The immune system is divided into two interconnected branches: innate immunity provides immediate, non-specific defense, while adaptive immunity provides delayed but highly specific and long-lasting protection against pathogens.
Innate Immunity
The innate immune system is the first line of defense, responding within minutes to hours of infection. It recognizes conserved molecular patterns shared by broad classes of pathogens. Physical barriers include the skin (keratinized epithelium, antimicrobial peptides), mucosal surfaces (mucus, cilia), stomach acid, and lysozyme in tears and saliva. Cellular components include neutrophils (phagocytosis, NETs), macrophages (phagocytosis, cytokine production), dendritic cells (antigen presentation), natural killer (NK) cells (killing virus-infected and tumor cells), eosinophils (anti-parasitic), and mast cells (allergy, inflammation). Pattern recognition receptors (PRRs) include Toll-like receptors (TLRs), which recognize LPS, flagellin, and nucleic acids; NOD-like receptors (NLRs), which detect intracellular pathogens; RIG-I-like receptors (RLRs), which detect viral RNA; and C-type lectin receptors, which recognize fungal carbohydrates. The complement system is a cascade of serum proteins that opsonize pathogens, recruit inflammatory cells, and directly lyse microbes through the membrane attack complex (MAC).
Acute Inflammation
Inflammation is characterized by redness, heat, swelling, pain, and loss of function, resulting from increased vascular permeability, leukocyte recruitment, and mediator release. Chemokines and cytokines (TNF-alpha, IL-1, IL-6, IL-8) coordinate the inflammatory response, recruiting neutrophils and macrophages to the infection site. The acute phase response includes fever, increased acute-phase proteins (CRP, serum amyloid A), and leukocytosis.
Adaptive Immunity
Adaptive immunity is characterized by specificity, diversity, memory, and self/non-self discrimination. It develops over days and improves upon repeated exposure. Humoral immunity involves B cells producing antibodies that neutralize toxins, opsonize pathogens, activate complement, and prevent pathogen attachment to host cells. Cell-mediated immunity involves T cells recognizing peptide antigens presented by MHC molecules; CD4+ helper T cells (Th1, Th2, Th17, Tfh, Treg) coordinate immune responses, while CD8+ cytotoxic T cells kill infected cells.
Antigen Presentation
MHC class I molecules present endogenous antigens (cytosolic proteins, viral antigens) to CD8+ T cells and are expressed on all nucleated cells. MHC class II molecules present exogenous antigens (phagocytosed pathogens) to CD4+ T cells and are expressed on professional antigen-presenting cells (dendritic cells, macrophages, B cells). Cross-presentation allows dendritic cells to present exogenous antigens on MHC class I to activate CD8+ T cells, which is critical for immunity against viruses and tumors.
Lymphocyte Development and Selection
B cells develop in bone marrow, while T cells develop in the thymus. Both undergo V(D)J recombination to generate diverse antigen receptors. Central tolerance eliminates self-reactive lymphocytes through negative selection: T cells that recognize self-antigens with high affinity undergo apoptosis. Peripheral tolerance mechanisms (anergy, regulatory T cells, immune privilege) prevent autoimmunity against self-antigens not present in the thymus.
Memory and Secondary Responses
After infection or vaccination, memory B and T cells persist for decades, enabling faster and stronger responses upon re-exposure (secondary response). Memory B cells produce higher-affinity antibodies with class switching to IgG, IgA, or IgE. Tissue-resident memory T cells (TRM) provide rapid protection at barrier sites, while central memory T cells (TCM) recirculate through lymphoid organs.
Coordination Between Innate and Adaptive Immunity
Dendritic cells bridge innate and adaptive immunity by migrating to lymph nodes and presenting antigen to naive T cells. Complement activation enhances antibody responses, and antibodies amplify complement and NK cell activity through Fc receptors. Cytokines from innate cells (IL-12, type I interferons, IL-1) shape the differentiation of adaptive T cell responses.
