Adaptive Immune Responses

• The immune system has two major adaptive responses

Cell-Mediated Immunity

• T-cell driven
• Combats intracellular pathogens

Humoral Immunity

• B-cell driven
• Combats extracellular pathogens through antibodies

Activation of CD4+ T Cells

• Step 1: T-cell receptor (TCR) binds to an antigen presented on MHC II molecules of antigen-presenting cells (APCs)
• Step 2: Co-stimulation occurs via CD28 binding B7 on APC, leading to full activation
• Step 3: Cytokines secreted by APC dictate differentiation into specialized T-helper cells

Th1 Cells

• Stimulated by intracellular bacteria and viruses
• Secretes interferon-gamma (IFN-γ) and IL-2
• Enhances macrophage killing (oxidative burst), CD8+ T cell proliferation, and NK cell activity

Th2 Cells

• Stimulated by parasitic infections
• Secretes IL-4, IL-5, and IL-13
• Induces B-cell production of IgE, mast cell degranulation, and eosinophil recruitment

Th17 Cells

• Stimulated by extracellular bacteria and fungi
• Secretes IL-17 which recruits neutrophils to infection sites

T Follicular Helper (Tfh) Cells

• Located in lymph node follicles
• Secretes IL-21 and IFN-γ which activates B cells to produce IgG and establish memory cells

Activation of CD8+ T Cells

• Step 1: Recognizes antigen on MHC I molecules, present on all nucleated cells
• Step 2: Binds tightly via LFA-1 adhesion molecules to stabilize interaction
• Step 3: Activation leads to targeted cell destruction

Mechanisms of Cytotoxicity

• Perforin forms pores in target cell membranes
• Granzymes induce apoptosis by activating caspases
• Fas-FasL Pathway binds Fas receptor on the target cell, triggering cell death

Natural Killer (NK) Cells

• Innate immune counterpart to cytotoxic T cells
• Kills cells lacking MHC I molecules, common in viral infections and tumors
• Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), IgG binds viral proteins on infected cells, and CD16 on NK cells binds Fc region of IgG which triggers cell lysis

Activation of B Cells

• Pathogen binding directly activates naïve B cells
• The complement system (CD21 receptor) enhances B-cell activation
• T-Dependent Activation (Isotype Switching) involves the B cell presenting antigen on MHC II to CD4+ T cell, CD40 (B cell) binds CD40L (T cell), and the helper T cell secretes cytokines (IL-4, IL-5, IFN-γ) which determine antibody class

B Cell Differentiation

• Activated B cells become plasma cells (antibody production) or memory B cells

Antibody Classes (Immunoglobulins)

• IgM is the first antibody produced, activates complement, and its pentameric form binds 10 antigens
• IgG is the most abundant, crosses the placenta, and mediates opsonization and ADCC with NK cells
• IgA is found in mucosal secretions (tears, saliva, breast milk) and neutralizes pathogens at entry points
• IgE is involved in allergic reactions and parasite defense, and binds mast cells and eosinophils
• IgD is present on immature B cells with a function that is still not well understood

Immune Response to Pathogens

• Bacterial Infections involves neutrophils and macrophages phagocytosing bacteria, Th17 cells recruiting neutrophils, and B cells producing IgG antibodies, leading to opsonization and complement activation
• Viral Infections involves infected cells displaying viral antigens on MHC I, CD8+ T cells recognizing and killing infected cells, NK cells targeting cells lacking MHC I, and IgG neutralizing extracellular viruses

Summary of Key Immune Cells & Functions

• CD4+ Helper T Cells coordinate immune responses and activate B cells and macrophages
• CD8+ Cytotoxic T Cells kill virus-infected cells via perforin and granzymes
• B Cells produce antibodies and present antigens to T cells
• NK Cells kill infected and tumor cells lacking MHC I
• Macrophages phagocytose pathogens and present antigens
• Neutrophils are first responders and destroy bacteria through phagocytosis