Chapter 16 Tortora

Innate Immunity-Nonspecific Defenses

Types of immunity

• Innate immunity-defense present at birth– Rapid response– No memory component– First line of defense and second line of

defense is in this category

• Adaptive or specific immunity is the defense that kicks in once the innate has been breached– This involves lymphocytes (T and B cells)

First line of Defense

• Skin and mucous membrane• Contain both physical and chemical features• Physical-intact skin is First barrier!

– Epidermis has keratin (protein) that helps waterproof skin

– Cells are closely packed and dry usually

• Mucous membrane-line openings to outside– Mucus keeps these openings moist– Some bacteria can penetrate the membrane like

Treponema pallidum

Physical barriers continued

• Lacrimal apparatus-produce and drain tears • Tears wash eye and cleans it• Saliva also washes out mouth and dilutes the

number of bacteria• Very small hairs found in nose help filter air and

trap bacteria• Cilia in lower respiratory tract move dust and

microorganisms trapped in mucous upward toward throat and you swallow it (cigarettes are toxic to this ciliary escalator)

More physical barriers

• Epiglottis-prevents microbes from entering lungs during swallowing

• Urine-cleans urethra

• Vaginal secretions-remove microbes from female

• Defecation-removes waste

• Vomiting-rids the body of harmful substances

Chemical factors

• Sebaceous glands produce sebum which prevents hair from drying out and forms a protective film over skin– Contain unsaturated fatty acids which inhibit growth of

some pathogens and fungi– Helps provide a pH of 3-5 which also discourages

bacterial growth

• Sweat glands produce perspiration which helps flush bacteria from surface of skin

• Contains lysozyme which breaks down cell wall of gram positive and some gram negative

Chemical continued

• Lysozyme is also in tears, saliva, nasal secretions, and tissue fluids– Alexander Fleming was studying lysozyme

when he accidentally discovered penicillin

• Gastric juice is a mixture of HCl, enzymes and mucus and provides a pH of 1-3– Some bacteria are protected by food or are

not bothered by this acid (Clostridium botulinum and Staphylococcus aureus)

– some like the acid (Helicobacter pylori)

Second line of defense

• Blood includes plasma (liquid portion) and formed elements (solid portion)

• During an infection the total number of WBC’s increase (leukocytosis) or decrease (leukopenia)

• Determine white blood cell count with differential white blood cell count

• See table 16.1 for normal values and photos

Types of WBC’s

• Divide into 2 categories:• 1. granulocytes-large granules in

cytoplasm that are present during staining– Neutrophils-or polymorphonucleocytes

(PMN’S)• Enter early in infection, can leave blood and enter

infected tissue• Most abundant type and are highly phagocytic

• http://www.unomaha.edu/hpa/blood.html#neutrophil

Granulocytes continued

• Eosinophils-can leave blood too• Major function is to produce toxic proteins

against parasites• Increase during parasite infestation and allergy• http://en.wikipedia.org/wiki/Image:Eosinophil.jpg• Basophils-release histamine and other

substances that are important in allergy and inflammation response

• http://www.unomaha.edu/hpa/blood.html#basophil

Agranulocytes

• 2. Agranulocytes-no visible granules in cytoplasm after staining

• Include monocytes-phagocytic after mature into macrophages and leave blood– One reason your lymph nodes swell during infection!– Destroy microbes and old blood cells

• The other type is the lymphocyte-including T, B, and Natural Killer (NK) cells-these have their own chapter

Phagocytosis

• Click here for a video clip of phagocytosis• http://highered.mcgraw-hill.com/sites/007249585

5/student_view0/chapter2/animation__phagocytosis.html

• Watch the video and remember the steps!• Order of importance-initial infection-neutrophils

are first then macrophages take over • Never Let Monkeys Eat Bananas! (order of

WBC’s in normal differential)

Steps in phagocytosis

• Chemotaxis• Ingestion• Digestion (then releases waste after ‘eating’)• Remember to watch the movie. This one has a

little more ‘kick’ http://www.sp.uconn.edu/~terry/Common/phago053.html

OR http://www.edumedia-sciences.com/a82_l2-phagocytosis.html

Microbial evasion of phagocytosis

• Some have M protein and or capsules that interfere with adherence– Streptococcus pneumoniae (must trap these to engulf)

• Some are ingested but aren’t killed in phagocyte – Staphylococcus may kill phagocyte by producing leukocidins

• Some can live inside phagocyte– Coxiella burnetti (Q fever), Listeria monocytogenes, Shigella,

Rickettsia can escape the phagocyte– Mycobacterium tuberculosis, HIV, Chlamydia, Plasmodium can

multiply inside the phagocyte and kills the phagocyte

Inflammation

• Triggered by damage to tissue• 4 signs

– Pain (dolor)– Redness (rubor)– Swelling (tumor)– Heat (calor)– May have a 5th sign-loss of function

• Functions are to remove infectious agent or limit it’s effects on body and repair or replace damaged tissue

Steps in inflammation

• 1. Blood vessels dilate (vasodilation) and increase blood flow (causes rubor and calor)

• Increased permeability due to dilated vessels is responsible for edema

• Vasodilation and increased permeability are caused by histamine and kinins

• Prostaglandins are released by damaged cells and intensify effect of histamine and kinins

• Leukotrienes are produced by mast cells and basophils and increase permeability and help phagocytes attach to pathogens

• Clots may form around the infection and prevent spread of pathogen or toxin and help form pus

Steps continued

• 2. phagocytes migration and phagocytosis• Phagocytes stick to inner surface of blood vessels

(margination) and squeeze through endothelial lining to enter infected area

• This is called emigration or diapedesis • 3. tissue repair-dead and damaged tissue is replaced• If only parenchyma (functional part) cells are involved

the reconstruction will be perfect (no scar)• If stroma (supporting connective tissue) is involved scar

tissue results

Fever

• Abnormally high temperature in response to infection, toxins, etc

• Hypothalamus controls body temperature• Pyrogens reset this thermostat • Body responds by shivering, increased metabolism, and

blood vessels constriction• Body temp is climbing but skin is cold causing the chill • After infection the blood vessels dilate and sweating

occurs, helping lower temperature• Crisis is when the person sweats and skin becomes

warm (fever is breaking)• Fever is good defense up to a point• Death results if fever gets 112 degrees

Antimicrobial substances

• Complement system-complex series of 30 proteins produced by liver that circulate in blood and tissues

• Help destroy microbes by cytolysis, inflammation, and phagocytosis

• These proteins stay inactive until split into fragments called a and b

• Use C to designate which is which C1-C9• Acts as a cascade, one triggers another.• C3 is one of the most important!• Have 3 pathways: classical, alternative, and lectin• Some bacteria can resist complement (capsules)

More antimicrobial substances

• Interferon-IFN’s antiviral proteins that are produced by certain cells like lymphocytes and macrophages AFTER viral stimulation

• These proteins interfere with viral replication • Have found 3 types so far: alpha, beta, and

gamma• Produced by viral infected cells and spread to

neighboring uninfected cells, inducing them to make antiviral proteins that disrupt viral multiplication

• Studying these as possible cure for cancer, etc.

One more time!

• Transferrins-iron binding proteins that inhibit bacteria growth by reducing the amount of available iron– Iron overload can suppress chemotaxis and

phagocytosis and increase risk of infection!

• Antimicrobial peptides-newly discovered, produced by mucous membrane cells and phagocytes– These bind to microbial plasma membrane

and cause lysis