Nonspecific Defense System

(Innate immunity)

responds immediately to protect from all foriegn substances and controls/contains infectionsstimmulate specific

*localized

2 barricades

• first line of defense-physical/mechanical- skin and musoca
• 2nd line- chemical/cells/inflammation

Specific Defense System

(adaptive immunity)

*recognizes specifec foriegn substances and immobolizes, neutralize and destroys them.

*systemic *amplifies inflammation

*must be primed by initial exposure to Antigens b4 it can protect

2 specific defenses

• humoral-b cells-found in spleen or lymph nodes useful agains bacteria and viruses in blood
• Cell-mediated-Tcells-90%of all immunity

2nd line of defense

(nonspecific defense system)

phagocytic cells opsinization or complement

types of phagocytes-monocytes precursors for macrophages live in lymph, spleen,liver

Macrophages- may be fixed or wandering can be APCs when activated

Neutrophils- digest infection agents and particles in blood can release defensin(antibac. chem. that kill cell and can kill themselves or cause cancer)

B-cell development

(humoral immunity)

-B-cells mature in bone marrow and become specialized

-B-cells migrate to lymphoid tissue (spleen IgD) where they are simulated to respond to antigens

*found in blood and lymph

*can lyse to kill cancer and virus-infected cells b4 3rd line of defense needed

*inhance inflammation

*act spontaneously

*inject cytoltic chemicals into cell membrane

Complement Protiens

Chemical denfeses(2nd line of nonspecific denfense)

Complement protiens-produced in liver and found in blood plasma. must be activated by exposure to Ig/Ant and histamine release from basophils of mast cells or exposure to collectins.

stimulate inflammation/opsonize, lyse bacteria.

attract phagocytes and active leukocytes

cytokines

Cytokines

(chemicals of nonspecific defesens system)

substance secreted by cells of immune system that carry signals locally between cells

*can be protiens, peptides, or glycoprotiens

-3 main kinds-

Interferons-antiviral protiens

Interleukins-secreted by macroph. and lymphocytes and enhance T-cell activity

Tumor Necrosis Factor-

kills cells thru apoptosis, activates inflammation and fever as well as neutrophils and endothelial cells-causes breakdown on muscle

Anti-microbial biochemicals

(chemical defense of nonspecif D.S)

3 types

Defensins-produced by WBC and other cells. cripple microbes by holes in cell walls

Collectins- protiens that grab/cling to pathogens and promote phagocytosis, inflammation, and activate complemtn

Perforins-cytolytic chem. that create holes in surface of invader cells like defensins

caused by trauma chemicals, viruses, bacteria, fungi, and heat.

Function is to prevent spread of damaging agents-brings fluid and chemicals and cells to inflammed area

possible harmful effects of inflammation

Systemic manifestations of inflammation

acute-phase response-liver produces elevated C-reative protein and fibrinogen>inc. ESR

-leukocytosis(inc. in WBC) and leukopenia

-elevated fever

-lymphadenitis-inflammation of lymph nodes

-muscle catabolism by TNF

-death(brain inflamm)

Mast cells-realse histamine>vasodialation or arteriols>inc permability of venules

Platelets-relese serotonin>same effects of histamine

Mast cells and basophils-release arachidonic acid(a fatty acid in cell mem. is a key inflammatory intermediate

*These mediators follow 2 pathways ending up in synthesis of prostoglandins or leukotrienes

develop in bone marrow and migrate to thymus for further maturation

Prostoglandins

(what cell-derived chemical mediators of inflammation become)

Leukotrienes

(what cell-derived chemical med. of inflamm. can become)

class of eicosonoids that promote inflammation, chemotaxis and bronchoconstriction

strongly associated with asthma and allergy

Kinin system- histamine is alsways relesased 1st then kinin sys.Bradykinin is peptide kinin that causes blood ves. dialation

Complement system

Plasmin and Thrombin-usually assoc. w/ blood clotting but assist in triggering inflammatory response.

-inc. of blood flow to ares

-inc. permability of capillaries causes fluid to leak out of blood vessels(exudate), brings o2, antimicrobials, and protiens and nutrients.  allows entry on fibrin and blood flow to slow

-can cause edema

-other WBC attracted to area

serous- watery low in protein

hemorrhagic-severe injury-RBC

fibrinous-large amnts ot fibrogen very thick(chronic inflamm)

catarrhal-mucos and WBC

purrulent-pus

granulomatous-balls of cells of macrophages, bacteria and other cells(chronic inflamm)

Acute inflammation

Anti-inflammatory drugs

ASA-aspirin inhibits synthesis of prostoglandins

NSAIDs-(non-steriodial anti-inflammatory drugs) ib profun and naprosin inhibit synthesis of prostaglandins

Cortisone(prednisone)-lesson the availability of chemicals need for prostaglandin synthesis

sometime a companion of inflamm. or can promote inflamm.

1. pyrogens released from leukocytes eposed to bacteria or injured cells>hypthalamus raises body tem

2.  mild fever beneficial bc inc. metabolic rate and makes Zn and Fe less avail. to bacteria

3. high fevers dangerous bc inactivate enzymes>dehydration and electrolyte imbalance

Manifestations of Fever

(stages of fever)

1. Prodone-headache, fatigue/malaise, aches&pains

2.  Chill-vasoconstriction of dermal capillaries. shivering, goosebumps, pale

3. flush-vasodialtion of derm. cap.

4. Defervescence-reach set pt. made by hypothalamus>initiate sweating

Antigens

(Specific Defense System)

foriegn agents that elicit an immune response

-can be proteins, polysaccharides, and glycolipids

-immune system responds to non-self and sometime self antigens

-receptors on b and t cell surfaces and other body cells enable recognition of antigens

when B and T cells become activated after first encountering antigens

-plasma cells(B cells) release Ig into lymph and are transported to blood and body

-Ig are in body for 5-10 days after ant. exposure

Clusters of Differentiation

CD

major histocompatability complex molecule than recognizes intracellular antigens

*found on most body cells

major histocompatablitly complex that recognize extracellular antigens

*found on phagocytic cells

-involve self-destructive Igs

a.drug/chemical binds to body cell>cell appears foriegn>B cells produce IgM and IgG>phagocytic cells attack and complement

b.  virus or body cell has antigen that resembles a body-cell antigen>Bcell produce Ig

c. neutrophils are overly sensitized

Ex-ABO/Rh blood groups, sptrepptoc. rheumatic fever, ITP

Tx. Corticosteroids to decrease immune response and inflammation

B-cell activation

-Macrophage+antigen=APC goes to lymph nodes and binds with helper Tcell>helper T releases cytokines which stimulate Bcells

-B-cells are activated when bound to and antigen and sometime to helper T

-1/2 cells become plasma cells which release Ig on any response after

-T suppressor cells inhibit further Ig production once pathogen is controlled

-other 1/2 become memory B-cells

made of 4 chains of amino acids liked by disulfide bonds. 2 chains are light and 2 are heavy.

heavy=more a.a.

*at one end of each light and heavy chain are variable regions where the are anitgen-binding sites

1. can directly attack antigens

2.  form Ig/Ant complex and cause antigens to agglutinate

3.  neutralize

4.  active complement (IgG and IgM)

found in plasma and tissue fluids. effective against bacteria, viruses and toxins. activate complement

Maternal Ig-cross placenta

secratory IgA found in exocrine gland secretions-breast milk,tears,nasal,gastric juice, bile and urine.

protect against digestive and respitory infections

*characterized by rapid proliferation of abnormal leuk. and causes abnormal immune response

Reed-Sternberg cell(bcell origin)

poss. etiology-carcinogens, genetic, immune

early symptoms: painless lymph node enlargement, fever night sweats

Advanced symptoms-probs w/ liver, lungs, GI tract

Dx-biopsy l. nodes, CT scans, bone marrow

Tx-radiation/chemo-5 yr cure rate 85%

found in exocrine gland secretions with IgA.

associated with allergic reactions

must bind to antigen and class II MHC on APC

-differentiate into TH1 and TH2

TH1-active cytotoxic Tcells

TH2-activate B-cells

*activated Helper T can secrete cytokines

-bind to antigen along with Class I MHC and influence of specific cytokines from Helper T-cells

-once activated, become cytotoxic T-cells and memory cells

when identical ant. is encountered in the future, memory B and T cells respond rapidly with Ig.

-dendridic cells in lymph may help by retaining and slowing releasing viral agents after initial infection

1. killed vaccines-inactivated polio virus

2.  Recombinant Virus- genetic manipulation-Hib

3.  Oral-live attenuated vaccinces-grown to loss of virulence-Sabin polio

 4. Toxoids

characterized by abnorm, malignant trans. or B and T cells in lymph.  can spread to lymph tissue all over body-spleen liver bone marrow

-more common than HL

transfer of humoral immunity in form of Ig

1.  specific Ig-Hepatitis A and B

2.  Specific antitoxins-botulism, snake bites

3.  Pooled gammaglobulins-given to over seas travelers.mixture of Ig. must be boosted every 6 mo.

allergic response occurs rapidly and the body produces Ig against harmless Ant.

-can be mild to anaphylaxis

a.Bcells exposed to allergen make IgE>IgE binds to mast cells(senitization)>mast cells degranulate and explode releasing inflammatory chemicals e.g histamine

Tx:antihistamines

Anaphalyatic Shock

(type 1 hypersensitivity)

systemic reaction with closed airways, massive-body swelling, hives , lower BP

Tx:Epinephrine-relaxe bronchial smooth muscle and reduce sympathetic vasodialation-and antihistamines

-Ig/Ant complexes that are normally removed by spleen stay in blood and precipitate on blood vessel walls

Arthrus reaction:-blood vessel wall destruction and inflammation>localized tissue necrosis

Ex. rheumatoid arth., schleroderma, SLE

Tx:Corticosteroids

SLE

Systemic Lupus Erythmatosus

-autoimmune connective tissue

-inflammation affects various body parts

Symptoms: fever, malaise, joint pain, myalgias, fatique, and temp. loss of cognitive abilities

S/Sx allow for diagnosis: dermatoglicial manifestations, joint pain(hands&wrist), anemia, inflammation of heart&lungs, hematuria, protienuria

Etiology-genetic, environmental, hormones

Pathophysiology-multi-factorial so patholgy largely unknown. defective immune response, B-cell hyperactivity

Dx-blood and urine tests, tissue biopsies(along with S/sx

Tx-NSAIDs, corticosteroids, anti-malarial drugs, immunosuppressants

-occurs after 24 hrs

-intiated by helper Tcells that release cytokines>stimulate macrophages and Tc cells to destroy body cells

Ex-TB shot, chronic infections, poison oak/ivy

TB test(purified protien derivative) inactivated TB. irritation if person is sensitised from TB. tcells and macrophages

-immunocompromised/immunosuppresed/deficiency that leave body vunerable to pathogens

Specific genetic mutations result in hypsensitivity disorders

Hyposensitivity

(primary immunodeficency disorders)

-Humoral Bcell-xlinked agammaglobulinemia

-cellular tcell-DiGeorge syn., Xlinked w/ hyper-IgM

-combined Tcell and Bcell -Severe Combined Immunodeficency(SCID)

-caused by HIV-1 and HIV-2 virus

Invasion

a. HIV attaches to 2 receptors on cell mem.

b. Reverse transcriptase copies RNA>viral DNA

c. viral DNA can stay in host cell for generations

d. viral DNA is copied to make many copies of viral RNA>packaged into protein coat

e.  viruses are released from cell into blood and attck Tcells and body cells

may take up to 2 years for body to make enough Ig against virus

ELISA test-detects Ig agains HIV in blook

-sero - not built enough IG

sero +

Western Blot-detect for Ig

Test for viral Antigen or viral RNA-may 8 wks after infection

Stages of HIV

Stage 1-virus has invaded body and person is very contagious. no S/sx or flulike. can last for mo. or yrs

Stage 2-Aids realate complex not as infectious as stage 1. Symptoms-tiredness, malaise, swollen lymph nodes, night sweats, aches fever

Stage 3-AIDS very contagious and begins to lose immune function. develop life threatning conditions. Tcell count<200

aids cocktail

Revere transcripatase inhibitor(AZT, DDI, TC30

integrase inhibitor(raltegravir)

Protease inhibitor-which is needed to make protein coat(saquinavir, ritonavir)

Neutropenia(less than 1500 cell/mcL)

Agranulocytosis(severy neutropenia less than 200 cells /mcL)

Etiology-aplastic anemia, bone marrow probs, autoimmune, drugs, enlarged spleen

Manifestations-fever, infections, Respitory infections common

Tx-antibiotics. colony stimulating growth factor to maturte neutrophils

caused by EBV. persist in body for lifetime.

*characterized by inc. # abnormal leukocytes(12-18000 cells/mcL)

Pathogenesis-saliva>spreads to lymph nodes in neck

1. EBV binds to Bcell lymphocyte receptors and infects them

2. virus kills some Bcells and infects others w/ DNA. cause Bcells to make heterophil Igs(which react w/ ant. to detect mono

3.  Virus specific Tc cells and NKC to kill virus infected B-cells

Symptoms- incubation period 4-8 weeks.  malaise, no appetite, chills, sore throat

Treatment- bed rest and pain killers to help with fever, headache and sore throat.

low grade, slow progressing that develop in lymph (5-10 yrs)

*eventually transform into aggressive lymphoma or leukemia and cause death

very aggressive and fatal if not treated with chemo/rad.

-sensitive to chemo and rad. bc of fast growth rate

*complete remission 60-80%

malignant neoplasm or cells originating from hematopoietic stem cells.

-leukocytes remain unstable and highly miotic.

result in anemia and bleeding probs

Etiology-radiation, chem, anti-tumor drugs, genetics

*most comon cause of death is internal hemm. and infection

Clinical manifestations-fatigue, anemia, palor, lymph node enlargement, infections, nose bleeding, bone pains, neutropenia, low platelet, enlarged spleen, leukostasis(100,000 cells/mcL)>leukoblastic emboli

DX- blood, bone marrow tests, CT scans, lp

Tx-chemo, blood transfusion, antibiotic, bone marrow transplant

Polycythemia

(abnormally high blood cell count with hematocrit more than 50%)

relative polycythemia-Decrease in plasma volume without loss of RBC due to dehydration, burns, excess diuretics

absolute polycythemia- increase in RBC due to cancer of bone marrow, decreases in PO2 also commonly w/ inc WBC and platelets>viscosity of blood inc

clinical manifestations-headaches, rose to bluish skin, hypertension

sudden s/sx or depressed bone marrow funtion

*80% of all childhood cases

-neoplasms precursors of immature B and T cell

-strongly linked w/ toxins and congenital disorders

Acute Myelogeneous or Myeloblastic Leukemia(AMl)

*characterized by proliferation or well-differentiated myeloid or lymphoid cells. may be asymptomatic for long time then acute

-Chronic Lyphocytic Leukemia(CLL)- occurs in older ppl esp. men. and malignant transformation of B cells become immunologically incompetent(fail to respond to ant.)

Chronic Myelogenous Leukemia(CML)-associate w/ Phildelphia Chromosome(translocation of 22 and 9), genetic alteration of stem cells. affects ages 30-50 esp. men

*usually adults over 60, esp african am.

Etiology-largely unknown. RF- chronic immune stimulation, autoimmune, radiation, pesticides, agent organe, HIV, hereditory

Pathogenesis- unregualted production of Bence Jones Protein and monoclonal Ig>proliferation of plasma cells in bone marrow>proliferation of osteoclast causing bone reabsorption and destruction>hypercalcemia

-condition of having less RBC or less than normal O2 carrying capacity>tissue hypoxia

*often associated with chronic disease and infection

Symptoms-weakness, dyspnea, angina, pallor, headache, tachycardia, ventricular hypertrophy, bone pain, jaundice

-Hemmhorragic anemia-blood loss

Acute-aneurysm, wound, trauma

Chronic-ulcer, polyps, cancer, excessive menstration

Hemolytic anemia-RBC lyse prematuraly due to hemoglobin abnormalities

Iron deficiency anemia-athletes, pregnant women, excessive menstration

Folic acid defic anemia- folic acid nedded for DNA synthsis and RBC maturation-ALCOHOLISM, pregnancy>can lead to megaloblastic anemia=enlarged RBC

Vit B12 anemia-(pernicious anemia) B12 needed for DNA syn. problems with intrinsinsic factor and carrier protein, die>>can lead to megaloblastic

decrease in plasma volume without loss of RBC due to dehydration, sever burns, excess diuretics etc.

-can be corrected by inc vascular fluid volume

increase in RBC due to bone marrow cancer, polycythemia vera, dec in PO2

primary polycythemia(p. vera)-due to excess RBC are produced as result of abnormality of bone marrow. Tx-reduce blood viscosity(remove blood, chemo)

Secondary polycythemia-due to in levels of EPO(high altitude, heart/lung disease, smoking) Tx-relieve hypoxia

platlets adhere to rough surfaces and form plug over break

release serotonin in response to vessel wall or pain receptor stimulus to maintain continual vasoconstriction

results of coagulation cascade

Vitamin K and Ca2+ must be present for blood to clot

has to be balance between coagulants and anit-coagulants

Promthrombin is converted to thrombin

Fibrinogen is converted to fibrin to form interlacing framwork

after platelet plug is formed, actin and myosin in platelets begin to contract to sqeeze out serum(plasma lacking fibrinogen and cloting proteins)

*shrinks clot

Plasminogen is activated to plasmin.

Plasmin digests fibrin strands=dissolves clot

Hypercoagulation

abnormal coagulation, hemostatis incresed which predisposes thrombosis

Thrombocytosis-above 1,000,000 cells.mcL

-due to platelet abnormalites, inc platelet function b/c of malignancies, polycythemia, inflammation, splenectomy, and increased clotting activity

-Heparin stops conversion of prothrombin

-Coumadin interferes with Vit K so liver cant make prothrombin

-Warfarin synthetic coumadin

-Aspirin, IB profun, Plavix stops platelet aggregation

Fibrolysin-proteolytic enzyme formed form profibrinolynsin

Streptokinase-protein from streptococcus

TPA-tissue plasminogen activator genetically engineered fibrinollysin

abnormal coagulation, vessel bleeds with causes hypoxia>necrosis

Platelet abnormalities-thrombocyopenia, leukemia, ITP

Plasma factor deficiencies-liver disease, diharrea, hemophilia

Blood vessel abnorm.

Tx-depend of E. regular infusion of factor, platlet transfusion, treatment of condition

Disseminated Intravascular Coagulation

DIC

wide-spread coagulation and bleeding in blood vessels that may be a complication of other disease

-begins as massive coagulation that occurs from excess thrombin>fibrin production

-anti-coagulant levels reduced

-thrombi form and occudle blood vessels>organ failure of necrosis and severe bleeding in other areas

-caused by obstetric complications, traumas, bacterial sepsis, cancers, blood statsis, shock