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Chapter 14 – Nonspecific Defenses of the Host
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II.
Skin and Mucous Membranes – the 1st line of defense
A. Mechanical Factors
1. intact skin – tightly packed epithelial cells
a. multiple layers – epidermis (outer) , dermis (inner)
b. cells with immune function – Langerhans cells
c. keratin – protein found in top epidermal layer – tough, waterproof
d. staphylococcus infections are the most likely
2. Mucous membranes
a. multiple layers – epithelial (top); connective tissue (underlying)
b. mucus – secreted by epithelial cells – inhibit entrance of microorganisms
c. GI tract, respiratory tract, genitourinary tract
3. Lacrimal apparatus – manufactures & drains away tears – continual washing
4. Saliva – dilutes microorganisms; washing action in mouth
5. Mucus – respiratory & GI tracts – traps microorganisms
6. Hairs – nose – filter air, trap organisms, dust, pollutants
7. Ciliary escalator – lower respiratory tract – propels mucus, dust, organisms upward
8. Epiglottis – keeps swallowed organisms out of respiratory tract
9. Urine – washes genitourinary tract
10. Vaginal secretions – flow – washes organisms out of female body
B. Chemical Factors
1. sebum – protective film over skin surface – unsaturated fatty acids inhibit bacterial growth
2. fatty acids on skin  low pH – inhibits bacterial growth
3. lysozyme – breaks down cell walls of gram positives, also some action against gram
negatives. Found in: tears, saliva, sweat, nasal secretions, tissue fluids
4. gastric juice - low pH ( doesn’t destroy botulism toxin or staph enterotoxin or h.pylori)
5. transferrins – blood proteins – bind iron – deny iron to bacteria
Phagocytosis – A 2nd line defense
the ingestion of any solid matter ( including microorganisms) by a cell
Phagocytes: white blood cells or derivatives of white blood cells
A. Formed elements of the Blood – cells or cell fragments
1. plasma – fluid portion of the blood
2. erythrocytes – red blood cells
3. leukocytes – white blood cells
a. Granulocytes – contain granules in cytoplasm
(1) Neutrophils – PMNs – phagocytic – initial stages of infection
(2) Basophils – release histamine – inflammation & allergic responses
Mast cells are tissue cells that are related to basophils and have si,ilar function
(3) Eosinophils – some phagocytosis – toxic against parasites, increased in allergic
reactions
b. Monocytes – circulate in blood – leave blood & move into tissues where they
differentiate to become macrophages ( highly phagocytic)
(1) wandering macrophages – migrate through blood into tissues
(2) fixed macrophages – located in certain tissues – liver, lungs, spleen, bronchi,
peritoneal cavity, nervous system, bone marrow
(3) Dendritic Cells – derived from monocyte lineage – found in tissues; act as antigenpresenting cells
c. Lymphocytes
(1) Not phagocytic; role is in specific immunity
(2) B-lymphocytes – produce antibodies
(3) T-lymphocytes – cell-mediated immunity ( killer cells, helper cells, suppressor cells)
(4) Found in: tonsils, spleen, thymus, bone marrow, lymph nodes, Peyer’s patches,
blood
4. Platelets – fragments of cells that function in blood clotting
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5. Leukocytosis – number of WBCs increases in infections : meningitis, mono, appendicitis,
pnemococcal pneumonia
6. Leukopenia – decrease in WBCs – salmonellosis, some viral or rickettsial diseases
III.
B. Actions of Phagocytic Cells
1. Activated by: Lipid A, LPS, cytokines ( protein hormones secreted by immune cells)
2. Shift: initial infection – mostly neutrophils; Later stages – mostly macrophages
C. Mechanism of Phagocytosis
1. Chemotaxis – chemical attraction of phagocytes to microorganisms
a. microbial products; components of WBCs, damaged tissue, complement proteins
2. Adherence – attachment of phagocyte to surface of microorganism or foreign material
a. inhibited by capsules or M-protein
b. opsonization – microorganisms are coated with particles ( antibodies or complement
proteins) – facilitates phagocytosis
3. Ingestion – plasma membrane extends pseudopods – engulfs microorganism in a vesicle
4. Digestion
a. vesicle pinches off from cell membrane & enters cytoplasm
b. fuses with lysosome to form large vesicle (phagolysosome)
c. lysosomal enzymes destroy microbial cells ( 10-30 minutes)
d. phagolysosome moves back to cell membrane – discharges waste outside the cell
Inflammation
A. Causes
1. microbial infection
2. physical agents – heat, radiation, electricity, sharp objects
3. chemical agents – acids, bases, gases
B. Five symptoms of inflammation
1. redness
2. pain
3. heat
4. swelling (edema)
5. loss of function
C. Functions of inflammation
1. destroy the harmful agent & remove it and its by-products from the body
2. limit the harm – confine or wall off the agent or its by-products
3. repair or replace tissue damaged by the agent or tis by-products
D. Three (3) Stages of inflammation
1. Vasodilation & increased permeability of blood vessels
2. Phagocytic migration and phagocytosis
3. Tissue repair
E. Vasodilation and Increased Permeability of Blood Vessels
1. vasodilation – increased diameter of blood vessels
a. increases blood flow to damaged area – redness & heat
2. increased permeability – edema (swelling)
3. chemicals released by damaged cells in response to injury
4. histamine – released by mast cells, platelets, basophils
5. kinins – e.g. bradykinin
6. prostaglandins
7. leukotrienes
8. blood clots
9. pus & abscess formation
F. Phagocytic Migration and Phagocytosis
1. margination – cells stick to the margin of the blood vessels ; squeeze through the blood
vessels to enter the tissues
2. emigration – wandering macrophages
3. pus formation
G. Tissue Repair
1. tissues replace dead or damaged cells
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IV.
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2. ability to regenerate depends on type of tissue ( e.g., cardiac muscle won’t regenerate)
3. may be replaced with new, active cells or scar tissue
Fever – an abnormally high body temperature
A. The hypothalalmus – controls the body temperature.
B. Certain substances (e.g., prostaglandins)affect the hypothalalmus – will reset it to a higher
temperature
C. Body response to higher setting – constrict blood vessels, increase metabolism, shiver
D. All designed to raise the body temperature – skin remains cold – chill
E. Infection ends – thermostat is reset to 370 – heat-loss mechanisms kick in – sweating, skin
warms – crisis
F. Fever as a defense
1. intensifies the effects of interferons
2. interferons denies iron to bacteria
a. iron is necessary for bacterial growth
b. iron suppresses chemotaxis and phagocytosis
3. speeds up body’s reactions, including repair mechanisms
Antimicrobial Substances
A. The Complement System
1. Complement – serum proteins that participate in the lysis of foreign cells, inflammation and
phagocytosis
2. Components
a. complement proteins ( about 20 ) in normal serum
b. classical pathway uses C1 through C9 (including C3)
c. alternative pathway – factor B, D and P, C3 C5 through C9
3. Pathways of Activation – a cascade
a. cascade – series of steps – each protein activates the next one in the series, usually by
splitting (cleaving it.
b. C3 plays a central role
c. Classical pathway – intiated by the binding of antibodies to antigens; binds C1,C2,C4
d. Alternative pathway – doesn’t involve antibodies; initiated by interaction between
polysaccharides of bacterial cell walls & factors B, D, and P. – important in combating
enteric gram negative bacteria
e. Lectin Pathway – lectin in serum binds to a sugar(mannan) in cell wall of microbe
4. Consequences of Complement Activation
a. Cytolysis – formation of the membrane attack complex (C5 thru C9)
b. Inflammation – C3a & C5a bind to mast cells, basophils & blood platelets – trigger
histamine release
c. Opsonization - C3b can bind to microbial surface and also to phagocytes – promotes
phagocytosis
d. inactivation of complement – blood proteins inactivate complement quickly
5. Complement and disease
a. C1, C2, C4 deficiencies – collagen vascular disorders – hypersensitivity (anaphylaxis)
b. C3 deficiency (rare) – increased susceptibility to bacterial infections
c. C5-C9 defects – increased susceptibility to N. meningitidis & N. gonorrhoeae
B. Interferons
1. a class of antiviral proteins produced by animal cells after viral stimulation
2. host-cell specific, but not virus-specific
3. alpha-interferon ( -IFN) – produced by virus-infected host cells
approved for treating Kaposi’s sarcoma, genital herpes, hepatitis B and C
4. beta-interferon ( -IFN) - produced by virus-infected host cells
slows progression & lessens severity of multiple sclerosis (MS)
5. Both -IFN and -IFN – cause uninfected neighboring host cells to produce antiviral proteins
( AVPs) – these disrupt viral multiplication
6. gamma-interferon (-IFN) – produced by lymphocytes ; causes neutrophils to kill bacteria