The Immune System

Chapter 15: The Immune System

Immune System

• Functions of the Immune System:
    - Protect against infection by microbes (viruses, bacteria, fungi, and parasites).
    - Isolate/remove non-microbial foreign substances.
    - Destroy cancer cells that arise in the body (immune surveillance).
    - Must distinguish between "self" and "non-self" to function effectively.

Overview of Immune System

• Classification of Immune Defenses:
    - Innate Immunity:
      - Non-Specific Immune System.
    - Adaptive (Acquired) Immunity:
      - Specific Immune System.

Leukocytes

• White Blood Cells (WBC):
    - Cells of the immune system.
    - Vary in structure, function, and number; generally larger than erythrocytes.
    - Types of Circulating Leukocytes:
      - Neutrophils
      - Eosinophils
      - Basophils
      - Monocytes
      - Lymphocytes

Leukocyte Counts:

• WBC count = 7000/mm³.
• Leukocyte concentration = 7 million/ml blood.
• Differential WBC count (percentage distribution of types of leukocytes):
    - Neutrophils: 60%–70%
    - Eosinophils: 1%–4%
    - Basophils: 0.25%–0.5%
    - Monocytes: 2%–6%
    - Lymphocytes: 25%–33%
• RBC count = 5,000,000/mm³.
• Platelet count = 250,000/mm³.
• Erythrocyte concentration = 5 billion/ml blood.
• Platelet concentration = 250 million/ml blood.

Development of Leukocytes

• Originate from Hematopoietic Stem cell (HSC):
    - Multi-potent stem cell located in the bone marrow.
    - Differentiation:
      - Megakaryocytes produce platelets.
      - Myeloid stem cell gives rise to:
        - Granulocytes (Basophil, Neutrophil, Eosinophil)
        - Erythrocytes
        - Monocytes
      - Lymphoid stem cell gives rise to lymphocytes (B and T lymphocytes).

Innate Immunity

• Components of Innate Immunity:
    - Body Surface Defenses
    - Inflammation
    - Complement System
    - Phagocytosis (Phagocytes):
      - Neutrophils
      - Monocytes/Macrophages
• Distinguishing Features:
    - Pathogen-Associated Molecular Patterns:
      - Recognized by Pattern Recognition Receptors (PRR), such as Toll-like receptors (TLR).

Inflammation in Innate Immunity

• Definition:
    - A local non-specific response to tissue injury.
    - Goals include isolating, destroying, or inactivating invaders, removing debris, and preparing for healing and repair.
• Sequence of Inflammation:
    - Entry of Microbe
    - Vasodilation of infected area
    - Increased endothelial permeability
    - Chemotaxis (migration of leukocytes)
    - Extravasion (Diapedesis)
    - Leukocyte invasion
    - Destruction of microbe
    - Tissue Repair

Fever

• Generated in response to inflammation.
• Macrophages release endogenous pyrogens in response to bacterial molecules, signaling the hypothalamus to increase body temperature, which is beneficial for the immune response.

Interferons

• Produced by virus-infected cells, these are a type of cytokine.
• Functions include promoting resistance to viral infection and can be used in treatments, such as for Hepatitis B.

Complement System

• A cascade of events involving proteins in blood that “complement” other parts of the immune system, promoting phagocytosis and inflammation.

Adaptive Immunity

• Characteristics:
    - Specific responses to pathogens.
    - Systemic: travels continuously through the body.
    - Has memory: capable of remembering past infections.
    - Late responders: takes time to activate via recognition of antigens.
• Definition of Antigen:
    - Any foreign molecule capable of triggering an immune response.

Lymphoid Organs

• Primary Lymphoid Organs:
    - Thymus: Site of maturation of T lymphocytes.
    - Bone Marrow: Site of B lymphocyte origin.
• Secondary Lymphoid Organs:
    - Spleen
    - Lymph nodes
    - Tonsils

Clonal Selection Theory

• Each lymphocyte is specific for a particular pathogen.
• Exposure to a pathogen results in the production of clones to effectively respond to that pathogen.

Types of Adaptive Immunity

• Antibody-Mediated Immunity (Humoral):
    - Involves the production of antibodies by B lymphocyte derivatives known as plasma cells.
• Cell-Mediated Immunity:
    - Involves production of activated T lymphocytes that directly attack unwanted cells and help other immune cells.

B Lymphocytes

• B Cell Receptors:
    - Surface plasma membrane receptors that bind to specific antigens.
• Upon binding to processed and presented antigens, B cells can differentiate into plasma cells and form memory cells for enhanced future responses.
• B cells are aided by Helper T cells through cytokines.
• Immunoglobulins (Antibodies) and Their Functions:
    - IgG: Main form circulating antibodies; increased production after immunization.
    - IgA: Present in external secretions (e.g., saliva, breast milk).
    - IgE: Involved in allergic responses.
    - IgM: Functions as antigen receptors on lymphocyte surface pre-immunization; secreted during primary response.
    - IgD: Functions as antigen receptors on lymphocyte surface; specific functions are still unclear.

Functions of B Cells

• Can directly bind to and inactivate toxins or viruses.
• Link microbes to macrophages and neutrophils, and stimulate other immune cells.

T Lymphocytes

• Carry out Cell-Mediated Immunity.
• Types of T Cells:
    - Cytotoxic T cells (Killer T cells):
      - Destroy host cells that harbor foreign substances, such as viruses and cancer cells (CD8+).
    - Helper T cells:
      - Modulate activities of other immune cells (CD4+).
    - Suppressor T cells (Regulatory):
      - Dampen immune responses.

Antigen Presentation to T Cells

• T cell receptors cannot combine with antigens unless these are first complexed with the body’s own proteins (MHC).
• Antigen Presenting Cells (APC):
    - Macrophages
    - Dendritic cells
    - B cells
• Major Histocompatibility Complex (MHC):
    - Proteins present on almost all body cells.
    - Pattern of MHC varies between individuals, enabling the immune system to recognize “self.”
    - Classes of MHC:
      - MHC Class I: Present on all nucleated cells.
      - MHC Class II: Present on APCs.

Antigen Presentation Process

• APCs engulf antigens, load them on MHC proteins, and move these complexes to the cell surface.
• The MHC-antigen complex binds to receptors on T cells, resulting in their activation.

MHC Class Restriction

• Helper T cell: Recognizes antigens presented on Class II MHC molecules.
• Cytotoxic T cell: Recognizes antigens on Class I MHC molecules.

Functions of Helper T Lymphocytes

• Stimulate the development of plasma cells that produce antibodies.
• Stimulate Cytotoxic T lymphocytes to destroy infected cells.

Cytotoxic T Lymphocytes

• Requirements:
    - Antigen Presentation
    - Activation by Helper T cells
• Function:
    - Destroy cancerous and virus-infected cells by secreting perforins and granzymes that induce target cell lysis.

Active and Passive Immunity

Active Immunity

• Developed in response to exposure to pathogens.
• Primary Response: Formation of effector cells and memory cells.
• Secondary Response: Memory cells allow for a more rapid and enhanced response upon subsequent exposure; basis of vaccines.

Passive Immunity

• Known as "borrowed immunity" resulting from the transfer of antibodies.
• Provides immediate protection (e.g., maternal antibodies transferred during pregnancy).

Classification of Immune Diseases

• Inappropriate Immune Responses:
    - Autoimmune diseases (loss of tolerance to self-antigens).
• Hypersensitivity Reactions:
    - Immune response to environmental antigens leading to conditions like allergies, asthma, and anaphylactic shock.
• Immunodeficiency:
    - Too little immune response due to genetic or environmental causes (e.g., HIV leading to AIDS).
• Malignancy:
    - Cancers affecting immune cells (e.g., lymphomas, leukemias, myelomas).

Autoimmune Disease

• Definition:
    - Condition resulting from loss of immune tolerance to self-tissues, leading to the production of autoantibodies.
    - Examples include rheumatoid arthritis, lupus, and Type 1 diabetes.

Immunodeficiency

• Consequences:
    - Increased susceptibility to infections and cancers.
• Example:
    - HIV infects and kills helper T cells leading to acquired immune deficiency syndrome (AIDS).

Inappropriate Immune Response

Hypersensitivity

• Immune response to harmless environmental antigens termed allergens.
    - Genetically predisposed individuals may experience hypersensitivity.
    - Examples:
      - Allergies
      - Asthma
      - Hives
      - Anaphylactic shock

Allergy Mechanism

• Mediated by IgE antibodies binding to allergens, activating mast cells to release histamines and other chemicals causing inflammatory responses.

Common Allergens

• Examples might include pollen, dust mites, and certain foods.

Lymphocytes and Tumor Cells

• Lymphocytes provide immunological surveillance against cancer.
• Tumor cells may evade immune surveillance, promoting malignancy.

Natural Killer (NK) Cells

• Related to T lymphocytes but part of the innate immunity.
• Recognize and kill malignant cells and cells infected with viruses similarly to cytotoxic T cells.

Effects of Aging and Stress

• Increased cancer risk with aging, attributed to reduced thymus function and cell-mediated immune function.
• Stress leads to cortisol release, known to suppress immune responses.

Malignancies of Immune Cells

• Lymphomas: Malignant transformations of lymphocytes.
• Leukemias: Malignancies of white blood cells originating in the marrow.
• Myelomas: Malignancies of plasma cells found in bone marrow.

Exam Preparation Points

• Explain the functions of the immune system.
• Compare innate immunity to adaptive immunity.
• Describe different cells of the immune system and their specific functions.
• Detail the role of Hematopoietic Stem Cells (HSC).
• Explain how the innate immune system recognizes pathogens.
• Describe the events that occur in local inflammation and define its cardinal signs.
• Provide a brief overview of the complement system and its functions.
• Discuss the role of interferons in the immune response.
• Define antigens and describe lymphoid organs involved in immunity.
• Explain how antibodies function and the activation of B lymphocytes into plasma cells.
• Identify different types of T lymphocytes, their functions, and activation processes.
• Elaborate on Antigen Presentation Cells and examples.
• Discuss the importance of MHC proteins in antigen presentation and their class restrictions.
• Compare primary and secondary immune responses with examples.
• Clarify the differences between active and passive immunity.
• Examine the relationship between the immune system and cancer, along with Natural Killer cell functions.
• Discuss the nature of autoimmune diseases and their examples.
• Define hypersensitivity and provide relevant examples.
• Explain the mechanisms of allergies.
• Discuss the relationship between HIV and AIDS, including affected cell types.
• Differentiate between myeloma, leukemia, and lymphoma.