Unit III: HomeostasisDefense Against Invasion

Chapter 21

HemostasisPlatelet Plug Formation

• broken vessel exposes collagen

• platelet pseudopods

– contract and draw walls of vessel together platelet plug

• degranulation

• serotonin (vasoconstrictor)

• ADP attracts and degranulates more platelets

• thromboxane A2 (an eicosanoid)

HemostasisCoagulation

• “Clotting” – conversion of plasma protein fibrinogen into insoluble fibrin

threads to form framework of clot

• Extrinsic mechanism – factors released by damaged tissues

• Intrinsic mechanism – factors found in blood (platelet degranulation)

• Procoagulants (clotting factors) Table 18.8

– activate one factor and it will activate the next to form a reaction cascade

Inactive

Inactive

Inactive

Extrinsic mechanism Intrinsic mechanism

Factor V

Factor XII Platelets

Fibrin

Thrombin

Factor VII

Inactive

Ca2+

Damagedperivascular

tissues

Thromboplastin(factor III)

Factor VIII(active)

Ca2+, PF3

Factor IX(active)

Factor XI(active)

Factor X(active)

Factor IIIFactor VCa2+

PF3

Prothrombinactivator

Prothrombin(factor II)

Fibrinogen(factor I)

Fibrinpolymer

Factor XIIICa2+

Coagulation Pathways

• Extrinsic mechanism– initiated by Factor III– fewer steps– 15 seconds formation

• Intrinsic mechanism– initiated by factor XII– cascade to factor XI to

IX to VIII to X– 3-6 minutes formation

• Calcium required for either pathway

Fibrin

Thrombin

Rea

ctio

n c

asca

de

(tim

e)

Prothrombinactivator

FactorXII

FactorXI

FactorIX

FactorVIII

FactorX

Fate of Blood Clots

• Reaction Cascade

• Clot retraction occurs within 30 minutes

• growth factor secreted by platelets

• Fibrinolysis (dissolution of a clot)

– Factor XII initiates small cascade of reactions kallikrein – Plasminogen plasmin, a fibrin-dissolving enzyme (clot buster)

Prevention of Inappropriate Clotting

• Platelet repulsion

• Thrombin dilution

– by rapidly flowing blood

• Natural anticoagulants

– heparin (from basophils and mast cells) interferes with formation of prothrombin activator

– antithrombin (from liver) deactivates thrombin before it can act on fibrinogen

Hemophilia

• Genetic lack of any clotting factor

• Sex-linked recessive (on X chromosome)

– hemophilia A missing factor VIII (83% of cases)

– hemophilia B missing factor IX (15% of cases)

note: hemophilia C missing factor XI (autosomal)

• Physical exertion causes bleeding

– hematomas

– transfusion of plasma or purified clotting factors

Coagulation Disorders

• Thrombosis - abnormal clotting in unbroken vessel– most likely to occur in leg veins of inactive people

• Embolism - clot traveling in a vessel− pulmonary embolism - clot may break free, travel from veins

to lungs

• Infarction may occur if clot blocks blood supply to an organ (MI or stroke)– 650,000 Americans die annually of thromboembolism

Clot Prevention in Patients•Salts, heparin•Vitamin K

–Needed for synthesis of clotting factors–Coumarin

•Aspirin–Suppresses formation of thromboxane A2

•Medicinal leeches

Functions of Lymphatic System

• Immunity

– Lymph nodes

• Lipid absorption

– Lacteals

• Fluid recovery

– 2 to 4 L/day

– interference leads to severe edema

Lymphatic Vessels

•Lymph

•Lymphatic capillaries

•Bud from veins

–Tunica interna, tunica media, tunica externa

–valves

Route of Lymph Flow

• Tissue fluid Lymphatic capillaries • Collecting vessels (lymph nodes) • 6 Lymphatic trunks • 2 Collecting ducts :

– right lymphatic duct R subclavian vein

– thoracic duct - begins as a prominent sac in abdomen called the cisterna chyli; empties into L subclavian vein

The Fluid Cycle

Lymphatic Cells

• Natural killer (NK) cells

– responsible for immune surveillance

• T lymphocytes (T-cells)

– mature in thymus

• B lymphocytes (B-cells)

– differentiation into plasma cells antibodies

• Antigen Presenting Cells (APCs)

– macrophages (from monocytes)

– dendritic cells (in epidermis, mucous membranes and lymphatic organs)

– reticular cells (also contribute to stroma of lymph organs)

Lymphatic Organs

• Primary lymphatic organs

– site where T and B lymphocytes become immunocompetent

– red bone marrow and thymus

• Secondary lymphatic organs

– immunocompetent lymphocytes populate these tissues

– lymph nodes, tonsils, and spleen

Lymph Node• Only organs that

filter lymph

• Fewer efferent vessels, slows flow through node

• Trabeculae - divides node into compartments

– Stroma

– Parenchyma

– subdivided into cortex (lymphatic nodules) and medulla

Lymph Node Diseases

• Lymphadenitis

– swollen, painful node

• Lymphoma (Metastatic cancer)

– swollen, firm and usually painless

Tonsil

• Tonsillar crypts and encounter lymphocytes

• 3 sets:

– Pharyngeal tonsil (adenoids)

– Palatine tonsils

– Lingual tonsils

Spleen

• Parenchyma tissues:– red pulp:

– white pulp:

• Functions– blood production in fetus– blood reservoir– RBC disposal (“graveyard”)– Stabilize blood volume

Thymus

• Both lymphatic and endocrine

– Maturation of T-cells and secretes hormones

• Most active in childhood (under age 14)

– If removed – no immunity

– Replaced by fibrous and fatty tissue

• Structure similar to lymph nodes

• Reticular epithelial cells

– Blood-thymus barrier

• isolates developing T lymphocytes from foreign antigens

– secretes hormones (thymopoietin, thymulin and thymosins)

Thymus

Lobule

Cortex

Medulla

Trabecula

Trabecula

Defenses Against Pathogens

• Nonspecific defenses

– first line of defense

• Skin, mucus membranes

– second line of defense

• phagocytic cells, antimicrobial proteins, inflammation and fever

• Specific defense -

– third line of defense

Defenses Against Pathogens

1st Line of Defense

•Skin – stratified squamous epithelium, acid mantle, dendritic cells

•Mucus membranes – respiratory and digestive tracts: goblet cells

Phagocytic Cells

2nd and 3rd Line of Defense

•Leukocytes and Macrophages

–Neutrophils – respiratory burst

–Eosinophils – kill parasites; limits histamine; promote basophils

–Basophils – secrete histamine and heparin

–Lymphocytes – 80% T-cells, 15% B-cells, 5% NK-cells

–Monocytes - transform into macrophages

Specific vs. Nonspecific Immunity

Nonspecific Immunity

• Immune surveillance, inflammation, fever

3rd Line of Defense: Immune System

• Specificity and memory

• Cellular immunity: cell-mediated (T cells)

• Humoral immunity: antibody mediated (B cells)– Comparison table: Table 21.5, p.850

Passive and Active Immunity

• Natural active immunity (produces memory cells)

– result of infection or natural exposure to antigen

• Artificial active immunity (produces memory cells)

– result of vaccination

• Natural passive immunity (through placenta, milk)

– temporary, fetus acquires antibodies from mother

• Artificial passive immunity (snakebite, rabies, tetanus)

– temporary, injection of immune serum (antibodies)

The Three “R”s of Immunity

Cellular Immunity

•Recognition

–Antigen presentation

–T-cell activation

•React (attack)

–Helper T-cells - attract neutrophils, natural killer cells, and macrophages, stimulate T and B-cell mitosis and maturation

–Cytotoxic T-cells – “lethal hit” of cytotoxic chemicals

•Remember

–T-cell recall response

The Three “R”s of Immunity

Humoral Immunity

•Recognition

–Receptors for one antigen on a B-cell

–Helper T-cell binds to complex

–B-cells differentiate into plasma cells

•React (attack)

–Neutralization, Complement fixation, Agglutination, Precipitation

•Remember

–Primary response

Notes on Immunity

• Memory lasts longer in Cellular Immunity than Humoral

• Both processes of immunity occur simultaneously and in conjunction with inflammation

• HIV attacks helper T-cells knocks out the central coordinating role in both processes

Test III

•Lecture•Chapters 24, 18, and 21

•Lab practical•Identification of slides: organ, cells, regions•Lab manual questions