.
- thymocytes two stage SELECTION process of quality control to make sure have function TCR and that don’t bind to MHC w self antigens (self attacking). only 2% of T cells pass both, process takes 2 weeks in cortex ends in medulla.
positive control: presenting ANTIGENS bound to MHC I, II if T lymphocytes fail to bind = apoptosis by macroph/ dendritic cells.
(starts w TEC in CYTORETICULUM of cortex, present thymocytes w peptides on MHC I,II important for development of CD 4 CD8 T cells=determines if functional. fail test of FALTY GENE of alpha and beta chain)
negative control: T cells that bind to MHC obtain SELF =apoptosis
(in medulla, T cells w function TCR encounter antigens on cytoreticular TEC+ dendritic cells (gene aire =autoiimune reg promotes expression of tissue specific antigens)
after both controls exit thymus as T HELPER cells or CTL CYTOTOXIC T lymphocytes.
CENTRAL IMMUNOTOLERANCE is due to deletion of both these cells. peripheral tolerance is mediated by T REGULATORY cells which also develop in medulla due to cytokines from hassal corpuscles.
DNES
diffuse neuroendocrine cell system
origin: endoderm of embryonic gut+bronchial buds
location: bronchopulmonary tract, islets of L (in enterochromaffin cells on both sides of islet +small duct of pancreas)
F: produces polypeptides+ NT (seratonin+ 5hydroxytruptamine= called APUD cells)+ reg motility and secretion in digestive tract
stain: chromium salt= enterochromaffin cells
silver nitrate= argentaffin cells
immunohistochemistry: antibody against (insulin- stains b cell)
Which lymphatic organs have corpuscle?
