IS LEC

Here is a comprehensive high-yield exam reviewer based on your Immunology & Serology (MLS 412) notes:

IMMUNOLOGY & SEROLOGY — HIGH YIELD EXAM REVIEWER

PART 1: HISTORY OF IMMUNOLOGY

Key Scientists to Remember:

Key Terms:

• Immunis = Latin for "exempt"

• Cross-reactivity = antibody for one antigen binds a similar antigen (cowpox → smallpox)

• Herd immunity = sufficient proportion immune → prevents spread

• Last natural smallpox case: Somalia, 1977

PART 2: ORGANS OF THE IMMUNE SYSTEM

Lymph Node Layers: Cortex (B cells, macrophages, follicular dendritic cells) → Paracortex (T cells) → Medulla

PART 3: INNATE vs. ADAPTIVE IMMUNITY

External Defense (1st line): Skin (keratin, lactic/fatty acids, pH 5.6), mucous membranes, lysozymes (attack gram+ bacteria), normal flora (competitive exclusion), cilia, HCl (stomach, pH ~1)

Internal Defense (2nd line): PRRs, PAMPs, Toll-Like Receptors (10 in humans), Acute Phase Reactants

Acute Phase Reactants (produced by hepatocytes/liver): CRP, Serum Amyloid A, Complement components, Alpha-1-antitrypsin, Haptoglobin, Fibrinogen, Ceruloplasmin

• Exceptions: C1 = intestinal epithelial cells; Factor D = adipose tissue

PART 4: C-REACTIVE PROTEIN (CRP) — HIGH YIELD

• Binds phosphocholine (calcium-dependent, nonspecific)

• Activates classical complement pathway via C1q

• Increases within 4–6 hours, peaks at 48 hours, half-life = 19 hours

• Increases 100–1000 fold during infection

• Most widely used indicator of acute inflammation

• Cardiovascular risk threshold: >2 mg/L (male: 1.5 mg/L; female: 2.5 mg/L)

• Pentamer (5 identical subunits); family = pentraxins

PART 5: INFLAMMATION

5 Cardinal Signs (Aulus Cornelius Celsus + Rudolf Virchow):

• Redness (Rubor), Swelling (Tumor), Heat (Calor), Pain (Dolor), Loss of function (Functio Laesa)

Key Cells:

• Diapedesis = WBC movement from blood vessel → tissue

• Chemotaxis = movement toward site of infection following chemokines

• Neutrophils mobilize in 30–60 min, last 24–48 hr

• Macrophages peak at 16–44 hr

PART 6: PHAGOCYTOSIS

Steps: Adherence → Engulfment → Phagosome → Phagolysosome → Digestion → Exocytosis

Most active phagocytes: Neutrophils, Monocytes, Macrophages, Dendritic Cells

Oxygen-Dependent Killing:

• HMP shunt → NADPH → Superoxide (O₂⁻) → H₂O₂ → Hypochlorite (OCl⁻/bleach) via Myeloperoxidase

• Superoxide kills anaerobes; H₂O₂ kills most aerobes (except catalase-producers like Staph, MTB); Hypochlorite = most powerful, kills ALL

Oxygen-Independent: Defensins (destroy cell wall), Cathepsin G (destroy cell membrane)

Chronic Granulomatous Disease (CGD): X-linked recessive; absent NADPH oxidase → no respiratory burst → bacteria survives in phagolysosome → granuloma formation

PART 7: CELLS OF THE INNATE IMMUNE SYSTEM

Macrophage Locations (HIGH YIELD):

PART 8: ADAPTIVE IMMUNITY

Key Features: Specificity, Memory, Increased response upon re-exposure

T cells (60–80% of lymphocytes):

• Mature in thymus

• CD4+ (Helper T) = 2/3 of peripheral T cells; recognize Class II MHC

• CD8+ (Cytotoxic T) = 1/3; recognize Class I MHC

• Mnemonic: CD4 × 2 = 8; CD8 × 1 = 8

T Cell Differentiation Stages:

1. Double Negative (DN) — no CD4/CD8

2. Double Positive (DP) — both CD4 and CD8

3. Positive Selection — must recognize MHC (intermediate binding)

4. Negative Selection — self-reactive clones eliminated (only 1–3% DP survive)

5. Single Positive — either CD4 or CD8

T Helper Cell Subtypes:

B Cell Development:

• Pro-B → Pre-B (μ chains in cytoplasm) → Immature B (complete IgM on surface) → Mature B (IgM + IgD)

• Plasma cells produce antibodies; Memory cells remember antigen

• Antigen-independent maturation = bone marrow

• Antigen-dependent maturation = spleen/lymph nodes

Clusters of Differentiation (CD):

• B cells: CD19 + surface antibody

• All T cells: CD3, CD2

• Helper T: CD4

• Cytotoxic T: CD8

• NK cells: CD16, CD56

PART 9: ANTIGENS

• Immunogen = induces immune response (all immunogens are antigens; not all antigens are immunogens)

• Hapten = small, antigenic but NOT immunogenic alone; needs carrier molecule; <10,000 daltons

• Epitope/Determinant = molecular shape recognized by B/T cells (found on antigen)

• Paratope = binding site on antibody

Factors Affecting Immunogenicity:

• Foreignness, Degradability, Molecular Weight (>10,000 Da recognized; >100,000 Da most potent), Structural Stability, Chemical Complexity

• Host factors: Age, Genetic predisposition (MHC genes), Overall health

• Exposure: Dose, Route of inoculation

Adjuvants = substances that enhance immune response (e.g., alum, water, squalene, Complete Freund's Adjuvant)

PART 10: ANTIBODIES (IMMUNOGLOBULINS)

Structure: 2 heavy + 2 light chains (Y-shape); Fab (antigen-binding) + Fc (complement/effector binding)

• Hinge region = disulfide bonds

• Fab = 1 light chain + ½ heavy chain

• Fc = 2 heavy chains

Heavy chain chromosomes: 14 | Kappa (κ): chromosome 2 | Lambda (λ): chromosome 22

• Kappa:Lambda ratio = 3:1

Immunoglobulin Classes (HIGH YIELD):

Bence-Jones Proteins = free light chains in urine; Multiple Myeloma; κ (60%) & λ (40%); precipitate at 60–70°C, dissolve at 100°C

Antigen-Antibody Reactions:

• Affinity = single Fab–single epitope attraction

• Avidity = overall strength of multivalent binding

• Agglutination = IgM best (large, multivalent, bridges zeta potential of RBCs)

• Precipitation = IgG best (small soluble particles)

• Opsonization = enhanced phagocytosis; C3b and IgG coat pathogen

• ADCC = NK cells lyse antibody-coated cells via CD16

Monoclonal Antibodies:

• Hybridoma = B cell (plasma cell) fused with myeloma cell

• PEG (Polyethylene Glycol) = promotes fusion

• HAT medium selects hybridomas (blocks myeloma without HGPRT)

• Drugs with -mab suffix = monoclonal antibodies

PART 11: COMPLEMENT SYSTEM

General: Heat-labile; major fraction of beta globulins; innate humoral immunity; produced by liver (except C1 = intestinal epithelial; Factor D = adipose)

Nomenclature:

• "b" fragment = larger (binds); "a" fragment = smaller (anaphylatoxin)

• Exception: C2 — "a" is LARGER, "b" is smaller

• Most potent anaphylatoxin = C5a

Three Pathways:

MAC (Membrane Attack Complex): C5b + C6 + C7 + C8 + C9 → pore formation → cell lysis

• C8 starts pore formation

• C9 polymerizes to initiate lysis

• C3 is present in ALL pathways

Complement Regulatory Proteins:

Disease Associations:

• C1 deficiency → SLE-like syndrome

• C2 deficiency → SLE-like + recurrent infection (affects classical & MBL)

• C3 deficiency → severe recurrent infections (ALL pathways affected)

• C5-C8 deficiency → Neisseria infections

• C1 INH deficiency → Hereditary Angioedema (↑ bradykinin → ↑ vascular permeability)

• Factor H deficiency → recurrent bacterial infection

Destruction In Vitro: EDTA (chelates Ca²⁺/Mg²⁺); Heat at 56°C/30 min inactivates C1, C2, C4; Storage affects C4

PART 12: HLA / MHC

• Coded on short arm of chromosome 6 (6p21)

• Named by Jean Dausset

• HLA-DR = highest expression of Class II

• HLA-C = lowest Class I expression

• MHC Class I holds 8–11 amino acids; Class II holds 13–18 amino acids

• HLA-G = expressed on fetal cells; prevents NK cell attack on fetus (inhibits maternal NK cells)

PART 13: CYTOKINES

Actions: Autocrine (self), Paracrine (nearby cells), Endocrine (distant sites via blood)

Five Attributes: Pleiotropy, Redundancy, Synergy, Antagonism, Cascade Induction

Key Cytokines:

Cytokine Storm = hypercytokinemia; caused Spanish flu deaths; COVID-19, Ebola, Toxic Shock Syndrome Toxic Shock Syndrome: S. aureus TSST-1 (superantigen) → massive T cell activation → cytokine storm → shock

PART 14: HYPERSENSITIVITY

Gell-Coombs Classification:

Type I — Key Points:

• IgE bound to mast cells/basophils via Fc-εRI receptors

• Sensitization phase = first exposure → IgE production

• Activation phase = re-exposure → degranulation → histamine release

• Prausnitz-Küstner experiment = demonstrated passive transfer of allergy via serum

• Test: Skin Prick Test (screening) → Intradermal (confirmatory); RIST = total IgE; RAST = allergen-specific IgE

Type II — Key Diseases:

• Hemolytic Disease of the Newborn (HDN): Rh- mother + Rh+ baby → anti-Rh IgG crosses placenta → destroys fetal RBCs; Kernicterus = bilirubin crosses blood-brain barrier; prevent with RhoGAM

• Myasthenia Gravis: Anti-ACh receptor antibodies → muscle weakness (inhibition)

• Grave's Disease: TSI/TRAb binds TSH receptor → hyperthyroidism (stimulation)

Type III — Key Diseases:

• SLE: ANA, anti-dsDNA, anti-Sm antibodies; immune complexes deposited in kidneys, skin, joints; butterfly rash; photosensitive; diagnosis: ANA test, ↓ complement (C3, C4)

• RA: RF (IgM vs. IgG Fc) + anti-CCP; anti-CCP more specific; HLA-DR4; smoking = strongest trigger; pannus formation

• Arthus Reaction: Local immune complex deposition at injection site

Type IV — Key Points:

• First described by Robert Koch (1890)

• Triggered by intracellular organisms: MTB, Leishmania, HSV; contact Ag: urushiol (poison ivy)

• Sensitization: APCs → Th1 → memory T cells (1–2 weeks)

• Re-exposure: IFN-γ, TNF → macrophage recruitment → tissue damage

PART 15: AUTOIMMUNITY

Definition: Immune system attacks self-antigens; Paul Ehrlich = "horror autotoxicus"

Tolerance Mechanisms:

• Central Tolerance: Negative/positive selection in thymus (T cells) and bone marrow (B cells) during fetal development

• Peripheral Tolerance: Backup; clonal deletion, anergy, Treg suppression

HLA Associations:

• HLA-B27 → Ankylosing Spondylitis

• HLA-DR3/DR4 → Type 1 Diabetes Mellitus, SLE

• HLA-DR4 → Rheumatoid Arthritis

• HLA-DR3/DQ → Sjögren's Syndrome

• HLA-DR2/DR3 + C4/C2 deficiency → SLE

Systemic Autoimmune Diseases:

Organ-Specific Diseases:

PART 16: IMMUNODEFICIENCY DISORDERS

Primary (inherited) vs. Secondary (acquired)

B-Cell Deficiencies:

QUICK REVIEW: BOARD EXAM FAVORITES

• Most potent anaphylatoxin = C5a

• C8 starts pore formation in MAC; C9 initiates lysis

• C3 is present in ALL complement pathways

• IgM = best at agglutination & complement fixation; first antibody in primary response

• IgG = most abundant; crosses placenta (not IgG2); longest half-life; best in secondary response

• IgE = allergies; binds mast cells; heat-labile at 56°C

• IgA = mucosal secretions; secretory component

• IgD = B cell maturation marker

• CD4 × MHC II = 8; CD8 × MHC I = 8

• MHC coded on chromosome 6p21

• Bruton's = BTK mutation; males only; pre-B cell arrest

• Chronic Granulomatous Disease = no NADPH oxidase; no respiratory burst

• Papain digestion = 2 Fab + 1 Fc (Pa-pa-in = 2+1=3)

• HAT medium selects hybridomas; HGPRT needed to survive

• Bence-Jones proteins = free light chains; precipitate at 60–70°C; dissolve at 100°C

• CRP half-life = 19 hours; peaks at 48 hours; family = pentraxins

• NK cells kill via "missing self" — target cells that lack Class I MHC

• Germinal center = where B cell differentiation occurs (in lymph nodes)

• HLA-G = protects fetus from NK cell attack

Good luck on your exams! Let me know if you want me to dive deeper into any specific topic.