interactions between microbes and their host unit 4: 6 days

Interactions Between Microbes and their Host

Unit 4: 6 days

March 17th and 24th: Principles of Disease and Epidemiology

• Disease causing microorganisms are called pathogens

• Pathogenic microorganisms have special properties that allow them to invade the human body or produce toxins

• When a microbe overcomes a body’s defenses a state of disease results

Vocabulary

• Pathology is the scientific study of disease

• Etiology is the cause of disease• Pathogenesis is the development of

disease• Infection is the invasion and growth of

pathogens in the body• A host is an organism that shelters and

supports the growth of pathogens

Normal Microbiota

• Animal, including humans, are usually germ free in utero

• Microbes begin colonization soon after birth

Normal Microbiota

• Microbes that establish permanent colonies inside of the body, without causing disease, are called normal microbiota

• Transient microbiota are microbes that are present for various periods and then disappear

Normal Microbiota

• The normal microbiota can prevent pathogens from causing infection– Called microbial

antagonism

• Normal microbiota and the host exist in symbiosis

Normal Microbiota

• There are three types of symbiosis:

– Commensalism

– Mutualism

– Parasitism

Normal Microbiota

• Opportunistic pathogens do not cause disease under normal conditions but cause disease under special conditions

• In some situations one microbe makes it easier for another to cause disease or produce more sever symptoms

Identification

• Koch’s Postulate:– Criteria for establishing that specific microbes

cause specific diseases– Same pathogen must be present in every

case of the disease– The pathogen must be isolated in pure culture– The isolated pathogen must cause disease in

healthy individuals– The pathogen must then be re-isolated from

the newly infected individual

Identification

• Exceptions:– Viruses and some bacteria cannot be grown

on media– Some diseases like tetanus have obvious

signs, and Koch’s Postulate is not needed– Some diseases like pneumonia are caused by

multiple pathogens– Some microbes, like S. pyrogens, cause

several diseases

Vocabulary

• Symptoms are subjective changes in body functions

• Signs are measurable changes

• A diagnosis is and identification of the disease

• A specific group of symptoms or signs that always accompanies a specific disease is called a syndrome

Vocabulary

• Communicable diseases are transmitted directly from one host to another

• A contagious disease is one that is easily spread from one person to another

• Noncommunicable diseases are caused by microorganisms that usually grow outside of the human body

Occurence

• Reported by incidence (the number of people contracting the disease) and prevalence (the number of cases at a particular time)

• Different classifications:– Sporadic– Endemic– Epidemic– Pandemic

Severity and Duration

• The scope of a disease can be:– Acute– Chronic– Subacute– Latent

• Herd immunity is the presence of immunity in most of the population

EIDs

• New diseases are called emerging infectious diseases (EIDs)

• EIDs can result from the use of antibiotics and pesticides, climatic changes, travel, and/or the lack of vaccinations

• The CDC, NIH, and WHO are responsible for surveillance and response to EIDs

Host Involvement

• A local infection affects a small area of the body

• A systemic infection spreads through the body via the circulatory system

• A secondary infection can occur after the host is weakened from a primary infection

• An inapparent or subclinical infection does not cause any signs of disease in the host

Host Involvement

• A continual source of infection is called a reservoir

• People who have disease, or who are carriers, are human reservoirs

• Zoonoses are diseases that affect wild and domestic animals and can be transmitted to humans

• Some pathogens grow in non-living reservoirs, like soil and water

Transmission– Direct contact– Fomites

• Non-living objects– Droplet transmission

• Coughing or sneezing, saliva or mucus

– Vehicle transmission• Medium like air, food, or water

– Airborne transmission• Water droplets or dust carried more

than 1 meter– Arthropods

Transmission

• Pathogens have preferred portals of exit

• Four common:– Respiratory tract

• Coughing and sneezing

– Gastrointestinal tract• Saliva or feces

– Urogenital tract• Vaginal or penile secretions

– Arthropods and syringes• For pathogens in the blood

Nosocomial Infections

• Any infection that is acquired during the course of stay in a hospital

• Between 5 and 15% of hospitalized patients acquire a nosocomial infection

Nosocomial Infections

• Certain normal microbiota are responsible for these infections when they are introduced to the body in abnormal ways– Surgery or catheterization

• Opportunistic drug-resistant gram negative bacteria are the most common culprits of nosocomial infections

Nosocomial Infections

• Patients with burns, surgical wounds, and depressed immune systems are the most susceptible

• Typically these infections are transmitted by direct contact

• Fomites can also play a large role in transmission– Catheters, syringes, respiratory devices, etc.

Nosocomial Infections

• Aseptic techniques can prevent nosocomial infections

• Hospitals have infection control staff that are responsible for overseeing proper cleaning, storage, and handling of equipment and supplies

Patterns of Disease• Predisposing factors:

– Makes the body more susceptible to disease or alters the course of the disease

• Gender• Climate• Age• Fatigue• Nutrition

Patterns of Disease

• Development of disease:– Incubation period

• Interval between initial infection and the first appearance of symptoms

– Prodromal period• The appearance of the first mild signs and symptoms

– Illness period• Disease is at its height, all symptoms and signs are apparent

– Decline period• Signs and symptoms subside

– Convalescence period• Body returns to predisease state

Epidemiology

• The study of disease transmission, incidence, and frequency

• Began in 1848 when John Snow studied a cholera epidemic in London

Epidemiology

• Descriptive epidemiology– Data about infected people are collected and

analyzed

• Analytical epidemiology– Infected people are compared with uninfected

people

• Experimental epidemiology– Controlled experiments

Epidemiology

• Case reporting provides data on incidence and prevalence to local, state, and national health offices

• The CDC is the main source for epidemiological information in the U.S.

• The CDC publishes the Morbidity and Mortality Weekly Report to provide information on morbidity (incidence) and mortality (deaths)

March 31st: Pathogenicity

• The ability of a pathogen to produce a disease by overcoming the defenses of the host

• Virulence is the degree of pathogenicity

Pathogenicity

• The specific route by which a pathogen enters a body is called its ‘portal of entry’

• Mucous membranes– Eye– Respiratory– Gastrointestinal– Urogenital

Pathogenicity

• Microbes that are inhaled with droplets of moisture and dust particles gain entry to the respiratory tract– The respiratory tract is the most common

portal of entry

• Microbes enter the gastrointestinal tract via food, water, and contaminated fingers

Pathogenicity

• Most microbes cannot penetrate intact skin

• Rather they enter hair follicles or sweat ducts

• Some fungi can infect the skin itself

• Typically microbes enter through the skin via bites, injections, and wounds– Called the parenteral route

Pathogenicity

• Many microbes only cause infections when they enter through a specific portal of entry

• Virulence can be expressed by LD50 and ID50

– Lethal dose and infectious dose for 50%

Penetrating Host Defenses

• Capsules– Prevent microbes from being phagocytized

• Cell Wall– Proteins can facilitate adherence– Allows some microbes to reproduce inside

phagocytes

Penetrating Host Defenses

• Enzymes– Leukocidins destroy neutrophils and

macrophages– Hemolysins lyse red blood cells– Local infections can be protected in a fibrin

clot caused by the bacterial enzyme coagulase

Penetrating Host Defenses

• Penetration into host cell– Salmonella bacteria

produce invasins, proteins that cause the actin of a host cell’s cytoskeleton to form a basket to carry the bacteria into the cell

Damage to Host Cells

• Direct damage is cause by pathogens metabolizing and multiplying inside of host cells

• Also, host cells can be damaged by the production of toxins, poisonous substances produced by microorganisms– Toxemia refers to the presence of toxins in

the blood– Toxogenicity is the ability to produce toxins

Damage to Host Cells

• Exotoxins are produced by bacteria and released into the surrounding medium– Exotoxins, not the bacteria itself, cause the

disease symptoms

• Antibodies produced against exotoxins are called antitoxins

• Cytotoxins include diptheria toxin (inhibits protein synthesis) and erythrogenic toxins (which damage capillaries)

Damage to Host Cells

• Neurotoxins include botulinum toxin (which prevents nerve transmission) and tetanus toxin (which prevent inhibitory nerve transmission)

Damage to Host Cells

• Vibrio cholerae toxin is an enterotoxin– Induce fluid and electrolyte loss from host

cells

• Endotoxins are lipopolysaccharides

• Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins

• Endotoxins allow bacteria to cross the blood brain barrier

Plasmids

• Plasmids may carry genes for antibiotic resistance, toxins, fimbriae, and capsules

Non Bacterial Organisms

• Viruses– Avoid the host’s immune response by growing

inside of cells– Gain access because they have receptors for

attachment sites on cells– Visible signs of viral infections are called

cytopathic effects– Some viruses cause cytocidal effects– Other cause noncytocidal effects (damage,

but not death)

Non Bacterial Organisms

• Fungi– Symptoms of fungal infections can be caused

by capsules, toxins, and allergic responses

• Algae– Some algae produce neurotoxins that cause

paralysis when ingested by humans

Non Bacterial Organisms

• Protozoa and Helminths– Symptoms can be caused by damage to host

tissue or the metabolic byproducts of the parasite

– Some protozoa change their surface antigens while growing in a host so that the host’s antibodies don’t kill the protozoa

April 2nd: Nonspecific Defenses

• The ability to ward off disease through the body is called resistance

• Lack of resistance is called susceptibility• Nonspecific resistance refers to all body

defenses that protect the body against any type of pathogen

Mechanical

• The structure of skin is waterproof and the protein keratin provides resistance to microbe invasion

• Some pathogens can penetrate mucous membranes

• Lacrimal apparatus protect the eye

• Saliva washes teeth and gums

Mechanical• Mucus traps microbes

entering the respiratory system and gastrointestinal tract

• Lower respiratory has a ciliary elevator

• Urine flow moves microbes out of the urinary tract

• Vaginal secretions move microbes out of the vagina

Chemical

• Sebum contain unsaturated fatty acids which inhibits the growth of pathogenic bacteria– Some bacteria can metabolize sebum, causes

acne

• Perspiration washes microbes off the skin

• Lysozyme found in tears, saliva, nasal secretions, and sweat

Chemical

• pH of stomach prevents microbial growth (1.2 – 3.0)

• Normal microbiota prevent growth of many pathogens

Phagocytosis

• The ingestion of microorganisms and particulate matter by a cell

• Performed by phagocytes, certain white blood cells, or their derivatives

• Blood is made from plasma and formed elements– RBC’s– Platelets– WBC’s

Phagocytosis

• 3 main categories of white blood cell:– Granulocytes

• Neutrophils• Basophils• Eosinophils

– Lymphocytes– Monocytes

Phagocytosis• Granulocytes predominate during the early

stages of infection

• Monocytes predominate as the infection subsides

Phagocytosis

• Neutrophils are the most important granulocyte phagocytes

• Enlarged monocytes become wandering macrophages and fixed macrophages

• Fixed macrophages are located in selected tissues

Phagocytosis

• Chemotaxis is the process by which phagocytes are attracted to microorganisms

• Pseudopods of phagocytes engulf the microbe and enclose it in a phagocytic vesicle to complete ingestion

Inflammation

• Inflammation is a bodily response to cell damage

• Four cardinal signs:– Redness– Pain– Heat– Swelling (edema)

– Sometimes loss of function

Inflammation

• The release of histamines, prostaglandins, and kinins causes vasodilation and increased permeability of blood vessels

• Blood clots can form around an abscess to prevent spread of an infection

Inflammation• Phagocytes have the ability to stick to the lining of

blood vessels (margination)• They also can squeeze through blood vessel walls

(emigration)• Pus is the accumulation of damaged tissue and

dead microbes, granulocytes, and macrophages

Tissue Repair

• A tissue is repaired when the stroma (supporting tissue) or parenchyma (functioning tissue) produces new cells

• Stromal repair often produces scar tissue

Fever

• Abnormally high body temperature produced in response to bacterial or viral infection

• Bacterial endotoxins can produce fever

• A chill indicates rising body temperature

• Crisis (sweating) indicates the body temperature is falling

Antimicrobial Substances

• Complement system– Group of serum proteins that activate each

other to destroy invaders– Serum is the liquid remaining after blood is

clotted– Complement deficiencies can result in

increased susceptibility to disease

Antimicrobial Substances

• Interferons– Antiviral proteins– Produced in response to viral infections– Three types of human interferons– Recombinant interferons have been made– They are host cell specific– They are NOT virus specific

April 8th: The Immune Response

Specific Defenses

• Called the “immune response”

• An individual’s genetically predetermined resistance to certain diseases is called innate resistance

• Individual resistance is affected by gender, age, nutritional status, and general health

Immunity

• Immunity is the ability of the body to specifically counteract foreign organisms or substances called antigens

• Immunity results from the production of specialized lymphocytes and antibodies

Acquired Immunity

• The specific resistance to infection developed during the life of an individual

• A person may develop or acquire immunity after birth

Naturally Acquired

• Immunity resulting from infection is called naturally acquired active immunity– This type of immunity is typically long lasting

• Antibodies transferred from a mother to a fetus (transplacental transfer) or to a newborn colostrum results in naturally acquired passive immunity in the newborn– This immunity can last for a few months

Artificially Acquired

• Immunity resulting from vaccination is called artificially acquired active immunity– Can be long lasting

• Vaccines can be prepared from attenuated, inactivated, or killed microorganism and toxoids

• Artificially acquired passive immunity refers to humoral antibodies that are injected– Can last for a few weeks

Artificially Acquired

• Antibodies made by a human or other mammal may be injected into a susceptible individual

• Serum containing

antibodies is often

called antiserum

Immune System Duality• Humoral immunity is in body fluids

– Involves antibodies produced by B cells in response to a specific antigen

– Primarily defend against bacteria, viruses, and toxins in blood plasma and lymph

• Cell mediated immunity is due to certain types of lymphocytes– Depends on T cells, no antibody production– Primarily a response to intracellular bacteria and

viruses, parasites, transplants, and cancer

Antigens and Antibodies

• An antigen is a chemical substance that causes the body to produce specific antibodies or sensitized T cells

• Typically antigens are foreign substances

• Most antigens are components of invading microbes

Antigens and Antibodies

• Antibodies are formed against specific regions on the surface of an antigen called antigenic determinants

• Most antigens

have several

different

determinants

Antigens and Antibodies

• And antibody is a protein produced by B cells in response to the presence of an antigen

• It is capable of combining specifically with that antigen

• An antibody has at least two identical antigen binding sites

Antibody Structure

• A single bivalent antibody unit is a monomer

• Most antibody monomers consist of four polypeptide chains– 2 heavy, 2 light

• Within each chain is a variable (V) region where antigen binding occurs

• Also a constant (C) region– Serves as the basis for distinguishing

between classes of antibodies

Antibody Structure

• An antibody monomer is Y or T shaped

• The variable regions form the tips

• The Fc region is the stem– Can attach to a host cell

Immunoglobulin Classes• IgG – Most prevalent, enhance

phagocytosis

• IgM – 5 monomer, help in agglutination

• Serum IgA – protect mucosal surfaces from invaders

• IgD – antigen receptors on B cells

• IgE – involved in allergic reactions

B Cells and Humoral Immunity

• Humoral immunity involves antibodies that are produced by B cells

• Bone marrow stem cells create B cells

• Mature B cells migrate to the lymphatic organs

• A mature B cell recognizes an antigen with antigen receptors

Apoptosis• Lymphocytes that are not needed undergo

apoptosis• Also called programmed cell death• They are

destroyed by

phagocytes

Immunological Memory

• The amount of antibody in serum is called the antibody titer

• The response of the body to the first contact with an antigen is called the primary response

• It is characterized by the appearance of IgM then IgG

Immunological Memory

• Subsequent exposures to the same antigen causes a very high antibody titer and is called the secondary or memory response– The antibodies are primarily IgG

April 22nd: Antimicrobial Drugs and Specific Disorders

Vaccines Review

• Edward Jenner – cowpox

• Herd immunity

• Types of vaccines:– Attenuated whole-agent (weakened microbes)

• Life long

– Inactivated whole-agent (killed microbes)– Toxoids (inactivated toxins)

Disorders of the immune System

• Hay fever, transplant rejection, and autoimmunity are examples of harmful immune reactions

• Infection and immunosuppression are example of immune system failure

Hypersensitivity

• Immunological responses to an antigen that lead to tissue damage instead of immunity

• Occur when a person has been sensitized to an antigen

• Four major classes:

Type I: Anaphylactic

• Involve production of IgE antibodies that bind to basophils and sensitize the host

• Causes release of histamine and/or prostaglandin

• Symptoms may develop in minutes after exposure– May result in circulatory collapse and death– Hives, hay fever, asthma

• Skin testing and desensitization useful

Type II: Cytotoxic

• ABO blood group system– Naturally occurring antibodies

are present

– Lysis of cells common

• Rh blood group system– 85% positive

– Subsequent exposure of Rh positive cells in an Rh negative person will lead to rapid and severe hemolysis

– Common issue with pregnancies

Type III: Immune Complex

• Occur when IgG antibodies and soluble antigen form small complexes that lodge in the basement membrane of cells

• Subsequent fixation results in inflammation

Type IV: Cell Mediated

• Sensitized T cells secrete cytokines in response to appropriate antigens

• Cytokines attract and activate macrophages and initiate tissue damage

• The tuberculin skin test and allergic contact dermatitis are examples of delayed hypersensitivities

Autoimmune Disease

• Results from a loss of self-tolerance

• Self-tolerance occurs during fetal development– T cells that will target host are eliminated or

inactivated

• Graves’ Disease and Myasthenia Gravis are type II autoimmune reactions in which antibodies react to cell surface antigens

Autoimmune Disease

• Systemic lupus and rheumatoid arthritis are type III autoimmune reactions in which the deposition of immune complexes results in tissue damage

• Hashimoto’s disease and insulin-dependent diabetes are type IV reactions mediated by T cells

Transplants

• Histocompatibility self molecules located on cell surfaces express genetic differences among individuals

• To prevent rejection HLA and ABO antigens are matched as closely as possible

Transplants

• Transplants recognized as foreign antigens may be lysed by T cells and attacked by macrophages

• Privileged sites and tissues:– Cornea– Pig heart valves

Transplants

• 4 types of transplants:– Autografts– Isografts– Allografts– Xenografts

• Bone marrow can cause graft vs. host disease

• Successful transplant surgery often requires immunosuppressants

Immune Deficiency

• Immune deficiencies can be congenital or acquired

• Congenital immune deficiencies are due to defective or absent genes

• A variety of drugs, cancers, and infectious diseases can cause acquired immune deficiencies

The Control of Cancer

• Cancer cells are normal cells that have undergone transformation, divide uncontrollably, and possess tumor associated antigens

• The response of the immune system to cancer is called immunological surveillance

The Control of Cancer

• Cancer cells can escape detection and destruction by the immune system

• Cancer cells may suppress T cells, or grow faster than the immune system can respond