Summary
Highlights
This section introduces cytokines as molecules mediating immune reactions, highlighting their five main properties: pleiotropic, redundant, antagonistic, additive, and synergistic. It lists key inflammatory, pro-inflammatory, anti-inflammatory, lymphoproliferative, and B-cell proliferative cytokines, as well as interferons. The speaker stresses the importance of memorizing these for exams. The latter part of this section moves on to T helper cell subsets, specifically CD4 cells, explaining their activation by antigen-presenting cells and their differentiation into TH1, TH2, TH17, regulatory T cells, and follicular T cells based on antigen type and cytokine secretion. Each subset's main function, secreted cytokines, and effects on B cells and macrophages are detailed.
This part delves into the complex interaction between B cells and T cells within lymph nodes, crucial for specific antibody production. It begins with the lymph node structure, differentiating between the B cell zone (cortex), T cell zone (paracortex), and medulla. It then explains the different types of B cells (B1, marginal B cells, and follicular B cells) and their activation process. The detailed four-step interaction involves naive B cells encountering antigens via follicular dendritic cells, T cells being activated by the same antigen, their subsequent migration and interaction in the marginal zone, and the ultimate formation of germinal centers. This process facilitates isotype switching, where B cells change the constant region of antibodies based on the helper T cell, and affinity maturation, where antibodies gain higher affinity for specific antigens through somatic hypermutation and clonal selection. The role of memory cells and IL-7 in maintaining them is also discussed.
This segment focuses on CD8+ cytotoxic T cells, emphasizing their primary role in killing virus-infected and cancer cells via MHC1 interaction and inflammatory cytokine production (especially interferon gamma). It outlines their activation mechanism, which requires simultaneous activation with TH1 cells by the same antigen-presenting cell. The two main killing pathways, intrinsic apoptosis (perforin, granzyme, cytochrome C, caspases) and extrinsic apoptosis (Fas ligand, TNF-alpha, lymphotoxin beta), are explained. The discussion then shifts to regulatory T cells, characterized by FOX P3 expression, whose main function is maintaining peripheral tolerance by suppressing other immune cells through IL2 receptor expression (CD25), IL-10, TGF-beta secretion, and CTLA4 expression.
Natural Killer (NK) cells are described by their CD16 and CD56 expression and their ability to kill cells with missing or altered MHC1. Their killing mechanisms, similar to cytotoxic T cells (perforin/granzyme) and specific ligands like TRAIL, are detailed. The decision-making process for NK cells to kill or spare a cell depends on the balance between activating (NKG2D, CD16) and inhibitory (KIR, NKG2) signals. Innate Lymphoid Cells (ILCs) are introduced as innate immune cells that do not express CD3, are tissue-fixed, and mimic the functions of TH1, TH2, and TH17 cells, but are activated by cytokines and alarmins rather than antigens.
This part covers the four types of hypersensitivity reactions, defined by an overactivated immune system causing trouble. Type 1 (allergy/atopy) is explained through the process of IgE production, binding to mast cells/basophils, and subsequent degranulation leading to immediate (histamine, leukotrienes) and late phase (TNF-alpha, eosinophil/neutrophil attraction) reactions. Clinical examples include hay fever, asthma, and anaphylaxis. Type 4 (cell-mediated, delayed-type) is detailed as a T-cell, macrophage, and neutrophil-mediated response starting 48 hours post-exposure, causing edema, tissue damage, and fibrin deposition; contact dermatitis and the tuberculin skin test are key examples. Type 2 (antibody-mediated cellular attack) involves antibodies directly attacking cells, seen in drug side effects, molecular mimicry (rheumatic heart disease), autoimmune diseases, and mismatched blood transfusions. Type 3 (immune complex-mediated) involves immune complexes depositing in blood vessels due to excess antigen-antibody, activating complement and mast cells, with the Arthus reaction as a classic example. Treatment involves corticosteroids, IVIG, or plasma exchange.
Tumor immunology explores the immune system's role in fighting cancer. Cancer cells are under constant immune surveillance, which occurs in three phases: elimination (killing emerging tumor cells), equilibrium (tumor mutation to evade the immune system, evidenced by post-transplant lymphoproliferative disorder), and escape (tumor overcoming the immune system). Tumor evasion techniques include low immunogenicity, expression of immunosuppressive signaling proteins (PDL1, CTLA4), antigenic modulation, release of IL-10 and TGF-beta, and collagen production forming a barrier. Two types of tumor antigens are discussed: tumor-specific transplantation antigens (TSTAs), unique to tumors (neopeptides, viral proteins in oncogenic viruses), and tumor-associated transplantation antigens (TATAs), normally found in humans but overexpressed or expressed at wrong times (e.g., MAGE, alpha-fetoprotein, HER2/neu). The section concludes with new cancer treatment techniques: chimeric antigen receptor (CAR) therapy (e.g., for CD19 in leukemia), monoclonal antibodies (checkpoint blockade against PDL1/CTLA4, opsonization, tumor tagging), oncogenic virus vaccines, and therapies inducing fasL expression.
This final section covers principles of vaccinology and diagnostic immunology. Vaccinology categorizes immunity as passive (direct antibody transfer for short-lived, no-memory response, like antitoxins) versus active (vaccines eliciting long-term B/T cell response and memory). Vaccines are further classified into killed (require boosters, short-lived) versus live attenuated (weakened live viruses, stronger/longer response, contraindicated in immunocompromised). Adjuvants are discussed as substances that enhance immune response to protein-based vaccines by stimulating antigen-presenting cells. Subunit vaccines use specific viral components (mRNA, capsid, protein) and are produced via genetic engineering in yeast or virus vectors (AstraZeneca and Pfizer COVID vaccines are examples). Conjugate vaccines link bacterial polysaccharides to carrier proteins to increase immunogenicity. The second part discusses laboratory techniques, including polyclonal and monoclonal antibodies for targeting specific antigens. Diagnostic methods cover antigen-antibody detection: agglutination, immuneprecipitation (both qualitative), radial immunodiffusion (quantitative), immunofluorescence (direct/indirect tagging with fluorophores), and ELISA (sandwich/indirect assays). Finally, T-cell detection primarily uses flow cytometry for accurate cell counting and specific tetramer assays for detecting antigen-specific T-cells.