Immunity Lecture Notes

Recalibrating for Unit 3

• Final Exam May 19th, in person from 8:30-10:30am

• Counts as 25% of lecture grade (Exam 1 and 2 were 20%)

• Not cumulative but should know repeated concepts

Immunity

• Immunity is the ability to ward off disease.

• Susceptibility is the lack of resistance to a disease.

• Immunity is divided into two sectors:

  • Innate immunity: defenses against any pathogen; rapid, present at birth.

    • Non-specific, first and second lines of defense.

  • Adaptive immunity: immunity or resistance to a specific pathogen; slower to respond, has memory component.

    • Highly specific-targeted, developed over lifetime, third line of defense.

First Line of Defense

• Skin and mucosal membranes.

  • Skin: Largest organ of the body, impactful protection against microbes.

    • Microbes rarely penetrate the intact healthy epidermis.

  • Mucosal membranes trap and prevent microorganism entry into the respiratory and digestive canal.

First Line of Defense: Physical Factors

• Skin and mucosal membranes.

• Additional physical barriers:

  • Lacrimal apparatus: drains tears and washes the eye.

  • Epiglottis prevents microorganisms from entering the lower respiratory tract.

  • Earwax prevents microbes from entering the ear.

  • Urine cleans the urethra via flow.

  • Vaginal secretions move microorganisms out of the vaginal tract.

  • Peristalsis, defecation, vomiting, and diarrhea.

First Line of Defense: Chemical Factors

• Sebum forms a protective film and lowers the pH of skin.

• Lysozyme in perspiration, tears, saliva, and urine destroys bacterial cell walls.

• Low pH of gastric juice in the stomach destroys most bacteria and toxins.

• Low pH of vaginal secretions inhibits microbes.

First Line of Defense: Microbiome

• Normal microbiota compete with pathogens via microbial antagonism (competitive exclusion).

  • Competitive advantage for space and nutrients.

  • Produce substances harmful to pathogens.

  • Alter conditions that affect pathogen survival.

  • Prevent the overgrowth of harmful microbes.

  • Play an important role in the development of the immune system.

Normal Microbiota and Innate Immunity

• Commensalism: one organism benefits while the other (host) is unharmed.

• Opportunistic pathogens among the normal microbiota:

  • E. coli, S. aureus, S. epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa.

• Probiotics: live microbial cultures administered to exert a beneficial effect.

• Prebiotics: chemicals (nutrients) that selectively promote the growth of beneficial bacteria.

• Studies show that taking probiotics relieves symptoms of upset stomach.

Second Line of Defense

• Commonly associated with inflammation and fever; also includes phagocytes and antimicrobial substances.

• Part of innate immunity.

Second Line of Defense: Defensive Cells

• Phagocytes:

  • Phagocytosis: the ingestion of a microorganism or other substance by a cell.

    • Include neutrophils, eosinophils, dendritic cells, and macrophages.

      • Neutrophils: highly phagocytic; most active in early stages of infection; can leave the blood and enter infected tissue (first responders).

      • Fixed macrophages (histiocytes): residents in tissues and organs (liver, lungs).

      • Free (wandering) macrophages: roam tissues and gather at sites of infection (clean-up crew).

Second Line of Defense: Defensive Cells (cont.)

• Natural Killer (NK) Cells:

  • Kill infected cells by releasing perforin, causing membrane to perforate and rupture.

  • Target infected or disturbed cells (cells infected by a virus, cancer cells).

  • Recognize cells due to altered protein expression.

  • Considered innate immunity due to absence of antigen-specific cell surface receptors.

Important Distinctions

• Leukocyte (leuko-white, cyte-cell):

  • White blood cells, protect against illness and disease (immunity cells).

  • Phagocytes and natural killer cells are leukocytes.

• Lymphocytes are a type of leukocyte.

Highlight on White Blood Cells (WBC)

• Sign and degree of infection can be monitored by WBC count.

• Healthy WBC range:

  • Adults: 4,000-11,000 WBC per {\mu}l of blood.

  • Children (2 months - 6 years): 5,000 to 19,000/{\mu}l.

• Leukopenia: low white blood cell count (lowered immune system).

• Leukocytosis: high white blood cell count (overactive immune system).

Second Line of Defense: Inflammation

• Contain infections when first-line defenses fail.

• Inflammation: local or systemic defensive response triggered by damage to tissues.

  • Damage may include microbial infection, physical agents (heat, electricity, sharp objects), or chemical agents (acids, bases, gases).

  • Signs and symptoms (P R I S H): pain, redness, immobility, swelling (edema), heat.

  • Dilated blood vessels = more heat.

  • Increased permeability of blood vessels permits leukocytes and defensive chemicals through.

Second Line of Defense: Inflammation (cont.)

• Acute inflammation: develops rapidly, lasts for few days to few weeks.

• Chronic inflammation: develops more slowly, lasts months to years; may be severe and progressive.

• Functions:

  • Destroys injurious agent or limits its effects on the body.

  • Repairs and replaces tissue damaged by the injurious agent.

Second Line of Defense: Fever

• Hypothalamus driven.

• Cytokines reset hypothalamus to create a fever until cytokines are eliminated.

  • Cytokines: signaling proteins regulating immunity and inflammation; can be produced by immunity or infected cells.

• Fever: abnormally high body temperature (38^{\circ}C or higher, 100.4^{\circ}F or higher).

  • Temperature of 103^{\circ}F is concerning, 104^{\circ}F should be treated.

  • Important to drink water + electrolytes.

Second Line of Defense: Fever (cont.)

• Fever considered a defense.

  • Phagocytes and T cells work better at a slightly higher temperature.

  • Higher temperatures intensify the effect or production of other antimicrobial substances.

  • Higher temperatures may slow growth of pathogens.

  • Increased metabolic rate speeds repair processes.

• Complications of fever:

  • Tachycardia, acidosis, dehydration, seizures, coma.

Second Line of Defense: Antimicrobial Substances

• Work via complement system: contributes to inflammation, promotes phagocytosis, and other innate immune responses to target microbes.

• Interferons: group of signaling proteins made and released by host cells in response to the presence of several viruses.

  • Ex: A cell infected with a virus will produce interferons.

• Iron binding proteins: restrict iron from pathogens, interfering with metabolic processes.

• Antimicrobial peptides: Short peptides produced in response to protein and sugar molecules on microbes; broad spectrum of activity.

Additional Contributors to Innate Immunity

• Genetic resistance: confers a selective survival advantage.

  • Ex: Sickle cell trait and Plasmodium falciparum (malaria).

• Age: very young and elderly are more susceptible to disease.

• Observing healthy protocols (hand hygiene, sneeze and cough hygiene, safer sex practices).

Third Line of Defense: Adaptive Immunity

• Learned immunity.

• Adaptive immunity: defenses that target a specific pathogen after exposure.

• Ability to distinguish "self" from "nonself".

• Activated when innate defenses fail to stop a microbe.

• Acquired through infection or vaccination.

• Primary response: first time the immune system combats a particular foreign substance.

• Secondary response: later interactions with the same foreign substance; faster and more effective due to "memory".

Dual Nature of the Adaptive Immune System

• Humoral immunity:

  • Produces antibodies that combat foreign molecules known as antigens.

    • Addresses threats outside of the cell.

  • B cells are lymphocytes (type of white blood cell) that are created and mature in red bone marrow.

    • Recognize antigens and make antibodies.

    • Once mature, reside in the blood and lymphoid organs.

Antigens

• Antigens: substances that cause the production of antibodies.

  • Usually components of invading microbes or foreign substances.

    • Capsules, cell walls, flagella, fimbriae, toxins, viral capsids, viral spikes.

  • Nonmicrobial antigens may include egg white, pollen, cell surface molecules.

• Antibodies interact with specific regions (epitopes, or antigenic determinants) on the antigen.

Dual Nature of the Adaptive Immune System

• Cellular immunity (cell-mediated immunity):

  • Targeting infected cells.

    • Involves T cell lymphocytes.

      • Recognize antigenic peptides processed by phagocytic cells.

      • Mature in the thymus.

      • Reside in blood and lymphoid organs.

  • T cell receptors (TCRs) on the T cell surface contact antigens, causing the T cells to secrete cytokines instead of antibodies.

  • Best at fighting virus-infected cells and intracellular bacteria.

Cytokines: Chemical Messengers of Immune Cells

• Cytokines are protein messengers produced in response to a stimulus.

  • Interleukins (ILs): communicate between leukocytes.

  • Chemokines: induce migration (chemotaxis) of leukocytes toward infection.

  • Interferons (IFNs): interfere with viral infections of host cells.

Types of T Cells

• Cytotoxic T cells: target and kill infected cells and destroy tumor cells; activated by antigens.

• Helper T cells: signal other cells to attack pathogen; most important T cell.

  • Detects antigen and releases cytokines.

• Suppressor T cells: regulate and reduce activity of other T cells as needed.

Humoral vs Cellular Immunity

• Humoral immunity fights invaders and threats outside cells.

  • Extracellular bacteria and toxins.

  • Viruses before they enter a host cell.

• Cellular immunity attacks antigens that have already entered cells.

  • Viruses; some intracellular bacteria such as M. leprae and L. monocytogenes.

Humoral Response

• B cells have antibodies on their surface and recognize specific epitopes.

• Two ways to activate a B cell:

  • T-dependent antigen: requires helper T cell to assist.

    • Both B and T cells recognize the antigen.

  • T-independent antigen: does not need helper T cell assistance.

    • Polysaccharides from bacterial capsules or LPS.

• Activated B cells turn into:

  • Plasmacytes: produce antibodies.

  • Memory cells: store information for future infections.

Humoral Immunity: Antibodies

• Compact soluble proteins called immunoglobulins (Ig).

• Recognize and bind to specific antigens, targeting them for destruction.

• Four protein chains form a Y shape.

• Five classes of Ig (IgG, IgM, IgA, IgD, IgE).

Key takeaways for immunoglobulins

• Know the main function for each.

• IgM associated with primary humoral immune response.

• IgG will be higher in secondary immune response.

• Easier to produce

Cellular Immunity

• T cells mature in the thymus.

• Selection to remove T cells that don’t recognize MHC of the host.

  • MHC: cell surface molecules indicating infection to T cells.

  • Two classes:

    • MHC I – produced when in contact with endogenous antigens.

    • MHC II – exogenous antigens found and presented on cell surface.

  • T helper cells recognize antigens on MHC II cells.

  • Cytotoxic T cells recognize antigens processed by all nucleated host cells and presented with MHC I.

• T cells later may differentiate into memory T cells.

Immunological Memory

• Memory cells can be made from both B cells and T cells and are part of adaptive immunity.

• Memory T cells recognize antigens presented on MHC class I or II molecules on the surface of abnormal cells.

• Memory B cells recognize free antigens in the body or lymph.

• Memory T cells last long periods, memory B cells must be replenished.

• Both assist the immune system to recognize the pathogen and elicit a faster response.

Building Immunity

• Natural adaptive immunity:

  • Active: experienced the disease and produced associated antibiotics and memory cells.

  • Passive: passed from mother to fetus, transferred in the last 3 months, temporary.

• Artificially acquired immunity:

  • Active: immunization or vaccination.

  • Passive: injection of antibodies generated by a different person or animal.

    • Ex: RhoGAM shot for expecting mothers.

Disorders of the Immune Response

• Allergies:

  • Histamines cause inflammatory response.

• Autoimmune disease:

  • Immune system cannot differentiate between pathogen and self, attacks self.

    • Ex: lupus, diabetes, rheumatoid arthritis.

• Severe combined immunodeficiency (SCID):

  • Absence of T and B cell function, genetic and life-threatening.

Acquired Immunodeficiency Syndrome (AIDS)

• Caused by the human immunodeficiency virus (HIV).

• Similar to SCID but typically not born with it.

• Targets white blood cells and weakens the immune system.

• Can be transmitted through unprotected sex, contaminated needles, and contact with contaminated blood.

• HIV gradually destroys the immune system, leading to onset of AIDS.

• No cure for HIV but can be controlled.

Things We Can Do to Help

• Vitamin C: acts as an antioxidant, contributes to collagen formation.

• Zinc: performs as signaling molecule for immune response, enhances cytokine production, stimulates development of T and B cells, protects the immune system from oxidative stress (women 8mg daily, men 11mg daily).

• Be sure to have enough fluids.

• Maintain healthy habits and lifestyle.

• Avoid exposure to limit secondary infections.