Humoral Immunity:
    1. Immunity results from antibodies.
    2. Involves B lymphocytes (B cells).

Cellular Immunity:
    1. Involves interaction of T lymphocytes (T cells).

Antibodies: (Immunoglobulins; Ig)

•Globular proteins made in response to antigens.

•Recognize and bind to the antigen they are made against.

 •Microbe may have several epitopes that different antibodies can be made against.

Epitope (antigenic determinant):

specific region on antigen that antibodies recognize.

Antibody Structure:

1) Four protein chains joined by disulfide links; form Y-shaped molecules.

Variable (V) regions: bind to epitopes.

     ► Lower parts of the arms and stem of the Y.
       ► Same for a specific class of immunoglobulin.
               ► Five major types of C regions = five major classes of immunoglobulins.

          ► Interacts with complement to destroy bacteria.

G-MADE

Five classes: IgG, IgM, IgA, IgD, and IgE 

Dimer: most common type in mucous membranes and secretions (mucus, saliva, milk).

IgE: 0.0002% of antibodies in serum.

     ► Allergic reactions; destruction of parasitic worms.

► Bound to mast cells and basophils in body.
  

Define

plasma cell and memory cell.

Plasma cell:   antibody producing cells.

Memory cells: involved in secondary response to                             antigen. 

► B cell surface antibodies bind to antigen.
► Antigen is taken inside and processed.
► Fragment of antigen binds with MHC (major histocompatibilty complex membrane         protein) class II.
►MHC class II-antigen complex displayed on membrane of B cell.

► Receptor on surface of T helper (TH) cell binds MHC II-antigen complex.
► TH cell is activated and releases cytokines.
► Cytokines activate B cells.

► B cell begins clonal expansion. 

 ● Memory cells: involved in secondary                         response to antigen.

T-independent Antigens:

antigens that stimulate B cells without the help of T

T-independent antigens stimulate B cells without the help of T-helper cells.  They are polysaccharides that bind to epitopes of B cell receptors directly, stimulating the B cells. 

Normally, a receptor on the helper T cell recognizes complex of MHC class II and antigen fragments, and then is activated.  This produces cytokines which activate the B cell.

Protective Results of Antigen-Antibody Complex Formation:

1) Agglutination

2) Compliment activation

3) Opsonization

4) Neutralization

5) Antibody-dependent cell-mediated cytoxicity

-ACONA-

Agglutination: antibodies cause antigens to clump together.

► Reduces number of antigens to deal with.
 

Opsonization:  coats antigen with antibodies.

► Enhances phagocytosis. 

► Resembles opsonization; microbe not engulfed by immune cell.

E.g. larger parasitic worms. 

Cellular immunity T cells combat intracellular pathogens, recognize cells that are non-self, and are specific for a certain antigen.

Humoral immunity B cells combat antigens not necessarily inside cells, but all throughout body fluids.

Antigen-presenting cells (APCs): must process antigens before T cells can recognize them.

    ► Antigen fragment presented on surface of APC bound to MHC.

Helper T cells (T_H)

1. Helper T Cells (TH):

► Initial binding and stimulatory molecule activate TH cell to produce cytokines

► Cytokines stimulate TH cell to proliferate.

 2. Cytotoxic T Cells (TC):

Cytotoxic T Cells (TC):

► Recognize antigen presented on non-self cells by MHC class I.

► Transforms TC cells into Cytotoxic T Lymphocytes (CTLs).

        • Perforins + granzymes = apoptosis (cell death).   

    ► Recognize antigen presented on APCs by MHC II.

  ► Recognize antigen presented on non-self cells by MHC class I.

Antigen-Presenting Cells (APCs):

2. Poor phagocytes; great APCs.

3. Activated by: ingestion of antigens and by cytokines from TH cells.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is used on pathogens that are too large to be ingested (protozoa or helminth) that are attacked externally.

• Coated with antibodies

• Various cells bind to the F_c region (stem) of the antibodies.

• Target is lysed by substances secreted by immune cells. 

 • proteins used by immune cells to communicate.
    

► Produced by immune cells; especially T_H cells.

Primary response: response after first contact with antigen.

Secondary response: response after second contact with antigen.

 Adaptive immunity: immunity against specific microbes and substances.

Naturally Acquired Active Immunity:

Naturally Acquired Passive Immunity:
    

2. Temporary immunity (polio, rubella).

Artificially Acquired Passive Immunity:
    

1. Injection of antibodies from immune individual into the body.

Vaccine:

suspension of organisms or fractions of organisms

used to induce immunity.

Inactivated whole-agent vaccines: killed microbes.

    ► Examples: Rabies, influenza, etc.

 Toxoids: inactivated toxins.

► Advantage: directed at toxins made by     pathogens.

►Examples: Tetanus, diphtheria.

Subunit Vaccines: made with antigenic fragments of the microbe.
    

► Advantages:
        • Safer; cannot reproduce.
        • No extra material; fewer side effects.
► Disadvantage: Can’t be made for all microbes
    

► Example: Hepatitis B vaccine.

Safety of Vaccines: Risks versus benefits

Chemotherapy:

destruction of pathogens without harming the host.

•substance produced by a microbe that inhibits another microbe.

Spectrum of microbial activity:

range of different microbes affected by drug.

Eukaryotic cells (fungi, helminths) and viruses: 

    •more difficult to target because humans have eukaryotic cells        also.  Drugs may harm humans in process of targeting these pathogens.    

Broad-spectrum antibiotics:

affect a broad range of gram(+) and gram(-) bacteria.

 Advantage: treat infection before identification of                     pathogen.

 Disadvantage: kill most normal flora. 

Cell ProPl Nu Meta

•Cell Wall Inhibitors 

•Inhibitors of Protein Synthesis 

•Injury to the Plasma Membrane

•Inhibition of Nucleic Acid Synthesis

• Inhibition of Synthesis of Essential Metabolites

Chloramphenicol

     Polymyxin B:

• Change permeability of plasma membrane; lose cell     contents.

 Rifampin
      

 ► Inhibit mRNA synthesis.
 ► Treat tuberculosis and leprosy.

Sulfanilamide

• sulfa drug that competes with PABA that is used for folic acid synthesis.

•enzyme that converts PABA to folic acid combines with drug instead 

Natural Penicillins: Penicillin G and V

    ► Natural penicillins: extracted from Penicillium.

    ► Useful against Streptococci and Staphylococci.

Give the disadvantages of natural penicillins and

examples of semisynthetic penicillins developed to

overcome the disadvantages.

• bacterial enzyme that breaks down penicillin.

•many bacteria produce penicillinase, so semisynthetic penicillins had to be developed as penicillinase-resistant. 

• Penicillins are cell wall inhibitors.

• Natural penicillin G and V useful against Strep- and Staph-

• Synthetic penicillins have a beta-lactam core made by mold with a side chain that is added chemically. 

•They are used to overcome disadvantages of natural penicillins (they are now penicillinase or beta lactamase-resistant, and extended-spectrum)  

• resistant to penicillinases;

• susceptible to other β-lactamases.

•Broad-spectrum

•Binds to 50S ribosomal subunit; inhibits peptide     bond formation, protein synthesis. 

        Aminoglycosides: (Ex. Streptomycin)

• Changes shape of 30S subunit; mRNA isn’t read             correctly.

•Inhibits protein synthesis. 

Vancomycin: last effective treatment MRSA.

• Is a cell wall inhibitor

•Polypeptide antibiotic 

 Polymyxin B

• Injury to the Plasma Membrane:
        • Change permeability of plasma membrane;                 lose cell contents.

Inhibition of Nucleic Acid Synthesis

1. Inhibit DNA replication and transcription.
2. Limited use; interfere with mammalian nucleic acid synthesis.

Rifampin: 

► Inhibits mRNA synthesis.
► Treat tuberculosis and leprosy.

Scalded Skin syndrome: underlying tissue becomes infected.
► Usually children under 2 as complication of Staph. infection.
► Symptoms: lesion around nose and mouth; become bright red areas that spread.
    • Within 48 hours affected skin peels off in sheets.
► Virulence factors: exfoliative toxin. ► Treatment: antibiotic therapy required.

Toxic Shock Syndrome (TSS):
► Causative agent: Staphylococcus aureus ► Transmission: endogenous infection.
► Symptoms: fever, vomiting, sunburn-like rash, followed by shock, sometimes organ failure. ► Virulence factors: Toxic shock syndrome toxin 1 (TSST-1); formed at infection site, circulates in the blood. ► Results from: highly absorbent tampons, nasal surgery, surgical incisions, complications after giving birth. 

Virulence factors:

    • Exoenzymes include: streptokinases, streptolysins,     hyaluronidase, deoxyribonucleases, etc.

Chickenpox: mild childhood disease; deaths due to pneumonia or encephalitis.

• Causative agent: Varicella-zoster virus (Herpesviridae) •Transmission: aerosol (via respiratory route). • Symptoms: infections localizes in skin in ~2 weeks. ► 3-4 day vesicular rash; vesicles fill with pus, rupture, form scabs. ► Virus becomes latent in a central nerve ganglion.

Shingles:
► Causative agent: Varicella-zoster virus reactivated by stress or lowered immune system. ► Transmission: endogenous virus from chickenpox infection.
    • Virus moves along nerves to the skin. ► Symptoms: vesicles appear in localized areas. • Limited to one side of the body, burning or stinging pain, nerve damage may occur (blindness, paralysis).

 Rubella (German measles):
Causative agent: Rubella virus.
Transmission: aerosol (via respiratory route)
Symptoms and Disease:
    ► 2-3 week incubation.
    ► Milder disease than measles; often undetected.
    ► Encephalitis occurs in 1 in 6000 (mostly adults).

Congenital rubella syndrome:
    ► Birth defects caused by infection (of German measles) of the mother during pregnancy. ► Deafness, heart defects, retardation, death.
    ► 15% of babies with congenital rubella die within the first year.

•Central Nervous System (CNS): brain and spinal cord. 

Define peripheral nervous system.

•Peripheral Nervous System (PNS):

all nerves that branch from the brain and spinal cord.

• inflammation of the brain.

In the CSF, there are low levels of compliment antibodies and phagocytic cells which allow easy multiplication.

CSF is susceptible to microbes in the blood because they can penetrate the blood-brain barrier capillaries that can lead to the CSF.

Rabies:
Causative agent: rabies virus (Lyssavirus).
Transmission: animal bite.
Symptoms:
    ► Initially: mild, varied symptoms; resemble other common infections.
    ► Periods of agitation and calm; mouth spasms or hydrophobia. ► Extensive damage to cells of CNS.

• Virulence factors: ► Enters PNS, moves to the CNS where it destroys nerve cells.
    ► Immune system response: death caused by encephalitis (inflammation of the brain). • Mortality rate: 100% with no treatment.

• Treatment: post exposure vaccination.

Cardiovascular system is made up of heart, blood, blood vessels.

Function is for circulation of fluids throughout body to distribute nutriens, carry away wastes. 

Lymphatic system is made up of lymph, lymph vessels, nodes and organs (tonsils, appendix, spleen, thymus).

Function is to help distribute nutrients, help carry away wastes, and to help clear body of pathogens.

Plague:
Causative agent: Yesinia pestis ► Disease of rats, squirrels, rodents.• Transmission: vector (fleas) or inhalation. ► Also: scratches, bites of domestic cats.• Symptoms: ► Buboes in groin and armpits, fever, septic shock.• Virulence factors: ► Ability to survive and grow inside phagocytes.• Disease: ► Bacteria enter blood; grow inside phagocytes in blood and lymph. ► Large number of organisms emerge.

Yellow Fever: “classic hemorrhagic fever”
Causative agent: yellow fever virus.• Transmission:► Vector: mosquito (Aedes aegypti) ► Natural reservoir: monkeys.• Symptoms: fever, chills, headache, nausea, vomiting, jaundice. ► Yellowing of skin indicates liver damage.• Virulence factors: viral replication.• Mortality rate: 20% • Treatment: none; mosquito control.

Upper Respiratory System: nose, pharynx, and the structures associated with them.

Lower Respiratory System: larynx, trachea, bronchial tubes, and alveoli. 

 Influenza:
Causative agent: Influenzavirus • Transmission: airborne.
Virulence Factors: hemagglutinin (H) spikes, neuraminidase (N) spikes, viral replication. ► H spikes: attachment to body cells. ► N spikes: allow virus to exit cells after replication. • Symptoms: chills, fever, headache, general muscle aches.
•Influenza viruses identified by variations in H and N spikes: ► 15 H subtypes.

► 9 N subtypes. • Antigenic shift: substantial alteration in the protein makeup of a spike. (H1 -> H4) ► Evasion of developed immunity. • Antigenic drift: minor changes in the H and N spikes. • Mortality: usually less than 1%.
► Pandemic of 1918: 20 million deaths; virus was able to invade lungs and cause     pneumonia.

Gastrointestinal (GI) tract: mouth, pharynx, esophagus, stomach, small and large                                         intestines.

    ► Accessory structures:teeth, tongue, salivary glands, liver, gallbladder, and                 pancreas.
    ► Some structures produce secretions that are carried into the GI tract.

Function: to digest food.
   

    ► Absorption: molecules produced during digestion move from small intestine                 into blood or lymph for distribution to body cells.
 

    ► Virulence factors: enterotoxin; non-invasive (intoxication)

► Transmission: ingestion (food/drink) ► Symptoms: loss of appetite, tiredness, nausea, diarrhea, abdominal discomfort, fever, chills, headache, jaundice, dark urine, tender liver.
    •Incubation: averages 4 weeks.
    • Symptoms last 2-21 days.
    • ~50% of cases are subclinical.
    • No chronic form.

► Diagnosed by detection of anti-HAV IgM. ► High risk groups: lower socioeconomic groups, travelers to endemic areas, homosexual men, injecting drug users. ►Treatment: none. • Risk of exposure, given immune globulin. • Vaccination available for high-risk groups.

► Transmission: parenteral, sexual contact (blood/semen).
► Symptoms: loss of appetite, tiredness, nausea, diarrhea, abdominal discomfort, fever, chills, jaundice, (no headache), cirrhosis, liver cancer.
    • Incubation: averages 12 weeks.
    • Frequently subclinical.
    • Up to 10% of patients become chronic carriers.

► Diagnosed by detection of anti-HBV IgM.
► High risk groups: health care workers, IV drug users.
► Treatment: childhood immunization
    • Acute hepatitis: none.
    • Chronic hepatitis: nucleoside analogs and alpha-interferon; liver transplant.

• Function of urinary system: regulates the chemical composition and volume of the blood and excretes nitrogenous waste and water.

• Urine is transported from the kidneys through ureters to the urinary bladder and is eliminated through the urethra.

• Valves prevent backflow to bladder and kidneys. 

• Flushing action  and acidity of urine have some antimicrobial value.                        • Bladder and upper UT are normally sterile.                                                   

The female reproductive system consists of two ovaries, two uterine tubes, the uterus,

 the cervix, the vagina, and the external genitals.

The male reproductive system consists of two testes, ducts, accessory glands, and the penis; seminal fluid leaves the male body through the urethra.