Microbiology – Introduction to the Immune System and

Nonspecific Immunity


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I.  Introduction to the Immune System


A.  The ability to ward off the pathogens that produce disease is called



B.  Lack of resistance is called __________________________.


C.  Resistance to disease can be grouped into two broad areas.

1.  Nonspecific immunity – the body’s first line of defense.

a.  Mechanisms that provide general protection against

invasion by a wide range of pathogens.

b.  This resistance is innate (unlearned).

c.  It responds the same to everything – bacteria, viruses,

parasitic worms, etc. are all treated the same.

d.  This resistance never learns.  It responds the same on

the 1st through the 100th exposures to the same pathogen.

            1)  __________________________ – disease-

            causing microorganism

2.  Specific immunity

            a.  Dependent upon lymphocytes (a type WBC or

            leukocyte found in the lymphatic system)

            b.  Specific lymphocytes and specific antibodies respond to

            specific antigens

                        1)  __________________________ – anything that

                        elicits a specific immune response. 

                                    a)  Antigens are usually foreign (nonself)

                                    b)  Antigens are usually macromolecules such

                                    as proteins and polysaccharides.

            c.  The specific immune system learns through exposure to


                        1)  Memory responses occur much more quickly upon

                        2nd and subsequent exposures to that antigen.

2)  Usually responds upon re-exposure before

symptoms of disease set in


D.  The body system that carries out specific immune responses is the

lymphatic system.


II.  Basic terminology & definitions


            A.  __________________________ – any change from a state of good

            health.  Classes of diseases include…

                        1.  Hereditary diseases – e.g. cystic fibrosis; many genetic

                        mutations in a certain gene cause this disease.

                        2.  Dietary diseases – vitamin, mineral, protein deficiencies;

                        mental/physical problems

                        3.  Environmental diseases – smog/air pollution; lung diseases. 

                        Also includes poverty & host (child) abuse leading to mental illness.

                        4.  Microbial induced diseases

                                    a.  Infectious diseases – diseases caused by the growth of a

                                    microbe in/on a host.

                                    b.  Toxin induced diseases – disease caused by toxins

                                    produced  by microbes, in which case the living microbe

                                    does not have to be present in the affected host.


            B.  ____________________________________ – the organism (species

            or strain) responsible for producing a disease


            C.  __________________________ – an association between 2+ different

            organisms that has evolved to a state where they are generally found in

            association with each other under natural condition & where one or both

            members of the association benefits from the relationship

                        1.  e.g. E. coli in humans


D.  __________________________________ – the organisms normal

found on or in a healthy host most of the time


            E.  __________________________ – a type of symbiosis where an

            organism lives on or in a host & obtains nutrients from that host.

                        1.  A parasite does not necessarily harm the host & in some cases

                        their presence is even beneficial to the host. 

                                    a.  e.g. Tiny mites live in our eyebrows.  These insects

                                    apparently life off the dead skin cells, oil, & excretions form

                                    our sweat glands & they do us no apparent harm or good.

2.  However, in most cases only one of the associates truly benefits

from the association.

            a.  e.g. head lice, fleas on your pets, pin worms, etc.


            F.  __________________________ – a parasite that causes a disease in

            its host


            G.  __________________________ – Growth on or in a host.  This

            growth may or may not harm the host.


            H.  __________________________ – An infection with a larger than

            single-celled organism.

                        1.  e.g. parasitic worms, pubic & body louse, etc.


            I.  Mutualistic symbiosis – a situation where 2+ species live in a situation

            where both benefit from the association. 

                        1.  In some cases, one or more of the symbiotic species are totally

                        dependent on the other.


            J.  __________________________ – the ability to cause a disease. 

            Many organisms are pathogenic under certain conditions (e.g. the normal

            bacteria in our gut, which usually do us no harm, can become highly

            pathogenic under specific circumstances like getting shot or stabbed in the

            gut), but some are almost always pathogenic (e.g. chicken pox & flu).


            K.  __________________________ – the degree of pathogenicity.  A

            virulent organism is one that usually produces a violent & severe disease,

            often leading to death.

                        1.  Chickenpox & the common cold virus, while clearly pathogens,

                        are not considered to be virulent.

                        2.  Yersinia pestis, the etiological agent of bubonic plague, & the

                        Ebola virus are both considered to be virulent.


            L.  ______________________________________ – a mutant of a virulent

            pathogen that has lost its ability to produce a disease.

                        1.  These organisms may be used in the production of vaccines


            M.  _____________________________________ – a normal flora

            organism that normally is not a pathogen, but   that becomes pathogenic

            when inoculated into the wrong place or when the host becomes

            weakened & immunologically compromised. 

                        1.  Immunologically compromised – a host whose immune system

                        is not working to its full capacity & thus the host’s defenses are


                                    a.  People undergoing chemotherapy for cancer are

                                    immunologically compromised because the drugs harm the

                                    immune system.

                                    b.  People who are under stress often have a lowered

                                    immunity & are more susceptible to catching infections.


III.  Introduction to the Blood – since many of the immune responses involve

cells of the blood, a brief introduction to the blood is needed.


A.  Whole blood consists of…

1.  Living cells - called formed elements that are suspended in the

2.  Nonliving fluid matrix - __________________________.


B.  Blood Plasma is composed of…

                        1.  90% H2O

                        2.  8% plasma proteins (mostly produced by the liver)

                                    a.  These proteins include immunoglobulins – (a.k.a.

                                    antibodies) made by plasma cells (a special B cell, which is

                                    a type of WBC)

                        3.  2% solutes that include nutrients, gasses, hormones, wastes,

                        products of cell activity, and ions.


            C.  Formed Elements of Blood

                        1.  __________________________ (a.k.a. red blood corpuscles or


                                    a.  What is the function of RBC’s?  Transport O2 and CO2
                                    b.  They are small cells that are biconcave in shape. 

c.  They lack nuclei and most organelles

                                                1)  Therefore, they cannot divide

                                                2)  They also can’t make new proteins or repair


                                                3)  Their average life span is 120 days

                                    d.  RBC contain mostly hemoglobin

                                                1)  Hemoglobin (Hg) is an oxygen-binding pigment

            a)  Hg is responsible for the transport of most

            of the oxygen in the blood.

                                                            b)  A Hg molecule consists of 4 globin proteins

                                                            bound to 4 red, iron-containing heme pigments.

                                                                        i)  Heme portion binds oxygen

                                                                        ii)  Globin portion binds carbon dioxide

                        2.  __________________________ (a.k.a. white blood cells or


                                    a.  Unlike RBC’s, WBC’s have nuclei and are complete cells

                                                1)  WBC’s are usually short-lived and make up less

                                                than 1% of the total blood volume.

                                                2)  They are critical to our defense against disease.

                                                3)  How do they move?

a)  amoeboid movement: using pseudopodia

b)  diapedesis: squeeze out between cells of

capillary walls
            c)  positive chemotaxis: attracted to stimuli

d) phagocytosis: "cell eating"

                                    b.  Granulocytes are large WBC’s with lobed nuclei and

                                    granules in their cytoplasm; all are phagocytic

                                                1)  __________________________ are the most

                                                numerous WBC.

a)  They are chemically attracted to sites of


b)  They are active phagocytes (digesting


c)  Light pink to blue-black with 2 or more lobes

to nucleus

d)  Release:
            i) prostaglandins (increase permeability)
                        ii) leukotrienes (attract other


2)  __________________________ have red


a)  They are relatively uncommon and attack

parasitic worms

b)  They have been implicated in allergic

inflammation response

3)  __________________________: large, granular

cells with purple to blue nuclei

                        a)  Release histamine and heparin that

                        promote inflammation

b)  Least numerous WBC

                                    c.  Agranulocytes lack visibly staining granules

1)  __________________________ have large oval

or kidney bean shaped nucleus

a)  They have amoeboid movement

b)  They become macrophages, eating debris

and pathogens

c)  They attract WBC's and fibroblasts to wall

off infection

d)  They activate T cells

2) __________________________ have large nuclei,

they are the size of a RBC with a thin halo of


                        a)  __________________________: cellular

                        immunity.  They directly attack viral-infected

                        and tumor cells.

                                                1) cytotoxic T cells: destroy foreign

                                                cells in tissues
                                                            2) helper T and suppressor T cells:

                                                stimulate or inhibit the activities of other

                                                b) __________________________: humoral


1)  They become plasma cells, and

produce antibodies (a.k.a.


2) antibodies bind to foreign (non-self)

antigens (surface proteins), marking the

invader for destruction by the immune


                                                            c)  A 3rd, and less common, lymphocyte is the

                                                            large, granular ________________________

1)  They are nonspecific cells that

interact with virus-infected cells & some

other abnormal cells, such as cancerous


2)  NK’s release ___________________

(a hole-forming protein) that kills the

targeted, abnormal body cell


D.  __________________________ (a.k.a. thrombocytes)

                        1.  Platelets are not complete cells, but fragments of large cells

                        called             megakaryocytes

                                    a.  Formation of platelets involves repeated mitoses of

                                    megakaryocytes without cytokinesis.

                        2.  Platelets are critical to the clotting process, forming the

                        temporary seal when a blood vessel breaks.




            A.  The functions of the lymphatic system

1.  Drains interstitial fluid

            a.  The circulatory system leaks plasma into the body tissues

            b.  This fluid becomes interstitial fluid

            c.  Interstitial fluid is drained from body tissues by the

            lympathic system.

2.  Returns leaked plasma proteins to the blood           

3.  Transports dietary fats, and        

4.  Protects against invasion by nonspecific defenses and specific

immune responses.


            B.  The lymphatic system consists of…

                        1.  A fluid called __________________________

                                    a.  Lymph is formed when interstitial fluid drains into

                                    lymphatic capillaries.

                        2.  Lymph capillaries merge to form larger vessels, called

                        lymphatic vessels

a.  Lymph vessels convey lymph into and out of structures

called lymph nodes.

3.  __________________________ are encapsulated oval

structures composed of specialized reticular tissue containing large

numbers of lymphocytes.

                                    a.  Lymph enters a node

                                    b.  Within the node, damaged cells, microorganisms, and

                                    foreign substances are filtered from the lymph.

                                                1)  Macrophages destroy some foreign substances by


                                                2)  Lymphocytes bring about the destruction of others

                                                by specific immune responses.

                                    c.  Lymph exits the node

                                    d.  Lymph nodes are also the site of proliferation of plasma

                                    cells and T cells.

                        4.  This “cleaned” lymph is then returned to the circulatory system

                        where it becomes part of the plasma




            A.  Nonspecific Defense Mechanisms

                        1.  Physical barriers, such as skin and mucous membranes

                        2.  Secretions, such as mucus, saliva, urine that flush out microbes

                        3.  Normal floral bacteria

                        4.  Antimicrobial substances in body fluids and phagocytes

                        5.  Inflammation

                        6.  Physiological defenses, such as fever


            B.  First Line of Defense: Surface Barriers – the skin and mucous


1.  Mechanical protection includes the intact epidermis layer of the

skin, mucous membranes, the lacrimal apparatus, saliva, mucus,

cilia, the epiglottis, and the flow of urine. Defecation and vomiting

also may be considered mechanical processes that expel microbes.

2.  Chemical protection is localized on the skin, in loose connective

tissue, stomach, and vagina.

a.  The skin produces sebum, which has a low pH due to the

presence of unsaturated fatty acids and lactic acid.

b.  Lysozyme is an enzyme component of sweat that also

has antimicrobial properties.

c.  Gastric juice renders the stomach nearly sterile because

its low pH (1.5-3.0) kills many bacteria and destroys most of

their toxins; vaginal secretions also are slightly acidic.

d.  Cells are capable of killing pathogens using a

peroxidase system.

e.  Cells can produce an iron-binding protein, lactoferrin,

that makes Fe unavailable to pathogens.  This limits the

replication of many pathogens.

                        3.  Competition by normal flora prevents infection with many

                        potential pathogens.


C.  Second Line of Defense: Internal Defenses

1.  The second line of defense involves…

a.  Internal antimicrobial proteins

b.  Phagocytic and natural killer cells

c.  Inflammation

d.  Fever


D.  Antimicrobial Proteins – Cytokines.  These proteins enhance the innate

defenses by attacking microorganisms directly or by hindering their ability

to reproduce.

            1.  __________________________ are small regulatory proteins

            essential for communication between cells. 

a.  Cytokines are important to …

1)  the development of the inflammatory response

2)  the development of fever

3)  the development of specific immune responses.

b.  They include…

                                    1)  Interferons

                                    2)  Interleukins

                                    3)  Colony-stimulating factors

                                    4)  Tumor necrosis factors

                                    5)  Complement

2.  __________________________ (IFNs) are produced and

released by body cells infected with viruses.

            a.  IFNs diffuse to uninfected neighboring cells and binds to

            surface receptors

            b.  Neighboring, uninfected cells, are induced to synthesize

            antiviral proteins that interfere with or inhibit viral replication.

            c.  Other effects of IFNs…

                        1)  Enhance the activity of phagocytes and natural

                        killer (NK) cells

                        2)  Inhibit cell growth

                        3)  Suppress tumor formation

3.  __________________________ – 18+ different cytokines

produced by leukocytes.  Their functions include…

            a.  Inducing fever

            b.  Signaling for the release of PMN’s (neutrophils) from

            bone marrow

            c.  Attracting WBC’s (leukocytes) to areas of inflammation

            d.  Inducing the proliferation of lymphocytes (T and B cells)

4.  _______________________________________ – direct

immature cells into appropriate maturation pathways to produce

needed cell lines.

            a.  Myeloid stem cells (in bone marrow) can be directed to

            become mature granulocytes (basophils, eosinophils, or

            neutrophils) and monocytes (which can become

            macrophages and dendritic cells).

            b.  Lympoid stem cells (in lymph nodes) can be directed to

            become mature lymphocytes (T cells, B cells, and natural

            killer cells).

                        c.  Megakaryoblasts will be directed to become

                        megakaryocytes which will become the platelets.

5.  _________________________________________________

            a.  Mast cell granules store tumor necrosis factor alpha.  Its


                        1)  Induces fever

                        2)  Recruits neutrophils to areas of inflammation

                        3)  It is also antiviral

                        6.  __________________________ - A group of about 20 proteins

                        present in blood plasma and on cell membranes.

                                    a.  These proteins “complement” or enhance certain

                                    immune, allergic, and inflammatory reactions.

                                    b.  Complement mainly acts on foreign cells by punching

                                    holes in their membranes to cause their lysis & death.

                                    c.  Complement works in concert with the specific antibodies

                                    that “point out” the cells to be attacked

                                                1)  The antibodies act as the “finger” to identify a

                                                target cell

                                                2)  Complement acts as the “hit man” that kills the

                                                targeted cell.

                                    d.  Complement  plus antibodies also designate which cells

                                    are to be engulfed by the phagocytic cells.

                                                1)  This is called opsonization.

                                    e.  Complement can cause a serious allergic response

                                    known as anaphylactic shock.


E.  Natural Killer Cells and Phagocytes

            1.  Natural killer (NK) cells are lymphocytes that lack the

membrane molecules that identify T and B cells.

            a.  NKs are able to lyse and kill cancer cells and virally

            infected cells before the adaptive immune system has been


                        b.  NK cells can release perforins.

1)  Perforins insert into the plasma membrane of cells,

causing them to become leaky.

2)  Cytolysis (death) occurs

                                    c.  NKs can also bind to target cells and inflict damage by

                                    direct contact.

                        2.  Phagocytes confront microorganisms that breach the external


                                    a.  __________________________ occurs in several steps:

1) chemotaxis – the phagocyte is attracted to nonself

antigens exposed on bacteria surfaces or virally

infected body cells

2) attachment

3) ingestion through endocytosis

4) fusion of resulting vacuole with lysosome produces

a phagolysosome

5) killing within phagolysosome due to lethal

oxidants contained within the lysosome

6) breakdown of dead materials

            a)  The phagocyte will present the resulting,

            processed nonself antigens together with self

            antigens to alert the specific immune system to


7) exocytosis of the resulting debris.

                                    b.  Phagocytic cells include…

                                                1)  Macrophages - the main phagocytes of the body.

                                                2)  Neutrophils - the first responders

                                                            a)  They become phagocytic when they

                                                            encounter infectious material.

                                                3)  Eosinophils which are weakly phagocytic

                                                            a)  They are important in defending the body

                                                            against parasitic worms.

                                                4)  Mast cells – these cells look like macrophages,

                                                but are in the body tissues, not the circulatory


                                                            a)  They have the ability to bind with, ingest,

                                                            and kill a wide range of bacteria.


F.  __________________________ occurs any time the body tissues are

injured by physical trauma, intense heat, irritating chemicals, or infection

by viruses, fungi, or             bacteria.

                        1.  The four cardinal signs of acute inflammation are…





                        2.  Substances that contribute to inflammation are histamines,

                        kinins, prostaglandins, leukotrienes, and complement.

                        3.  The three basic stages of inflammation are…

a.  __________________________ - chemicals cause

dilation of surrounding blood vessels.  This leads to

increased blood flow to the area increased permeability.

            1)  Vasodilation results in clotting factors and

            antibodies leaving the plasma to enter the tissues.

b.  Phagocyte migration -  soon after inflammation begins,

the damaged site is invaded by neutrophils and


            1)  Phagocytes engulf damaged tissue and microbes

            2)  Eventually, the phagocytes die. 

            3)  This forms a pocket of dead phagocytes and

            damaged tissue and fluid called pus.

            4)  Pus must drain out of the body or it accumulates in

            a confined space, causing an abscess.

c.  Tissue repair.


            G.  Physiological Changes contribute to body defense

                        1.  Fever - an abnormally high body temperature.

                                    a.  Fever is a systemic response to infection from bacteria

                                    (and their toxins) and viruses.

                                    b.  Fever is caused by pyrogens that act on the

                                    hypothalamus to increase body temperature.

                                    c.  The high body temperature inhibits some microbial


                                    d.  Fever speeds up body reactions that aid repair.

                        2.  Changes in Iron Availability. Iron is made less available to

                        Microorganisms, hindering their replication.

                        3.  Changes in Protein and Carbohydrate Metabolism. Host

                        protein and carbohydrate metabolism is increased to meet the

                        demands of the active immune response.


VI.  Nonspecific defense mechanisms of the body’s weak spots – where our

fragile body is actually open to the cold, cruel microbial world around us.


            A.  Skin – tough, dry, salty, oily, rich in fatty acids & urea, low in nutrients

(lots of dead, empty cells), & thick.

                        1.  Sweat glands secrete a mixture of salt & fatty acids that inhibit

                        many microbes

                        2.  The skin is host of normal flora organisms that are antagonistic

                        to potential pathogens.

                                    a.  Normal flora eat up potential nutrients on the skin surface

                                    b.  To wash or not to wash?  Washing our skin helps to

                                    remove transient (potentially disease-causing) organisms. 

1)  However, our obsession with cleanliness also

washes away the acid mantle of our skin that helps

prevent infection with disease-causing organisms. 

(Cure – weak solution of apple cider vinegar sprayed

on after bath or shower.)

2)  Further, the use of antimicrobial soaps kills much

of the good, normal flora & can help produce

antimicrobial resistant “super bugs”.


            B.  Mouth & Gastrointestinal tract

                        1.  The mouth – harbors a host of microbes that live more or less

                        permanently, on the inside surface & in the nooks & crannies of the

                        mouth tissues.  These microbes are symbiotic & usually do us little

                        harm as long as we remain healthy.

                                    a.  Some of these species do us harm by contributing to the

                                    production of cavities, but many are beneficial because they

                                    out-compete harmful microbes that otherwise would live in

                                    our oral cavity & do us harm in the process.

                                    b.  Mouth microbes have evolved elaborate systems for

                                    sticking to things (e.g. pili)

                                    c.  In addition, there is a continuous flow of fluid (saliva)

                                    through the mouth which flushes loose microbes into the


                        2.  The stomach – contains a strong acid, hydrochloric acid.  Many

                        microbes are killed by this acidic environment & digested by the

                        proteolytic enzymes in the digestive system.

                                    a.  It is important to thoroughly chew food in order to expose

                                    potential pathogens to this acid bath.

                                    b.  Some bacteria can live & thrive in this low pH

                                    environment.  E.g. Helicobbacter pylori, the cause of

                                    stomach ulcers & stomach cancers.  This needs to be taken

                                    into account when treating stomach ulcers.

                        3.  The small intestine – full of digestive enzymes & detergents

                        (bile) that agreeably digest microbes as well as hamburger & pizza. 

a.  Even though the small intestine may be full of nutrients,

the absorption system of the healthy body is so efficient that

these nutrients are absorbed from the intestine so rapidly

that residential microbes have little to live on.

b.  Further, the intestines are anaerobic, so obligate aerobes

are unable to grow there even if they should survive the trip

through the stomach.

                        4.  The large intestine – is a different story.  It collects & processes

                        undigested material that passes through the small intestine. 

                        Bacteria, including some very nasty potential pathogens, grow

                        robustly on this debris & yet they rarely manage to invade the body.

                                    a.  The wall of the large intestine is coated with a protective

                                    mucous layer that separates the contents from direct contact

                                    with the cells lining the large intestine.

                                    b.  Epithelial cells of the mucosal epithelium lining body

                                    channels that sometimes communicate with air (e.g. the gut,

                                    lungs, urogenital tract, etc.) secrete antibiotic peptides

                                    (defensins) that kill bacteria by membrane disruption.

c.  The normal flora of the large intestine evolved to live on

the available food supply in the anaerobic conditions found

there.  Feces are approximately 40% bacteria by weight.

                                                1)  One problem with antibiotics taken by mouth is

                                                that they may upset the natural microbial balance &

                                                allow unusual microbes to establish themselves in our

                                                mouth, intestinal tract, or bowel.  This often results in

intestinal problems (e.g. excess gas & diarrhea) until

the original mix of microbes is again established.

C.  Genitourinary Tract – this region of the body is a rich source of

infection for obvious reasons. 

            1.  The urinary tract

a.  The urine is a good nutrient for many microbes. 

b.  The kidneys provide numerous nooks and crannies

where microbes can hide form the body’s defense systems. 

c.  Sexual activity significantly increases the exposure to

potential pathogens. 

d.  The efficiency of our nonspecific immune system is

shown by the fact that we don’t suffer more urogenital

infections than we do.

            1)  Microbes are prevented from reaching the bladder

            & kidneys mainly due to the vigorous flushing of urine

            out of the body through the urethra.

            2)  Because the urethra in women is shorter than in

            men, bladder infections are more common in women.

            3)  People subject to frequent bladder infections

            should drink lots of water & should urinate soon after

            sex to wash out potential pathogens that may have

            entered the urethra during intercourse.

                        2.  The vaginal area

                                    a.  Normally the vagina is acidic due to the growth of

                                    lactobacilli that produce lactic & acetic acid.  Also there is a

                                    continuous outward flow of mucus that expels microbes from

                                    the vagina.  Further, the entry to the reproductive organs is

                                    blocked by a mucous plug much of the time.

                                    b.  However, the vaginal lining is thin & easily damaged by

                                    unsuitable physical activity, including the improper use of

                                    sanitary napkins.  Its rich blood supply makes it an easy

                                    entry point for pathogens. 

                                    c.  Damage to the vaginal lining is  a major reason why

                                    women are more likely to become infected with HIV from

                                    fewer exposures.

                        3.  The anal area

                                    a.  It is continually exposed to fecal microbes that should not

                                    be introduced into the blood or tissue.

                                    b.  Such introduction is usually prevented by a mucous

                                    covering over the delicate anal membrane lining.

                                    c.  Anal penetration by foreign objects is very dangerous

                                    because these delicate membranes are easily torn & begin

                                    bleeding.  This explains why sexually transmitted diseases

                                    (STD’s) are so readily contracted through anal intercourse.


            D.  Respiratory tract – the lungs, with their large surface area &

            numerous small chambers, offer a rich source of nutrients & a great

            potential for concealing pathogens.

                        1.  Everyday we breathe in hundreds of liters of air contaminated

                        with dust, pollen, and microbes, yet rarely do we get lung infections.

                        2.  The nose is designed so that the turbulent flow of air throws

                        particulate matter onto the sticky mucous lining where much of it


                        3.  Particles trapped in mucous in the nose & lungs are moved by

                        the beating of cilia that line the air passages into the throat where

                        they are swallowed.

                        4.  Cells lining the air passages also secrete defensins that punch

                        holes in the membranes of many bacteria & destroy them.

                        5.  Sneezing & coughing expels material out of the air passages.