Immunity PowerNotes 2021

Immune System Overview

• Protection relies on two intertwined concepts: Inflammation + Immunity → working together = immunocompetence
• Immunity = body’s ability to resist disease
• Three overarching purposes of every immune response
  • Defense
  • Homeostasis (maintaining internal equilibrium)
  • Surveillance (constant scanning for “non-self”)
• Major anatomical/functional components repeatedly referenced
  • Complement system, thymus, bone marrow, spleen, lymph nodes, tonsils, Peyer’s patches, appendix, skin-associated lymphoid tissue, gut/genital/bronchial lymphoid tissue, hormones that influence immunity
  • Circulating cellular elements = Leukocytes (white blood cells)
• Each person’s cells display unique surface proteins = Human Leukocyte Antigen (HLA) → think of it as the body’s barcode; only an identical twin shares the same HLA set

Self/Non-Self Recognition & Self-Tolerance

• Self-tolerance = immune system normally recognizes & respects host tissues
• Failure → autoimmune disease
• Immune system must discriminate against a vast range of potential invaders
  • Pathogens: viruses, bacteria, fungi, protozoa
  • Environmental triggers: pollen, bee venom, foods, poison ivy resin
  • Iatrogenic/medical: transplanted tissue & transfused blood
• When triggered, the system acts to
  1. Neutralize
  2. Destroy
  3. Eliminate

The Three Processes Required for Protection

1. Inflammation (Innate, non-specific) – rapid mobilization of neutrophils & monocytes
2. Antibody-Mediated Immunity (AMI) / Humoral Immunity – B-cell driven, immunoglobulin production
3. Cell-Mediated Immunity (CMI) – T-cell and NK-cell driven, direct cellular attack

Types of Immune Response

• Innate (Natural) Immunity
  • Immediate, non-specific, present at birth
  • Barriers & reactions
  • Physical: intact skin, mucous membranes
  • Mechanical: coughing, sneezing, vomiting
  • Biochemical: gastric juice, tears, saliva, normal flora, interferons
  • Cellular/chemical: phagocytosis, complement cascade
  • Functions as the first line of defense
• Adaptive (Acquired) Immunity
  • Specific, has memory → second & third lines of defense
  • Two branches
  1. Antibody-Mediated (B-cell)
  2. Cell-Mediated (T-cell)
  • Acquisition routes
  • Naturally acquired active: infection with pathogen (e.g., \text{COVID-19})
  • Artificially acquired active: vaccination (e.g., mRNA COVID vaccine)
  • Naturally acquired passive: maternal IgG crossing placenta / breast-milk IgA
  • Artificially acquired passive: monoclonal antibody infusion or antiserum (e.g., laboratory-prepared COVID antibodies)

Lymphoid Organs

• Primary (site of development):
  • Bone marrow – B-cell maturation & all blood cell production
  • Thymus – T-cell maturation, thymic hormones guide differentiation
• Secondary (site of function/interaction):
  • Lymph nodes, spleen, tonsils, Peyer’s patches, appendix, mucosa-associated lymphoid tissue (MALT) in gut, genital, bronchial, skin

Leukocytes – “The Army”

• Granulocytes (contain cytoplasmic granules that release histamine, bradykinin, prostaglandins)
  • Basophils – “baaaad” allergies; elevation → allergic / hypersensitive reaction
  • Eosinophils – “eeeeewwww” worms; rise in parasitic infection & allergy
  • Neutrophils – primary bacterial defenders
  • Immature forms = bands (“left shift”) → lots of bands = severe infection/sepsis
  • Mature forms = segs (segmentals)
• Monocytes / Macrophages – “Pac-Man” professional phagocytes, antigen-presenting cells
• Lymphocytes
  • B cells → produce antibodies (AMI)
  • T cells → orchestrate & execute CMI (CD4 helpers, CD8 cytotoxic)
  • Natural Killer (NK) cells → innate, nonspecific cytotoxicity against tumor & virus-infected cells

Antibody-Mediated Immunity (Humoral Response)

• B-cells recognize extracellular antigens → differentiate into plasma cells → secrete immunoglobulins (antibodies)
• Five major classes (Table relationships captured below)

• Memory B-cells persist → quicker, stronger response on re-exposure

Cell-Mediated Immunity (T-cell Dominant)

• Activated when antigens reside inside cells (viruses, mycobacteria), with fungal infections, transplant rejection, or certain hypersensitivity reactions
• Major effector cells
  • T-Cytotoxic (CD8) – directly lyse target cells displaying foreign antigen
  • T-Helper (CD4) – “coordinators,” secrete cytokines that amplify B & T responses
  • Clinical tie-in: in HIV, monitor CD4; when count drops below 200 cells/µL → AIDS → high susceptibility to opportunistic infections
  • Natural Killer (NK) – innate lymphocytes, no prior sensitization, attack tumor & virus-infected cells; bridge innate + adaptive
• Visual mnemonic: killer T cell saying “You’re history!” while terminating cancer/virus-infected cell

Complement System (Brief Link)

• Group of >30 plasma proteins that, once activated, opsonize pathogens, recruit inflammatory cells, and puncture membranes (MAC formation)
• Tightly regulated to avoid host damage

Categories of Immunity – Summary Matrix

• Active vs. Passive & Natural vs. Artificial

• Active = long-lasting (memory)
• Passive = immediate but temporary (no memory)

Inflammatory Response – Key Points (Innate)

• Vasodilation, ↑ vascular permeability, leukocyte migration
• Chemical mediators released by granulocyte granules: histamine, bradykinin, prostaglandins
• Cardinal signs: redness, heat, swelling, pain, loss of function

Mechanical/Physical/Chemical Barriers – First Line Specifics

• Intact skin & mucous membranes
• Secretions containing lysozyme (tears, saliva)
• Gastric acidity, normal flora competition
• Mechanical clearance: cilia movement, coughing, sneezing, vomiting, urine flow
• Interferons – antiviral cytokines produced by infected cells

Ethical & Practical Implications / Real-World Links

• Transplantation: HLA matching crucial to minimize rejection (CMI involvement)
• Hypersensitivity reactions: Elevation in basophils/eosinophils & IgE hallmark; clinical preparedness for anaphylaxis
• Vaccination: Harnesses adaptive active immunity without disease burden; central to public health
• Monoclonal antibody therapy: Example of passive artificial immunity, offers targeted immediate protection (e.g., COVID neutralizing Abs)
• Autoimmunity: Breakdown of self-tolerance; understanding antigen recognition drives therapeutic development

Quick Memory Hooks & Metaphors

• Basophils = “Baaaad allergies”
• Eosinophils = “Eeeew worms”
• Macrophages = “Pac-Man” gobbling pathogens
• Bands vs. Segs = baby vs. adult neutrophils; lots of babies → severe infection
• HLA = body’s barcode

Numerical / Statistical References Recap

• Immunoglobulin serum percentages listed in LaTeX above (e.g., 76\% IgG)
• CD4 threshold for AIDS diagnosis: <200 cells/µL
• Complement cascade involves >30 proteins

Foundational Connections to Previous Lectures (Implied)

• Inflammation mediators parallel clotting cascade topics
• Relationship between endocrine hormones (e.g., cortisol) and immune suppression

Study Strategy Tips

• Master distinctions: Innate vs. Adaptive; AMI vs. CMI
• Associate immunoglobulin class with location & role (e.g., IgA → mucosa)
• Remember cellular nicknames to cue test answers (Pac-Man, worms, allergies)
• Use the active/passive matrix to categorize clinical scenarios quickly
• Practice interpreting CBC w/ differential: look for bands, eosinophilia, basophilia as clues