Disorders of the Immune Response
Disorders of the Immune Response
First Lines of Defense (Nonspecific)
Mechanical Barriers
Definition: Physical obstructions that prevent pathogen entry. These are the body's initial defense.
Examples:
Skin: Provides a physical barrier.
Layers: Epidermis, dermis, and hypodermis.
Function: Prevents pathogen penetration.
Mucous Membranes: Line body cavities and trap pathogens.
Locations: Respiratory tract, digestive tract, urogenital tract.
Secretions: Mucus, enzymes, and antibodies.
Function: Traps and expels pathogens.
Cilia: Hair-like structures that sweep away pathogens.
Location: Respiratory tract.
Action: Wavelike motion to move mucus and trapped particles.
Function: Clears pathogens from the airway.
Chemical Barriers
Definition: Substances that create inhospitable environments for pathogens.
Enzymes:
Antibacterial Agents: Like lysozyme, found in tears and saliva.
Function: Degrades bacterial cell walls.
Mechanism: Hydrolyzes peptidoglycans in bacterial cell walls.
Result: Lysis of bacteria.
Acid (pH):
Definition: Creates an inhospitable environment.
Examples:
Stomach Acid: Kills ingested pathogens.
pH: Ranges from 1.5 to 3.5.
Component: Hydrochloric acid (HCl).
Function: Denatures proteins and kills bacteria.
Skin pH: Inhibits microbial growth.
pH: Ranges from 4.5 to 5.5.
Source: Secretions from sweat and sebaceous glands.
Function: Inhibits bacterial and fungal growth.
Salt:
Definition: Inhibits microbial growth through osmotic effects.
Example: Sweat.
Composition: Water, electrolytes, and urea.
Mechanism: Creates a hypertonic environment, causing water to leave bacterial cells.
Result: Dehydration and growth inhibition of bacteria.
Biological Barriers
Phagocytosis:
Definition: Ingestion of pathogens by cells.
Cells: Macrophages and neutrophils.
Macrophages: Phagocytose pathogens and present antigens to T cells.
Neutrophils: Most abundant white blood cell; engulf and kill bacteria.
Function: Clearing pathogens and cellular debris.
Process: Chemotaxis, adherence, ingestion, digestion, and elimination.
Outcome: Removal of pathogens and cellular debris from the body.
Fever:
Definition: Elevated body temperature.
Function: Inhibits pathogen growth and enhances immune responses.
Mechanism: Increases metabolic rate and enhances immune cell activity.
Regulation: Hypothalamus regulates body temperature.
Pyrogens: Substances that induce fever.
Inflammation:
Definition: Localized response to tissue damage.
Characteristics: Redness, swelling, heat, and pain.
Redness (Rubor): Increased blood flow to the area.
Swelling (Tumor): Accumulation of fluid.
Heat (Calor): Increased metabolic activity.
Pain (Dolor): Stimulation of nerve endings by chemical mediators.
-Function: Contains the infection and promotes healing
-Vasodilation: Increased permeability
-Recruitment of immune cells
-Tissue repair
"Friendly" Microorganisms:
Definition: Compete with pathogens.
Example: Gut microbiota.
Composition: Bacteria, fungi, viruses, and other microorganisms.
Location: Large intestine.
Function: Prevent pathogen colonization.
Mechanism: Produce antimicrobial substances and compete for nutrients and attachment sites.
Result: Inhibition of pathogen growth and maintenance of gut health.
Interferon and Complement Proteins
Interferon Production and Action
Activation: Infected cells activate interferon and complement proteins.
Interferons: Cytokines that interfere with viral replication.
Types: Interferon-alpha, interferon-beta, and interferon-gamma.
Function: Induce antiviral state in neighboring cells.
Complement Proteins: Enhance antibody and phagocytic cell clearance.
Pathways: Classical, alternative, and lectin pathways.
Components: C1 to C9, factors B, D, and P.
Function: Opsonization, chemotaxis, cell lysis, and inflammation.
Interferon Production:
Infected Cell (Host Cell 1): Turns on interferon genes.
Trigger: Viral nucleic acids.
Transcription Factors: Activate interferon gene expression.
Result: Produces interferon molecules.
Interferon-alpha and Interferon-beta: Major types produced by infected cells.
Host Cell 1: Eventually killed by the virus.
Mechanism: Viral replication leads to cell lysis.
Interferon Action:
Interferon Stimulates Nearby Cell (Host Cell 2):
Receptor: Interferon binds to interferon receptors on the cell surface.
Result: Turns on genes for antiviral proteins.
Examples: RNA-dependent protein kinase (PKR) and 2'-5' oligoadenylate synthetase (OAS).
Host Cell 2: Protected against the virus by interferon from Cell 1.
Antiviral State: Reduced viral replication and spread.
Antiviral Proteins: Block viral reproduction.
Function: Interferes with various stages of the viral life cycle.
Inhibition of viral entry, replication, assembly, and release.
Viral Nucleic Acid (mRNA): Genetic material of the virus.
Target: Antiviral proteins inhibit viral replication.
PKR: Phosphorylates eIF2alpha, inhibiting protein synthesis.
OAS: Activates RNase L, degrading viral RNA.
New Viruses: Production is inhibited by antiviral proteins.
Result: Reduces viral load and spread.
Complement System
Pathways of Activation:
Classical Pathway: Initiated by antibody-antigen complexes (adaptive immunity).
Components: C1q, C1r, C1s, C4, and C2.
Trigger: IgG or IgM binding to antigen.
Alternative Pathway: Initiated by pathogen surfaces (innate immunity).
Components: Factor B, factor D, and properdin.
Trigger: LPS, peptidoglycan, and other microbial components.
Lectin Pathway: Initiated by mannose-binding lectin (MBL) binding to pathogens (innate immunity).
Components: MBL, MASP-1, MASP-2, C4, and C2.
Trigger: Mannose residues on microbial surfaces.
Outcomes of Complement Activation:
Opsonization: Coating pathogens to enhance phagocytosis.
Component: C3b.
Mechanism: Binds to pathogens and facilitates recognition by phagocytes.
Chemotaxis: Attracting immune cells to the site of infection.
Components: C3a and C5a.
Mechanism: Recruit neutrophils, macrophages, and other immune cells.
Cell Lysis: Direct killing of pathogens by forming membrane attack complex (MAC).
Components: C5b, C6, C7, C8, and C9.
Mechanism: Inserts into the pathogen membrane, creating pores and causing cell lysis.
Inflammation: Promoting inflammation to enhance immune responses.
Components: C3a and C5a.
Mechanism: Induce mast cell degranulation and release of histamine and other inflammatory mediators.
Inflammatory Response
Initiation and Mechanism
Trigger: Tissue damage by injury or infection.
Causes: Physical trauma, chemical exposure, infection by pathogens.
Detection: Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs).
Function: Disinfects tissues, limits further infection, and promotes healing.
Goals: Eliminate pathogens, remove debris, and repair damaged tissue.
Mechanism:
Tissue Injury: Release of chemical signals, such as histamine and cytokines (Step 1).
Examples of Chemical Signals: Histamine, prostaglandins, leukotrienes, cytokines (TNF-alpha, IL-1, IL-6).
Source: Mast cells, macrophages, and damaged tissue cells.
Function: Increases blood flow and attracts immune cells.
Dilation and Increased Leakiness of Local Blood Vessels (Step 2).
Vasodilation: Increased blood flow to the affected area.
Increased Permeability: Allows fluid and immune cells to move from blood vessels into the tissues.
Endothelial Cell Contraction: Creates gaps between endothelial cells.
Result: Immune cells and fluid enter the affected area.
Edema: Accumulation of fluid in the tissues.
Migration of Phagocytes:
Macrophages and neutrophils migrate to the area (Step 2).
Chemotaxis: Movement of cells along a chemical gradient.
Adhesion Molecules: Help immune cells stick to the blood vessel walls and migrate into the tissues.
Examples: Selectins, integrins, and ICAMs.
Function: Engulf and destroy pathogens and cellular debris.
Phagocytosis: Ingestion and digestion of pathogens and debris.
Respiratory Burst: Production of reactive oxygen species (ROS) to kill ingested pathogens.
Phagocytes Consume Bacteria and Cell Debris; Tissue Heals (Step 3).
Macrophage Activation: Release of growth factors, cytokines, and other mediators to promote tissue repair.
Fibroblast Proliferation: Synthesis of collagen and other extracellular matrix components.
Resolution of Inflammation: Tissue repair and restoration of function.
Angiogenesis: Formation of new blood vessels.
Scar Tissue Formation: Replacement of damaged tissue with collagen fibers.
Visible Signs and Components
Visible Signs: Swelling, redness, heat, and pain.
Swelling (Tumor): Caused by fluid accumulation in the tissues (edema).
Redness (Rubor): Increased blood flow to the area (vasodilation).
Heat (Calor): Increased metabolic activity and blood flow.
Pain (Dolor): Stimulation of nerve endings by chemical mediators (prostaglandins and bradykinin).
Components: Chemical signals, white blood cells, phagocytes, and fluid.
Chemical Signals: Histamine, prostaglandins, leukotrienes, cytokines (TNF-alpha, IL-1, IL-6).
White Blood Cells: Neutrophils, macrophages, basophils, eosinophils, and lymphocytes.
Phagocytes: Neutrophils and macrophages.
Fluid: Plasma that leaks from blood vessels into the tissues.
Phagocytic System
Definition and Action
Definition: Composed of polymorphonuclear leukocytes (neutrophils) and mononuclear phagocytes (monocytes and macrophages).
Neutrophils: Most abundant white blood cell; first responders to infection.
Monocytes: Circulate in the blood and differentiate into macrophages in tissues.
Macrophages: Resident phagocytes in tissues; engulf pathogens and present antigens.
Action of Cells:
Migrate to the Site of Infection.
Mechanism: Chemotaxis.
Chemokines: Chemical signals that attract phagocytes.
Examples: IL-8 and C5a.
Aggregate Around the Affected Tissue.
Function: Contain the infection.
Mechanism: Form a barrier to prevent the spread of pathogens.
Envelope the Invading Microorganisms.
Mechanism: Phagocytosis.
Steps: Recognition, ingestion, phagosome formation, fusion with lysosome (phagolysosome), digestion, and elimination.
Receptors: Toll-like receptors (TLRs) and complement receptors.
Generate Microbicidal Substances.
Examples: Reactive oxygen species and lysosomal enzymes.
Reactive Oxygen Species (ROS): Superoxide, hydrogen peroxide, and hydroxyl radicals.
Lysosomal Enzymes: Lysozyme, proteases, and lipases.
Function: Kill ingested pathogens.
Mechanism: Oxidative stress and enzymatic degradation.
Specific Immunity
Antigens, Active Immunity, and Passive Immunity
Antigens: Foreign molecules that elicit an immune response.
Examples: Proteins, polysaccharides, or lipids on pathogens.
Proteins: Surface proteins on bacteria, viruses, and fungi.
Polysaccharides: Capsules of bacteria.
Lipids: Lipopolysaccharide (LPS) on Gram-negative bacteria.
Epitopes: Specific regions on antigens that bind to antibodies and T cell receptors.
B Cell Epitopes: Recognized by antibodies.
T Cell Epitopes: Presented by MHC molecules to T cells.
Active Immunity: The immune system reacts to antigens.
Result: Long-lasting protection.
Development of Memory Cells: Provide a rapid and robust response upon subsequent exposure to the same antigen.
Acquisition: Infection or vaccination.
Infection: Natural exposure to pathogens.
Vaccination: Administration of weakened or inactive pathogens or antigens.
Passive Immunity: Temporary immunity from another source.
Examples: Maternal antibodies or antibody injections.
Maternal Antibodies: IgG antibodies that cross the placenta from mother to fetus.
Antibody Injections: Administration of pre-formed antibodies (e.g., intravenous immunoglobulin).
Benefit: Immediate but short-lived protection.
No Development of Memory Cells: Protection lasts only as long as the antibodies are present in the body.
Lymphocyte Development
Stem Cells, T Cell Processing, and B Cell Processing
Stem Cells: Located in red bone marrow.
Function: Give rise to undifferentiated lymphocytes.
Hematopoiesis: The process of blood cell formation in the bone marrow.
Lymphoid Progenitor Cells: Give rise to lymphocytes (T cells, B cells, and NK cells).
T Cell Processing: Some undifferentiated lymphocytes processed in the thymus gland.
Result: Become T cells.
Types: Helper T cells (CD4+), cytotoxic T cells (CD8+), and regulatory T cells.
Process: Selection and maturation for self-tolerance and functionality.
Positive Selection: T cells that recognize self-MHC molecules survive.
Negative Selection: T cells that strongly recognize self-antigens undergo apoptosis.
B Cell Processing: Some undifferentiated lymphocytes processed in bone marrow.
Result: Become B cells.
Types: Plasma cells (antibody-secreting) and memory B cells.
Process: Selection and maturation.
Negative Selection: B cells that recognize self-antigens undergo apoptosis.
Transportation: T cells and B cells are transported to lymphatic organs.
Organs: Lymph nodes, lymphatic ducts, and spleen.
Lymph Nodes: Filter lymph and initiate immune responses.
Lymphatic Ducts: Collect lymph and return it to the bloodstream.
Spleen: Filters blood and initiates immune responses.
Function: Encounter antigens and initiate immune responses.
Antigen Presentation: APCs present antigens to T cells and B cells.
Lymphocytes and Immune Response
B Cells, T Cells, and Lymphatic Organs
Two Kinds of Lymphocytes: B cells and T cells.
B Cells: Responsible for humoral immunity (antibody-mediated).
T Cells: Responsible for cell-mediated immunity (direct cell killing and regulation of immune responses).
B Cells: Secrete antibodies.
Function: Attack antigens (humoral immunity).
Antibodies: Bind to antigens and neutralize them, mark them for destruction by phagocytes, or activate complement.
Clonal Selection: B cells that bind to specific antigens proliferate and differentiate into plasma cells.
T Cells: Attack infected cells.
Function: Cell-mediated immunity.
Helper T Cells (CD4+): Activate B cells and cytotoxic T cells by releasing cytokines.
Cytotoxic T Cells (CD8+): Kill infected cells that display foreign antigens on their surface.
Regulatory T Cells: Suppress immune responses to prevent autoimmunity.
BONE MARROW: Origin of stem cells and immature lymphocytes.
Function: Primary site of hematopoiesis.
Red Bone Marrow: Site of blood cell formation.
Yellow Bone Marrow: Stores fat and does not actively produce blood cells.
THYMUS: Site of T cell maturation.
Function: Establishes T cell tolerance and functionality.
Thymic Epithelial Cells: Present self-antigens to T cells.
Positive and Negative Selection: Ensures that T cells are self-tolerant and functional.
Lymphatic Organs: Lymph nodes, spleen, and other lymphatic organs.
Function: Final maturation of B and T cells.
Lymph Node Structure: Cortex (B cell zones) and medulla (T cell zones).
Spleen Structure: Red pulp (filters blood) and white pulp (immune responses).
Cell-Mediated Immunity
Antigen-Presenting Cells and the Process of Antigen Presentation
Antigen-Presenting Cell (APC): Displays a foreign antigen and self proteins (MHC molecules).
Function: Presents antigens to a helper T cell.
Types of APCs: Dendritic cells, macrophages, and B cells.
MHC Molecules: Major histocompatibility complex molecules (MHC I and MHC II).
MHC Class I: Presents antigens to cytotoxic T cells (CD8+).
MHC Class II: Presents antigens to helper T cells (CD4+).
Process:
Macrophage Processes a Microbe:
Function: Engulfs and digests the microbe.
Result: Becomes an APC.
Presents microbial antigens on its surface in complex with MHC molecules.
APC Displays Antigen:
Presents nonself molecule (antigen) and self protein (MHC molecule).
Helper T Cell Binds to the APC:
Mechanism: Via its T cell receptor (TCR).
TCR: Recognizes the antigen-MHC complex.
CD4: Co-receptor on helper T cells that binds to MHC II molecules.
Recognition: Self-nonself complex.
T Cell Activation: Leads to the release of cytokines.
Binding Site:
Self protein (MHC) and antigen.
Helper T Cells and Cytotoxic T Cells
Function of Helper T Cells and Cytotoxic T Cells
Main Effectors: Helper T cells and cytotoxic T cells.
Helper T Cells (CD4+): Activate B cells and cytotoxic T cells.
Cytotoxic T Cells (CD8+): Kill infected cells.
Helper T Cell Function: Stimulate humoral responses.
Mechanism: Activates B cells.
B Cell Activation: Leads to antibody production.
Cytokine Release: Activates other immune cells.
Production: Cytokines that enhance immune cell activity.
Examples: IL-2, IL-4, IL-5.
Effects: Promote T cell and B cell proliferation, differentiation, and activation.
Overall: T cells mount the cell-mediated defense and aid humoral immunity.
Coordination: Helper T cells coordinate the immune response by activating other immune cells.
Regulation: Regulatory T cells suppress immune responses to prevent autoimmunity.
Helper T Cell Activation
Recognition, Activation, and Outcomes
Recognition: Helper T cell receptors recognize self-nonself complexes on the APC.
TCR Binding: TCR on the helper T cell binds to the antigen-MHC II complex on the APC.
Co-stimulation: Additional signals from the APC are required for full T cell activation.
Examples: B7-CD28 interaction.
Activation: Interaction activates the helper T cells.
Cytokine Production: Activated helper T cells produce cytokines, such as IL-2, IL-4, and IFN-gamma.
T Cell Proliferation: IL-2 promotes the proliferation of activated T cells.
Cytotoxic T Cell Activation: Helper T cells activate cytotoxic T cells.
Mechanism: Helper T cells secrete IL-2, which activates cytotoxic T cells.
Interleukin-2: Stimulates cell division and activates T cells and B cells.
Effects: Promotes the clonal expansion of T cells and B cells.
Interleukin-1: Activates helper T cell.
Effects: Enhances the production of IL-2 and other cytokines.
Outcomes:
Cell-Mediated Immunity:
Mechanism: Attack on infected cells by cytotoxic T cells.
Perforin and Granzymes: Cytotoxic T cells release perforin and granzymes, which induce apoptosis in infected cells.
Humoral Immunity:
Mechanism: Secretion of antibodies by plasma cells.
Antibody Functions: Neutralization, opsonization, and complement activation.
Immunological Memory
Memory Cells, Primary Response, and Secondary Response
Memory Cells: Confer lifelong immunity.
Types: Memory T cells and memory B cells.
Memory T Cells: Provide a rapid cell-mediated immune response upon re-exposure to the same antigen.
Memory B Cells: Provide a rapid antibody-mediated immune response upon re-exposure to the same antigen.
Characteristics: Long-lived and can quickly differentiate into effector cells.
Primary Response: First exposure to antigen X.
Lag Phase: Time required for antigen processing and lymphocyte activation.
Antibody Production: Relatively slow and low levels of antibody production.
Cell-Mediated Immunity: Slower and less effective compared to the secondary response.
Secondary Response: Second exposure to antigen X, first exposure to antigen Y.
Characteristics: Faster and stronger response due to memory cells.
Memory Cell Activation: Rapidly differentiate into effector cells.
Antibody Production: Higher levels of antibody production and more effective cell-mediated immunity.
Specificity: Memory cells are specific for the antigen to which they were previously exposed.
Antibody Concentration: Increases more rapidly and reaches a higher level in the secondary response.
Isotype Switching: Memory B cells can switch to producing different antibody isotypes (e.g., IgG, IgA, IgE).
Cytotoxic T Cells
Binding, Perforin, and Apoptosis
Function: Bind to infected body cells and destroy them.
Target Cells: Cells infected with viruses, bacteria, or other intracellular pathogens.
Mechanism:
Cytotoxic T Cell Binds to Infected Cell (Step 1):
Recognition: Antigen on MHC class I molecules.
TCR Binding: TCR on the cytotoxic T cell binds to the antigen-MHC I complex on the infected cell.
CD8: Co-receptor on cytotoxic T cells that binds to MHC I molecules.
Perforin Makes Holes in Infected Cell’s Membrane (Step 2).
Perforin: A protein that forms pores in the target cell membrane.
Granzymes: Enzymes that enter the target cell and activate apoptosis.
Infected Cell Is Destroyed (Step 3):
Mechanism: Apoptosis.
Activation of Caspases: Initiates a cascade of events that leads to cell death.
Perforin Molecule: Creates holes in the infected cell.
Function: Allows granzymes to enter the target cell.
Foreign Antigen: Displayed on infected cell surface.
MHC Class I: Presents the antigen to the cytotoxic T cell.
Cancer and Cytotoxic T Cells
Cancer Cell Alteration and Cytotoxic T Cell Role
Cancer Cell Alteration: Surface molecules are altered by the disease.
Tumor-Specific Antigens: Antigens that are expressed only on cancer cells.
Examples: Mutated proteins, overexpressed proteins, and viral proteins.
Immune Evasion: Cancer cells can downregulate MHC I expression to avoid recognition by cytotoxic T cells.
Escape Mechanisms: Mutations and epigenetic changes.
Cytotoxic T Cell Role: May attack cancer cells and help prevent cancer.
Immune Surveillance: Cytotoxic T cells patrol the body and eliminate cancerous cells.
Cancer Immunotherapy: Enhancing the ability of cytotoxic T cells to recognize and kill cancer cells.
B Cells and Humoral Immunity
Activation, Effector Cell, and Plasma Cell Function
Activation: Triggered by a specific antigen, a B cell differentiates into an effector cell.
Antigen Binding: B cell receptor (BCR) binds to the antigen.
T Cell Help: Helper T cells provide signals that activate B cells.
CD40 Ligand: Binds to CD40 on B cells, providing a co-stimulatory signal.
Cytokine Signals: Cytokines from helper T cells promote B cell proliferation and differentiation.
Examples: IL-4, IL-5, IL-6.
Effector Cell: Plasma cell.
Plasma Cell Differentiation: Activated B cells differentiate into plasma cells.
Plasma Cell Function: Secretes antibodies.
Antibody Production: Plasma cells produce large quantities of antibodies with the same specificity as the BCR.
B Cell Role: Main warriors of humoral immunity.
Neutralization: Antibodies bind to antigens and prevent them from infecting cells.
Opsonization: Antibodies coat pathogens and enhance their uptake by phagocytes.
Complement Activation: Antibodies activate the complement system, leading to cell lysis and inflammation.
Antibody Molecules
Structure of Antibody Molecules
Light Chain: One of the polypeptide chains that make up an antibody.
Types: Kappa (κ) and lambda (λ).
Variable Region: Contains the antigen-binding site.
Antigen-Binding Sites: Regions on the antibody that bind to specific antigens.
Hypervariable Regions: Highly variable sequences within the variable region that determine antigen specificity.
Disulfide Bonds: Stabilize the antibody structure.
Heavy Chain-Heavy Chain: Connects the two heavy chains.
Light Chain-Heavy Chain: Connects each light chain to a heavy chain.
Variable Region: Region of the antibody that varies from one antibody to another.
Amino Acid Sequence: Determines the antigen specificity.
Constant Region: Region of the antibody that is the same for all antibodies of a given class.
Isotypes: IgG, IgM, IgA, IgD, and IgE.
Effector Functions: Determines the function of the antibody (e.g., complement activation, Fc receptor binding).
Types of Immunoglobulins
IgG, IgA, IgM, IgD, and IgE
IgG:
Location: Tissue fluid and plasma.
Most Abundant: ~75% of serum antibodies.
Function: Activates complement, defends against bacteria, viruses, and toxins.
Opsonization: Enhances phagocytosis.
Neutralization: Blocks viral binding and neutralizes toxins.
Complement Activation: Activates the classical complement pathway.
IgA:
Location: Exocrine gland secretions (breast milk, saliva, mucus).
Dimeric Form: Two IgA molecules joined together by a J chain.
Function: Defends against bacteria and viruses in mucosal tissues.
Neutralization: Blocks pathogen attachment to mucosal surfaces.
Types of Immunoglobulins (Continued)
IgM:
Location: Plasma.
Pentameric Form: Five IgM molecules joined together by a J chain.
Function: Reacts with naturally occurring antigens on RBCs, activates complement.
First Antibody Produced: During a primary immune response.
Agglutination: Effective at clumping pathogens together.
IgD:
Location: Surface of most B lymphocytes.
B Cell Receptor: Acts as a receptor for antigens on B cells.
Function: Plays a role in B cell activation.
Signaling: Triggers B cell activation when it binds to antigen.
IgE:
Location: Exocrine gland secretions and bound to mast cells and basophils.
Fc Receptors: Binds to Fc receptors on mast cells and basophils.
Function: Promotes inflammation and allergic reactions.
Mast Cell Activation: Triggers the release of histamine and other inflammatory mediators.
Antibody Actions
Neutralization, Agglutination, Precipitation, Complement Activation, and Enhanced Phagocytosis
Neutralization: Blocks viral binding sites; coats bacterial toxins.
Mechanism: Antibodies bind to the pathogen, preventing it from infecting cells or exerting its toxic effects.
Examples: Neutralizing antibodies against viruses and toxins.
Agglutination of Microbes: Clumping of pathogens for easier elimination.
Mechanism: Antibodies bind to multiple pathogens, cross-linking them and forming large aggregates.
Enhances Phagocytosis: Makes it easier for phagocytes to engulf and destroy the pathogens.
Precipitation of Dissolved Antigens: Makes antigens easier to phagocytose.
Mechanism: Antibodies bind to soluble antigens, forming insoluble complexes that precipitate out of solution.
Removal: These complexes are then phagocytosed by macrophages and neutrophils.
Activation of Complement: Leads to cell lysis.
Classical Pathway: Antibodies activate the classical complement pathway.
Membrane Attack Complex (MAC): Formation of MAC leads to lysis of pathogens.
Enhances Phagocytosis: Makes pathogens more appealing to macrophages.
Opsonization: Coating pathogens with antibodies and complement fragments.
Fc Receptors: Phagocytes have Fc receptors that bind to the constant region of antibodies, facilitating phagocytosis.
Primary and Secondary Immune Responses
Primary Response and Secondary Response
PRIMARY RESPONSE (initial encounter with antigen):
Antigen Binds to Antigen Receptor on a B Cell.
B Cell Activation: Leads to proliferation and differentiation.
Cell Growth, Division, and Differentiation into Plasma Cells and Memory B Cells.
Plasma Cells: Antibody-secreting cells.
Memory B Cells: Long-lived cells that provide immunological memory.
Antibody Molecules are Produced by Plasma Cells.
IgM: First antibody produced during the primary response.
IgG: Produced later in the primary response.
SECONDARY RESPONSE (can be years later):
Later Exposure to Same Antigen.
Memory B Cells: Quickly recognize the antigen and initiate a rapid immune response.
Memory B Cell is Activated, Leading to Cell Growth, Division, and Further Differentiation.
Effector Cells: Plasma cells and memory B cells.
Larger Clone of Plasma Cells and Antibody Molecules are Produced.
IgG: Predominant antibody during the secondary response.
Affinity Maturation: Antibodies have higher affinity for the antigen.
IgE-Mediated Allergic Reactions
Atopic Disorders, Nonatopic Disorders, and Mechanism
Atopic Disorders:
Hereditary Predisposition and Production of a Local Reaction to IgE Antibodies.
Genetic Factors: Increased susceptibility to allergies.
Environmental Factors: Exposure to allergens during early childhood.
Examples: Urticaria (hives), allergic rhinitis (hay fever), atopic dermatitis, food allergies, some forms of asthma.
Nonatopic Disorders:
Lack the Genetic Component and Organ Specificity of the Atopic Disorders.
Triggers: Irritants, infections, and other non-allergic factors.
Mechanism:
Sensitization: Initial exposure to allergen leads to IgE production.
Allergen Binding: IgE binds to mast cells and basophils.
Mast Cell Activation: Subsequent exposure to allergen triggers mast cell degranulation.
Hypersensitivity Reaction - Type I
Type I Hypersensitivity, Examples, and Phases
Type I: Immediate-reaction allergy.
IgE-Mediated: Requires sensitization to an allergen.
Examples:
Hives (Urticaria): Skin rash with itchy, raised welts.
Hay Fever (Allergic Rhinitis): Inflammation of the nasal passages.
Asthma: Chronic inflammatory disease of the airways.
Atopic Dermatitis (Eczema): Chronic, itchy skin condition.
Gastric Disturbances: Nausea, vomiting, and diarrhea.
Anaphylactic Shock: Severe, life-threatening allergic reaction.
Type I Hypersensitivity Reactions: Phases
Primary or Initial-Phase Response:
Vasodilation: Increased blood flow to the affected area.
Vascular Leakage: Fluid leaks from blood vessels into the tissues.
Smooth Muscle Contraction: Bronchospasm and constriction of blood vessels.
Secondary or Late-Phase Response:
More Intense Infiltration of Tissues with Eosinophils and Other Inflammatory Cells.
Tissue Destruction: Damage to epithelial cells and other tissue components.
Type I Hypersensitivity Mechanism
Sensitization, Primary Early Response, and Secondary Late Response
Sensitization:
B Cells are Stimulated by T Helper Cells (TH) and IL-4 to Produce IgE-Secreting Plasma Cells.
T Cell Activation: Helper T cells recognize the allergen and activate B cells.
Cytokine Production: IL-4 stimulates B cells to switch to IgE production.
IgE Antibodies Bind to Mast Cells.
Fc Receptors: IgE binds to Fc receptors on mast cells and basophils.
Primary Early Response:
Antigen Binds to IgE on Mast Cells, Causing Degranulation and Release of Mediators.
Cross-Linking: Antigen cross-links IgE molecules on mast cells and basophils.
Degranulation: Release of histamine, leukotrienes, prostaglandins, and other inflammatory mediators.
Leads to Vasodilation, Vascular Damage, and Smooth Muscle Spasm.
Histamine: Causes vasodilation and increased vascular permeability.
Leukotrienes: Cause bronchospasm and mucus production.
Secondary Late Response:
Release of Cytokines Leads to Recruitment and Activation of Inflammatory Cells.
Cytokine Production: Mast cells release cytokines that recruit eosinophils, neutrophils, and other inflammatory cells.
Causes Mucosal Edema, Mucus Secretion, Leukocyte Infiltration, Epithelial Damage, and Bronchospasm.
Eosinophils: Release toxic substances that damage tissues.
Membrane Phospholipids are Converted into Arachidonic Acid.
Arachidonic Acid: Metabol