Immune Response Types and Cells

Immune Response Types

• Innate Immunity: Pre-existing defenses that recognize microbes and protect against infections.
  • Components:
    • Epithelial barriers, e.g., skin
    • Phagocytic cells: neutrophils, macrophages
    • Natural killer (NK) cells
    • Complement system proteins
• Adaptive (Acquired) Immunity: Activated by microbes and can recognize non-microbial substances (antigens).
  • Types:
    • Cell-Mediated Immunity: Targets intracellular microbes; mediated by T lymphocytes (thymus-derived)
    • Humoral Immunity: Targets extracellular microbes and their toxins; mediated by B lymphocytes (bone marrow-derived) and secreted antibodies.

Immune Cells

• T Lymphocytes (T Cells): 60-70% of circulating lymphocytes.
  • T Cell Receptor (TCR): Recognizes specific antigens; composed of α and β polypeptide chains
    • Variable region: Binds to antigen
    • Constant region: Links to CD3 complex
  • CD3 Complex: Involves in signal transduction for TCR activation.
  • Somatic Rearrangement: TCR gene rearrangements create diversity.
  • CD4 and CD8 Coreceptors:
    • CD4: Present in about 60% of T cells; binds to class II MHC molecules on antigen-presenting cells.
    • CD8: Present in about 30% of T cells; binds to class I MHC molecules.
  • T Helper (TH) Cells:
    • TH1: Secrete IL-2 and IFN-γ; involved in delayed hypersensitivity, macrophage activation.
    • TH2: Secrete IL-4, IL-5, and IL-13; aid in antibody production and eosinophil activation.
  • CD8+ Cytotoxic T Cells: Kill other cells, primarily in cell-mediated immunity.
  • T Cell Activation: Requires two signals:
    • Engagement of TCR by appropriate MHC-antigen complex with CD4 or CD8 coreceptors.
    • Interaction of CD28 on T cells with CD80 or CD86 on antigen-presenting cells.
    • Absence of the second signal: T cells undergo apoptosis or become unresponsive (anergic), preventing autoimmune reactions.
• B Lymphocytes (B Cells): 10-20% of circulating lymphocytes.
  • B Cell Receptor (BCR): Monomeric IgM; serves as an antigen receptor on B cells.
  • Somatic Rearrangement: Immunoglobulin gene rearrangements result in unique antigen specificity.
  • Other B Cell Molecules: CD19, CD20, CD21 (complement receptor, EBV binding), CD40 (interacts with CD154 on activated T cells)
  • Differentiation:
    • Plasma Cells: Secrete antibodies (IgG, IgM, IgA, IgE).
• Macrophages: Role in immune response:
  • Antigen presentation to T cells via class II MHC molecules.
  • Cytokine production to influence other immune cells (T cells, B cells, endothelial cells, fibroblasts).
  • Secretion of toxic metabolites and enzymes to kill tumor cells.
  • Effector cells in delayed hypersensitivity reactions.
• Dendritic Cells and Langerhan's Cells: Dendritic cell processes and high expression of class II MHC molecules.
  • Dendritic Cells: Found in lymphoid tissue.
  • Langerhan's Cells: Found in the epidermis.
  • Efficient Antigen Presentation: Low phagocytic activity.
  • Follicular Dendritic Cells: Found in germinal centers; express antibodies on their surface and have Fc receptors.
• Natural Killer (NK) Cells: 10-15% of peripheral blood lymphocytes; not express TCR or immunoglobulin.
  • Larger Than Small Lymphocytes: Contains azurophilic granules (large granular lymphocytes).
  • Part of Innate Immunity: Kill tumor and virally infected cells without prior sensitization.
  • Identification: CD16 (Fc receptor for IgG-coated cells) and CD56.
  • Receptors:
    • Activators: Recognize ill-defined molecules on abnormal cells.
    • Inhibitors: Recognize class I MHC on normal cells.
  • Secrete IFN-γ:
• Antibody-Dependent Cell Mediated Cytotoxicity (ADCC): NK cells kill antibody-coated cells via CD16.

Major Histocompatibility Complex (MHC)

• Function: Present peptide fragments of foreign proteins to T cells.
• MHC Gene Location: Clustered on chromosome 6 (Human Leukocyte Antigen - HLA).
• MHC Molecules:
  • Class I:
    • Expressed on all nucleated cells and platelets.
    • Encoded by HLA-A, HLA-B, and HLA-C loci.
    • Present endogenous antigens (e.g., viral proteins) to CD8+ cytotoxic T cells.
  • Class II:
    • Encoded by HLA-DP, HLA-DQ, and HLA-DR regions.
    • Present exogenous antigens (e.g., extracellular microbes) to CD4+ helper T cells.
  • Class III: Encode components of the complement system.

Hypersensitivity Reactions (Types)

• Type I (Immediate) Hypersensitivity: Rapid immune reaction within minutes of antigen-antibody binding to mast cells in previously sensitized individuals.
  • Phases:
    • Immediate Phase: Vasodilatation and exudation (5-30 minutes, subsiding in 60 minutes).
    • Late Phase: Leukocyte influx (2-4 hours, lasting for days)
  • Examples: Anaphylaxis, bronchial asthma, allergic rhinitis.
• Type II Hypersensitivity: Antibodies against antigens on cell surfaces or extracellular matrix.
  • Mechanisms of Destruction:
    • Opsonization and Fc receptor-mediated phagocytosis.
    • Antibody-dependent cellular cytotoxicity (ADCC).
    • Antibody-mediated cellular dysfunction.
  • Examples:
    • Transfusion reactions
    • Autoimmune hemolytic anemia
    • Drug reactions
    • Myasthenia gravis
    • Grave's disease
    • Glomerulonephritis
    • Organ rejection
• Type III Hypersensitivity: Immune complex (antigen-antibody) deposition in tissues causing inflammation and damage.
  • Examples:
    • Systemic lupus erythematosus
    • Polyarteritis nodosa
    • Poststreptococcal glomerulonephritis
    • Serum sickness.
• Type IV (Cell-Mediated) Hypersensitivity: Initiated by antigen-activated T lymphocytes.
  • Mechanisms:
    • Delayed type hypersensitivity (CD4+ T cells): Defense against intracellular pathogens (e.g., mycobacteria, fungi, parasites).
    • Direct cell cytotoxicity (CD8+ T cells): Graft rejection.
  • Examples:
    • Contact dermatitis
    • Tuberculin reaction
    • Transplant rejection
    • Tumor immunity.

The Immune Response

• Innate immunity comprises defenses present before infection. It includes epithelial barriers, phagocytic cells, NK cells, and complement system proteins.
• Adaptive immunity is stimulated by infection and can recognize microbes and nonmicrobial substances (antigens).
• Cell-mediated immunity protects against intracellular microbes and is mediated by T lymphocytes.
• Humoral immunity protects against extracellular microbes and toxins and is mediated by B lymphocytes and antibodies.

Cells of the Immune System

• T-lymphocytes

  • 60-70% of circulating lymphocytes.
  • Found in lymph nodes and spleen.
  • Contain a T cell receptor (TCR) composed of α and β chains with variable and constant regions.
  • Express CD4 or CD8 as coreceptors.
  • CD4+ T cells bind to class II MHC molecules and include TH1 (IL-2 and IFN-γ) and TH2 (IL-4, IL-5, and IL-13) subsets.
  • CD8+ T cells bind to class I MHC molecules and mainly function as cytotoxic cells.
  • T cell activation requires TCR engagement with MHC-antigen complex and CD28 interaction with CD80/CD86.

• B-lymphocytes

  • 10-20% of circulating lymphocytes.
  • Found in lymph nodes and spleen.
  • Transform into plasma cells secreting antibodies.
  • Express a B cell receptor (BCR) composed of monomeric IgM.
  • Express CD19, CD20, CD21, and CD40.

• Macrophages

  • Present antigens to T cells via class II MHC molecules.
  • Produce cytokines influencing other immune cells.
  • Secrete toxic metabolites and enzymes.
  • Important effector cells in delayed hypersensitivity.

• Dendritic and Langerhans' cells

  • Have dendritic processes and high class II MHC expression.
  • Found in lymphoid tissue (dendritic) and epidermis (Langerhans).
  • Efficient antigen presenters with poor phagocytic activity.
  • Follicular dendritic cells in germinal centers trap antibodies.

• Natural killer cells (NK cells)

  • 10-15% of peripheral blood lymphocytes.
  • Lack TCR and immunoglobulin.
  • Larger than lymphocytes and contain azurophilic granules.
  • Kill tumor and virally infected cells without prior sensitization.
  • Express CD16 and CD56.
  • Possess activating receptors and inhibitory receptors that recognize class I MHC.

Major Histocompatibility Complex (MHC)

• MHC molecules bind peptide fragments of foreign proteins for presentation to T cells.

• Located on chromosome 6 and classified into class I, class II, and class III.

• Class I MHC

  • Expressed on all nucleated cells and platelets.
  • Bind peptides derived from intracellular proteins (e.g., viral antigens).
  • Recognized by CD8+ cytotoxic T cells (class I MHC-restricted).

• Class II MHC

  • Encoded by HLA-DP, HLA-DQ, and HLA-DR.
  • Present exogenous antigens (e.g., extracellular microbes).
  • Recognized by CD4+ helper T cells (class II MHC-restricted).

Hypersensitivity Reactions

• Type I (immediate) hypersensitivity: Rapid reaction (minutes) triggered by antigen-antibody binding to mast cells.

  • Immediate phase (5-30 min): Vasodilatation and exudation due to vasoactive amine release.
  • Late phase (2-4 hours): Influx of leukocytes (bronchial asthma, allergic rhinitis).

• Type II hypersensitivity: Antibody-mediated against cell surface or extracellular matrix antigens.

  • Mechanisms: Opsonization and phagocytosis, antibody-dependent cell cytotoxicity (ADCC), antibody-mediated cellular dysfunction.
  • Examples: Transfusion reactions, autoimmune hemolytic anemia, drug reactions, myasthenia gravis, Grave's disease, glomerulonephritis, organ rejection.

• Type III hypersensitivity: Immune complex-mediated.

  • Complexes deposit in various organs, primarily blood vessels.
  • Examples: Systemic lupus erythematosus, polyarteritis nodosa, poststreptococcal glomerulonephritis, serum sickness.

• Type IV hypersensitivity (cell-mediated): Initiated by antigen-activated T lymphocytes.

  • Delayed type hypersensitivity: Mediated by CD4+ T cells, involved in defense against intracellular pathogens (mycobacteria, fungi, parasites), transplant rejection, tumor immunity.
  • Direct cell cytotoxicity: Mediated by CD8+ T cells, mainly encountered in graft rejection.

Immune Response

• Two major types of immune response: innate and adaptive
• Innate immunity: present at birth, non-specific defense against pathogens
  • Components: epithelial barriers, phagocytes (neutrophils and macrophages), natural killer (NK) cells, complement system proteins
• Adaptive immunity: develops after exposure to pathogens, highly specific
  • Two types: cell-mediated and humoral immunity

Cells of the Immune System

• T-lymphocytes (T cells): key players in cell-mediated immunity, originate in bone marrow and mature in thymus
  • T cell receptor (TCR): recognizes specific antigens
  • CD4 and CD8: coreceptors on T cells, determine which MHC class they interact with
  • CD4+ T cells: helper T cells, promote immune response by secreting cytokines
  • CD8+ T cells: cytotoxic T cells, directly kill infected or cancerous cells
• B-lymphocytes (B cells): key players in humoral immunity, originate in bone marrow
  • Antibodies (immunoglobulins): secreted proteins that bind to antigens, neutralizing or eliminating pathogens
  • B cell receptor (BCR): recognizes specific antigens
  • Plasma cells: mature B cells that secrete antibodies
• Macrophages: phagocytose foreign material and pathogens, present antigens to T cells
  • Produce cytokines: proteins that influence the behavior of other immune cells
  • Secrete toxic metabolites and enzymes: for killing tumor cells
• Dendritic cells: antigen-presenting cells with dendritic processes
  • Efficient antigen presentation: activate T cells
  • Found in various tissues: lymph nodes, skin (Langerhan's cells)
• Natural killer (NK) cells: part of innate immunity, kill infected or cancerous cells without prior sensitization
  • Don't express TCR or immunoglobulins: use other mechanisms for target recognition
  • Secrete IFN-γ: immune-stimulating cytokine

Major Histocompatibility Complex (MHC)

• MHC proteins: expressed on cell surfaces, present antigen fragments to T cells
• Class I MHC: expressed on all nucleated cells, presents antigens from inside the cell (e.g., viral proteins)
  • Recognized by CD8+ T cells
• Class II MHC: expressed on antigen-presenting cells (macrophages, dendritic cells), presents antigens from outside the cell (e.g., bacterial proteins)
  • Recognized by CD4+ T cells

Hypersensitivity Reactions

• Hypersensitivity: exaggerated or inappropriate immune response to an antigen, causing tissue damage
• Type I (Immediate): mediated by IgE antibodies binding to mast cells, triggering immediate release of histamine and other inflammatory mediators
  • Examples: allergies, anaphylaxis
• Type II (Cytotoxic): mediated by antibodies directed against cell surface antigens, leading to cell lysis or dysfunction
  • Examples: transfusion reactions, autoimmune hemolytic anemia
• Type III (Immune Complex-mediated): mediated by antigen-antibody complexes depositing in tissues, triggering inflammation and tissue damage
  • Examples: systemic lupus erythematosus, serum sickness
• Type IV (Cell-mediated): mediated by T cell activation, leading to delayed tissue damage
  • Examples: contact dermatitis, graft rejection, tuberculin skin test