Lymphatics & Immunity Flashcards
What does the lymphatic system consist of?
Lymph
Lymphatic vessels
Lymphatic tissue
Lymph
A liquid type of connective tissue that is clear and colourless.
Found in lymphatic vessels and tissues
In between cells = interstitial fluid
In blood = plasma
Lymphatic tissues
Lymph organs, RBM.
Specialized forms of reticular connective tissue that contain a large number of lymphocytes
Lymphocytes
Agranular white blood cells that participate in adaptive immune response (B and T cells)
(Plus granular nonspecific NK cells)
3 Major functions of the lymphatic system
- Drains excess interstitial fluid
- - returns it to the blood via subclavian veins
- - approximately 3 litres/day
- - also returns lost plasma protein to blood stream - Transports dietary lipids
- - plus lipid soluble vitamins (A, D, E and K) - Carries out immune responses
Lymphatic vessel pathway
Blood capillaries –> interstitial space –> lymphatic capillaries –> lymph vessels –> lymph trunks –> lymph ducts –> veins
Lymphatic capillaries
- Located in the spaces between cells
- Have terminal (closed) ends on one end
- Cells overlap so interstitial fluid flows in by not out
- when pressure greater in interstitial fluid, cells separate; when greater in lymph, cells adhere - Unite to form lymphatic vessels
- HIghly permeable
Anchoring filaments
Contain elastic fibres; attach lymphatic endothelial cells to surrounding tissues.
Also when excess interstitial fluid accumulates and tissues swell, filaments are pulled and openings between cells increase.
Lacteals
Specialized lymphatic capillaries in small intestines that carry dietary lipids into lymphatic vessels
Chyle
Lymph containing dietary lipids drained from small intestine, carried in lacteals. Appear creamy white.
Principle Lymph Trunks
- Lumbar (lower limbs, wall and viscera of pelvis, kidneys, adrenals, abdominal walls)
- Intestinal (stomach, intestines, pancreas, spleen, part of liver)
- Bronchomediastinal (thoracic wall, lung, heart)
- Subclavian (upper limbs)
- Jugular (head and neck)
Lymph Ducts
- Thoracic (Left Lymphatic) Duct
- - begins ate Cisterna Chyli
- - located anterior to L2
- - main duct for return of lymph to blood
- - receives from: R&L lumbar trunks; R&L intestinal trunks; Left jugular trunk; left subclavian trunk; left bronchomediastinal trunk - Right Lymphatic Duct
- - Receives lymph from the: Right jugular, Right subclavian, and Right bronchiomediastinal trunk
Where do the lymph ducts drain?
Thoracic (Left Lymphatic) duct drain into venous blood at the junction of the left internal jugular and left subclavian veins
Right Lymphatic duct drains into venous blood at the junction of the right internal jugular and right subclavian veins
Like veins, lymph flow is affected by
Valves
Skeletal muscle pump
Respiratory pump
Primary lymphatic organs
Where stem cells divide and become immunocompetent
Red bone marrow and thymus
Secondary lymphatic organs
Sites where most immune responses occur
Lymph nodES, spleen, lymph nodULES
Pluripotent cells in the RBM give rise to:
- Mature immunocompetent B Cells
2. Pre-T cells
Thymus
Bilobed
In mediastinum, between sternum and aorta
Two lobes divided by CT capsule
Each lobule contains outer cortex and inner medulla
Mature T cells leave thymus via blood and travel to lymph nodes, spleen, and other lymphatic tissue.
Large in infants; after puberty not so much. Gets replaced by adipose and areolar CT
Trabeculae (thymus)
Extension of the CT capsule which penetrate inward and divide each lobe into lobules
Outer cortex (thymus)
Receive pre-T cells from RBM
Dendritic cells (derived from monocytes) assist T cell maturation
Epithelial cells: produce thymic hormones; educate pre-T cells through Positive Selection
Macrophages: clear out debris
Only 2% of developing T cells survive
Inner medulla (thymus)
Mature T cells
Epithelial cells: created clusters called thyme (Hassall’s) corpuscles. (function unknown)
Dendritic cells
Macrophages.
Lymph nodes
Secondary lymphatic organs
Usually occur in groups
Encapsulated
Important Lymph Nodes
Neck 1. supraclavicular Arms 2. axillary 3. cubital Legs 4. inguinal 5. popliteal Thorax 6. paraspinal 7. parasternal
Trabeculae (lymph)
Capsular extension which:
- divide lymph node into compartments
- provide support
- provide a route for blood vessels
Stroma (lymph)
Structural supportive framework
Composed of :
- capsule
- trabeculae
- reticular fibres
- fibroblasts
Parenchyma (lymph)
Functional part of lymph node Composed of: 1. Superficial cortex a. outer cortex b. inner cortex 2. Deep medulla
Lymphatic sinuses
In lymph nodes
Series of irregular channels that contain branching reticular fibres, lymphocytes and macrophages
Route through lymph node
Afferent lymphatic vessels
Subcapsular –> trabecular –> medullary sinuses
Efferent lymphatic vessels emerging from hilum
Hilum
Fissure of depression through which nerves or blood vessels enter an organ.
Lymphatic nodules (in lymph nodes)
Found in the outer cortex. Mostly secondary lymphatic nodules.
Primary Lymphatic Nodules
composed mostly of B cells
Secondary Lymphatic Nodules
Form in response to anagenetic challenge
Sites of plasma cell and memory B cell formation
Inner lymphatic cortex
In superficial cortex of lymphatic node.
Consists mainly of T cells and dendritic cells (APC/support cells) that enter lymph cell from other tissue
Spleen
Largest single mass of lymphatic tissue
Located in left hypochondriac region between stomach and diaphragm
Splenic artery, vein and efferent lymphatic vessel travel through hilum
Splenic arteries – central arteries – white pulp – B and T cells carry out immune functions
Structure of spleen
Encapsulated by dense CT, covered by visceral peritoneum (serous membrane)
Trabeculae extend inwards from capsule
Splenic stroma
Capsule +
Trabeculae +
Reticular fibres +
Fibroblasts
Splenic parenchyma
White Pulp: lymphatic tissue; lymphocytes and macrophages arranged central arteries of spleen
Red Pulp: blood filled venous sinuses and cords of splenic tissue called splenic (Bilroth’s) cords. Closely associated with veins.
3 Functions of Red Pulp
- Removal by macrophages of ruptured, worn out or defective blood cells or platelets
- Storage of platelets (up to 1/3 supply)
- Fetal hemopoesis
Ruptured Spleen
Most often damaged in abdominal trauma
Can cause significant haemorrhage and shock
After splenectomy, RBM and liver can take over some of the functions
Lymphatic Nodules
Eggs shaped masses of lymphatic tissue
NOT encapsulated
Scattered through lamina propria of mucous membranes lining GI, urinary, reproductive and respiratory tracts = MALT (mucosa associated lymphatic tissue)
Often small and solitary, but can occur in aggregations.
Where lymphatic nodules aggregrate
Tonsils Pharyngeal/adenoid x 1 Palentine x 2 Lingual x 2 Peyer's Patch (ileum of small intestine)
Innate Immunity
Non-specific immunity
Includes external and internal defences
First line of defence (innate immunity)
- skin - epidermis
- physical barrier, plus shedding removes microbes
- mucous membranes
What elements of the muscosa combine to help first line of defence?
Mucus Hairs Cilia Lacrimal apparatus Saliva Lysosomes Effluents (urine, vaginal secretions, barfing) Chemicals -- all acidic to discourage bacterial growth
Second line of defense
- Antimicrobial substances
- - Interferon
- - Complement
- - Iron binding proteins
- - Antimicrobial Proteins - Natural killer cells and phagocytes
Interferon
IFN
Released by virus-infected cells
Interfere with viral replication in neighbouring cells
Complement
Normally inactive proteins in blood plasma and plasma membranes
When infected enhance immune reactions:
–> cytolysis
–> phagocytosis (opsinization)
–> inflammation (histamine release, chemotaxis)
Iron binding proteins
inhibit bacterial growth by reducing amount of available iron (transferrin, lactoferrin, ferreting, hemoglobin)
Antimicrobial proteins
Short peptides that have a broad spectrum of antimicrobial activity
ex. dermicidin, defensin, catherlicidins, thrombocidin
Natural Killer Cells
5-10% lymphocytes in blood. Also in spleen, lymph nodes and RBM
Attack any cell with unusual plasma membrane proteins
Release perforins and granzymes
Perforins
Cytokine released by NK cells that act like spears, poking holes in the membrane of the target cells
Granzymes
Cytokine that causes target cell to undergo apoptosis. Released by NK cells
Phagocytes
Neutrophils and macrophages
5 steps of phagocytosis
- Chemotaxis
- Adherence
- Ingestion
- Digestion
- Killing
Inflammation
Nonspecific response of the body to tissue damage.
Characterized by swelling, heat, altered function, redness and pain.
3 stages of inflammatory response
- vasodilation and increased vasopermeability
- emigration of phagocytes from blood to interstitial fluid
- tissue repair
Histamine
Released by mast cells, blast cells, and platelets.
Release stimulated by neutrophils and macrophages
Cause vasodilation and increased permeability
Kinins
Polypeptides formed in blood, induce vasodilation and permeability.
Chemotactic.
Ex. bradykinin
Prostaglandins
Lipids released by damaged cells; intensify effects of histamine and kinins
May also stimulate emigration of phagocytes
Leukotrienes (LTs)
Produced by basophils and mast cells
Cause increased permeability
Adherence of phagocytes to pathogens
Chemotactic agents
Complement (inflammatory response)
Stimulates histamine release, attracts neutrophils by chemotaxis, promote phagocytosis
Leukocytosis
Increase in total local WBCs
A result of emigration
Fever
intensifies the effects of interferons, inhibits the growth of some microbes, and speeds up reactions that aid repair
Adaptive specific immunity
The ability of the body to defend itself agains specific invading agents
Antigens
substances that are recognized as foreign and provoke immune response
Two properties of specific immunity
- specificity
2. memory
Immunocompetence
The ability to carry out adaptive immune response.
In T cells before they leave the thymus; B cells before they leave RBM
Two types of mature T cells leave thymus
Helper T (CD 4) Cytotoxic T (CD 8)
Two types of adaptive immunity
- Cell mediated
2. Antibody meditated
Cell mediated immunity
Cytotoxic T cells directly attack invading antigens (endogenous)
Intracellular pathogens: viruses, bacteria, fungi, some CA cells, foreign tissue transplants
Antibody mediated immunity
B cells transform into plasma cells, secrete antibodies/immunoglobulins
Effective against exogenous/extracellular pathogens (viruses, bacteria, fungi in fluids outside cell)
Clonal selection
The process by which lymphocytes 1) proliferate and 2) differentiate in response to a specific antigen
(antigenic challenge)
Results in population of clones that can recognize the original lymphocyte
Occur secondary lymphatic organs
Clonal selection gives rise to two types of cell:
- Effector cells
2. memory cells
Effector cells
Result of clonal selection
Carry out immune response to destroy or deactivates antigen.
Gets shit done. Then dies.
Active helper and cytotoxic T cells, plasma cells
Memory Cells
Result of clonal selection
Do not actively participate in initial immune response
Response quicker in subsequent invasion
Memory helper T, memory cytotoxic T, memory B cells
Antigen
Proteins (or protein aggregates) located on or associated with a pathogen (can also be nucleic acids, lipoproteins, glycoproteins, large polysaccharides)
May be entire microbe, or just a part of it.
Epitope
Fragment of microbe which acts as an antigen
Two important characteristics of antigens
- Immunogenicity (provokes response)
2. Reactivity (reacts to responding cells)
Three routes of antigens past innate defences
- blood stream to spleen
- skin through lymphatic vessels to lymph nodes
- mucous membranes to MALT
Haptens
Like antigens, have reactivity but lack immunogenicity
Can stimulate an immune response but only if attached to a carrier protein
ie Poison Ivy
Major Histocompatibility Complex (MHC)
Self-antigens
AKA human leukocyte antigens (HLA)
Help T cells recognize cell as self/foreign
Two types of MHC
MHC 1: Built into the PM of all body cells except RBC’s
MHC 2: Appear on the surface of Antigen Presenting Cells (macrophages, dendritic cells, and B cells)
Pathway of Antigen Processing.
Antigenic proteins broken down into peptide fragments – associates with MHC
Antigen-MHC complex is inserted into the PM of a body cell [Antigen presentation]
Processing Exogenous Antigens
Bacteria, worms, pollen and dust, viruses that are still outside the cell
APCs ingest AG Digestion of antigen into peptide fragments Synthesis of MCH-2 Packaging of MCH-2 Fusion of vesicles Binding of peptide fragment + MHC-2 Insertion of AG-MHC2 complex into PM
Located in areas where AGs are likely to penetrate innate defences
After processing and presenting, migrate tissues –> lymph vessels –> lymph nodes
Processing Endogenous Antigens
Bacterial toxins, abnormal proteins synthesized by CA cells, viruses inside cells
Digestion of AG Synthesis of MHC-1 molecules Binding of peptide fragments to MHC-1 Packaging of AG-MHC1 complexes Insertion of AG-MHC1 complex into PM
Cytokines
Small protein hormones that stimulate or inhibit many normal cell functions, such as cell growth and differentiation
Ex: interleukins, TNF, granzymes, perforin, interferons
What secretes cytokines?
Secreted by lymphocytes, APCs, fibroblasts, endothelial cells, monocytes, heptocytes and kidney cells
Interleukin 1
Cytokine
Produced by macrophages
Promotes proliferation helper T cells
Acts on hypothalamus to cause fever
Interleukin 2
Cytokine
Secreted by helper T cells
Costimulates proliferation of helper T cells, cytotoxic T cells, and B cells
Activates NK cells
Interleukin 4
Cytokine B stimulating factor Produced by helper T cells Costimulator for B cells. Causes plasma cells to secrete IgE Promotes growth of T cells
Interleukin 5
Cytokine
Produced by some helper T and mast cells
Costimulator by B cells
Causes plasma cells to secrete IgA
Interleukin 6
Produced by helper T cells
Enhances B cell proliferation, B cell differentiation into plasma cells, and secretion of Abs
Tumour Necrosis Factor
Cytokine
Produced mainly by macrophages
Stimulates accumulation of neutrophils and macrophages at sites of inflammation and stimulates their killing of microbes
Interferons
Cytokine
Produced by virus-infected cells to inhibit viral replication in uninfected cells
Activate cytotoxic T cells and natural killer cells
Inhibits cell division and suppresses tumour formation
Macrophage migration inhibiting factor
Cytokine
Produced by cytotoxic T cells
Prevents macrophages from leaving site of infection
Cell Mediated Immunity
Activation of T cells by a specific antigen
T Cell Receptors
Antigen receptors on the surface of T cells that recognize and bind to specific foreign Ags that are presented in Ag-MHC complexes
Coreceptors
Surface proteins on T cells that help maintain TCR-MHC coupling
CD-4 (Helper) or CD-8 (Cytotoxic)
Antigen recognition by a TCR with CD4 or CD8 protein is the first signal in T cell activation
Costimulation
A second (chemical) signal required for a T Cell to activate after binding to an antigen
Prevents accidental immune response
Ex. IL-2, twinned plasma membrane molecules
What does a T cell need in order to activate?
Bind to an antigen, with coreceptor
Costimulation
Anergy
Immune recognition with no costimulation
State of prolonged inactivity
CD4 Cells
Helper T cells
What sort of Ags are recognized by Helper T cells?
exogenous
What type of MHC molecules are associated with Helper T cells?
MHC-2
What do Active Helper T Cells secrete
Cytokines, especially IL-2
Needed for virtually all immune responses and prime trigger of T cell proliferation
Memory Helper T Cells
Not active
Upon second exposure to same Ag, quickly proliferate and differentiate into more Active Helper T cells and Memory Helper T Cells
CD8 Cells
Cytotoxic T cells
What type of MHC molecules are associated with Cytotoxic T Cells?
endogenous
In order to become active, Cytotoxic T cells need costimulation by
IL 2 or other cytokines produced by Active HTC
How do cytotoxic T cells kill?
Granzymes: trigger apoptosis
Perforin & Granulysin: pierce membrane –> cytolysis
Lymphotoxin: activates enzymes in the target cell that causes its DNA to fragment
Antibody mediated immunity
B cells activate into plasma cells and release Ab/Ig
B cells remain in lymphatic tissue
B cells can react to unprocessed Ag
In B cells, clonal selection results in
Plasma cells and Memory B cells
Plasma cells
Activated B cells that secrete Ab that travel in lymph and/or blood
What cytokines help B cell proliferation?
IL4 and IL6
Produced by HTCs
Antibodies
aka Immunoglobulins (because they belong to the Globulin glycoprotein group)
Combine specially with the epitope on the Ag that triggered its production
Contain 4 polypeptide chains (2 heavy, 2 light)
What antibodies can be passed between mother and child?
IgG
IgA
IgG
Smallest, most numerous
Found in blood, lymph and intestines
Only Ab that can cross placenta
IgA
Second most common
Found in exocrine glands (sweat, tears, saliva, mucous, breast milk)
IgM
Largest, third most numerous
makes up ABO antibodies
Short lived, first to be secreted by plasma cells
Presence indicates recent invasion
IgD
Found in B-cells as antigen receptors.
Remain in plasma membrane.
IgE
Least common.
Located on mast cells and basophils
Allergic, parasitic and hypersensitivity reactions
5 Ways Igs disable and Ag
- neutralize
- immobilize
- compliment activation
- enhances phagocytosis
- agglutination/precipitating
Complement System
Defensive system made up over 30 proteins produced by liver Destroys microbes by: 1) phagocytosis 2) cytolysis (MAC) 3) inflammation
Primary Response
Slower, weaker, generates initial population of immune cells
Secondary Response
Faster, stronger, generates second population of immune cells
Where memory happens
Attenuated
In vaccine, a weakened microbe
4 types on invoked immunity
Naturally Acquired Active (normal)
Naturally Acquired Passive (mother-child)
Artificially Acquired Active (typical vaccine)
Artificially Acquired Passive (direct injection of Abs – antivenom)
HIV
Retrovirus that cause AIDS
Infectious Mononucleosis
Epstein-Barr Virus
Herpes Type 4 virus
Results in fatigue, headache, dizziness, sore throat, enlarged lymph nodes and fever
Type 1 Allergic Reaction
Anaphylactic, mostly due to reexposure
Mostly IgE
Type 2 Allergic Reaction
Cytotoxic
Antibodies directed again person’s own cells
IgG or IgM
Type 3 Allergic Reaction
Immune Complex
Ag/Ab complexes that escape phagocytosis lead to inflammation
IgA or IgM
Type 4 Allergic Reaction
Cell Mediated
AKA Delayed hypersensitivity
12-72 hours after exposure, immunocompetent T cells return to site and stimulate inflammation
SLE
Lupis
Chronic autoimmune inflammatory disease that affects multiple body systems
Most common symptom: butterfly rash
Rheumatoid arthritis
Body’s Ab’s recognize joints as foreign and attract them
Pain, inflammation, joint deterioration
Myasthenia Gravis
Body produces Abs that block ACh receptors at neuromuscular junction
Progressive muscle weakness and atrophy
Hodgkins Disease
Lymphoma
mostly affects men 15-35
Painless, nontender enlargement of one or more lymph nodes in the neck, chest and axilla
Can metastasize
Non-hodgkin lymphoma
All age groups
Like hodgekins but also enlarged spleen, anemia and general malaise.
