The study of small pathogens and the disease they cause.  

Pathogens are disease causing organisms.

Disease is something that interrupts homeostasis.  

Prions are infectious proteins that cannot be autoclaved or flamed.  

Prions cause spongiform encephalopathies with open areas of plaque.

Disease they cause: Mad cow disease, Kuru in cannibals, Creutzfeld Jakob disease (CJD).  

• Viruses are non-living genetic elements/particles.
• Obligate parasite that cannot replicate with host cell.
• Survive outside hostcell(capsid coat, envelope)
• Metabolically inert (no metabolism)
• Examples: Influenza, polio, chicken pox, herpes, AIDS, measles, Ebola.

• Have DNA or RNA, not both, inside protein shell.
• Viral genomes are generally linear.
• Encode machinary for host subjugation.
• Largest virus is about same size as smallest cell.
• All cells have viruses.

• Saprophytes.
• Single celled or multicellular.
• Examples include:  molds, yeasts, mushrooms, parasites, saprovores.
• Disease: yeast infections, athletes foot.

• Tough cells walls made of chitin sterols.
• Physiology--saprophytes, acid/temp tolerant.
• Yeast or mold morphologies, spore common.

• Molds are multicellular.
• Yeast are unicellular, and sugar loving.
• Many yeasts are dimorphic.

• Motile, unicellular "animals"
• no cell wall
• fresh/marine water or parasites
• Examples: Malaria, Toxoplasmosis, Giardia, Entamoeba, Montezuma's revenge.

Non-Specific:  tears, skin, flow of liquids out, phagocytes, pH of tummy.

Specific:  Immunity=Immunology

• Humoral: Antibody; protein molecules that bind to foreign material and inactivate it.
• Cellular: cells interact with foreign with foreign material to kill also control immune response. CD4, CD8, etc.  

The man who developed the postulate for disease  etiology.

Studied TB, Anthrax, and Cholera.  

1. Associate with disease.
2. Isolate in pure culture.
3. Inject animal and get same disease.
4. Recover in pure culture.  

Louis Pasteur

Developed attenuated vaccines for anthrax and chicken cholera.  He produced first vaccine for Rabies.  

Penicillin

Fleming, Chain and Florey

1. Free Living--couldn't care less.
2. Commensal--"eat at the same table," no damage
3. Symbiotic--both gain, eg normal flora
4. Parasite--it harms you.  May or may not cause disease.  For disease there must be a PATHOLOGICAL change in the host.
5. Saprophytic--lives on dead and decaying material.  

1. Transmission--get from host to host.
2. Correct Portal of Entry 
3. Find correct "niche"

1. Direct Contact--staph, herpes, athletes foot.
2. Sexual or Veneral
3. Respiratory--Strep, influenza
4. Fecal/Oral--salmonella, giardia
5. Water/Food
6. Food--botulism, salmonella
7. Fomite--inanimate objects (drinking fountain, forks)
8. Vectors--orgnaims that transmit disease.  

• Oxygen level (eg Areobic, Anaerobic)
• Correct pH (Acidic or Basic)
• Correct Nutrients
• Overcome other organisms
• Overcome host defenses.

1. Most common--we control and destroy with no symptoms, Immune system protect us.
2. We get sick and then recover, destroying the agent.
3. We control it but we become carriers (eg typhoid Mary)
4. It kills us.

What are the different ways to classify infections?

Exogenous--from without

Endogenous--from within

Local--remains at one site (eg zit)

Focal--spreads to other sites from a point source (eg tetanus)

Systemic--throughout the body (eg Plague)

Primary--results from invading agent

Secondary--disease caused by other agents as a result of devility due to disease or therapy (eg chemotherapy, AIDS)

Mixed--two or more agents involved.

Inapparent or subclinical--you have an immune response with no symptoms.

Bacteremia--transitory state where bacteria are in blood moving to another place.

Septicemia--blood is the infected tissue.

Pyemia--pyogenic bacteria in blood (eg staph/strep)

Toxemia--poison in blood (eg Tetanus)

Viremia--virus in blood

Parasitemia--parasite in blood (eg Malaria)

1. Ability to invade (enzymes)
2. Capsules (polysaccaride, antiphagocytic)
3. Toxins (endo and exo)
4. Motility (cilia, flagellum)
5. Adherence (velcro for a microbe)
6. Antigenic variation (ability to change surface at high rate to confuse IR)

1. Premunition (ability to resist infection due to generations of contact)
2. Age (hard on very young and very old)
3. Genetic ability to resist disease
4. Nutrition/Health
5. Occupation
6. Other diseases

1. Skin--Integument
2. Mucous Membranes
3. Ears
4. Nasopharynx
5. Oropharynx
6. Respiratory Tract
7. Eye
8. Gut
9. Urogential Tract

Skin--salinity, pH 5, normal flora

MMs--neuramic acid, mucous

Ears--ear wax

Nasopharynx and Oropharynx--mucous expectorant, oro--lysozyme, Naso--hair

Eye--mucous, tears, lysozyme

Gut--pH, normal flora

Urogential--flushing with urine, pH, normal flora

Chemical--acids, bases, bile salts, enzymes, 

Mechanical--flow of tears, saliva, urine blood is all out!  Washes organisms away.

Normal Flora--organisms that live within us cover up sites, produce antimicrobial agents.  

Granulocytes--have granules

Agranulocytes--no granules.  

Grandules stain purple with basic dye.  Grandules are mainly HISTAMINE, the stuff of inflammation.  Up-regulate inflammation.

If they become bound or fixed in endothelium they are called Mast Cells.  

1. Monocytes
2. Lymphocytes
3. Platelets
4. Natural Killer Cells

Increase in metabolism leads to O₂ being converted to O₂^- (superoxide) which spontaneously generates H₂O₂.  

H₂O₂ + Cl^- = HOCl (hypochlorite)

Response to tissue damage.  Short term (good) long term (bad).

Tissue damaged mast cells release Histamine and other pharmacological mediators.  

• Chemotatic for PMNs and Macrophage.
• increase vascular permeability (bring plasma to site)
• increase vascular dilation (bring core blood to site)
• Constricts smooth muscle, compresses area to restrict motion of bad guys.
• Causes pain
• Macrophages compound the reaction by releasing longer acting cytokines such as leukotrienes and prostaglandins.  

1. Heat--increased blood flow
2. Pain--pressure of plasma and cells, histamine causes pain
3. Swelling--bolume of plasma, swollen vessels and cells 
4. Redness--increased blood flow

Macrophage--large phagocyte

Thymus derived lymphocytes (T-cells)--cellular immunity and immune regulation

• T_helper that up regulate the IR (T_H)

• T_{delayed type hypersensitivity} Effector Response (T_DTH)

1. T-Suppressor that down regulates the (T_S)
2.  T-Cytotoxic that directly kill cells (T_C)

Afferent responses are the reactions that lead to an immune response.  An example would be a foreign material gains access and is ingested by a macrophage. 

Efferent responses are those reactions which result from the immune response.  An example would be after be immune response triggerged to destroy all of the foreign material.  

Immunogen--afferent; stimulates immune response; must be foreign, complex, ridged, large, epitope density; proteins are the best, carbohydrates and nucleic acids; lipds are poor.

Antigen--efferent molecule; any molecule that reacts with the immune system.  

1. Antibody--glycoprotein released by B-cell bind specifically to antigen.  
2. Cell-mediated immunity--CD4+ delayed hypersensitivity T-cells + macrophage; Cytotoxicity-CD8+ cytotoxic T-cells

• Afferent reactions take time to product effector response.  Non-specific defense mechanism must protect body during this time.

1. tolerance--a specific non-response to self-antigens.

What are the fiveclasses of antibodies?

1. I_GM--largest Ab
2. I_GG--serum Ab
3. I_GA--secretory or mucousal
4. I_GD--B-cell receptor
5. I_GE--binds ot mast cells, immune mediated inflammation.  

• Neutralization--cover up toxic sites
• Opsonization--antibody enhanced phagocytosis.
• Precipitation/Agglutination--cross linking (make antigens stick together)
• Complement Fixation--activation of 11 serum proteins thalt burst cells.
• Immobilization--binding to motility structures.  

The primary response encompasses afferent branch activities.

The secondary response encompasses efferent branch activities.  

• Natural--(fetus during utero and breast milk)
• Artificial--(body is injected (anti-toxin, gamma globin)

1. Hypersensitivity (tissue damage occurs as a result of the normal response)
2. Autoimmunity (attack on self)
3. Toxicity (vaccine preparation is poisonous)
4. Reversion (revert back to virulance)
5. Immunocompromised host (patients immune system can't handle, dies)

• Enahnced phagocytosis.
• Prolonged antigen release.
• non-specifically enhance immune reactive cells

A sub-unit vaccine is an immunogen which incorporates a single component or molecule to stimulate a protective immune response.  Examples include Hepatitis B and Influenza.  

A lot of work is going into developing peptide or epitope vaccines which offer the ability to focus the immune response to a minimal exposed portion of the protective antigen.  

Vaccines which employ recombinant DNA techniques to produce and or deliver defined immunogens.

Hope to develop single does multi-disease vaccines to focus on local needs.  

Disadvantes:  expensive, only one approved: Hep B