Comprehensive notes on MHC, T/B cells, antibodies, vaccines, and immunity

MHC overview and T cell coordination

• MHC stands for major histocompatibility complex; two main classes: MHC I and MHC II.
• MHC I
  • Found on the surface of all nucleated cells (every body cell that isn’t an red blood cell).
  • Presents intracellular or endogenous peptides (e.g., virus-infected, damaged, or cancerous cells).
  • Recognized by CD8+ cytotoxic T cells (often called cytotoxic T cells).
• MHC II
  • Found only on antigen-presenting cells (APCs): macrophages, dendritic cells, and B cells.
  • Presents extracellular or exogenous peptides that have been taken up by the APCs.
  • Recognized by CD4+ helper T cells (often called T helper cells or CD4 cells).
• Purpose in immune response
  • MHC I presentation signals intracellular threat and activates cytotoxic CD8+ T cells to kill the compromised cell.
  • MHC II presentation signals an extracellular threat and activates helper CD4+ T cells to coordinate a broader immune response (including B cells, macrophages, and other T cells).
  • Helper T cells help determine whether to recruit more CD8s, establish memory, and coordinate B cell and T cell responses.
• Important reminder
  • T cell receptor (TCR) interacts with the peptide-MHC complex; the T cell itself has a separate receptor from the MHC receptor.
  • MHC I is not a receptor on T cells; it is a peptide-presenting molecule on other cells that T cells scan.

APCs, receptors, and antigen processing

• Antigen-presenting cells (APCs)
  • Macrophages, dendritic cells, and B cells are APCs.
  • APCs process and present antigens on MHC II to CD4+ T helper cells.
• Receptors involved in pathogen detection on APCs
  • Toll-like receptors (TLRs): recognize broad classes of pathogens; trigger immune activation.
  • Mannose receptor: recognizes bacteria; helps identify bacterial components for uptake and presentation.
• Process flow for extracellular threats
  • APC detects a pathogen via TLRs or mannose receptor.
  • APC phagocytoses the threat and digests it.
  • Antigen fragments are presented on MHC II on the APC surface.
  • CD4+ T helper cell with a TCR recognizes the MHC II–peptide complex via its CD4 receptor; then activation occurs.

CD4+ T helper cells: the coordinators

• Role and communication
  • Helper T cells act as officers in the immune system army; they coordinate responses by activating macrophages, B cells, and other T cells.
  • They communicate via cytokines (chemical messengers) to recruit and regulate other immune cells.
  • Cytokines can recruit neutrophils, macrophages, more CD8+ T cells, or B cells to produce antibodies.
• Activation and outcomes
  • When a CD4+ T cell recognizes an antigen presented on MHC II, it activates.
  • Activated helper T cells undergo clonal expansion and differentiate to:
  • Establish memory (for quicker future responses).
  • Coordinate an active response now (via interleukins and other cytokines).
• CD4–MHC II interaction specifics
  • CD4 receptor on helper T cells binds to MHC II on APCs.
  • This interaction triggers helper T cell activation and downstream orchestrated responses.
• Helper T cell outputs
  • Release interleukins (cytokines) that function as alarms and signals to recruit other immune players.
  • Call over NK cells, neutrophils, macrophages, CD8 T cells, and B cells as needed.
• Conceptual note on memory and response
  • Activated helper T cells establish memory via memory T cells and/or promote a robust immediate response by coordinating effector cells.

CD8+ cytotoxic T cells: the direct killers

• Role
  • Directly kill cells that are compromised by intracellular threats (e.g., viruses, cancer cells).
  • Scan all nucleated cells for intracellular danger via MHC I peptide presentation.
• Activation and killing mechanisms
  • Upon activation, cytotoxic T cells perform clonal expansion, producing many effector cells and memory cells.
  • Killing methods include:
  • Perforins: form pores in the target cell membrane.
  • Granzymes: enter through pores and induce apoptosis inside the target cell.
  • Lymphotoxins: disrupt essential cellular processes.
  • Fas pathway (Fas receptor): triggers apoptosis in target cells.
• Outcome
  • Direct cytotoxic destruction of compromised cells to prevent viral replication and spread.
  • Some cytotoxic cells become memory CD8+ T cells for faster responses to future encounters.
• Important caveat
  • CD8+ T cells operate primarily on intracellular threats; they do not rely on coordinating all other immune cells the way helper T cells do.

Humoral immunity: B cells and antibodies

• What humoral immunity means
  • “Humoral” refers to bodily fluids (e.g., blood, lymph, mucus).
  • Focuses on B cells and the antibodies they produce that circulate in fluids.
• B cell origin and diversity
  • B cells are produced in the bone marrow with a diverse repertoire of B cell receptors (BCRs).
  • Diversity comes from random generation of receptors to anticipate many possible pathogens.
• B cell activation (requires help)
  • Many B cells require help from CD4+ T helper cells to become fully activated.
  • B cells present processed antigen on MHC II to helper T cells, which then provide signals to activate the B cell.
• Outcomes of B cell activation
  • Clonal expansion forms a population of B cells specific to the antigen.
  • Some clones become plasma cells; others become memory B cells.
  • Plasma cells secrete antibodies (immunoglobulins) into bodily fluids.
• B cell–T cell collaboration emphasis
  • Helper T cells are essential for most B cell activations, except possibly some direct recognition scenarios; B cells often require T cell “permission” to fully activate and proliferate.
• Antibody structure reminder (immunoglobulins)
  • Antibodies are proteins composed of two heavy chains and two light chains (a Y-shaped molecule).
  • Each antibody has:
  • Variable regions (at the tips of the Y) that determine antigen binding specificity.
  • Constant regions (the stem) that determine the class and effector function.

Antibodies: structure, classes, and distribution

• General structure
  • Two heavy chains and two light chains.
  • Variable region (binding site) vs constant region (effector function).
• Antibody classes (isotypes)
  • IgG: most diverse class; circulates in blood; can cross the placenta; key defense in the bloodstream.
  • IgA: found on mucosal surfaces (saliva, tears, digestive tract, respiratory tract, vaginal canal) and in breast milk.
  • IgM: large pentamer; primarily in blood; first antibody produced during an initial immune response; strong in binding and agglutination; important in ABO blood type reactions.
  • IgE: involved in allergic responses and defense against parasites; triggers histamine release from mast cells and basophils.
  • IgD: roles are less well defined; participates in B cell receptor function.
• What each class does best
  • IgG: systemic defense, memory, and placental transfer.
  • IgA: mucosal defense and neonatal protection via breast milk.
  • IgM: early systemic defense; strong agglutination; primary responder.
  • IgE: allergy and antiparasite responses.
  • IgD: B cell receptor component.
• Quick memory aid
  • IgG, IgA, IgM, IgE, IgD: G, A, M, E, D order of commonality and roles described above.

Antibody functions: how antibodies help fight pathogens

• Neutralization
  • Antibodies bind to pathogens (or their toxins) and physically block their ability to attach to host cells.
  • Visual metaphor: antibodies form a barrier around the pathogen, preventing infection.
• Agglutination
  • Antibodies bind multiple pathogens and link them together (via their constant regions), forming clusters that are easier for phagocytes to clear.
• Precipitation
  • Soluble antigens (toxins, small molecules) are cross-linked by antibodies and become heavy enough to precipitate out of solution, aiding removal from the body.
• Opsonization
  • Antibodies tag pathogens to enhance recognition and ingestion by phagocytes (e.g., macrophages and neutrophils).
• Complement fixation
  • Antibodies recruit and activate complement proteins; this can lead to formation of MAC (membrane attack complex) that creates holes in target cell membranes and promotes lysis.
  • Complement activation can also enhance inflammation by stimulating mast cells and basophils to release histamines.
• Why these mechanisms matter
  • Antibodies are not themselves cells; they are specialized proteins that assist in eliminating threats and shaping the overall immune response.

Vaccines and immunity: natural vs artificial; active vs passive

• Key terms
  • Immunity can be natural or artificial (acquired through intervention).
  • Immunity can be active (your immune system creates the response) or passive (you receive components created by another source).
• The four major types
  • Natural active immunity: exposure to a pathogen leads to an immune response with antibody production and memory (e.g., natural infection).
  • Artificial active immunity: vaccination; exposure to a safe form of a pathogen (dead or attenuated or a protein) triggers an immune response and memory without causing disease.
  • Natural passive immunity: transfer of antibodies from mother to baby (placenta or breast milk); provides temporary protection to the infant.
  • Artificial passive immunity: transfer of antibodies produced in another person or animal via IV or injection; provides immediate, short-term protection.
• Examples and practical notes
  • Flu vaccine: can be inactivated (dead virus) or live-attenuated (nasal spray); builds memory without causing full disease; may not always prevent infection but often reduces severity.
  • COVID vaccines: expose the immune system to the spike protein (or its components); aim to generate antibodies and memory without infectious exposure.
  • Vaccination versus natural exposure: vaccines create a head start by producing memory and specific antibodies so that a real infection is less severe if encountered.
• Important caveats about immunity
  • Vaccines do not always prevent infection but can reduce severity and duration by providing an existing pool of antibodies and memory.
  • Exposure to a pathogen in real life may trigger illness before memory fully develops if not vaccinated.
• Memory and booster concept
  • The immune system remembers previous encounters and responds more rapidly and robustly upon re-exposure.

Immune competence, disorders, and disease contexts

• Immune competence
  • Immune competence = the immune system’s ability to function properly and respond appropriately.
  • Immune incompetence or immunodeficiency occurs when parts of the immune system fail or are suppressed.
• Lymphatic disorders vs cancers
  • Lymphadenopathy: enlarged or swollen lymph nodes due to heightened immune activity or infection.
  • Lymphoma: cancer of lymphocytes; usually a solid tumor in lymph nodes, spleen, thymus; often B-cell origin in Hodgkin lymphoma.
  • Leukemia: cancer of blood cells; liquid cancer affecting circulating white blood cells.
  • Distinction: leukemia is typically a liquid cancer; lymphoma is typically a solid cancer.
• Immunodeficiency types
  • Genetic/congenital (e.g., SCID): severe combined immunodeficiency; lack of T and B cells; highly dangerous susceptibility to infections.
  • Acquired (e.g., AIDS): caused by HIV targeting CD4+ T cells; when CD4 count falls below a threshold (commonly cited as <200 cells/mm^3), AIDS develops and opportunistic infections/cancers often become fatal.
  • Immunosuppressive medications (e.g., steroids like prednisone, hydrocortisone): can dampen immune responses.
• Autoimmune and allergic conditions
  • Autoimmune disorders: immune system attacks self-tissues (e.g., rheumatoid arthritis, lupus, psoriasis, celiac disease).
  • Allergies: inappropriate IgE-mediated responses to harmless substances (peanuts, pollen, etc.); often involve mast cells and histamine release.
• HIV/AIDS specifics (brief recap)
  • HIV primarily targets CD4+ T cells, weakening coordination of immune responses.
  • Without enough CD4+ T cells, the body struggles to coordinate B cell and cytotoxic T cell responses, leading to vulnerability to infections and cancers.

Memory and the practical takeaway

• The immune system uses a combination of innate-like detection (APCs with TLRs), antigen presentation (MHC I and II), T cell coordination (CD4 and CD8), B cell antibody production, and memory formation to respond to threats.
• Vaccination leverages this system to establish memory without causing disease, while natural infection may provide memory but carries risk.
• Understanding the interplay between MHC classes, T cell subsets, B cells, and antibodies helps explain why different pathogens require different arms of the immune response and why some diseases involve autoimmunity or immunodeficiency.

Quick reference: key terms and links

• MHC I: presents intracellular peptides; recognized by CD8+ T cells.
• MHC II: presents extracellular peptides; recognized by CD4+ T helper cells.
• APCs: macrophages, dendritic cells, B cells.
• T helper cells: CD4+; coordinate immune responses via cytokines; activate B cells, macrophages, and CD8+ T cells.
• Cytotoxic T cells: CD8+; kill infected cells via perforins, granzymes, lymphotoxins, Fas pathway.
• B cells: produce antibodies; activated with help from CD4+ T cells; form plasma cells and memory B cells.
• Antibodies (Ig classes): IgG, IgA, IgM, IgE, IgD; structure (heavy/light chains; variable/constant regions).
• Antibody functions: neutralization, agglutination, precipitation, opsonization, complement fixation.
• Immunity types: natural vs artificial; active vs passive (natural active, artificial active, natural passive, artificial passive).
• Disorders: lymphadenopathy, lymphoma, leukemia; SCID; HIV/AIDS; autoimmune diseases; allergies.
• Receptors and sensing on APCs: Toll-like receptors, mannose receptor; MHC II presentation.
• Intracellular vs extracellular threats: MHC I handles intracellular threats; MHC II handles extracellular threats.
• Vaccination concepts: memory formation, booster rationale, protection versus infection prevention.