Biology Immune System notes

Human Immune Response

Innate Immunity

Pathogen: disease-carrying agent

• Includes:

  • Bacteria

  • Viruses

  • Protists

  • Fungi

Two types of responses to pathogens

• Innate:

  • Non-specific, doesn’t distinguish one pathogen from another

  • Rapid response to pathogens

  • Is present before any exposure to pathogens

  • Is effective from the time of birth

• Acquired:

  • Specific response to particular antigen

  • Slower response to pathogens

  • Requires previous exposure to the pathogen

  • Built over a life time of exposure to pathogens

Two types of innate immunity:

• First line of defense:

  • External defesnes like:

  • Skin

    • Cannot normally be penetrated by bacteria and viruses

    • Secretions from sebaceous and sweat glands keep the skin in a pH range of 3 to 5 (acidic) which kills microbes

  • Mucous membranes

    • Line digestive, repiratory, and genitourinary tracts

    • Secrete a muous that traps microbes and particles

    • In the trachea, ciliated epithelial cells sweep out mucus and trapped microbes

    • Prevent these form entering the lungs

    • Swwalling exposes them to acidic environment of the stomach

  • Chemical secretions

    • Microbial infection is also inhibited by saliva, tears, and mucus secretions

    • All of these secretions contain antimicrobial proteins

    • An example os lysozyme, an enzyme that digits the cell walls of many bacteria

• Second line of defense:

  • Internal defenses like:

  • Phagocytic cells

    • White blood cells (leukocyctes) that ingest invading organisms

    • 3 types:

      • Macrophages

        • Large, long-llived phagocyctes

        • Cells extend long pseudopodia, engulf the microbe into a vessicle which fuses with a lysosome

      • Esinophils

        • Help fight large parasitic invaders

        • Position themselves alongside the parasite and discharge destructive enzymes through exocytosis

      • Neutrophils

        • Most abundant white blood cell

        • Recruit activate other cells of the immune system

        • Have three strategies for directly attacking micro-organisms:

          • Pahgocytosis (ingestion)

          • Release of anti-microbial proteins

          • Generation of neutrophil extra cellular traps (NETs)

  • Natural killer cells

    • Do not attack microbes directly

    • They destroy infected (typically those infected with viruses)

    • Also attack abnormal body cells that could be cancerous

    • They attack the cell’s membrane and cause the cell to lyse

  • Antimicrobial proteins

    • A variety of proteins attack mircobes directly or impede microbe reproduction

    • Example: 

      • Lysozyme: reference to earlier

      • Interferons: secreted by virus-infected cells, do not benefit the infected cell but induce neighboring cells to produce chemicals that inhibit viral reproduction

  • Inflammation

    • 2nd line defense

    • Tissue damage leads to a localized inflammatory response

      • Could be injury

      • Could be invasion by microbes

    • Capillaries respond by

      • Increased dilation (widening to allow more leukocytes to access the damaged issue)

      • Increased permeability (capillaries have pores that widen to allow more immune proteins through to access the damaged tissue)

      • Enhanced delivery of clotting elements

    • Leads to increased redness, heat, and swelling

  • Fever

    • 2nd line defense

    • If damage or infection is severe, a widespread non-specific reponse may occur

    • Increased body temperature

    • Inhibits growth of some microbes by denaturing their enzymes

    • Facilitates phagocytosis

    • Speeds up repair of tissue

Immune Technologies

Vaccination:

• is the purposeful administration of ot antigenic material ot produce immunity to a disease

• Live but weakened forms of pathogens

• Killed or inactivated forms of pathogens

• Purified material such as proteins

• The vaccine stimulates clonal selection and development of memory cells, but without developing the disease symptoms

• If an infection of the disease occurs naturally after vaccination, the body reacts as if it is the second exposure to the disease

• Vaccination is generally considered to be the most effective and cost-effective method of preventing infectious diseases

• Benefits:

  • Eradication of a disease from a population

  • Reduced death from disease

  • Reduced disabilities from disease

  • Decreased loss of work days due to disease

• Dangers: 

  • Vaccine immunity less effective than natural immunity

  • Side effects of vaccination

Antibiotics

• Are substances that kills bacteria or inhibits its growth

• (action) Antibiotics block metabolic pathways and structures found in bacteria

  • The bacteria cell wall 

  • Bacterial ribosomes

  • Enzymes that are specific to bacteria

• Viruses can’t do metabolism, so they aren’t effected by antibiotics

• Drugs that inhibit bacterial growth

  • Agar plate (nutrient growth medium) with bacterial colonies spread uniformly across its surface

Summary of Evolution by Natural Selection

• Overproduction: species produce more young than the environment can support

  • (In bacteria, variation is due to mutation)

• Survival of the fittest phenotype: the individuals with the most favorable characteristics will be most likely to survive and pass their genes

• The mutation may code for an ability to inactivate the antibiotic

  • A mutated enzyme produced in the bacterium destroys the antibiotic. 

  • Many bacteria that are resistant to penicillin possess such an enzyme (called penicillinase). 

  • Penicillinase inactivates penicillin by catalyzing the destruction of bonds within the penicillin molecule, thereby inactivating it.

• A mutant gene may code for an ability to alter the target of the antibiotic

  • Some antibiotics (e.g. streptomycin) inhibit bacterial protein synthesis. 

  • However, if only one amino acid in either of two positions on a ribosome is replaced, a bacterium can develop streptomycin resistance. 

  • Some antibiotics, such as penicillin, interfere with cell wall synthesis. Therefore, mutations to the cell wall proteins can result in resistance.

• The mutation may alter the permeability of the bacterial cell to the antibiotic

  • Resistance can be acquired by excluding the antibiotic or by slowing its entry enough to render the antibiotic ineffective. 

  • Bacteria can develop proteins that actively pump antibiotics out of their cell faster than the antibiotics can enter.

• Favorable characteristics increase:  Each new generation will contain more offspring from individuals with favorable characters than those with unfavorable ones, changing the population over time

• Over generations, the gene frequency in the population changes to favor the antibiotic resistant bacteria

Acquiring Resistance

• Bacteria can acquire antibiotic resistance by conjugation.

  • A plasmid containing antibiotic resistance is transferred via a sex pilus between the bacteria during the process of conjugation.

  • These bacteria may be the same or different species. 

• Antibiotic resistance can be spread between bacteria by transduction.

  • Bacterial DNA, carried by a viral vector, integrates into the

  • bacterial cell’s genome, providing antibiotic resistance.

• The spread of antibiotic resistance between bacteria can occur through  transformation.

  • Naked DNA containing a gene for antibiotic

  • resistance is engulfed by the bacterium.

History: 

• HIV

• HIV from SIV (HIV is a descednant of a Simian Immunodeficiency Virus (SIV))

• Wild chimps infected simultaneously with two different SIVs which had “viral sex” to form a third virus that could be passed on to other chimps and was capable of infecting humans and causing AIDS

• A study in 2008 dated the origin of HIV to between 1884 and 1924

• Hunter theory:

  • An article publsihed in the Lancet (2004) shows how retroviral transfer from primates to hunters is still occurring even today

• The earliest known instances of human HIV infection

  • A plasma sample taken in 1959 from an adult male living in what is now the Democratic Republic of Congo

  • A lympth node sample taken in 19560 from an adult female, also from the country above

  • HIV found in tissue samples from an American teenager who died in St. Louis in 1969

  • HIV found in tissue samples from a Norwegian sailor who died around 1976

• It spread by travel, blood industry, intravenous drug use, unsafe sexual practices

• HIV infection is now pandemic

  • About 3 million lives a year

  • ⅓ of them are in sub saharan africa

    • Increasing poverty

    • Many orphans

• HIV infects lymphocytes

  • HIV infects T cells

  • When the T-lymphocyte numbers decline below a critical level, cell-mediated immunity is lost

  • The body progressively more susceptible to opportunistic infections

• Acquired Immuno deficiency syndrome

  • Acquired relates to the infectious nature of AIDS through the transmission of the HIV virus

  • Immuno deficient relaetes to the way disease affects the immune system

  • Syndrome relates to the variation in the way the disease can manifest itself, people who develop AIDS can be affected by quite different set of diseases

  • Transmission:

    • Through contact with the blood fluis of an infected person (blood, semen, pre-ejaculate, vaginal mucus, breast milkl)

Monoclonal Antibodies

• Is an artifically produced antibody for a specific antigen

• Useful for 3 reasons

  • They are totally uniform

  • They can be produced in large quantities

  • They are highly specific

• Have many therapeutic uses:

  • Neutralizing endotoxins produced by bacteria in blood infections.

  • Preventing organ rejection, e.g. in kidney transplants, by interfering with T cell activity.

  • Treatment of some autoimmune disorders such as rheumatoid arthritis and allergic asthma.

  • The monoclonal antibodies bind to and inactivate factors involved in the inflammatory response.

  • Immunodetection and immunotherapy of cancer.

  • Newer methods specifically target tumor cells shrinking solid tumors without harmful side effects.

  • Inhibition of platelet clumping to prevent reclogging of coronary arteries after angioplasty.

  • The monoclonal antibodies bind to the receptors on the platelet surface, interfering with clotting.

  • Production:

    • Stimulate the production of B-cells in mice by injecting them with the antigen. 

    • These B-cells produce an antibody against the antigen. 

    • B-cells isolated and fused with immortal tumor cells.  

    • Immortal cells cultured indefinitely in a suitable growing medium.  

    • Antibodies isolated via protein chromatography

  • Diagnostic uses of monoclonal antibodies, have many diagnostic uses:

    • Detecting the presence of pathogens such as Chlamidia an streptococcal bacteria, distinguishing between Herpesvirus I and II, and diagnosin AIDS.

    • Measuring protein, toxin, or drug levels in serum.

    • Blood and tissue typing.

    • Detection of antibiotic residues in milk.

    • Detecting pregnancy.

      • Human chorionic gonadotropin (HCG) is released from the placenta of pregnant women

        • HCG accumulates in the bloodstream and is excreted in the urine.

        • HCG is a glycoprotein. Antibodies against it can be used in simple test kits to determine if a woman is pregnant. 

        • A blue colored band above the dipstick indicates a positive test

    • Direct treatment of disease (i.e. rabies)

Acquired Immunity

Aka adaptive immunity!

• The third line of defense

• The key cells of the third line of defense are lymopcytes

  • B cells: humoral immune response

    • “Challenge and response” → the immune system needs to be “challenged” by the presence of an antigen, the immune system responds by producing a clone of “B” cells which produce large amounts of antibodies to fight and eliminate the pathogen

    • 1. Antigen floating in blood binds to receptor on B cell surface

    • 2. B cell divides into 2 cell types

      • Plasma B cells:

        • Secrte antibodies into the blood immediately

        • Antibodies are proteins that attack to specifc pathogen antigens

          • Tip of antibodies become specialized for specifc antigens

        • The antibody/ antigen complex makes the microbe easier targets for phagocytes

      • Memory B cells:

        • Long-lived cells bearing receptors for the same specific antigen

        • Eventually, a few cells give rise to thousands of new cells-- all clones of original and all specific to original invading antigen

        • Memory cells with continue to divide and create antibodies for the rest of the life of the organism

    • Division of antigen specific B cells is called clonal selection:

      • A blood stem cell undergoes differentiation and genetic rearrangement to produce immature lymphocytes with many different antigen receptors. Those that bind to the body’s own tissues are destroyed, while the result mature into inactive lymphocytes. Most of these will never encounter a matching foreign antigen, but those who not are activated and produce many clones of themselves!

  • T cells: cell mediated immune response

    • A macrophrase cell exposes the antigen on its own cell surface

    • “Helper T cell” binds to the antigen exposed on the surface of macrophage

    • “Helper T cells” release chemicals called cytokines that activate “killer T cells” 

    • These cells respond by destroying the infected cell

    • The rate of the immune response is different depending on if the body has “seen” the antigen before

      • If it’s the first exposure:

        • About 10 to 17 days required for peak  plasma B cell response 

      • Second (and subsequent) exposure:

        • Response is faster (2 to 7 days)

        • Magnitude is greater

        • Duration is longer

• Lymphocyes recognize and respond to specific microbes and the molecules on the foreign cells membrane (antigens)

• Antigens include:

  • Potentially damaging microbes and their toxins

  • Substances such as pollen and flea and dust mite feces

  • Blood cell surface proteins

  • The surface proteins of transplanted tissues and organs

• Lympocytes:

  • Lymphocytes originate from pleuropotent stem cells in the bone marrow or liver of a developing fetus

    • If they migrate to the thymus to mature, they become T cells

    • If they stay in the bone marrow to mature, they become B cells

    • How they recognize antigens?? They have antigen receptors

      • A single B or T cell has about 100,000 receptors, all with exactly the same specificity

      • There is an enormous variety of B and T cells in the body, each with different specificity

      • This allows response to millions of potential pathogens

      • While B cells and T cells are developing, their antigen receptors are tested for potential self-reactivity

        • Will I attack cells of my own body? If yes, rendered non0functional or destroyed by apoptosis

        • This leaves only lymphocytes that react to foreign substances

        • Autoimmune diseases result when this self-reactivity check malfunctions

Types of Acquired Immunity:

• Naturally acquired:

  • Active: infection, contact with pathogen

    • Microbes cause the person to catch the disease

    • There is a sub-clincial infection (one that produces no evident symptoms)

    • The body produces specialized lymphocytes and antibodies

  • Passive: antibodies pass from mother to fetus via placenta or to infant in her milk

    • The infant’s body does not produce any antibodies of its own

• Artificially acquired:

  • Active: vaccine, dead or attenuated pathogens

    • The body produces specialized lymphocytes and antibodies

  • Passive: injection of immune serum (gamma globulin)

    • The body does not produce any antibodies