Infectious Diseases

Topic 6.3 and 11.1

BILL • Explain the ventilation of the lungs in terms of volume

and pressure changes.

1. As Volume increases, pressure decreases and vice versa2. Inhalation causes the diaphragm to contract and the abdominal and intercostal

muscles help raise the rib cage, increasing the volume of the thoracic cavity3. As volume increases, the pressure of the cavity decreases, leading to less

pressure pushing on the lungs4. The volume of lung tissue increases, because of the decreased pressure5. The pressure inside the lungs now decreases, creating a partial vacuum6. Air comes in through the oral/nasal cavity because of the vacuum and fills the

alveoli of lungs with air7. Opposite occurs during exhalation, diaphragm relaxes, volume decreases,

pressure increases, and air is force out of the lungs.

6.3.1 Define Pathogen

• Pathogen- any living organism or virus that is capable of causing a disease.

• Pathogens typically include bacteria, virus, fungi, protozoa and worms.

6.3.2 – Explain how antibiotics work against bacteria

• Antibiotics – chemicals that damage or kill prokaryotic cells, but not damaging eukaryotic cells by taking advantage of the biochemical differences between the two .

• Common antibiotics work by blocking cell wall synthesis so new cells can’t be produced.

• Antibiotics also block protein production in prokaryotic cells, but have no effect on eukaryotic cells

• NO EFFECT ON VIRUS! WHY???

6.3.3 – Outline the role of skin and mucous membranes in defense

SKIN• Skin is an obvious barrier to

diseases. • Made of two layers• Dermis, bottom layer that

contains sweat glands, capillaries, sensory receptors and dermal cells for structure and strength

• The outer layer, the epidermis, is primarily dead skin cells, creates barrier against pathogens.

Role of Mucous membranes

Mucous Membranes• Mucous Membranes are types

of tissues that line routes of entry to the body

• Produces and secretes lining of sticky mucus to trap pathogens

• Lined with Cilia (hair like extensions), also trap pathogens

• Secretes Lysozyme, enzyme that chemically damages pathogens

6.3.3 Continued, Location of Mucus Membranes

• Trachea – tube carries air to lungs• Nasal Passages – tube that allows air to enter

nose• Urethra – Tube that carries urine from bladder

to the outside• Vagina – Reproductive tract leading from

uterus to the outside.

Trachea

6.3.4 – Outline how phagocytic leucocytes ingest pathogens in the blood and in body tissues.

• Leucocytes (White Blood Cells) – cells in blood stream used to fight infection and provide an immunity to many pathogens encountered a second time– Macrophage – fight pathogens via phagocytosis.– Protein molecules on the bacterial membrane (antigens)

identify the pathogen as either “self” or “non-self”– Macrophage will engulf non-self pathogens where pathogenic

remains are digested in lysosome – This is considered a non specific immune response, because

the identity of pathogen was not determined, it was simply a non-self molecule.

BILL

• What is an antigen? What is an antibody?

Antigens & Antibodies

• Antigens are proteins embedded in cell membrane of a foreign invader

• Antibodies are Y-shaped protein molecules produced in response to specific pathogens

• Antibodies contain binging sites at the end of each fork, which will bind to Antigens and attach to pathogen

Antibodies are produced in response to a specific pathogen

• Leucocytes that produce antibodies are B lymphocytes (b cells)– Antigen is first identified– Specific B lymphocyte is identified that can produce an antibody

which will bind to antigen– B lymphocytes clone themselves (repeated mitosis) and increase

in number, then begin producing antibodies– Massive amounts of antibody production– New antibodies circulate in bloodstream and attach to antigen,

helping to eliminate pathogen– Some of the new lymphocytes remain in blood stream to prevent

secondary infection – known as memory cells.

Antibody Production

• Problem – leucocytes represent about 1% of all body cells, so you cannot have enough of each type of B cell for the amount of antibody secretion needed.

• Body uses cellular communication to lead to the cloning of B cells to secrete antibodies necessary to fight infections

Antibody Production• Macrophage recognizes pathogen as non-specific “not-self ”

organism• Engulfs pathogen by phagocytosis and partially digest it• Remaining pieces are displayed in manner called “antigen

presentation”• Leucocytes called Helper T cells recognize the antigen and

turn immune response from non-specific to specific• T cells chemically communicate to specific B lymphocytes, or

B cells to produce antibodies• Each B lymphocyte is capable of producing a specific

antibody which binds to a specific antigen

Antibody Production - Cell Cloning

• When Helper T Cells signal for production of B lymphocytes, Cell cloning begins

• Clone Two types of cells– Antibody-secreting plasma cells – cells secret

antibodies immediately to fight primary infection– Memory Cells – cells do not secrete antibodies,

but have long life in bloodstream waiting for secondary infection

Primary vs. Secondary response

• Primary Immune Response - occurs the first time after a body is exposed to an antigen. 10-17 days are required for B cells to produce enough antibodies to help clear antigen

• Secondary Immune Response – occur when an individual is exposed to an antigen again. Takes 2-7 days to produce enough antibodies to help clear antigen.

Principles of Immune Response System

• Challenge and response: Immune system is challenged by antigen, response by macrophage, helper t cells, b lymphocytes.

• Clonal Selection: Identification of B lymphocytes that secrete specific antibody and multiple cell divisions

• Memory Cells: Cells provide long term immunity

Polyclonal vs. Monoclonal Antibodies

• Primary immune response (before memory cells) is a polyclonal response – This is because the pathogen is being recognized

by many antigens– Results in clonal selection of many B cells, so

several kinds of antibodies are produced and several different memory cells are produced

Monoclonal Antibodies• Procedure used to produce monoclonal antibodies occur when only

one type of antibodies are produced– Inject antigen into laboratory animal (mouse) – The animal goes through the primary immune response, resulting in

specific antibodies being produced – Spleen is harvested and leucocytes that were cloned for injected antigen

are identified– B cells are fused with cancerous myeloma cells, forming cells called

hybridoma, which produce antibodies and are long lived – Cells are cultured in separate containers and tested for the presence of

desired antibodies– An ELISA (Enzyme-linked immunosorbent assay) test identifies desired B

cells, which can be cultured for a long time and continuously produce desired antibodies

ELISA – Enzyme linked immunosorbant assay

Uses of Monoclonal Antibodies

• Diagnosis – Pregnancy Tests– Early in pregnancy, human chorionic gonadotrophin

(HCG) hormone is produced by the embryo. – Hormone shows up in small amounts in urine and

blood stream. – Hybridomas can be produced using HCG as an antigen,

and thus producing antibodies that will bind to HCG– These antibodies are chemically bound to enzymes

that change color when the antibody binds to HCG, indicating the presence of an embryo

Uses of Monoclonal Antibodies

• Treatment – Cancer Cells – Cancer cells produce a specific antigen that can be

used to produce monoclonal antibodies – Antibodies can be modified to carry a toxin

specific for type of cancer, or a radioisotope for radiation therapy

– Able to target cancer cell directly, so less toxin and radiation are needed.

Medical uses of Ab’s

Active vs. Passive Immunity

• Active immunity - described in previous slides, results in production of memory cells and provides a long-term immunity to pathogen

• Passive Immunity – when one organism acquires antibodies that were produced in another organism, but no memory cells are produced

Examples of Passive Immunity

• Transfer of antibodies from mother to fetus through placenta, so memory cells are not transferred

• Acquisition of antibodies from mother’s colostrum, which is the breast milk produced in late pregnancy and the first days after birth. Colostrum is high in antibodies

• Injection of antibodies in antisera (antivenoms for snake/spider bites). Venom is a protein that can illicit antibody production, but primary response is typically too slow and would result in massive damage, so antivenoms are used.

BILL • What is the difference between active and passive immunity? What

is an example of passive immunity?

• Active immunity occurs when a body is challenged by an antigen, responds with clonal selection and the production of memory cells

• Passive immunity occurs when the body gets antibodies that were produced by another organism and no memory cells are formed.

• Transfer of antibodies through placenta from mother to offspring, or transfer from colostrum (breast milk) to offspring

• Anti-venom is used to treat bites from venomous snakes/spider

11.1.1 Describe the process of blood clotting

• When your skin is punctured, typically you puncture the capillary bed that is delivering blood to that area. With that, you release blood (remember—capillary walls are only 1 cell thick)

• The plasma portion of your blood contains many different proteins that are involved in the clotting. The clotting of blood stops blood loss and prevents pathogens from entering body.

Blood Clotting – platelets stick together to damaged/torn area and seal the “leak”

If wound is more serious clotting process takes over1. Platelets release thromboplastin (clotting factors)2. Thromboplastin converts prothrombin (plasma

protein) into thrombin3. Thrombin converts fibrinogen into fibrin4. Fibrin forms a network of strands that trap RBCs and

platelets to form clot5. Once the healing is complete, plasmin (enzyme)

dissolves the fibrin clot

Blood Clotting

Viruses • Pathogens that consist of nucleic acid, a protein coat, and in

some cases, a membranous envelope • May have double or single stranded DNA, double or single

stranded RNA• Protein shell is called a capsid• Viruses can only reproduce within a host cell

– Lytic cycle – reproductive cycle that breaks down hosts DNA, uses it to produce proteins and nucleotides, and destroys host cell at end of cycle

– Lysogenic cycle – reproductive cycle that integrates viral DNA into host DNA, forming a prophage, DNA is replicated normally, producing a colony of prophages, or can initiate lytic cycle at a later time.

Viruses

• Bacteriophage – virus that infect bacteria • Eukarytotic viruses – diverse and dependent

on type of nucleic acid found inside

How HIV Damages the immune system

• Viruses need a type of cell that is complementary to own proteins

• Depending on the cell it infects, different viruses can have different symptoms/severities

• Human immunodeficiency virus (HIV) is the virus that eventually leads to AIDS (acquired immune deficiency syndrome.

• HIV infects Helper T cells – cells that communicate which B cells need to undergo cloning and produce antibodies.

T-Helper Cells

• HIV infects T-Helper cells of the immune system. • Helper T cells help identify which antibodies need

to be produced. Frequently, the virus will go undetected for years (virus has a latency period).

• HIV is a retrovirus - A retrovirus is an RNA virus that is replicated in a host cell via the enzyme reverse transcriptase to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme.

HIV Damages Immune System

• When helper T-cells begin to die no communication between cells no antibodies produced

• Individual no longer fights off pathogens and symptoms of AIDS appear

• Secondary infections ultimately take the life of someone with AIDS

Once detected, HIV mutates incredibly fast so it is very difficult to treat with medications.

Why is HIV/AIDS Difficult to treat

• Virus can be hidden in body cells for years because of latency period

• Virus mutates relatively quickly, vaccines may not recognize/affect it after several mutations

• Association w/ Sexual Activity & Drug abuse led to reluctance in funding

Vaccinations

• Bodies cannot be immune to a pathogen they have not been exposed to.

• Vaccines act as first exposure– Pathogen is weakened by exposure to heat or

chemical treatment– Leucocytes respond to “not-self” pathogen and

primary immune response occurs– Memory Cells form capable of producing

antibodies if there is a real infection

Vaccinations• Do not prevent infection but speed up

secondary response of immune system compared to primary response

Benefits and Dangers of VaccinationsPossible total elimination of disease. This has occurred with smallpox and many people believe it is possible to eradicate both polio and measles

Prior to 1999, many vaccines contained thimerosal, a mercury based preservative. Mercury has been shown to be a neurotoxin to which infants and young children are susceptible.

Decrease in the spread of epidemics (localized infections) and pandemics (worldwide infections) Increased international travel has made this more important than ever because of how easily infections can travel

The perception exists that multiple vaccines given to children in a relatively short period of time may overload their immune system

Preventative medicine is typically the most cost effective approach. Costs associated with vaccinations are small compared to costs of treating preventable diseases

Anecdotal evidence that suggest MMR (measles, mumps, rubella) vaccine may have a link to onset of autism. No clinical studies support this

Each vaccinated individual benefits because the full symptoms of the disease do not have to be experienced to gain immunity.

Cases have been reported of vaccines leading to allergic reactions and autoimmune responses.

Exercises• When a person is bitten by a poisonous snake, they are given

an antivenom. The antivenom is composed of antibodies which recognize protein molecules on venom and bind to them. This type of treatment is referred to as passive immunity and does not confer long term immunity. Why is that?

• Why are some viruses potentially lethal, while others cause fairly mild symptoms?

• Describe how skin and mucus membranes act as barriers to pathogens?

Antivenom

• Antibodies produced by another organism. The memory cells that are capable of producing these antibodies are located in the organism that produced them, not in the organism who receives the antivenom. Long term immunity comes from memory cells. This is called passive response

Severity of Symptoms

• Severity of symptoms depends on two factors:– Tissue type that is the target of a particular virus,

some tissue types are potentially more dangerous when infected

– How quickly virus replicates could result in less time the immune system has to respond

Skin/Mucous Membrane Barriers

• Skin is a physical barrier to entry, dry skin inhibits growth of bacterial cells; bacteria on skin prevents growth of other bacterial cells; sweat contains anitmicrobial/lysozyme to keep bacterial growth in check

• Mucous Membrane traps bacteria in sticky mucus; cilia sweep/trap bacteria; secretes lysozyme to destroy bacteria; contain macrophages to perform phagocytosis