Structure and Function of the Human Immune System Notes

9.1 Pathogens and Disease

  • Types of Disease
    • Diseases are classified into two main categories:
      • Non-infectious
      • Infectious
  • Non-infectious Diseases
    • Caused by factors like toxins, radiation, genetic disorders, and poor nutrition.
    • Non-communicable (cannot be passed from person to person).
    • Example: Diabetes.
  • Infectious Diseases
    • Communicable, caused by pathogens (disease-causing agents).
    • Many pathogens are microorganisms, but not all microorganisms are harmful.
    • Host-Specificity: Most pathogens infect only one type of host.
    • Vectors: Some pathogens use vectors to transmit themselves to a host.
    • Virulence: Measure of a pathogen's harmfulness, causing damage and spreading quickly.
    • Susceptibility: How easily a host contracts a disease.
    • Symptoms: Observable effects of the pathogen on the host, used for diagnosis and treatment decisions.
  • Pathogens
    • Different types of pathogens cause different diseases.

Non-cellular Pathogens

  • Viruses
    • Not true cells; lack a plasma membrane and are surrounded by a protein coat.
    • Contain either DNA or RNA but cannot replicate on their own; they inject nucleic acids into a host cell to replicate.
    • Host cell uses viral DNA/RNA to build new viruses.
    • All viruses are pathogenic.
    • Typically host-specific.
    • Difficult to fight with medication because they 'hide' inside host cells.
    • Antibiotics are ineffective against viruses.
    • Vaccines prevent many viral infections.
    • Examples: Influenza, chicken pox, rubella, polio, HIV, Hepatitis B.
  • Prions
    • Do not contain DNA or RNA; they are infectious protein molecules with an abnormal secondary structure.
    • Cause diseases that damage brain and nerve tissue.
    • Infectious prions can change normal proteins into the infectious form.
    • Examples: Scrapie in sheep, Creutzfeldt-Jakob disease in humans, and bovine spongiform encephalopathy (BSE) in cows.
    • Can spread between species (e.g., BSE through contaminated beef).

Cellular Pathogens

  • Bacteria
    • Prokaryotic organisms found in most environments.
    • Only a few types are pathogenic; many are beneficial.
    • Reproduce quickly via binary fission.
    • Can break down host tissue directly or produce toxins as waste products.
    • Antibiotics target bacteria and help the body's immune system.
      • Broad-spectrum antibiotics affect a wide range of bacteria.
      • Narrow-spectrum antibiotics target a few types of bacteria.
    • Different antibiotics work in different ways (e.g., penicillin destroys bacterial cell walls, erythromycin inhibits protein synthesis).
    • Examples: Pneumonia, food poisoning, bubonic plague, botulism, tuberculosis, cholera.
  • Protists
    • Single-celled, eukaryotic organisms (protozoa, unicellular algae, slime molds).
    • Very few are pathogens.
    • Limited vaccines and treatments for protist diseases.
    • Protozoa cause most protist diseases in humans and often have complex life cycles involving different hosts.
    • Examples:
      • Sleeping sickness (Trypanosoma, spread by tsetse flies).
      • Diarrhoea (e.g., Giardia, spread by contaminated water).
      • Malaria (Plasmodium, spread by mosquitoes).
  • Fungi
    • Eukaryotic organisms including molds, mushrooms, toadstools, and yeasts.
    • Can be unicellular or multicellular.
    • Only some species are pathogenic; these infect a wide range of hosts, including plants and animals.
    • Secrete digestive enzymes onto the host and absorb nutrients through their cellular membranes.
    • Fungal diseases are often contagious.
    • Examples: Ringworm, thrush (Candida), athlete's foot.
    • Antibiotics are ineffective against fungi.
  • Parasites
    • Organisms that complete some or all of their life on or inside another organism (the host).
    • Many have complex life stages and infect different hosts at different stages.
    • Developing parasites infect intermediate hosts.
    • The host infected by the adult parasite is the primary/definitive host.
    • Vectors are often intermediate hosts.
    • Classified into:
      • Endoparasites (live inside the host, e.g., tapeworm, heartworm, hookworm).
      • Ectoparasites (live on the surface of the host, e.g., ticks, fleas, lice).
    • Antibiotics have no effect on parasites.
    • Successful treatment requires correct identification of the parasite.

10.1 The Human Immune System

  • Overview
    • Protects against infection from pathogens.
    • Composed of various organs and specialized cells, collectively known as white blood cells (WBCs).
    • WBCs travel via the circulatory and lymphatic systems.
  • Components of the Lymphatic System
    • A network of tubes (lymph vessels) similar to blood vessels but blind-ended (not a connected loop).
    • Found throughout the body, except in bones and the central nervous system; located close to blood capillaries and connected at lymph nodes.
    • Functions:
      • Returning fluids and proteins that leak from blood vessels to the circulatory system.
      • Producing and transporting lymphocytes (WBCs).
      • Providing a place for lymphocytes to mature.
    • Lymph is a fluid in lymph vessels containing fats, proteins, and WBCs (lymphocytes and phagocytes).
    • Lymph is moved by muscle contractions and one-way valves prevent backflow.
    • Lymph nodes filter lymph, trapping pathogens, cancerous cells, and foreign particles; they also store WBCs.
    • Nodes swell as WBCs move to fight infections.
  • Lymphocytes
    • WBCs found in lymph vessels and nodes.
    • Produced in bone marrow; some mature in the thymus, others in lymph nodes.
  • Self and Non-Self
    • The immune system distinguishes between the body's cells (self) and pathogens (non-self).
  • MHC Markers
    • Glycoproteins (major histocompatibility complex proteins) on cell surfaces.
      • Class I MHC markers: Found on all nucleated cells; identical within an individual but different between individuals. altered in cancerous or virally infected cells.
      • Class II MHC markers: Found on some immune cells like macrophages.
  • Antigens
    • Molecules or fragments that trigger an immune response.
    • Include molecules on pathogen surfaces, cell fragments, and toxins.
    • Lymphocytes respond to antigens.
  • Allergens
    • Harmless substances (e.g., pollen, fur) that trigger an immune response (allergic reaction).

10.3 The First Line of Defence

  • Overview
    • The body's first line of defense consists of non-specific immune responses.
    • Non-specific responses are innate (present since birth).
  • Physical and Chemical Barriers
    • Prevent pathogens from entering the body.
  • Skin
    • Largest organ, a physical barrier.
    • Pathogens cannot enter unless there are cuts or abrasions.
    • Produces sebum and sweat, which contain substances that kill microorganisms.
  • Tears, Mucus, and Saliva
    • Protect orifices (eyes, nose, mouth).
    • Tears contain lysozyme, which breaks down bacterial cell walls and physically washes away pathogens.
    • Saliva and mucus also contain lysozyme.
    • Mucus and wax trap pathogens.
    • Cilia (fine hairs) push mucus and trapped pathogens away from susceptible tissues.
  • Acids
    • Stomach produces acids to lower pH, denaturing pathogenic proteins and killing pathogens.
    • The female reproductive tract also produces acids and mucus for protection.
  • Urine
    • The flow of urine flushes pathogens out of the urinary tract and bladder.
  • Natural Flora
    • Beneficial bacteria that grow on and inside the body (skin, mouth, stomach, intestines).
    • Compete with pathogenic microorganisms for space and resources.
    • Aid in digestion and vitamin production.
    • Broad-spectrum antibiotics can kill natural flora as well as pathogens, leading to upset stomachs or fungal infections.

10.4 The Second Line of Defence

  • Overview
    • The second line of defence comes into play when pathogens bypass the first line.
    • It is also non-specific and innate.
    • Involves cells of the immune system that do not target particular pathogens.
  • Cells of the Second Line of Defence
    • Leukocytes (white blood cells or WBCs).
    • Larger than RBCs and contain a nucleus.
    • Platelets
      • Blood cell fragments, responsible for blood clotting, do not interact with pathogens.
    • Mast Cells
      • Found in connective tissue, produce and release histamine to trigger inflammation.
    • Neutrophils
      • Phagocytes, the most common type of WBCs, mature in the blood, and primarily attack bacteria.
      • Release cytokines and antimicrobial compounds.
    • Macrophages
      • Phagocytes, circulate in the blood but mature at the site of infection.
      • Release cytokines and are antigen-presenting cells (APCss).
    • Natural Killer (NK) Cells
      • Mature in bone marrow and lymph nodes, attack virus-infected and cancerous cells, and respond quickly.
  • Immune System Chemicals
    • Cytokines
      • Protein signaling molecules produced by WBCs.
      • Trigger various immune responses: WBC production, activation, regulation, and attraction to the site of infection.
    • Interferons
      • A group of cytokines produced by virus-infected cells.
      • Trigger apoptosis, prevent viral nucleic acid translation, slow virus spread, and attract natural killer cells.
    • Complement Proteins
      • About 30 types in the blood.
      • Increase inflammatory response, help phagocytosis, and directly destroy cellular pathogens by lysis.
    • Histamine
      • Released by activated mast cells.
      • Causes capillaries to dilate and become 'leaky,' allowing WBCs and complement proteins to move into infected tissue.
      • Increases blood flow, causing redness, heat, and swelling (inflammation).
  • The Inflammatory Response
    • Triggered by damaged cells, pathogens, or histamine release.
    • Key purpose: bring WBCs to the site of injury or infection.
    • Steps:
      1. Pathogens enter the body through a cut.
      2. Platelets release clotting factors to close the wound.
      3. Damaged cells release cytokines that attract neutrophils.
      4. Mast cells release histamine, causing capillary dilation and leakiness.
      5. Neutrophils are activated, producing compounds that break down bacterial and fungal cell walls and attract macrophages.
      6. Complement proteins cause pathogens to lyse.
      7. Macrophages are activated and release cytokines to attract more WBCs and ingest pathogens via phagocytosis.
  • Fever
    • A secondary immune response where the body core temperature increases.
    • The hypothalamus increases the set point in response to cytokines released by WBCs.
    • Increased temperature can:
      • Speed up tissue repair due to higher metabolic rates.
      • Increase blood flow to the site of infection.
      • Denature pathogen enzymes (optimal at 37°C).

10.5 The Cell-Mediated Response (Third Line of Defence)

  • Overview
    • Adaptive and acquired, develops over time, and can result in immunity.
    • Distinguished by specificity and immunological memory.
      • Specificity: Targets particular antigens.
      • Immunological memory: 'Remembers' encountered antigens, leading to faster and stronger responses upon re-exposure.
    • Specific immune responses are slower than innate responses, especially during first contact with a new pathogen.
  • Cells Involved in Adaptive Immunity
    • Lymphocytes (B cells and T cells).
      • B cells mature in the bone marrow.
      • T cells mature in the thymus.
    • Mature lymphocytes circulate through the lymphatic system and are activated by specific antigens.
    • Until activated, B and T cells are called naive cells.
    • T cells carry out the cell-mediated response.
    • B cells carry out the humoral response.
  • Antigen Presenting Cells (APCs)
    • Show antigens to T cells.
    • Macrophages engulf pathogens, break them down, and present antigens on their surface using class II MHC markers.
    • APCs circulate until they encounter a T cell.
  • The Cell-Mediated Response - T cells
    • T cells carry T cell receptors (TCRs) on their membrane surfaces.
    • TCRs consist of an α and a β chain, each with a constant and a variable region.
    • Variable regions form the antigen-binding site, which binds to antigens attached to class II MHC markers, specific to the 3D shape.
  • T Cells in Action
    • When a TCR binds to the antigen-MHC-II complex on an APC, the T cell is activated.
    • Activated T cells divide rapidly to produce helper T cells, cytotoxic T cells, and memory T cells.
    • Helper T Cells
      • Produce and secrete cytokines, triggering inflammation and activating macrophages, B, and T cells.
      • Essential for full B cell activation.
    • Cytotoxic T Cells
      • Destroy infected cells by detecting changes in class I MHC markers.
      • Secrete cytotoxins that break the cell membrane, causing lysis.
      • Also destroy foreign cells from transplanted tissue and some cancer cells.
      • Immunosuppressants are used to switch off cytotoxic T cells during organ transplants.
    • Memory T Cells
      • Remain in lymph nodes after the infection is under control.
      • Upon re-exposure to the same pathogen, they rapidly produce many cytotoxic T cells specific to that pathogen.

10.6 The Humoral Response

  • Overview
    • Involves B cells that carry Y-shaped B cell receptors (BCRs) on their surface.
  • B Cell Receptors (BCRs)
    • Consist of four polypeptide chains (two heavy, two light) held together by disulphide bridges.
    • Each chain has a constant and a variable region; the variable regions form the antigen-binding sites.
    • All BCRs on a particular B cell are identical, but different B cells have different BCRs that bind to different antigens.
  • Self-Tolerance
    • The immune system destroys immature T or B cells with receptors complementary to self-MHC markers to prevent self-attack.
  • Clonal Selection
    • When a T or B cell encounters a complementary antigen, it rapidly divides.
    • This process selectively activates and clones particular lymphocytes.
  • B Cells in Action
    • B cells can interact directly with free pathogens in the lymph.
    • When a naive B cell binds to a pathogen, it phagocytoses the pathogen and presents antigens on its surface.
    • Helper T cells interact with the antigen-presenting B cell, and cytokines released by the Helper T cell fully activate the B cell.
    • Activated B cells undergo clonal expansion to form plasma cells and memory B cells.
  • Plasma Cells and Antibodies
    • Most cloned cells differentiate into plasma cells, which secrete thousands of antibodies per second.
    • Antibodies (immunoglobulins, Ig) are glycoprotein molecules similar in structure to BCRs (except they are not attached to a cell).
    • Antibodies bind to complementary antigens and pathogens, working individually or in groups.
    • Antibodies interact with antigens in different ways:
      • Neutralisation of toxins
      • Neutralisation of pathogens
      • Precipitation
      • Agglutination
  • Memory B Cells
    • The remaining cells differentiate into memory B cells, which carry specific BCRs.
    • Memory B cells remain in the lymphatic system for years or a lifetime.
    • They activate the humoral response during secondary infections.
    • Upon re-exposure to a familiar pathogen, they rapidly divide into plasma cells.
  • Immunological Memory
    • Both memory B and T cells contribute to immunological memory, which allows faster and stronger responses to subsequent exposures to the same pathogen.

11.1 Different Types of Immunity

  • Immunity
    • The ability of an organism to fight a disease without getting sick.
    • Innate immunity: Non-specific ability to fight disease, present from birth (first and second lines of defense).
    • Acquired (adaptive) immunity: Developed through exposure to different pathogens over a lifetime; can be passive or active, natural or artificial.
  • Passive Immunity
    • An individual is given antibodies produced by another organism.
      • Advantage: Faster immune response due to no delay in antibody production.
      • Disadvantage: No memory B or T cells are produced; therefore, no immunological memory.
    • Natural passive immunity: Mother passes ready-made antibodies to her child via the placenta or breastmilk.
    • Artificial passive immunity: Injection of ready-made antibodies (antiserum) used during virulent infections or for treating toxins (e.g., snake venom).
  • Active Immunity
    • The body produces its own antibodies in response to a specific antigen.
      • Advantage: Memory B and T cells are produced, leading to long-lasting immunity.
      • Disadvantage: Slower initial response.
    • Natural active immunity: Results from normal cell-mediated and humoral responses to a pathogen, producing memory B and T cells.
    • Artificial active immunity: Antigens are injected in the form of a vaccine, stimulating B and T cell responses without exposure to a harmful pathogen.
      • Vaccines can contain:
        • Attenuated (weakened) pathogens
        • Inactivated (dead) pathogens
        • Subunit (isolated antigens)
          *Immune system responds as if it were the real pathogen, producing memory B and T cells.
  • Vaccination
    • Process of gaining immunity through the use of a vaccine.
      • Advantages
        • producing memory B and T cells
        • immunity w/o harmful pathogens
        • Disadvantages:
        • Attenuated vaccines can cause a mild form of the disease
        • Inactivated subunit vaccines stimulate a weaker immune response.
  • Herd Immunity
    • If enough people in a population are vaccinated and immune to a particular pathogen, the spread of disease can be slowed or stopped.
    • This protects individuals who cannot be vaccinated.

11.4 Malfunctions of the Human Immune System

  • Overview
    • Three main types of immune system disorders: hypersensitivity, immunodeficiency disorders, and autoimmune diseases.
  • Hypersensitivity
    • The immune system responds to harmless antigens.
    • Only Type I hypersensitivity (allergy): Allergic reactions in response to harmless allergens (e.g., pollen, fur, dust, insect bites, foods).
    • Plasma cells produce immunoglobulin E (IgE) antibodies in response to an allergen.
    • IgE binds to mast cells; when an allergen binds to two IgE molecules, the mast cell releases histamine.
    • Histamine triggers the inflammatory response and other allergic reactions (itchiness, runny nose, watery eyes).
    • Reactions vary; mild include hay fever, extreme is anaphylaxis (life-threatening).
    • Antihistamines reduce mild allergic reactions by blocking histamine receptors.
  • Immunodeficiency
    • The immune system does not respond properly to pathogens.
    • Primary: Born with it, genetic factors (e.g., severe combined immunodeficiency disease (SCID)).
    • Secondary: Acquired during a lifetime (e.g., extreme stress, malnutrition, exposure to a pathogen).
    • HIV and AIDS
      • Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV).
      • HIV is a retrovirus that targets helper T cells, impairing both B and T cell function.
      • The loss of functioning B and T cells impairs the adaptive immune system, resulting in AIDS.
      • People with AIDS are more susceptible to other pathogens.
      • Antiretroviral medications can slow or prevent viral replication and prevent AIDS from developing, but there is no cure.
  • Autoimmune Diseases
    • Self-tolerance breaks down; B and T cells attack self-cells.
    • Can affect the whole body or a specific organ.
    • Multiple Sclerosis (MS)
      • Autoimmune disease that affects Schwann cells and myelin in the nervous system.
      • Plasma cells produce antibodies that bind to myelin sheath proteins and lipids.
      • B and T cells attack Schwann cells.
      • Demyelinated axons cannot pass nerve impulses quickly or clearly.
      • Symptoms vary (e.g., problems with vision, sensation, balance, memory, seizures).
      • There is no cure, but symptoms can be managed with medication, and progression can be slowed with immunosuppressants.