Chapter 11-Innate and Adaptive Immunity

Innate and Adaptive Immunity

Introduction

• Chapter 11 is crucial for understanding Chapters 9 and 12, as well as inflammatory conditions discussed throughout the course.
• Focus on the PowerPoint and videos provided in Module 02, supplementing with the textbook as needed.
• Pay close attention to the objectives, as they will guide your learning and form the basis of test questions.
• The videos associated with this chapter are designed to reinforce understanding and are a valuable use of your time.

Objectives

1. Discuss and describe the function of the immune system.
2. Contrast and compare the general properties of innate and adaptive immunity.
3. Characterize the chemical mediators that orchestrate the immune response.
4. Understand the recognition systems for pathogens in innate immunity.
5. Describe the functions of the various cytokines involved in innate immunity.
6. Define the role of the complement system in immunity and inflammation.
7. Characterize the significance and function of Major Histocompatibility Complex (MHC) molecules.
8. Compare and contrast the development and function of the T and B lymphocytes.
9. Describe the function of cytokines involved in the adaptive immune response.
10. Explain the transfer of passive immunity from mother to fetus and from mother to infant during breast-feeding. (Neonatal/childhood)
11. Characterize the development of active immunity in the infant and small child. (Neonatal/childhood)
12. Describe the changes in the immune response that occur during the normal aging process. (Geriatrics)

Case Study: Melissa, a 15-Year-Old with Mononucleosis

• Melissa experiences fatigue, sore throat, headache, and enlarged lymph nodes, leading to a diagnosis of mononucleosis.

Overview of the Immune System

• Watch the video "Overview of the Immune System" in Module 02 for a broad introduction before diving into more detailed discussions.

Immune Response

• Definition: The collective, coordinated response of the cells and molecules of the immune system.
• Types of Immune Defenses:
  • Innate (Nonspecific) Immunity: Natural resistance present from birth.
  • Adaptive (Specific) Immunity: A slower but more effective response that develops over time.

Cytokines—Mediators of the Immune System

• Cytokines are soluble proteins that act as chemical messengers, facilitating communication between immune and tissue cells.
• They are pleiotropic (producing multiple effects) and redundant (duplicating the effect of another cell).
• Types of Cytokines:
  • Interleukins (ILs): Produced by macrophages and lymphocytes; they enhance acquired immunity.
  • Interferons (INFs): Primarily protect against viral infections and modulate the inflammatory response.
  • Tumor Necrosis Factor Alpha (TNF-α): An endogenous pyrogen that induces fever.
  • Chemokines: Control the migration of leukocytes to the site of action in the immune response.
    • Implicated in diseases like atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, allergic asthma, chronic bronchitis, multiple sclerosis, systemic lupus erythematosus, and HIV infection.
  • Colony-Stimulating Factors: Stimulate the growth and differentiation of bone marrow progenitors of immune cells.
    • These are named based on their target cell, such as granulocyte/monocyte stimulating factor.

Principal Cells of the Immune System

• Lymphocytes: Cells that specifically recognize and respond to foreign antigens.
• Accessory Cells: Macrophages and dendritic cells function as antigen-presenting cells (APCs).
  • They process complex antigens into epitopes required for lymphocyte activation.

Normal Blood Cells:

• Non-Specific Immunity:
  • Eosinophil
  • Monocyte
  • Neutrophil
  • Basophil
• Specific Immunity:
  • Lymphocyte

Innate and Adaptive Immunity

• Refer to Norris (11th ed.), p. 284 and pp. 286-7.

Cells of the Immune System

• Watch the video "Cells of the Immune System" in Module 02 for an overview.

Innate Immunity

• Think of it as the immunity "you were born with," before exposure to foreign substances (antigens).
• Components:
  • Epithelial Barriers: (Review Chapter 10).
  • Cells of Innate Immunity:
    • Neutrophils (Polymorphonuclear Neutrophils [PMNs]): Early responders, predominantly in the blood.
    • Eosinophils: Ingest antigen-antibody complexes and viruses.
    • Monocytes: Released from bone marrow, migrate into tissues, and mature into macrophages and dendritic cells.
    • Macrophages: Essential for clearing bacteria; phagocytic cells that engulf and digest microbes; limit infection spread until adaptive immunity occurs.
    • Dendritic Cells: Bridge between innate and adaptive immune systems; have surface projections like brain dendrites.
      • Immature Forms: Sense and capture foreign agents, transport to secondary lymphoid tissues.
      • Mature Forms: Initiate adaptive immunity as APCs; release molecules directing the adaptive immune response.
    • NK Cells (Natural Killer Cells): Kill target cells infected with intracellular pathogens; mediate cytotoxicity without previous exposure; assist in dendritic cell maturation and control viral infections.

Natural Killer Cell Receptors

• A. NK cells express activating receptors that respond to ligands from virus-infected or injured cells and inhibiting receptors that bind to the class I major histocompatibility complex (MHC-I) self-recognition molecules expressed by normal cells. Normal cells are not killed because inhibitory signals from normal MHC-I molecules override activating signals.
• B. In virus-infected or tumor cells, increased expression of ligands for activating receptors and reduced expression or alteration of MHC molecules interrupts the inhibitory signals, allowing activation of NK cells and lysis of target cells.

Pathogen Recognition in Innate Immunity

• Pattern Recognition:
  • Pathogens have pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRRs) on innate immune cells.
  • PRRs are diverse (~1000), allowing recognition of many pathogen classes.
• Toll-Like Receptors (TLRs):
  • Glycoproteins that, upon binding to a PAMP, produce proteins important for the innate immune system.

Soluble Mediators of Innate Immunity

• Opsonins: Molecules coating cell membranes, activating phagocytosis after binding to a PRR on the phagocytic cell (opsonization).
• Inflammatory Cytokines: Chemical messengers mediating interactions between immune and tissue cells; short duration of action.
• Acute-Phase Proteins: Produced in the liver in response to proinflammatory cytokines; activate the alternative complement pathway.
  • Mannose-Binding Ligand (MBL)
  • C-Reactive Protein (CRP): Clinically important for evaluating many disease processes.

The Complement System

• Essential for the activity of antibodies, found in the blood.
• Increases bacterial aggregation, making them susceptible to phagocytosis.
• Three Phases:
  1. Initiation/Activation
  2. Amplification of Inflammation
  3. Membrane Attack Response
• Composed of proteins in circulation and extracellular fluids.
• Usually inactive compounds, making up ~15% of plasma proteins.
• Must be activated to function, and it's generally a well-controlled system.

Understanding the Complement System

• Refer to Norris (11th ed.), p. 292 for visual illustrations.
• Watch the following videos in Module 04:
  • Complement 1—Overview
  • Complement 2—Alternative Pathway
  • Complement 3—Classical and MBL (Manose Binding Lectin) Pathways

Phagocytosis

• Refer to the Key Points, INNATE IMMUNITY, p 287, Norris (11th ed.)

Recognition Systems of Innate and Adaptive Immunity

• Focus on similarities and differences in recognition, receptors, and cellular expression.

Adaptive Immunity

• The final line of defense against infection.
• Activated after the innate immune response initiates inflammation.
• Recognizes and reacts to many microbes and non-microbial substances.
• Distinguishes between closely related microbes and "remembers" pathogens for a heightened response upon subsequent encounters.

Antigens

• Substances foreign to the host that stimulate an immune response, leading to B-cell production.
• Examples: Bacteria, fungi, viruses, protozoa, parasites, non-microbial agents (e.g., Rh positive red cells, insect venom, plant pollen, transplanted organs), vaccines.

Functionally, Two Types of Immune Cells

• Regulatory Cells: Assist in orchestrating and controlling the immune response.
• Effector Cells: Accomplish the final stages of the immune response, eliminating the antigen.
  • Activated T-lymphocytes, mononuclear phagocytes, and other leukocytes function as effector cells.

Cells of Adaptive Immunity

• Lymphocytes: Approximately 35% of total white blood cells; primary cells of the adaptive immune response; differentiate into B and T lymphocytes.
• Macrophages and Dendritic Cells: Act as antigen-presenting cells (APCs).
• Major Histocompatibility Complex Molecules (MHCs): Important for recognizing self vs. non-self.

Antigen-Presenting Cells (APCs)

• Bridge the innate and adaptive immune systems, driven by cytokines that up-regulate MHCs.
• Macrophages are the principal APCs, capturing antigens and enabling their recognition by T cells.
• Macrophages and dendritic cells process and present antigen peptides to CD4+ helper T cells.
• Tissue macrophages are found in various body tissues (lung, liver, spleen, lymph nodes, peritoneum, CNS).

Major Histocompatibility Complex (MHC)

• Essential for distinguishing between self and non-self.
• HLA Antigens:
  • Class I: HLA-A, HLA-B, HLA-C
  • Class II: HLA-DR, HLA-DP, HLA-DQ

Lymphocytes: B-Cells

• B-Cells: HUMORAL IMMUNITY
  • Produced in bone marrow; classified by MHC II proteins, Ig, and complement receptors.
  • Mediated by antibodies in the blood; principal defense against extracellular microbes and toxins.
  • Mature B-cells encountering complementary antigens and T-cell antigen presentation differentiate into memory B-cells or plasma cells (secreting antibodies).

Lymphocytes: B-Cells - Video

• Watch the video titled “B-Cells 1: What are Antibodies” found in the YouTube VIDEO section of Module 02

Lymphocytes: B-Cells - Video 2

• Watch the video entitled “B Cells 2—Antibody Production and Recombination” found in the YouTube video section of Module 04. Refer to Norris (11th ed., 2025) to page 300, Table 11.4

Lymphocytes: T-cells

• T-Cells: CELL-MEDIATED IMMUNITY
  • Helper T-cells (CD4+): Master regulators, releasing cytokines to activate other immune cells.
  • Regulatory T-cells: Control immune responses; CD4+ act as "negative regulators," CD8+ down-regulate T-cell activation.
  • Cytotoxic T-cells: Monitor and destroy cells threatening the body's integrity.
• Cell-Mediated Immunity: Defends against intracellular microbes, responds to surface protein antigens.
• CD4+ cells stimulate B cells to produce plasma cells and antibodies.
• CD8+ cells are cytotoxic.
• Functions include activating other T and B cells, controlling viral infections, rejecting foreign tissue grafts, and mediating delayed hypersensitivity reactions.

Types of Adaptive Immune Responses - Video

• Watch the YouTube video titled “T Cell Development” also found in the VIDEO section of Module 04.Clinically, the most important content is found at the end of the video (8:45 to the end).

Lymphoid Organs

• Include thymus, adenoids, tonsils, bronchus-associated lymphoid tissue, intestine, axillary lymph nodes, spleen, Peyer patches, appendix, inguinal lymph nodes, and bone marrow.

Functions of the Lymphoid Organs

• Central Lymphoid Organs (Bone Marrow and Thymus): Provide environment for immune cell production and maturation.
  • Thymus: Production of mature, immunocompetent T-lymphocytes; "storage site" of macrophages and dendritic cells.
• Lymph Nodes: Removal of foreign material and site of immune cell proliferation.
• Spleen: Filters antigens from the blood and is important in the response to systemic infections.
• Secondary Lymphoid Tissues: Nonencapsulated clusters of lymphoid tissue around membranes lining the respiratory, digestive and urogenital tracts
  • Tonsils, appendix and Pyers patches in the intestine

Antibodies (Immunoglobulins [Ig])

• Recognize specific antigens, bind with receptors on immune cells, and activate cellular response; secreted proteins produced by B-cells that matured into PLASMA CELLS

Classification of Antibodies

• IgG: Most common; late phase production; crosses the placenta; activates complement and binds to macrophages.
• IgA: Prominent in body secretions; protects mucous membranes.
• IgM: Early immune responses; activates complement.
• IgD: Needed for B-cell maturation.
• IgE: Binds to mast cells; involved in allergic and hypersensitivity reactions.

Primary and Secondary Memory Phase and Response

• The primary response occurs when the body encounters the antigen for the first time. Takes one to two weeks to occur
  *Aantibody is generally produced for several weeks beyond the resolution of the infections process.
• The secondary response or memory phase occurs on subsequent exposure to the antigen (this is why we give a series of vaccinations and boosters)

Question: Diphtheria, Pertussis, and Tetanus Immunization in Infants

• Why is the second DPT immunization often less tolerated by infants than the first?

Answer: DPT Immunization in Infants

• The primary immune response to the first DPT shot generates memory B-cells and T-cells.
• The second shot triggers a faster, stronger response from memory B-cells, leading to higher antibody levels and a generalized inflammatory reaction causing irritability and fever.

Case Study Question 1

• What is the interaction between macrophages and T lymphocytes during antigen presentation?

Question: MHC Molecules

• True or false: The function of MHC molecules is to mark foreign proteins, rendering them antigenic.

Answer: MHC Molecules

• False. MHC molecules differentiate host tissue from foreign tissue.

Case Study Question 2

• Where are type I interferons (INFs) produced, and why are they important in combating viral infections?
  *See Table 11.2, p 283, Norris (11th ed., 2025)

Case Study Question 3

• What are the general mechanisms of action that make antibodies a key component of an immune response?

Question: Type of Immunity

• Which type of immunity is characterized by the development of a specific response to an antigen?
• A. Innate immunity
• B. Acquired immunity
• C. Autoimmunity
• D. Alloimmunity

Answer: Type of Immunity

• B. Acquired immunity --The body develops humoral and cell-mediated immune responses.

Types of Immune Response

• Active Immunity: Specific protection induced after exposure to the antigen; requires B and T lymphocyte activation.
• Passive Immunity: Transferred antibodies against an antigen; maternal IgG crosses the placenta, IgA in colostrum, gamma globulin injections.

Development of an Immune Response

• Fetal immune development begins at 5 to 6 weeks; lymphoid cells colonize fetal liver.
• Secondary lymphoid organs are well developed at birth.
• IgA and IgM production starts shortly after birth and reaches adult levels by 1 year.

Immunity from Mother to Infant (Passive)

• Neonatal immune system is immature; protection through maternal IgG transfer across the placenta (largest amount during the last weeks of pregnancy).
• Preemies are generally immune deficient.
• Cord blood generally lacks IgM and IgA (presence indicates intrauterine infection).
• IgM rises sharply at 6 days, reaching adult levels by 1 year.
• IgA is detected early postpartum, and protects intestinal mucosa; IgG and IgA are transferred in breast milk.

The Elderly Immune System

• Declining ability to adapt to stresses, decreased immune responsiveness.
• Decline in thymus gland size (starts at puberty).
• Decreased peripheral lymphoid tissue, biological clock in T cells.
• Altered responses to antigen stimulation; B-cell numbers diminish but response to antigens remains unchanged

Question: Aging Immune Stystem

• The aging immune system is less responsive due to which of the following?
• A. Decline in immune responsiveness
• B. Decrease in the size of the thymus gland
• C. Biological clock in T-cells
• D. Altered responses of the immune cells to antigen stimulation
• E. All of the above are possibilities.

Answer: Aging Immune Stystem

• E. All of the above are possibilities.

Case Study Answers

1. Macrophages are responsible for the phagocytosis of microbes and processing of antigen and act as antigen-presenting cells.
2. Type I interferons are produced by macrophages and fibroblasts. They inhibit viral replication and allow a virally infected cell to be recognized by lymphocytes
3. Antibodies contribute to the agglutination of microbes to prevent their spread, facilitate phagocytosis, and encourage their destruction. They have the ability to neutralize bacterial toxins and inhibit the ability of viruses to invade host cells.