Innate and Adaptive Immunity

Learning Objectives

• Learners will be able to compare and contrast innate and adaptive immunity.
• Learners will be able to identify innate immune strategies for pathogen identification.
• Learners will be able to identify innate immune cells.
• Learners will be able to describe surface barriers and innate internal defences.
• Learners will be able to explain how inflammation works.

The Immune System

• The immune system is a functional system, not an organ system.
• The structures are diverse molecules plus trillions of immune cells.
• The function of the immune system is to protect against pathogens.
• The immune system is broadly classified into innate and adaptive defenses.
• A pathogen is a harmful or disease-causing microorganism, such as bacteria, a virus, fungi, or parasite.

The Immune System: Categories

• The Innate Immune System provides general defense strategies that are not tailored.
• The Innate Immune System is present at birth and fast-acting, for example, inflammation.
• The Adaptive Immune System provides specific defense tactics that are tailored.
• The Adaptive Immune System is acquired over time and is slow, but powerful
• Cell-mediated and humoral-mediated responses and memory are features of the adaptive immune system.

The Immune System: Categories

• Humans come "fully equipped" with innate immune defenses at birth.
• Innate defenses include both surface and internal defenses.
• Innate defenses alone can ward off invading pathogens in many cases.

The Immune System

• Surface barriers include skin and mucous membranes.
• Internal innate defenses include phagocytes, natural killer cells, inflammation, antimicrobial proteins, and fever.

The Innate Immune System - Surface Barriers

• The intact epidermis is a mechanical barrier to harmful pathogens and other harmful substances.
• The epidermis consists of 4-5 layers of epidermis dermis, or 25-45 cells thick
• Intact epidermis contains keratin.
• Intact epidermis is resistant to most weak acids and bases and bacterial enzymes.
• Integumentary system secretions include sweat and sebum.
• Slightly acidic substances inhibit bacterial growth.
• Dermcidin is an antimicrobial.

The Innate Immune System

• Intact mucous membranes secrete lysozyme, an enzyme that breaks down the bacterial cell wall.
• Lysozyme has been found Tears (lacrimal gland) and Respiratory mucus (nasal cavity)
• Intact mucous membranes contain mucin.
• Mucin is a thick sticky mucous that traps microorganisms.
• Mucins combine with water to form a thick sticky mucus.
• Mucus lines the digestive and respiratory passageways.

The Innate Immune System

• Skin and mucous membranes also contain acids, which inhibit bacterial growth.
• Protective acidic secretions can be found in skin (sebum), stomach and vagina
• Defensins are broad-spectrum antimicrobial peptides.

The Immune System

• Surface barriers include skin and mucous membranes.
• Internal innate defenses include phagocytes, natural killer cells, inflammation, antimicrobial proteins, and fever.

The Innate Immune System - Internal Innate Defenses

• Internal innate defenses are also known as second-line defenses.
• Internal innate defenses identify potentially harmful substances and recognize/bind molecules that are part of infections organisms (but not part of normal human cells).
• The innate internal defenses recognize general molecules

The Innate Immune System - Internal Innate Defenses

• General molecules common to many pathogens are Pathogen-associated molecular patterns (PAMPs).
• Lipoteichoic acid (LTA), peptidoglycan (PGN), lipoproteins, DNA, flagellin, and lipopolyssacharide (LPS) are all examples of PAMPS

The Innate Immune System - Internal Innate Defenses

• General molecules common to many damaged or diseased cells: Damage-associated molecular patterns (DAMPs).
• Damage Associated Molecular Patterns cause “sterile inflammation”
• Signals for phagocytosis occur due to DAMPs
• Nucleotides, Alarmins, stress proteins (e.g., heat shock proteins), and calcium-binding proteins are types of DAMPs
• DAMPs are intracellular molecules

The Innate Immune System

• PAMPs and DAMPs are recognized by immune cell receptors.
• These immune cell receptors are Pattern Recognition Receptors.

The Innate Immune System

• There are many classes of PRR
• Toll-like receptors (TLRs) are a class of PRR
• TLRs are present on many types of immune cells (e.g., macrophages).
• When molecular "patterns" bind to a TLR, this alarms the immune system of an invader, triggers an immune response, and leads to inflammation.

The Innate Immune System - Phagocytes

• Pathogens that invade underlying tissue are confronted by phagocytes.
• Phagocytosis is the ingestion/killing of other cells.
• Neutrophils are the most abundant white blood cell
• Neutrophils become phagocytic upon encountering a pathogen.

The Innate Immune System - Phagocytes

• Macrophages are very active phagocytic cells.
• "Macro" means large.
• "Phage" means eat.
• Monocytes are found in the blood and migrate to tissues and become macrophages.
• Examples are Microglia found in the brain, Alveolar macrophages found in the alveoli, and Langerhans found in the skin

The Innate Immune System - Natural Killer Cells

• Natural killer cells kill cancerous and virus-infected cells before the adaptive immune system is activated.
• Natural killer cells are NOT phagocytic
• Natural killer cells detect cell abnormalities
• Natural killer cells attach to cells, inject chemicals, and induce apoptosis.
• Apoptosis is programmed cell death.

The Innate Immune System - Natural Killer Cells

• Natural killer cells also secrete cytokines to call other immune cells and initiate inflammation.
• Cytokine: any molecule secreted by a body cell that induces an immune response (umbrella term).
• Examples of cytokines are interferons, interleukins, and tumor necrosis factor.
• Cytokines act by signaling nearby (paracrine) cells or by secreting into the blood (endocrine).

The Innate Immune System - Inflammation

• Inflammation is a general response mechanism.
• Injuries can be due to trauma, heat, irritating chemicals, or infections by microorganisms.
• Cytokine release calls other immune cells to respond and leads to inflammation

The Innate Immune System - Inflammation

• Inflammation protects by preventing the spread of damaging agents,
• Inflammation disposes of cell debris and pathogens
• Inflammation alerts the adaptive immune system
• Inflammation sets the stage for repair

The Innate Immune System - Stages of Inflammation

• Inflammation is a localized response, and consists of 3 stages
• Inflammatory chemical release is the first stage.
• Vasodilation and increased vascular permeability is the second stage.
• Cell mobilization is the third stage.
• The signs and symptoms of inflammation are redness, swelling, and pain.

The Innate Immune System - Inflammation

• Inflammatory chemical release involves a chemical "alarm" being set off by cells at the site of injury
• Mast cells release histamine
• Kinins, Prostaglandins and Cytokines are released
• Inflammatory chemicals cause local arteriole dilation and increased permeability of blood vessels.

The Innate Immune System - Inflammation

• Increased blood flow to the area impacts the area an is termed hyperemia
• Signs and symptoms of inflammation result as this vasodilation and increased blood flow result in redness and heat
• Hyperemia results in more immune cells at the injury site
• Increased permeability causes fluid to seep from the blood to the tissue (Exudate)
• Exudate leads to swelling/ edema
• Exudate contains complement.
• Clotting factors are also present in Exudate and important for walling off the injury site to prevent infection spread
• Lymphatic vessels pick up the fluid from the interstitial fluid,.
• Excess fluid in lymph nodes causes swelling when sick or fighting infection

The Innate Immune System - Inflammation

• Leukocytosis is the first step in cell mobilization
• Injured cells secrete leukocytosis-inducing factors
• Neutrophils enter the blood from bone marrow
• Leuko refers to white and Cyt refers to Cell, Osis refers to condition

The Innate Immune System - Inflammation

• Margination is the second step in cell mobilization
• Phagocytes cling briefly to inner walls (margins) of inflamed endothelial cells.
• Margination causes slow rolling movement

The Innate Immune System - Inflammation

• Diapedesis which involves inflammatory chemicals that call neutrophils to flatten and squeeze between the endothelial cells of the blood vessel
• Diapedesis means across and Pedesis means jump

The Innate Immune System - Inflammation

• The fourth step in cell mobilization is Chemotaxis
• Chemotaxis: 'Bread crumb' trail (gradient) of inflammatory chemicals calls the neutrophils to the site of injury.
• Chemo means chemical, and Taxis means movement

The Innate Immune System - Inflammation

• the final step in cell mobilization is Chemotaxis
• Monocytes follow behind neutrophils
• Once in the tissues, they differentiate to become Macrophage
• Macrophages are termed the "Large Eaters"

The Innate Immune System

• A variety of antimicrobial proteins enhance innate immunity by:
• Attacking microorganisms directly.
• Hindering their ability to reproduce.
• Important antimicrobial molecules: Interferon and Complement.

Understanding Viruses

• Virus: Infectious substance that contains genetic material encased in a proteins capsule
• Viruses can contain a phospholipid envelope and their existence depends on using host's cells to replicate

Antimicrobial Proteins: Interferons

• Interferons (IFNs) help protect cells that are not yet infected with a virus.
• Signals to neighboring cell to destroy RNA and reduce protein synthesis- stopping virus-making factory
• Signals to neighboring cell to undergo apoptosis meaning there are now less cells for virus to infect
• Activates immune cells meaning there will be more cells to fight off the virus

Antimicrobial Proteins: Complement

• Aka complement system
• A series of 20+ plasma proteins (normally in circulation) activation leads to the lysis of bacteria as well as the destruction of foreign substances (incl. viruses) and the Amplification and activation of immune system
• Complement activation leads to Inflammatory processes, and Adaptive immunity defenses

Antimicrobial Proteins: Complement

• The classic pathway (Antibodies), Lectin pathway (Bacteria (lectin)) or an Alternative pathway (Spontaneous) lead to complement activation
• Opsonization occurs when a protein-coated pathogen is tagged for phagocytosis
• MAC
  • Hole in bacterium cell lysis (death)
• The process enhances Inflammation
  • Histamine release
  • Blood vessel permeability
  • Chemotaxis
  • Attracts phagocytes

The Innate Immune System

• Inflammation is a localized response
• Fever results when the invasion of a microorganism is more widespread.
• Fever: abnormally high body temperature

The Innate Immune System - Fever

• Leukocytes and macrophages exposed to foreign substances release pyrogens
• Pyro means fire
• Gen: Starter (produce)
• Pyrogens effect the body's internal thermostat (hypothalamus)
• Pyrogens Change the body's set point above 37°C

The Innate Immune System

• Benefits of fever: increased metabolism (speeds up repair, Liver and spleen sequester;iron and zinc important for bacterial function, increase neutrophil and monocyte function , potential to "cook" the bacteria to death
• Potential costs of a fever: "can cook" yourself. denaturing of protiens. . tissue damage including brain tissue

The Immune System: Categories

• The Innate Immune System provides general defense strategies that are not tailored.
• The Innate Immune System is present at birth and fast-acting, for example, inflammation.

Summary

• The innate immune system has many surface defences and non-specific internal cellular defences.
• Innate immune cells recognize general pathogen patterns.
• There are many immune signalling molecules.
• The innate immune system utilizes inflammation and fever as major defence strategies.