Animal defence part 1

Immunology Concepts

Learning Outcomes

• The discussion will cover concepts related to immunology and the immune system.

Immune System

• The immune system defends the body against microorganisms.
• Pathogen: Any microorganism that can cause harm or disease.
• The immune system differentiates between self and non-self (harmful) microorganisms.

Phases of Immune Response

1. Recognition Phase:
   • Discrimination between self and non-self.
2. Activation Phase:
   • Immune cells mobilize and interact with the pathogen.
3. Effector Phase:
   • Immune cells perform specific actions to remove the pathogen.

Types of Defenses

1. Non-Specific Defense (Innate Immunity)
   • Acts quickly and is not specific to the pathogen.
   • First line of defense.
   • Recognizes a potential non-self pathogen and attempts to tackle it quickly.
2. Specific Defense (Adaptive Immunity)
   • Highly specific to the pathogen.
   • Takes longer to activate but is long-lasting.
   • Innate immunity informs adaptive immunity to produce specific weapons (antibodies).
   • Adaptive immunity remembers the pathogen for future encounters.

Coordinated Immune System Components

• Lymphoid Tissues:
  • Tissues involved in the production of immune cells.
  • Examples: Thymus, bone marrow, spleen, lymph nodes.
• Blood Plasma:
  • Contains ions, small molecules, and proteins.
  • Contains red and white blood cells, and platelets.
• White Blood Cells (Leukocytes):
  • Key cells of the immune system found in the blood and lymphatic system.
• Lymphatic System:
  • A parallel system to the bloodstream for white blood cell circulation and maturation.
  • Composed mostly of lymphocytes.
• Thoracic Duct:
  • The point of exchange between the circulatory and lymphatic systems.

Cell Generation

• Red and white blood cells originate from multipotent stem cells in the bone marrow.
• Multipotent Hematopoietic Cell Differentiation:
  • Differentiates into myeloid progenitor cells and lymphoid progenitor cells.
• Myeloid Progenitor Cells
  • Generate red blood cells, platelets, and some white blood cells (leukocytes).
  • Can further differentiate into granulocytes: basophils, eosinophils, neutrophils, mast cells, macrophages, and dendritic cells.
  • Macrophages are phagocytic cells.
• Lymphoid Progenitor Cells
  • Generate lymphocytes: B lymphocytes, T lymphocytes, and natural killer cells.

Cell Functions

• Phagocytes:
  • Cells that engulf and digest pathogens.
  • Generally larger than lymphocytes.
• Lymphocytes:
  • Do not perform phagocytosis.
  • Include B cells, T cells, and natural killer cells.
  • Produce antibodies (B lymphocytes).
  • Adaptive Cell's instructions to recognize pathogen are called antigens.

Antigen Presentation

• Major Histocompatibility Complex (MHC):
  • Complexes on cell surfaces that present antigens to immune cells.
  • MHC Class I: Found on all nucleated cells.
    • Red blood cells are an exception as they do not have a nucleus and, therefore, lack MHC Class I.
  • MHC Class II: Primarily found on immune cells.
• T Cells:
  • Lymphocytes with receptors that recognize antigens presented by MHC complexes.

Signaling Molecules (Cytokines)

• Promote recruitment and activation of immune cells.

Non-Specific Defenses (Innate Immunity)

Physical and Chemical Barriers

• Prevent pathogen invasion.
• Skin: A major physical barrier.
• Flora: Creates an unfavorable environment for exogenous pathogens.
• Tears, Nasal Mucus, Saliva: Contain enzymes that destroy pathogens.
• Mucus Membranes: Contain protective agents.

Complement System

• A system that complements the action of the immune system.
• Activated with innate immunity to target pathogens.
• Forms pores on pathogen surfaces, causing lysis.

Interferons

• Signaling molecules produced by infected cells.
• Increase resistance to pathogens in surrounding cells.

Phagocytes (Macrophages)

• Actively seek pathogens.
• Recognize viruses, bacteria, and pathogen fragments.
• Engulf and destroy pathogens.

Natural Killer Cells

• Lymphocytes of the innate immunity.
• Recognize and destroy virus-infected and tumor cells.

Inflammation Process

• Indicates immune system activation.
• Recruits immune cells to the site of infection.
• Mast Cells: Release substances upon encountering pathogens, triggering an immune response.

Cytokines and Chemokines

• Tumor Necrosis Factor: Kills target cells and activates immune system.
• Prostaglandins: Weaken blood vessel membranes, allowing immune cell movement into tissues.
• Histamine: Causes itching and allergic reactions.

Symptoms of Inflammation

• Redness
• Heat
• Pain
• Blood vessel dilation and increased permeability.
• Activation of complement and involvement of phagocytic cells.

Macrophage Function

• Engulf pathogens and produce cytokines.
• Cytokines recruit other cells and signal the brain, causing fever.

Fever

• Increases the rate of lymphocyte and phagocyte production and activity.
• Creates an unfavorable environment for pathogen growth.

Over-Inflammation

• May indicate immune system dysfunction.
• Results from allergies or autoimmune diseases.
• Sepsis: Uncontrolled inflammation spreading through the bloodstream.

Pathogen Recognition

• Pathogens have specific molecules on their surface.
• Leukocytes (e.g., macrophages) have Toll-Like Receptors (TLRs) that recognize these molecules.
• TLRs are a family of receptors that recognize non-self structures.

Toll-Like Receptors (TLRs)

• Recognize sugars, DNA fragments, and other structures on pathogens.
• CD14 Protein: Produced by macrophages; binds to TLRs and enhances their activation.
• TLR activation leads to signaling pathways involving NFKB transcriptional factor.
• NFKB Transcriptional Factor: Activates genes involved in the macrophage response, such as digestion and cytokine release.

Adaptive Immunity

• Triggered by pathogens or toxins.
• Passive Immunization: Transferring antibodies from a person affected by a specfic pathogen. Provide temporary immunization.

Key Factors of Specific Immunity

1. Specificity: Ability to produce specific weapons against pathogens.
2. Self/Non-Self Discrimination: Ability to differentiate between self and non-self.
3. Diversity: Ability to produce specific weapons for different pathogens.
4. Immunological Memory: Ability to remember pathogens and quickly produce antibodies upon re-exposure.

Lymphocyte Specificity

• Lymphocytes recognize specific information (antigens) from pathogens using receptors.
• Antigen Presentation: MHC complexes present antigens to lymphocytes.

Antigen Types

• Antigens are peptides (amino acid chains).
• Length varies depending on the antigen and MHC complex.
• Lymphocytes recognize antigens presented by MHC I or MHC II complexes.

Self vs. Non-Self Recognition

• Lymphocytes are screened during production for their ability to recognize self antigens.
• Tolerance: Lymphocytes do not interact with self antigens due to this screening process.
• Lymphocytes attack non-self structures (pathogens) that are unusual to the body.

Diversity of Immune System

• The immune system responds to different pathogens by activating specific lymphocytes.
• The immune system can differentiate among billions of potential pathogens.

Immunological Memory

• Upon encountering a pathogen, lymphocytes (B cells) remember it.
• Upon re-exposure, specific antibodies are produced quickly.

Types of Immune Responses

1. Humoral Immune Response:
   • Involves B cells and antibody production.
2. Cellular Immune Response:
   • Involves cytotoxic T cells.

• Both responses work simultaneously.
• Key Event: Antigen presentation to T and B lymphocytes.
• T Helper Lymphocytes: Instruct B cells to produce antibodies and stimulate T cytotoxic cells.

T Helper Cell Function

• Stimulate T cytotoxic cells to recognize and destroy infected cells.
• Stimulate B cells to produce antibodies.
• Antibodies bind to antigens on infected cells or free antigens (e.g., toxins, pathogen fragments).

T Cell Activation

• Infected cells present antigens through MHC complexes.
• T cell receptors recognize the antigen and become activated.
• Activated T cells proliferate and kill infected cells (cytotoxic T cells).

Receptor Diversity

• Receptors on lymphocytes are diverse due to gene reorganization.
• Two genes encode lymphocyte receptors (not one gene, one protein).

Antibody and Cell Generation

• Antigen is recognized by receptors on B lymphocytes.
• B lymphocytes clone themselves, creating more cells with the same receptor.
• T helper cells instruct these cells to become plasma cells (releasing antibodies) or memory cells.

Primary vs. Secondary Immune Response

• Primary Immune Response: Initial contact with antigen; lymphocyte proliferation and memory cell creation.
• Secondary Immune Response: Re-exposure to the same antigen; memory cells proliferate into plasma cells, producing antibodies.

Active Immunity

• Immune system develops a specific response through memory cells.
• Provides long-lasting protection.

Vaccination

• Instructs the immune system to produce antibodies.
• Involves presenting an inactive or attenuated pathogen to the immune system.
• Uses recombinant DNA technology.
• Stimulates the immune system without causing disease.

Tolerance

• Mechanism to prevent immune cells from recognizing self antigens.
• Involves screening lymphocyte receptors during production.
• Clonal Selection: Lymphocytes that recognize self antigens are eliminated.