HLTH1004: Human Bioscience - The Immune System

The Immune System: Pathogens and Innate Defenses

• Pathogens: microscopic organisms that cause disease, including viruses, bacteria, fungi, and parasites
• Not all microorganisms are pathogens; many form part of our normal flora

Importance of Microbiology

• Studies microorganisms that can only be seen under a microscope
• Includes multicellular organisms like parasites and fungi, unicellular organisms like bacteria, and acellular organisms like viruses and prions

Infection and Immunity

• Infection: the invasion of the body by pathogens
• Immunity: the ability to resist and defend against infectious organisms and other damaging substances
• Innate immunity: nonspecific defense against any type of invading agent
• Adaptive immunity: specific defense against specific pathogens, involving lymphocytes (B cells, T cells, and NK cells)

Innate Defenses

• Physical barriers: skin, mucous membranes, and epithelial surfaces that prevent pathogens from entering the body
• Phagocytic cells: neutrophils, macrophages, and dendritic cells that engulf and destroy pathogens
• Natural killer (NK) cells: recognize and destroy abnormal cells and infected cells
• Interferons: proteins released by activated lymphocytes and macrophages to combat viral infections
• Complement system: a group of proteins that work together to help eliminate pathogens

Inflammation

• Localized tissue response to injury, triggered by any stimulus that kills cells or injures tissue
• Cardinal signs and symptoms: redness, swelling, heat, pain, and loss of function
• Phases of inflammation: vascular, cellular, and leukocyte activation and phagocytosis

Acute Inflammatory Response

• Vascular phase: increased blood flow to the infected area, causing heat and redness
• Cellular phase: leukocytes follow chemical attractants to reach the pathogen and phagocytose it

Effects and Products of Inflammation

• Temporarily repair injury, prevent spread of pathogens, and mobilize local, regional, and systemic defenses
• Products of inflammation: necrosis, pus, and abscesses### Innate Immune System
• Prevents the invasion of microorganisms into the body
• First line of defense against microorganisms
• Mechanisms:
  • Attraction of phagocytes, especially neutrophils
  • Dilation of blood vessels, increased blood flow, and vessel permeability
  • Removal of debris by neutrophils and macrophages
  • Stimulation of fibroblasts and tissue repair
• Phagocyte attraction to remove pathogens and debris
• Dilation of blood vessels, increased blood flow, and vessel permeability to allow phagocytes to reach site of infection
• Removal of debris by neutrophils and macrophages
• Stimulation of fibroblasts and tissue repair to heal damaged tissue

Adaptive Immune System

• Long-lasting protective immune response without causing disease
• Aim is to produce large numbers of long-lived memory B and T lymphocytes
• Mechanisms:
  • Vaccines (antigen) cause short-lived primary immune response (B and T lymphocyte)
  • Booster injections cause multiple secondary immune responses (memory B and T lymphocytes)
  • Result: large numbers of long-lived memory B and T lymphocytes, ready to fight pathogens
• Primary types of T cells:
  • Cytotoxic T cells: attack antigens physically and chemically
  • Helper T cells: stimulate responses of T cells and B cells
  • Regulatory T cells: moderate immune response
  • Memory T cells: respond to antigens previously encountered
• B cells:
  • Make up 10-15% of circulating lymphocytes
  • Differentiate into plasma cells that produce and secrete antibodies
• Natural killer (NK) cells:
  • Make up 5-10% of circulating lymphocytes

Cellular/T-Cell Mediated Immunity

• Defends against intracellular microorganisms (viruses and bacteria), fungi, protozoa, and cancers
• Plays a major role in transplant rejection
• T-Lymphocytes that originate from the bone marrow and mature in the thymus are its mediators

Humoral/Antibody-Mediated Immunity

• Defends against extracellular microorganisms and other antigens
• Causes transfusion reaction in incompatible blood transfusion
• B-Lymphocytes that originate and mature in the bone marrow are its mediators
• Primary response:
  • Antibodies from plasma cells react with antigen on bacteria
  • Complement system and macrophages kill bacteria, liver and spleen clear remaining complexes
• Secondary response:
  • Rapid proliferation of memory cells
  • Increased amounts of more specific IgG antibodies

Adaptive Defenses

• Adaptive immunity:
  • Antigens: chemical targets that stimulate immune response
  • When a lymphocyte contacts an appropriate antigen, it becomes activated
  • Activated lymphocyte divides to produce a clone
  • Clonal selection: process of an antigen “selecting” lymphocytes for cloning
• Forms of immunity:
  • Innate immunity: present at birth
  • Adaptive immunity: acquired after birth
  • Active immunity: develops after exposure to antigen
  • Passive immunity: produced by transferring antibodies from another source

T Cells and Immunity

• T cells are activated by exposure to an antigen

• Antigen presentation:

  • T cells recognize only antigens that are “presented” by antigen-presenting cells
  • MHC proteins: membrane glycoproteins that bind antigens

• Memory TC cells:

  • Produced with cytotoxic T cells
  • Stay in circulation
  • Immediately form cytotoxic T cells if same antigen appears again

• Regulatory T cells:

  • Secrete suppression factors
  • Inhibit responses of T and B cells
  • Act after initial immune response
  • Limit immune reaction to single stimulus### T Cells and Immunity

• Interleukins (IL-1 and IL-2) stimulate and maintain the immune response

• IL-1 and IL-2 stimulate activities of other immune cells and the secreting cell, creating a positive feedback loop that recruits additional immune cells

• Tumor necrosis factors (TNFs) slow tumor growth and kill sensitive tumor cells

• TNFs stimulate granular leukocyte production, promote eosinophil activity, cause fever, and increase T cell sensitivity to interleukins

• Activated macrophages secrete one type of TNF and carry the molecules in their membranes

• Cytotoxic T cells produce a different type of TNF

• Phagocyte-activating chemicals coordinate immune defenses by adjusting activities of phagocytic cells

• Colony-stimulating factors (CSFs) stimulate production of blood cells in red bone marrow and lymphocytes in lymphoid tissues and organs

Cytokines

• Classified according to origin: lymphokines (produced by lymphocytes), monokines (secreted by active monocytes, macrophages, and other antigen-presenting cells)
• Cells involved in adaptive immunity and tissue repair can also secrete cytokines

B Cells and Immunity

• Responsible for antibody-mediated immunity
• Attack antigens by producing specific antibodies
• Millions of populations, each with different antibody molecules

B Cell Sensitization

• Antigens in interstitial fluids bind to corresponding B cell receptors
• B cell prepares for activation
• During sensitization, antigens are taken into the B cell, processed, and reappear on the surface bound to class II MHC proteins

Helper T Cells

• Sensitized B cell is prepared for activation but needs a helper T cell to become activated
• Helper T cell binds to the MHC complex and secretes cytokines that activate the B cell

Activated B Cells

• Divide into plasma cells and memory B cells
• Plasma cells synthesize and secrete antibodies into interstitial fluid
• Memory B cells remain in reserve to respond to the next infection

Antibodies

• Soluble proteins with two pairs of polypeptide chains (heavy and light chains)
• Each chain contains constant and variable segments
• Constant segments of heavy chains determine classes of antibodies (IgG, IgE, IgD, IgM, IgA)

Antibody Classes

• IgG: largest and most diverse class, responsible for resistance against many viruses, bacteria, and bacterial toxins, can cross the placenta
• IgE: attaches to basophils and mast cells, stimulating the release of histamine and other chemicals that accelerate inflammation
• IgD: on surfaces of B cells, where it can bind antigens in extracellular fluid
• IgM: first class of antibody secreted after an antigen is encountered, forms a polymerized starburst, responsible for agglutination of incompatible blood types
• IgA: found primarily in glandular secretions, attacks pathogens before they gain access to internal tissues

Actions of Antibodies

• Neutralization of antigen binding sites
• Precipitation and agglutination
• Activation of the complement system
• Attraction of phagocytes
• Opsonization increasing phagocyte efficiency
• Stimulation of inflammation
• Prevention of bacterial and viral adhesion

Responses to Antigen Exposure

• First exposure: produces primary response
• Next exposure: triggers secondary response, which is more extensive and prolonged due to memory cells already being primed