Chapter 22: Immunity

Chapter 22: Immunity

• Chapter focuses on the concept of immunity, exploring its various aspects and mechanisms

Primary Locations of Immune Function

• Immune functions are located throughout the body in various organs and tissues
• Key locations include:
  • Adenoids
  • Tonsils
  • Thymus
  • Bone marrow
  • Lymph nodes (axillary and inguinal)
  • Bronchus-associated lymphoid tissue
  • Spleen
  • Intestine
  • Peyer's patches
  • Appendix

Innate vs. Adaptive Immunity

• Immunity is divided into two main types: innate and adaptive
• Innate immunity is a rapid response system
  • Utilizes cells such as:
    • Macrophages
    • Natural killer cells
    • Complement proteins
    • Neutrophils
    • Eosinophils
    • Basophils
    • Dendritic cells
    • Mast cells
    • Granulocytes
• Adaptive immunity is a slower response system
  • Employs:
    • B cells (producing antibodies)
    • T cells (including γδ T cells, CD4+ T cells, and CD8+ T cells)
    • Natural killer T cells
• The two immunity types differ based on:
  • Cells involved
  • Specificity of cell response
  • Mechanisms of eliminating harmful substances
  • Response time

Innate Immunity Details

• Innate immunity involves defenses that respond rapidly
  • Species resistance
  • Mechanical barriers
  • Chemical barriers
  • Natural killer cells
  • Inflammation
  • Phagocytosis
  • Fever
• It involves nonspecific protection against a variety of substances
• Skin and mucosal membranes act as barriers
• Cellular and molecular internal defenses are included
• No prior exposure to a substance is needed for this immediate response

Adaptive Immunity Details

• Adaptive immunity is acquired and specific
• Responses are tailored to specific antigens
• T- and B-lymphocytes are involved
• It can differentiate between foreign substances
• Develops over several days
• Innate and adaptive immunities, though distinct, work together in body defense
• Adaptive immunity's specific defenses, develop slowly and are carried out by lymphocytes recognizing a specific invader

Lines of Defense in the Immune System

• The immune system's defense strategies are divided into three categories:
  • First line of defense
  • Second line of defense
  • Third line of defense
• The first and second lines are specific to the innate immune system
• The adaptive immune system uses the third line of defense strategies

First Line of Defense: Mechanical Barriers

• Unbroken skin and mucous membranes create mechanical barriers
• Physical barriers stop pathogen entry
• These barriers include hair, mucus, and sweat
• They are the body's first line of defense
• The rest of the innate defenses form the second line

Second Line of Defense: Chemical Barriers

• Chemical barriers, such as gastric juice's acidity and lysozyme in tears, kill pathogens
• Interferons are hormone-like peptides produced by cells infected with viruses
  • Induces nearby cells to produce antiviral enzymes
  • Stimulates phagocytosis
• Activation of complement stimulates inflammation
  • Attracts phagocytes
  • Enhances phagocytosis

Second Line Continued: More Barriers

• Natural Killer (NK) cells are lymphocytes defending against viruses and cancer cells
  • Secrete perforins, cytolytic substances
  • Secrete chemicals enhancing inflammation
• Inflammation is characterized by:
  • Redness
  • Swelling
  • Heat
  • Pain
• Inflammation_has responses:
  • Dilation of blood vessels
  • Increased blood volume
  • Invasion of white blood cells

Second Line Continued: Phagocytosis and Fever

• Neutrophils and monocytes are the most active phagocytes
  • Leave the bloodstream at injury sites by diapedesis
  • Attracted to injured areas by chemotaxis
  • Neutrophils engulf smaller particles; monocytes tackle larger ones
  • Monocytes become macrophages fixed in tissues.
• Phagocytosis removes foreign particles from the lymph
• Fever protects against infection by interfering with conditions promoting bacterial growth.
  • Iron in the blood decreases during fever, limiting nutrients for pathogens
  • Phagocytic cells become more vigorous at higher temperatures

Innate Immunity: Phagocytes

• Phagocytic cells: neutrophil, macrophage, and dendritic cell
• Infectious agent is engulfed, and residue is then exocytosed

Apoptosis-Initiating Cells: NK Cell

• Apoptosis-initiating cells: NK cell
• Perforin and granzyme are released during the process
• Perforin forms a transmembrane pore
• Granzymes enter this pore, which causes apoptosis of unhealthy or unwanted cells

Defense Line Summary

• Pathogen attempts to gain entrance into the body
• First line of defense: mechanical barriers like skin and mucous membranes
• Pathogen enters body
• Second line of defense: chemical barriers, natural killer cells, inflammation, phagocytosis, fever
• Third line of defense: cellular and humoral immune responses

Overview of the Immune System

• Immune system has innate and adaptive aspects

Effects of Interferon (IFN)

• Infected cell triggers a cascade of events with interferon

Innate Immunity: Complement System

• Complement system contains a group of over 30 plasma proteins
• Works along with complements of antibodies
• Each protein is identified with letter "C" and number (e.g., C2)
• Synthesized by the liver
• Continuously released once inactive

Innate Immunity: Inflammation part 1

• Inflammation has key events
• Injured tissue, basophils, mast cells, infectious organisms releases chemicals to start response
• Histamine, leukotrienes, prostaglandins, chemotactic factors are included
• Released chemicals cause vascular changes:
  • Vasodilation
  • Increased capillary permeability
  • Increased endothelial expression for leukocyte adhesion
  • Recruitment of Leukocytes

Innate Immunity: Inflammation part 2

• More Inflammation events
• Macrophages may release pyrogens
• Delivery of plasma protein to site
• Immunoglobulins includes complement, clotting proteins, and kilins
• Clotting proteins form clots
• Kinins stimulate pain receptors

Innate Immunity: Inflammation part 3

• Effects of Inflammation
• Fluid moves from blood to injured area
• Fluid, protein, immune cells work to eliminate pathogens
• Vasodilation brings more blood
• Increase in capillary permeability
• Loss of plasma proteins, leads to fluid up take by lymphatic capillaries
• Some fluid is still left in interstitial space
• Macrophages eat bacteria
• Tissue repair begins

Innate Immunity: Inflammation Summary

• Inflammation steps
• Chemical Gradient
• Vascular Changes
• Recruitment of Immune Cells
• Delivery of Plasma Proteins

Cardinal Signs of Inflammation

• Cardinal Signs of Inflammation include:
  • Redness from increased blood flow
  • Heat from increased blood flow and metabolic activity
  • Swelling from increase in fluid loss from capillaries
  • Pain from stimulation of pain receptors
  • Compression from fluid
  • Chemical irratants
  • Loss of function from pain and swelling in severe cases.
• Duration of active inflammation about 8-10 days

Innate Immunity: Fever

• Fever (Pyrexia) has definition/s
• Abnormal body temperature elevation
• 1°C or more from normal (37°C)
• Results from release of pyrogens from immune cells or infectious agents
• Fever events:
• Pyrogens circulate through blood and target hypothalamus
• Hypothalamus releases prostaglandin E2
• Hypothalamus raises temperature set point

Innate Immunity: Benefits/Risks of Fever

• Benefits of Fever
  • Inhibits reproduction of bacteria and viruses
  • Promotes Interferon Activity
  • Increases activity of adaptive immunity
  • Can leave a low fever untreated
• Cons of High Fever
  • Potentially dangerous
  • Changes can cause seizure

Adaptive Immunity: An Introduction

• Adaptive immunity involves specific lymphocyte responses to an antigen
• Contact with antigen causes lymphocyte proliferation
• Immune response consists of lymphocytes and their products
• Slow response time than innate immunity
• Since it takes days to develop, it is the third line of body's defense
• Two branches of adaptive immunity exist:
  • Cell-mediated immunity involving T-lymphocytes
  • Humoral immunity involving B-lymphocytes

Adaptive Immunity's Two Branches

• Adaptive immunity can be cell mediated or humoral immunity

Formation of Lymphocytes

• Naive Immunocompetent Lymphocytes B and T
• Red Bone Marrow primary structure for production of Lymphocytes
• Primary Lymphatic structure for maturation of T-Lymphocytes in Thymus

Note on T-Cells

• Another sub-type of T-Cells is formed during the thymic selection is a:
  • Regulatory T-lymphocytes
    • They are a type Helper T-Cells
    • CD4+ formed that mildly bind self-antigens

T-Lymphocytes vs. B-Lymphocytes

• T and B Lymphocytes are different in receptors but can work with immunity's overall scheme

Activation of T-Lymphocytes

• Cells display a foreign antigen on their membranes
• The T-Cells can bind with antigen to activate an immune response
• These cells are Antigen Presenting Cells (APCs)
• Two cells can present Antigens
  • Own body cells (They present self, which T-Cells recognize but don't attack)

Immune Antigen Presenting Cells part 2

• Dendrites and macrophages are professional APCs in the body

MHC class I molecules

• MHC class I molecules can dock in a healthy or unhealthy cell

Effector Responses of T-Lymphocytes

• Helper and Cytotoxic T Lymphocytes can produce Apoptosis

B- Lymphocytes:

• Production of B-Cells occur in red bone marrow
• Migrate to the secondary lymphoid structure
• Unlike T-Cells, B-Lymphocytes don't require presentation from another cell to be activated

Activation of B-Lymphocytes

• Activation of B-Lymphocytes is unique per cell type
• After foreign cells, they can engulf the call using phagocytosis
• B-Cells can differentiate into plasma and memory cells
  • Plasma cells produce antibodies
  • Memory B Cells are used upon exposure to cells

Immunoglobulins (Antibodies)

• Immunoglobulin is the protein product against antigens
• Target pathogens for destruction by immune class
• Provides good defense against toxins or spores

Antibody Functions

• Antibody functions can attack
• Precipitation through agglutination, neutralisation and inflammation or complement
• Opsonizaation & Phagocytosis enhances this process

Antibody Types

• There are 5 immunoglobulin types
• IgG defends against bacteria cells
• IgA prevents attachment of bacteria
• IgM is found in blood
• IgD is found on B-Lymphocutes for cell activation

Humoral Immunity

• Humoral Immunity has lagged primary response
• More IgM, then IgG with first response

Practical Classification of Immunity

• Active and Passive Immunity have different paths
• Naturally acquired active immunity occurs after exposure to the antigen itself but naturally

Active and Passive Immunities

• Natural and Artificial have different results in the system
• Active Immunity produces contact with antigens
• Artificial immunity is antigen exposure
• Passive exposure has no production in cells

Practical Classification of Immunity

• Weakened or dead microorganism or component
• Stimulate immune system to develop memory B-lymphocytes
• If later exposed, secondary response triggered

Summary of Vaccine

• How COVID-19 vaccine works
• Look up video for more details

Hypersensitivities

• Immune system response is abnormal and exaggerated
• Acute Hypersensitivities occuring
• Subacute involve homoral immunity
• Delayed involve cell-mediated immunity