Immunology and Homeostasis

• The lecture is about cell physiology, homeostasis, and immunity in week 8.

Objectives

• Explain homeostasis and the mechanisms of negative and positive feedback.
• Identify the immune system, including specific and non-specific defense mechanisms.
• Describe the pillars of inflammation and the difference between innate and acquired (adaptive) immunity.
• Demonstrate cell-mediated and antibody-mediated immunity.
• Identify types of acquired immunity, the five types of antibodies, as well as the different hypersensitivity types, and factors affecting the immune response.

Outlines

• Homeostasis
• Negative and positive feedback mechanisms
• The lymphatic system
• Non-specific and specific defense mechanisms
• First and second lines of defense
• Innate and acquired (adaptive) immunity
• Inflammation
• Cell-mediated immunity
• Antibody-mediated immunity (humoral)
• Five types of antibodies
• Types of acquired immunity
• Hypersensitivity
• Factors affecting the immune response

Homeostasis

• "Homoios" means same.
• "Stasis" means standing.
• Homeostasis means "Standing or Staying the same".
• Homeostasis is a condition that remains constant inside the body.
• Homeostasis is important for the survival of body cells.
• Claude Bernard (1813-1878) first made these observations.
• Walter B. Cannon (1871-1945) confirmed them and defined homeostasis as the maintenance of the constant internal environment.

Examples of Homeostasis

• The average internal body temperature is 37°C.
• Temperature varies slightly above or below this point under different physiological conditions, so blood homeostasis is 37°C.
• Glucose concentration in blood ranges from 80-100 mg per 100 ml under normal healthy conditions.
• It varies slightly above or below this level under different physiological conditions, so the blood glucose level is about 80-100 mg/100 ml in homeostasis.

Mechanism of Action of Homeostasis (Control System)

• Homeostasis is operated by the control system known as the feedback mechanism.
• Feedback mechanisms are classified into two types.

Negative Feedback Mechanism

• Negative feedback means that if a system's activity increases, the control system immediately reduces that activity to maintain homeostasis.
• In negative feedback: Information goes along the afferent pathway to the receptor (sensor), which changes detected by the receptor. Information goes along the afferent pathway to the control center. An output such as information is sent along an efferent pathway via the effector. The effector's response feeds back to influence the magnitude stimulus and returns a variable to homeostasis.

Example of Negative Feedback Mechanism

• Thyroxin hormone is secreted by the thyroid gland under the influence of thyroid-stimulating hormone (TSH), which is secreted by the pituitary gland.
• Whenever thyroxin secretion increases, TSH secretion from the pituitary gland decreases. As a result, thyroxin secretion also decreases.
• A normal level of thyroxin maintains the body.

Positive Feedback Mechanism

• A stimulus progressively increases the response, amplifying it as long as the stimulus continues.

Example of Positive Feedback Mechanism

• Four steps to blood coagulation occur whenever a blood vessel is ruptured and blood is shed to stop the blood shed.
• These steps are called blood coagulation: Prothrombin activator is formed.
• Prothrombin is converted to thrombin.
• Thrombin converts fibrinogen into fibrin.
• Fibrin formation stops the blood shed and blood coagulation occurs.

Basic Immunology

• Basic immunology studies the physiological mechanisms that enable the body to recognize materials as foreign.
• Basic immunology also covers the mechanisms that neutralize, eliminate, or metabolize harmful materials without injury to the host tissue.

The Lymphatic System

• The lymphatic system consists of: lymph vessels, lymph nodes and other lymphatic tissues, the spleen, the thymus gland, and red bone marrow.
• It has three main functions: Draining excess interstitial fluid, transporting dietary lipids, and providing an immune response.

Primary Lymphatic organs:

• Thymus gland: Differentiation of immature lymphocytes into T-cells.
• Red bone marrow: Differentiation of B-cells.
• Secondary lymphatic organs: The sites where most immune responses occur.

Defense mechanisms:

• A pathogen is an infectious agent that causes disease.
• An infectious disease occurs when a microorganism succeeds in evading host defenses and establishes a local site of infection and replication.
• Non-specific defense mechanisms (innate or natural immunity) offer protection against all dangers.
• Specific defense mechanisms (specific or acquired immunity) protect against only one specific antigen.

Non-specific defense mechanisms (innate or natural immunity):

• The first line of defense has physical and chemical factors.
• Physical factors include: the epidermis of the skin, mucous membranes, mucus, hairs, cilia, lacrimal apparatus, saliva, urine, defecation, and vomiting.
• Chemical factors include: sebum, lysozyme, gastric juice, and vaginal secretions.
• Second line of defense: antimicrobial proteins, natural killer cells, phagocytes, inflammation, and fever.

Second Line of Defense

• Antimicrobial Proteins: Interferons (IFNs): Interferons (IFNs) protect uninfected host cells from viral infections and the Complement system, which consists of about 30 proteins and causes microbe cytolysis, promotes phagocytosis, and contributes to inflammation.
• Transferrins: Transferrins inhibit the growth of certain bacteria by reducing the amount of available iron.
• Natural killer (NK) cells: Natural killer cells kill infected target cells by releasing granules containing perforin and granzymes.

Phagocytes

• Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells.
• Macrophages and dendritic cells within tissues are immune cells (phagocytes).
• Neutrophils are phagocytes that reside in the blood but can migrate to tissues during information.

Inflammation

• Inflammation is the inflammatory response, characterized by redness, heat, swelling, pain, and loss of function.
• Inflammation confines and destroys microbes and starts tissue repair.

Fever

• Fever intensifies the effects of interferons, inhibits growth of some microbes, and speeds up the body's reactions which aid in repair.

Specific Defense Mechanisms

• Cell-mediated immunity
• Antibody-mediated (humoral) immunity.

Cell-mediated immunity

• T lymphocytes provide cell-mediated immunity.
• T-lymphocytes recognize and bind to antigen particles processed by antigen-presenting cells and differentiate into four main types:
  • Helper T-lymphocytes release cytokines to support cytotoxic T and B lymphocytes.
  • Cytotoxic T-lymphocytes bind antigen and destroy it.
  • Memory T-lymphocytes are long-lived and provide immunity to the same antigen.
  • Suppressor T-lymphocytes turn off the immune response

Antibody-mediated (humoral) immunity

• B lymphocytes provide antibody-mediated (humoral) immunity.
• B lymphocytes recognize and bind to antigen (foreign) particles and differentiate into two main types:
  • Memory B lymphocytes are long-lived and provide immunity to the same antigen.
  • Plasma cells produce and release antibodies that bind to antigens.

Antibodies

• Antibodies are synthesized by plasma cells and released into plasma or other bodily fluids.
• There is 5 types of antibodies
  • IgA: IgA is found in body secretions like breast milk and saliva and prevents antigens from crossing membranes and diving deeper tissues.
  • IgD: IgD is made by B-cells and displayed on their surfaces where antigens bind to activate B-cells.
  • IgE: IgE is found on cell membranes like basophils and mast cells. It activates an inflammatory response if it binds to its antigen and is often found in excess in allergy.
  • IgG: IgG is the largest and most common type of antibody. It attacks many different pathogens and crosses the placenta to protect the fetus.
  • IgM: IgM is produced in large quantities in the primary response and is a great activator of complement.

Summary of Types of Acquired Immunity

• Acquired immunity can be active or passive, with four different outcomes.
  • Clinical disease subclinical infection=Natural active.
  • Vaccine/toxoid=Artificial active.
  • From mother=Natural passive.
  • Immunoglobulins antibiotics=Artificial passive.

Abnormal Immune Function

• Hypersensitivity: - Hypersensitivity is a powerful immune response to an antigen.
  • Hypersensitivity includes:
    • Type I: Immediate (anaphylactic) hypersensitivity (e.g. Peanut allergy).
    • Type II: Cytotoxic hypersensitivity (e.g. RA, transfusion reaction, hemolytic disease of the newborn).
    • Type III: Immune Complex: Glomerulonephritis.
    • Type IV: Delayed type hypersensitivity: Graft rejection and nickel allergy.

Factors Affecting Immune Response

• Age: very old and very young subjects are susceptible to disease.
• Nutrition: Dietary deficiency leads to immune dysfunction and can cause toxic effects of allergic reactions.
• Stress: Stress can causes lymphoid atrophy, decreased phagocytosis and decreased lg A secretion along which respiratory functions also worsen.

Summary

• Homeostasis is a concept that refers to balance in the system.
• It shows the body's attempt to maintain a constant internal environment.
• Innate immunity which is conjuctioned with acquired immunity.
• Rapid response to agression being the organisms first line of defense.
  • Mechanisms include physical, chemical and biological barriers.
  • Cellular components, as well as soluble molecules.
• Adaptive immune resonse happens in the cell mediated immunity by antigen-specific effector T-cells and is responsible for a direct killing of infected cells or effectors/functions of other immune cells.
• Humoral immunity leads to the release of antigen-specific antibodies aimed at invading a microbe. Thus it can be partly cell-mediate immunity.

Explore the chemical factors in the first line of defense and the role of antimicrobial proteins in viral infections. Understand the function of phagocytes and Natural Killer cells in the innate immune response. Learn about negative and positive feedback mechanisms and their roles in maintaining homeostasis, especially in thyroxine regulation and blood coagulation.