Immune System Overview

Overview

Lecture covers the human immune system: barriers, innate immunity, adaptive immunity, information processing, and major immune disorders. Emphasis on dynamic coordination, antigen recognition, and immune memory.

Big Picture: What Immune Systems Do

• All cellular life has immune defenses against parasites/pathogens; barriers, recognition, and killing tools are universal.
• Human immunity has specialized cells, blood/lymph transport, and adaptive learning of novel antigens.
• Immune systems also surveil and eliminate cancer cells using mechanisms similar to antiviral responses.

Three-Part Human Defense Strategy

• Barriers: skin and mucosal membranes block entry; actively patrolled and antibody-coated.
• Innate immunity: fast, broad responses always on alert; includes inflammation and complement.
• Adaptive immunity: pathogen-specific, slower to activate, boosts innate functions; establishes memory.

Infection Dynamics and Immune Memory

• Primary response: innate limits early growth; adaptive ramps up later, augments innate to clear pathogen.
• Secondary response: faster, stronger adaptive response from memory cells; often prevents symptoms.
• Vaccines mimic primary exposure safely to establish memory; protection strength varies by host and pathogen.

Key Molecules

• Receptors:
  • Pattern recognition receptors (PRRs) bind pathogen-associated molecular patterns (PAMPs) shared across taxa.
  • Antigen receptors (antibodies, T-cell receptors, MHCs) bind species/strain-specific antigens.
• Toxins:
  • Antimicrobial peptides and cytotoxic packets kill pathogens; delivered extracellularly or within phagosomes.
• Cytokines:
  • Immune signaling molecules coordinating responses; interferons trigger antiviral states and apoptosis.
• Circulating proteins:
  • Complement (innate) and antibodies (adaptive) kill directly and/or recruit immune cells.

Immune Cells (Leukocytes)

• Origin: hematopoiesis in bone marrow from hematopoietic stem cells; erythrocytes and platelets are non-immune.
• Major categories:
  • Lymphocytes: T cells, B cells (adaptive); natural killer (innate-like).
  • Phagocytes: monocytes, macrophages, dendritic cells, neutrophils.
  • Granulocytes: neutrophils, basophils, eosinophils; plus mast cells.

Antigen Presentation and Adaptive Cell Types

• Antigen-presenting cells (APCs): dendritic cells and macrophages process microbes, present antigens to T/B cells via MHC.
• T cells:
  • Cytotoxic T cells (CD8+): kill virally infected or cancerous cells presenting matching antigen on MHC.
  • Helper T cells (CD4+): recognize antigen on immune cells; secrete cytokines to boost especially innate responses.
• B cells:
  • Require antigen and helper T-cell “double check” for activation.
  • Differentiate into plasma cells secreting antibodies; also generate memory B cells.

Immune Tissues and Transport

• Barriers: skin dermis houses macrophages; mucosa coated with antibodies, especially IgA.
• Circulatory system: moves immune cells/proteins, enables body-wide patrol.
• Bone marrow: site of blood and leukocyte production.
• Lymphatic system: drains tissues; lymph nodes host T/B cell activation; thymus matures T cells.
• Spleen: major B-cell activation site; liver: major complement production.
• Nervous system: regulates fever and modulates immune intensity.

Innate Mechanisms

• Phagocytosis: engulfment into phagosomes; fusion with lysosomes to kill/digest.
• Degranulation: granulocytes/mast cells release antimicrobial compounds at infection sites.
• Complement system:
  • Opsonization marks microbes for phagocytes.
  • Membrane attack complex forms pores causing osmotic lysis; host cells resist complement.
• Interferons: produced upon detection of double-stranded RNA; induce antiviral proteins and programmed cell death.
• Inflammation: histamine and cytokine-driven; increases blood flow and immune cell recruitment.
• Fever: hypothalamus-mediated systemic temperature rise; enhances leukocyte function but can be self-damaging if excessive.

Adaptive Mechanisms

• Shared features: antigen specificity, delayed activation, memory cell formation, and distinct cell-mediated vs humoral arms.
• Genetic diversification:
  • TCR and antibody genes undergo recombination in developing T/B cells; random combinations create millions of specificities.
  • Additional mutation in antibodies further diversifies B-cell receptors.

Antibodies (Humoral Immunity)

• Structure: two heavy and two light chains; variable ends bind antigen; constant region defines isotype and functions.
• Isotypes and roles:
  • IgG: abundant in blood; strong opsonization.
  • IgM: effective complement activation.
  • IgA: predominant at mucosal surfaces; strong neutralization by coating pathogens.
  • IgE: binds mast cells; triggers degranulation and inflammation in skin/mucosa during allergies.
• Functions: neutralization, opsonization, complement activation, and recruitment of other immune components.
• Distribution: isotypes vary by location and longevity (e.g., IgA in mucosa, IgG in blood).

Information Processing in Immunity

• Core decisions: self vs non-self, pathogen-specific tailoring, when to escalate or resolve responses.
• PRRs and PAMPs: limited, hardcoded set detects broad microbial signatures (e.g., LPS, flagellin, peptidoglycan).
• Cytokine networks: diverse families (chemokines, interleukins, TNFs, interferons); effects depend on receptor expression.
• APCs: convert whole pathogen information into antigen snippets to query T/B cell repertoires.

Immune Disorders

• Hypersensitivities (allergies): harmful responses to harmless antigens.
  • Type I (IgE/mast cell): rapid degranulation and histamine-driven inflammation on re-exposure to allergen.
  • Types II–III: antibody-mediated variants.
  • Type IV: T-cell mediated; delayed (days), diverse outcomes including contact dermatitis and transplant reactions.
• Autoimmune disorders: immune attack on healthy self tissues.
  • Examples: rheumatoid arthritis (joints), multiple sclerosis (myelin), type 1 diabetes (pancreatic beta cells).
• Immunodeficiencies:
  • Primary: inherited defects causing missing leukocyte types or immune molecules.
  • Secondary: acquired via diseases like leukemia (destroys leukocytes) or AIDS (HIV targets/destroys leukocytes).

Summary Table: Components and Functions

Key Terms & Definitions

• Antigen: unique molecule from a pathogen or abnormal cell recognized by adaptive receptors.
• PRR (Pattern Recognition Receptor): host receptor for conserved microbial patterns (PAMPs).
• PAMP (Pathogen-Associated Molecular Pattern): conserved microbial molecule (e.g., LPS).
• MHC (Major Histocompatibility Complex): host receptor presenting peptide antigens to T cells.
• Opsonization: marking of pathogens to enhance phagocytosis.
• Memory cells: long-lived adaptive cells enabling rapid secondary responses.
• Hematopoiesis: formation of blood cells in bone marrow.

Action Items / Next Steps

• Review textbook sections on antimicrobial peptides, PRRs/PAMPs, complement, and cytokine categories.
• Practice diagramming: barrier→innate→adaptive flow; APC-T/B activation; antibody isotype functions and locations.
• Compare primary vs secondary response timelines and roles of memory cells.
• Study immune disorders: mechanisms of Type I and Type IV hypersensitivities; key autoimmune examples; primary vs secondary immunodeficiencies.