Understanding the Immune System

Overview of the Immune System

• Immunology studies the immune system and its response to invading pathogens.
• The immune system is a collection of cells, tissues, organs, and molecules.
• The immune system combats infection and cancer.
• An immune response involves coordinated actions of cells, tissues, and molecules.
• The physiological function is to prevent and eradicate infections.

Immunity

• Immunity's purpose is to resist or eliminate harmful foreign materials or abnormal cells.
• Immunity defends against invading pathogens.
• Immunity removes worn-out cells like old red blood cells and tissue debris from injuries or disease.
• It identifies and destroys abnormal or mutant cells as a primary defense against cancer.
• Immunity rejects foreign cells like organ transplants.
• Immunity exhibits inappropriate responses like allergies to harmless substances as well as autoimmune diseases.

Innate vs Adaptive Immunity

• Innate Immunity is the first line of defense. Adaptive Immunity is the second line of defense.
• Innate immunity has no lag time, while adaptive immunity has a lag period.
• Innate immunity is not antigen-specific. Adaptive immunity is antigen-specific.
• Innate immunity has no memory; adaptive immunity develops memory.

Types of Innate Immunity

• Species Immunity: Offers resistance to pathogens. Ex: B.anthracis affects humans but not chickens.
• Racial Immunity: Different races within a species show varying susceptibility or resistance. Ex: sickle cell anemia is immune to P.falciparum.
• Individual Immunity: Varies among individuals of the same race and species.

Factors Effecting Innate Immunity

• Age: Newborns and the elderly are more susceptible to infections.
• Hormones: Hormonal disorders like diabetes mellitus, adrenal dysfunction, and hypothyroidism increase susceptibility.
• Nutrition: Malnutrition predisposes individuals to bacterial infections, reducing both humoral and cell-mediated immune responses.

Anatomical Barriers - Mechanical Factors

• Skin is an anatomical barrier.
• The mucociliary escalator is an anatomical barrier,
• Flushing actions of saliva, tears, and urine are anatomical barriers.

Anatomical Barriers – Chemical Factors

• Antimicrobial peptides in sweat are chemical barriers.
• HCl in the stomach is a chemical barrier
• Lysozyme in tears and saliva is a chemical barrier.

Anatomical Barriers – Biological Factors

• Normal flora consisting of microbes exists in many body parts
• Normal flora includes over 1000 species of bacteria.
• Normal flora competes with pathogens for nutrients and space.

Innate Immune System Components of Blood

• The innate immune system is composed of :
  • Complement proteins
  • Extracellular proteins
  • Cytokines
  • White blood cells (WBCs)

White Blood Cells (WBCs)

• Types of WBCs include:
  • B-lymphocytes
  • T-lymphocytes
  • Natural killer (NK) cells
  • Macrophages
  • Mast cells

Neutrophils

• Neutrophils are the most abundant WBCs, making up approximately 50-60%.
• Neutrophils are efficient phagocytes.
• Neutrophils find, eat, and digest microbes.
• Neutrophils are important cells of the innate immune system.

How Neutrophils Eat and Digest Microbes

• Neutrophils use digestive enzymes to phagocytose microbes.
• Lysosomes digest bacterial cell walls and other antimicrobial proteins.
• Neutrophils can also trigger an inflammatory response.

Monocytes

• Monocytes constitute about 5% of WBCs.
• Once monocytes migrate into tissue, they become macrophages.
• Macrophages are "big eaters."
• Macrophages perform phagocytosis of microbes in tissue, whereas neutrophils operate primarily in the blood.
• Macrophages participate in antigen presentation.

Natural Killer Cells

• NK cells are neither B-lymphocytes nor T-lymphocytes.
• NK cells play an important role in the innate immune system.
• They kill virus/bacteria-infected cells (intracellular pathogens) and cancer cells.

How Natural Killer Cells Kill

• Natural killer release granules with perforins and proteases.
• Release of granules with perforins and proteases, kills both host cells and microbes.

Pathogen Recognition

• Pathogens are recognized by macrophages and dendritic cells via pathogen-associated molecular patterns (PAMPs).
• PAMPs on the pathogen interact with pattern-recognition receptors (PRRs) on immune cells, such as TLR.
• Binding of PRRs with PAMPs leads to cytokine release, signaling other cells to fight back.

Toll-like Receptors (TLRs)

• TLRs are transmembrane proteins that are present on macrophages/few other cells.
• TLRs are conserved across vertebrates.
• TLRs play a key role in the innate immune system.
• TLRs search for microbes or their components, and bind to the microbes or parts of microbes.
• TLRs trigger a cascade of events to kill or protect against pathogens.

Consequences of TLR Binding

• When a TLR binds to a microbe it causes enhanced immune response and enhances secretion of cytokines/interferon.
• Binding of TLRs to microbes also causes inflammation and/or phagocytosis of infected cells, as well as apoptosis of infected cells and killing of infected cells.

Summary of Innate Response – Internal Defenses

• Internal defenses are cellular (involving WBCs) and come into play when external defenses are breached.
• It comes into play via: Neutrophils, Monocytes/macrophages, NK cells and TLRs.

Cytokines

• Cytokines are small proteins secreted by immune system cells.
• They affect the behavior of other cells, acting as signaling molecules.
• Cytokines are key players in both innate and acquired immunity.

Which cells release cytokines?

• Neutrophils release cytokines when they encounter a pathogen.
• Macrophages release cytokines when they encounter a pathogen.
• TLRs release cytokines when they bind to a microbe/ components of a microbe.
• NK cells release cytokines when they encounter a microbe infected cell /tumour cell.
• Lymphocytes release cytokines when activated.

Examples of Cytokines

• Examples include interferons, interleukins, and tumor necrosis factor (TNF).

Interferons

• Interferons are signaling proteins produced by virus-infected monocytes and lymphocytes.
• They are secreted proteins called “Key anti-viral proteins”.
• They “Interfere” with virus replication.
• Interferons warn neighboring cells that a virus is around.

How Interferons Inhibit Viruses

• Interferons can inhibit virus replication.

Interleukins

• There are multiple interleukins - numbered 1-37
• They are not stored inside cells but are quickly synthesized and secreted in response to infection.
• Interleukins are key modulators of behaviour of immune cells -Mostly secreted by T-lymphocytes & macrophages

Action of Interleukins

• Interleukins cause proliferation of immune cells, inflammation. and increase the amount of antibody Production
• Interleukins activate immune cells.

Tumor Necrosis Factor (TNF)

• As cytokines are released also cause cancer to be destroyed and fever, as well as inflammation to occur.

Complement

• Consist of distinct plasma proteins C1 through C9 that react with one another
• Complement systems can bind to and coat microbe.
• Complement system enhances essential part of innate immune response
• Complement enhancements adaptive immune response.

Complement Proteins

• Complement proteins facilitate phagocytosis.
• Complement proteins directly cause lysis of pathogens, and cause inflammation.

Compliment Proteins facilitating phagocytosis

• Bacteria are coated with C`. Which activated C compliment receptors of Neutrophils that initiates phagocytosis.

Compliment Proteins lysing Pathogens

• Membrane attack complex is formed by compliement proteins to acheive this.

Coagulation Proteins

• Coagulation is a mechanism to stop bleeding after injury to blood vessels and uses platelets, coagulation factors and vitamin K.
• Coagulation: mechanism to stop bleeding after injury to blood vessels
• Complex pathway involves
• Platelets
• Coagulation factors
• Vitamin K

Coagulation Balance

• Coagulation proteins, blood clotting, Inflammation & apoptosis need to be balanced with anti-coagulation methods such as preventing blood clotting, Inhibiting inflammation & prohibiting apoptosis.
• Too much nor too little of either is problematic leading to loss of maintenance.

Coagulation and innate immunity

• Pathogens cytokines need to be balanced with anti-coagulants or will cause increased inflammation and increased apoptosis of infected cells

Inflammation

• It is a Complex biological process by which body responds to pathogens and irritants
• Associated with swelling of tissue.
• A key player in innate immune response

All Roads Lead to INflammation

• Inflammation is caused by: Neutrophils, Monocytes /macrophages, NK cells, .Cytokines /IFN, TLRs & C proteins which can be either cellular or Extra cellular.

Inflammation and vascular changes

• Inflammation can lead to Vasodilatation and Increased capillary permeability.

Signs of inflammation

• Signs of inflammation due to vascular changes include: Heat redness, Swelling, Fever & Temporary loss of function Pain.

Inflammation Role in Innate Immunity

• Inflammation Initiates of phagocytosis killing of pathogen
• It Limits the spread of infection, stimulates adaptive immune response and Initiates tissue repair.

Role of Good and Bad Inflammation

• Acute /short-term Inflammation - Cured by good Progressive Healing due to frostbite or chemical irritation of lacerations/stabbing related Allergies and Burn issues.
• Chronic /long-term Inflammation - Caused by bad progressive destruction due to Cardio vascular disease, Autisim and Rheumatoid or neurological disease.

Chronic Information

• Chronic inflammation in injured tissue contains macrophages that release toxins (including reactive oxygen species or ROS) that injure tissues.and isAlmost always accompanied by tissue destruction.

Role of Innate Components

• If external defense fails innate components will: Create a Phagocytic response by Phagocytic cells, a Antimicrobial proteins & Inflammatory response, trigger Natural killer cells and release compliment .