Immune System Review
Immune System Overview
The immune system provides resistance to disease.
Composed of two intrinsic systems working together to destroy pathogens:
Innate immune system (rapid but nonspecific)
First and second lines of defense:
First line of defense: External body membranes (skin and mucosae)
Second line of defense: Antimicrobial proteins, phagocytes, and other cells.
Inhibits the spread of invaders; inflammation is the most important mechanism.
Adaptive immune system (slower but highly specific)
Third line of defense
Attacks particular foreign substances and takes longer to react than innate immunity.
Innate and adaptive defenses are intertwined, both releasing and recognizing many of the same defensive molecules.
Innate responses release proteins that alert cells of the adaptive system to foreign molecules.
Innate Immunity
First Line of Defense: Surface Barriers
Surface barriers include skin and mucous membranes, along with their secretions.
Functions:
Acts as a physical barrier to most microorganisms.
Produces protective chemicals that inhibit or destroy microorganisms:
Acid: Acidity of skin and some mucous secretions inhibits growth, known as the acid mantle.
Enzymes: Lysozyme found in saliva, respiratory mucus, and lacrimal fluid kills many microorganisms; enzymes in the stomach also kill many microorganisms.
Mucin: Sticky mucus lines the digestive and respiratory tracts and traps microorganisms.
Defensins: Antimicrobial peptides that inhibit microbial growth.
Other chemicals: Lipids in sebum and dermicidin in sweat are toxic to certain bacteria.
Respiratory system modifications to stop pathogens:
Mucus-coated hairs in the nose trap inhaled particles.
Cilia in the upper respiratory tract sweep dust- and bacteria-laden mucus toward the mouth.
When surface barriers are breached (e.g., nicks or cuts), the internal second line of defense is triggered, protecting deeper tissues.
Components of the Second Line of Defense
Phagocytes: White blood cells that ingest and digest foreign invaders.
Neutrophils: Most abundant phagocytes that die fighting. They become phagocytic upon exposure to infectious material and are attracted via chemotaxis from the bloodstream to the affected area.
Macrophages: Develop from monocytes and are the chief phagocytic cells. Examples:
Free macrophages: Wander through tissue spaces (e.g., alveolar macrophages).
Fixed macrophages: Permanent residents of specific organs (e.g., alveolar macrophages in lungs, stellate macrophages in the liver, microglia in the brain).
Natural Killer (NK) Cells: Nonphagocytic, large granular lymphocytes that police the blood and lymph.
Can kill cancer and virus-infected cells before the adaptive immune system is activated.
Attack cells lacking "self" cell-surface receptors and induce apoptosis in infected cells, secreting potent chemicals that enhance the inflammatory response.
Inflammation: Tissue Response to Injury
Triggered whenever body tissues are injured by trauma, heat, irritating chemicals, or infections by microorganisms.
Benefits of inflammation:
Prevents the spread of damaging agents.
Disposes of cell debris and pathogens.
Alerts the adaptive immune system.
Sets the stage for repair.
Four cardinal signs of acute inflammation:
Redness
Heat
Swelling
Pain
Sometimes a fifth sign, impairment of function, may occur if movement or use of the area is hampered.
Stages of Inflammation
Inflammatory chemical release:
Inflammatory chemicals flood the extracellular fluid, released by injured or stressed tissues.
E.g., mast cells release histamine.
Other mediators include kinins, prostaglandins, cytokines, and if pathogens are involved, complement proteins.
Induces vasodilation of local arterioles, increased capillary permeability, and attracts phagocytes to the area.
Vasodilation and increased vascular permeability:
Brings more immune cells and chemicals to the site of injury, causing redness and heat.
Phagocyte mobilization:
Neutrophils flood the area first, followed by macrophages and adaptive immunity elements if needed.
Phagocyte Mobilization
Steps for phagocyte mobilization:
Leukocytosis:
Injured cells release leukocytosis-inducing factors that trigger the release of neutrophils from the bone marrow into the bloodstream.
Margination:
Phagocytes cling to the inner walls of capillaries through cell adhesion molecules (CAMs) that attract passing neutrophils, causing them to slow and stick.
Diapedesis:
Neutrophils flatten and squeeze between endothelial cells, entering interstitial spaces.
Chemotaxis:
Inflammatory chemicals act as a “honing device” to promote positive chemotaxis of neutrophils toward the injured area, where they begin devouring pathogens and foreign objects.
Antimicrobial Proteins
Various antimicrobial proteins enhance innate defenses, notably interferons and complement proteins.
Interferons:
Released by infected cells to warn nearby uninfected cells, inhibiting viral replication.
Act on gene expression in uninfected cells, increasing resistance to infection; also involved in tumor surveillance.
Complement Proteins:
Group of at least 20 plasma proteins that circulate in inactive states.
Major mechanism for destroying foreign substances; activation unleashes inflammatory responses and directly destroys bacteria.
Non-specific but complement both innate and adaptive defenses.
Fever
A systemic response to invading microorganisms indicating widespread infection.
Fever is characterized by an abnormally high body temperature due to pyrogens secreted by leukocytes and macrophages exposed to foreign substances.
Benefits of moderate fever:
Causes the liver and spleen to sequester iron and zinc (needed by microorganisms).
Increases metabolic rate, accelerating repair processes.
Adaptive (Acquired) Immunity
The body's specific defense system targeting identified pathogens after recognizing antigens.
Involves lymphocytes (B and T cells), which are NOT involved in innate immunity.
Characteristics:
Specificity: Recognizes and targets specific pathogens initiating an immune response.
Systemic: Not restricted to local infection sites.
Memory: Mounts a stronger attack after initial exposure.
Two overlapping arms of adaptive immune system:
Humoral Immunity
Cellular Immunity
Adaptive Immunity: Humoral vs. Cellular
Humoral Immunity:
Antibody-mediated immunity controlled by activated B cells and antibodies present in body fluids (humors).
Antibodies circulate, binding to extracellular targets and marking them for destruction by macrophages or complement.
Cellular Immunity:
cell-mediated immunity carried out by T cells targeting intracellular pathogens (infected or cancerous cells).
Lymphocytes kill the infected cells or enhance the inflammatory response.
Antigens
Antigenic determinants: Parts of an antigen that antibodies or lymphocyte receptors bind to.
Naturally occurring antigens can mobilize different populations of lymphocytes and form various antibodies.
Self-antigens: Proteins found on cell surfaces that are not antigenic to self but may be to others (e.g., in transfusions).
Major Histocompatibility Complex (MHC) proteins: Unique glycoproteins on cell surfaces coded by MHC genes that help the immune system recognize foreign vs. self.
Antigens are generally large, complex molecules perceived as foreign intruders by the body.
Lymphocytes and Antigen-Presenting Cells (APCs)
Three crucial types of cells in adaptive immunity:
B lymphocytes (B cells): Responsible for humoral immunity producing antibodies. Clone themselves upon recognizing a foreign antigen.
Most clones become effector cells; few remain as memory cells for faster response to future exposures.
T lymphocytes (T cells): Carry out cellular immunity.
Antigen-Presenting Cells (APCs): Engulf antigens and present fragments for recognition by T cells. Major types include dendritic cells, macrophages, and B-lymphocytes.
Humoral Immune Response
Activation of B cells provokes the humoral immune response.
Antibodies specific to the target antigen are produced:
B cells activated when antigens bind to surface receptors, leading to proliferation and differentiation into effector cells.
Most cloned cells become plasma cells that secrete specific antibodies at 2000 molecules per second for 4 to 5 days before dying.
These antibodies circulate, binding to free antigens, marking them for destruction by innate or other adaptive mechanisms.
Clone cells that do not become plasma cells become memory cells, providing immunological memory for future infections.
Immunological Memory
Primary immune response: Cell proliferation and differentiation occur upon first exposure to antigen, with a 3 to 6 day lag period before peak antibody levels are reached in 10 days, after which levels decline.
Secondary immune response: Faster, more prolonged, and effective response upon re-exposure to the same antigen, with memory cells responding within hours:
Antibody levels peak in 2 to 3 days at much higher levels and with greater affinity, possibly remaining high for weeks to months.
Active and Passive Humoral Immunity
Active humoral immunity: Occurs when B cells encounter antigens and produce specific antibodies, which can be:
Naturally acquired: Develops in response to actual bacterial or viral infections.
Artificially acquired: Formed in response to vaccines of dead or attenuated pathogens.
Passive humoral immunity: Occurs when ready-made antibodies are introduced into the body (e.g., maternal antibodies delivered through the placenta or in milk; serum injections).
Immunological memory does not occur as B cells are not challenged by antigens; protection ends when antibodies degrade.
Antibodies
Antibodies (Immunoglobulins, Igs): Proteins secreted by plasma cells that detect germs and harmful substances, neutralize them, and attract other immune system cells for assistance.
Bind directly to the surfaces of viruses or bacteria, or to their toxins, preventing attachment to body cells and infection.
Produced by B lymphocytes, binding only to matching antigens like a key in a lock, inactivating and tagging them for destruction by innate defenses.
Form antigen-antibody (immune) complexes.
T-Cells and Cellular Immunity
T Lymphocytes (T-cells): Provide defense against intracellular antigens (e.g., virus-infected cells, cancer cells, foreign cells).
Respond to processed fragments of antigens displayed on cell surfaces.
Types of T cells:
Helper T cells: Activate other immune cells, releasing cytokines to enhance both humoral and cellular immune responses.
Cytotoxic T cells: Do the destructive work by destroying infected or abnormal cells and can induce apoptosis.
Review: The Second Line of Defense
Innate Cellular and Chemical Defenses
Phagocytes: Engulf and destroy pathogens, contributing to adaptive immune responses.
Natural Killer (NK) Cells: Promote apoptosis by attacking virus-infected/cancerous cells; recognize general abnormalities.
Inflammatory Response: Prevents the spread of injurious agents and promotes healing.
Antimicrobial Proteins: Interferons and complement proteins that enhance immune responses.
Fever: Systemic response inhibiting microbes and enhancing repairs.
Immunodeficiencies
Immunodeficiency: Conditions impairing function/production of immune cells or molecules.
Acquired Immune Deficiency Syndrome (AIDS): Caused by Human Immunodeficiency Virus (HIV), which attacks helper T cells, leading to severe infections and complications.
Autoimmune Diseases
Occurs when the immune system fails to distinguish self from foreign.
Results in the production of autoantibodies that destroy body tissues.
Examples include:
Rheumatoid arthritis
Myasthenia gravis
Multiple sclerosis
Graves’ disease
Type 1 diabetes mellitus
Systemic lupus erythematosus (SLE)
Hypersensitivities
Hypersensitivities: Immune responses to perceived threats causing tissue damage.
Immediate Hypersensitivity: Quick response to allergens causing inflammation/development of allergies by IgE antibodies.
Delayed Hypersensitivity: T cell mediated response, takes longer to develop.