Microbiology Unit VI: Adaptive Immunity & Immune System Diseases - Comprehensive Notes

Adaptive Immunity Attributes

• Specificity: Adaptive immunity recognizes and targets specific antigens.
• Memory: It can remember past encounters with an antigen and mount a faster, stronger response upon re-exposure.
• Clonality: Adaptive immune responses involve the proliferation of lymphocytes (B and T cells) that recognize a specific antigen, forming a clone of cells.
• Self-recognition: The immune system can distinguish between self and non-self antigens, preventing attacks on the body's own tissues.

Humoral vs. Cellular Immunity

• Humoral Immunity: Involves B cells and antibodies. Antibodies are produced by plasma cells (differentiated B cells) and circulate in the blood and lymph, targeting extracellular pathogens.
• Cellular Immunity: Involves T cells. T cells directly kill infected cells (cytotoxic T cells) or help activate other immune cells (helper T cells).

Definitions

• Antigen: A substance that can elicit an immune response.
• Epitope: The specific part of an antigen that an antibody or T cell receptor binds to (also known as an antigenic determinant).
• Hapten: A small molecule that can bind to an antibody but cannot elicit an immune response on its own. It must be attached to a larger carrier molecule to become immunogenic.

Characteristics of a Good Antigen

• High molecular weight: Larger molecules are generally more immunogenic.
• Structural complexity: Complex molecules with diverse epitopes are better antigens.
• Foreignness: The more different a molecule is from the body's own molecules, the stronger the immune response it will elicit.
• Accessibility: The antigen must be accessible to immune cells.

Antibody Structure

• Typical human antibody (immunoglobulin) consists of two heavy chains and two light chains, forming a Y-shaped structure.
• The variable regions at the tips of the Y are responsible for antigen binding, while the constant region determines the antibody's class and effector functions.

Immunoglobulin Classes

• IgG: Most abundant in serum; crosses the placenta; provides long-term immunity; opsonization, complement activation, neutralization.
• IgM: First antibody produced during an immune response; good at agglutination; complement activation.
• IgA: Found in mucosal secretions (e.g., saliva, breast milk); protects mucosal surfaces.
• IgE: Involved in allergic reactions and parasitic infections; binds to mast cells and basophils.
• IgD: Found on the surface of B cells; role in B cell activation.

Antibody Functions

• Opsonization: Antibodies coat pathogens, making them more easily recognized and phagocytosed by phagocytes.
• Neutralization: Antibodies bind to pathogens or toxins, preventing them from infecting cells or causing damage.
• Complement Activation: Antibodies activate the complement system, leading to pathogen lysis or opsonization.
• Agglutination: Antibodies cross-link pathogens, causing them to clump together, which enhances phagocytosis.
• Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Antibodies bind to infected cells, recruiting NK cells to kill the infected cells.

MHC in Immunity

• MHC (Major Histocompatibility Complex): Molecules that present antigens to T cells.
• MHC I: Found on all nucleated cells; present intracellular antigens to cytotoxic T cells (CD8+ T cells).
• MHC II: Found on antigen-presenting cells (APCs); present extracellular antigens to helper T cells (CD4+ T cells).

Antigen-Presenting Cells (APCs)

• APCs: Cells that capture and process antigens, then present them to T cells.
• Examples: Dendritic cells, macrophages, B cells
• Dendritic cells are the most effective APCs at initiating T cell responses.

Lymphocyte Development & Function

• B cell development: Occurs in the bone marrow; B cells undergo receptor editing to eliminate self-reactive B cells.
• T cell development: Occurs in the thymus; T cells undergo positive and negative selection to ensure they recognize MHC and do not react to self-antigens.
• Function: B cells produce antibodies; T cells mediate cellular immunity (killing infected cells or helping other immune cells).

Central Tolerance/Self-Tolerance

• Importance: Prevents the immune system from attacking the body's own tissues (autoimmunity).
• Mechanisms: Deletion of self-reactive lymphocytes (central tolerance) and suppression of self-reactive lymphocytes by regulatory T cells (peripheral tolerance).

Types of T Lymphocytes

• Cytotoxic T cells (CD8+ T cells): Kill infected cells and tumor cells by recognizing antigens presented on MHC I molecules.
• Helper T cells (CD4+ T cells): Help activate other immune cells (B cells, macrophages, cytotoxic T cells) by releasing cytokines; recognize antigens presented on MHC II molecules.
• Regulatory T cells: Suppress the activity of other immune cells, preventing excessive immune responses and autoimmunity.

Cluster of Differentiation (CD) Molecules

• CD molecules: Surface proteins on immune cells that can be used to identify and classify cells.
• Role in immunity: Serve as receptors or co-receptors in immune cell activation and function. Example: CD4 and CD8.

Roles in Specific Immunity

• Plasma cells: Secrete antibodies.
• Memory cells: Long-lived cells that provide immunological memory.
• Helper T cells: Activate B cells, cytotoxic T cells, and macrophages.
• Cytotoxic T cells: Kill infected cells.
• Regulatory T cells: Suppress immune responses.
• Antigen-presenting cells: Present antigens to T cells.
• Perforin: Protein produced by cytotoxic T cells and NK cells that creates pores in the target cell membrane.
• Granzymes: Enzymes produced by cytotoxic T cells that enter target cells through perforin pores and induce apoptosis.
• Natural killer cells: Kill infected cells and tumor cells.
• MHC I and II molecules: Present antigens to T cells.
• TCRs: T cell receptors; recognize antigens presented on MHC molecules.
• BCRs: B cell receptors; recognize free antigens.

Differentiation

• Naïve and Effector Cells:
  • Naïve cells are lymphocytes that have not yet encountered their specific antigen.
  • Effector cells are lymphocytes that have been activated by their specific antigen and are actively involved in an immune response.
• Effector Cells and Memory Cells:
  • Effector cells are short-lived and act to eliminate pathogens during an active infection.
  • Memory cells are long-lived and provide immunological memory, allowing for a faster and stronger response upon re-exposure to the same antigen.
• TH1 and TH2 Cells:
  • TH1 cells primarily activate macrophages and cytotoxic T cells, promoting cell-mediated immunity.
  • TH2 cells primarily activate B cells, promoting antibody production and humoral immunity.

T-Cell Activation of B Cells

• T-cell independent activation: Antigens bind directly to B cell receptors, activating B cells without T cell help (typically weaker response).
• T-cell dependent activation: B cells present antigens to T cells, which then provide signals that fully activate B cells (leads to a stronger, longer-lasting response).

Primary and Secondary Response

• Primary response: The initial immune response to an antigen; slow and weak; IgM is the predominant antibody.
• Secondary response: The immune response to an antigen after a previous exposure; rapid and strong; IgG is the predominant antibody; memory cells are involved.

States of Immunity

• Active specific immunity: Immunity acquired through exposure to an antigen, leading to the production of antibodies and memory cells.
  • Natural: Exposure to a pathogen (e.g., getting sick with the flu).
  • Artificial: Vaccination (e.g., getting a flu shot).
• Passive specific immunity: Immunity acquired through the transfer of antibodies from one individual to another; temporary.
  • Natural: Antibodies passed from mother to fetus through the placenta or to infant through breast milk.
  • Artificial: Injection of antibodies (e.g., receiving antivenom after a snake bite).
• Herd Immunity: Protection of a population from infection due to a high percentage of individuals being immune.

Antigen Preparations for Vaccines

• Live attenuated vaccines: Weakened form of the pathogen (e.g., measles, mumps, rubella vaccine).
• Inactivated vaccines: Killed pathogen (e.g., influenza vaccine).
• Subunit vaccines: Contain only specific antigens from the pathogen (e.g., hepatitis B vaccine).
• Toxoid vaccines: Contain inactivated toxins produced by the pathogen (e.g., tetanus vaccine).
• Conjugate vaccines: Polysaccharide antigens linked to a protein carrier (e.g., Haemophilus influenzae type b vaccine).

Hypersensitivity Reactions

• Malfunction of the immune system that causes exaggerated or inappropriate immune responses, leading to tissue damage and disease.

Types of Hypersensitivity Reactions

• Type I (Immediate): IgE-mediated; involves mast cell and basophil activation; examples include allergies (e.g., hay fever, asthma).
• Type II (Cytotoxic): IgG or IgM antibodies bind to cell surface antigens, leading to cell lysis or damage; examples include blood transfusion reactions, hemolytic disease of the newborn.
• Type III (Immune Complex): Antigen-antibody complexes deposit in tissues, activating complement and causing inflammation; examples include serum sickness, rheumatoid arthritis.
• Type IV (Delayed-Type): T cell-mediated; delayed response; examples include contact dermatitis (e.g., poison ivy), tuberculin test.

ABO Blood Group System and Rh Factor

• ABO blood group system: Based on the presence or absence of A and B antigens on red blood cells; antibodies against non-self antigens can cause transfusion reactions.
• Rh factor: Presence or absence of the Rh D antigen on red blood cells; Rh-negative individuals can develop antibodies against Rh-positive blood, leading to hemolytic disease of the newborn in subsequent pregnancies.

Sensitization

• The process by which an individual becomes allergic to an allergen; involves initial exposure to the allergen, leading to the production of IgE antibodies.

Histamine in Allergic Response

• Histamine is a mediator released by mast cells and basophils during an allergic reaction; causes vasodilation, increased vascular permeability, and bronchoconstriction.

Allergen

• An antigen that elicits an allergic response.
• Categories:
  • Inhalants: Pollen, dust mites, mold spores.
  • Ingestants: Food (e.g., peanuts, shellfish), drugs.
  • Injectants: Insect venom, drugs.
  • Contactants: Poison ivy, latex.

Hypersensitivity Diagnosis

• Skin testing: Involves injecting small amounts of allergens into the skin and observing for a reaction.
• Blood tests: Measure the levels of IgE antibodies specific to certain allergens.

Hypersensitivity Treatment

• Avoidance: Avoiding exposure to the allergen.
• Antihistamines: Block the effects of histamine.
• Corticosteroids: reduce inflammation.
• Epinephrine: Reverses severe allergic reactions (anaphylaxis).
• Immunotherapy: Desensitization by gradually increasing exposure to the allergen.

Autoimmune Disease

• Malfunction of the immune system that causes it to attack the body's own tissues.

Organ-Specific vs. Systemic Autoimmune Disease

• Organ-specific: Targets a specific organ or tissue (e.g., type 1 diabetes, Hashimoto's thyroiditis).
• Systemic: Affects multiple organs and tissues throughout the body (e.g., rheumatoid arthritis, lupus).

Immune System in Organ Transplantation and Rejection

• The immune system recognizes transplanted organs as foreign and can attack them, leading to rejection.
• Immunosuppressants are used to suppress the immune system and prevent rejection.

Immunodeficiency

• Malfunction of the immune system that leads to increased susceptibility to infection.

Primary and Secondary Immunodeficiency

• Primary immunodeficiency: Genetic or congenital defects in the immune system (e.g., severe combined immunodeficiency (SCID), DiGeorge syndrome).
• Secondary immunodeficiency: Acquired as a result of infection, malnutrition, or immunosuppressive drugs (e.g., HIV/AIDS, chemotherapy-induced immunodeficiency).