Type I — Immediate Hypersensitivity

Mechanism: First exposure → B cells make IgE antibodies → IgE coats mast cells (sensitization). Second exposure → antigen cross-links IgE on mast cells → mast cells degranulate → histamine flood → vasodilation, bronchoconstriction, increased permeability, itching.

• Mild: Hay fever (rhinitis), hives (urticaria), watery eyes
• Severe: Anaphylaxis — airway closure, BP crash, death within minutes without epinephrine

Type II — Cytotoxic Hypersensitivity

Mechanism: Antibodies (IgG or IgM) bind directly to antigens on your own cell surfaces → complement activates → cell is lysed (destroyed). The antibody paints a target on your cells, and complement blows them up.

• ABO transfusion reaction: Give type A blood to a type B patient → anti-A antibodies attack the donated RBCs → massive hemolysis → kidney failure
• Erythroblastosis fetalis: Rh-negative mom makes antibodies against Rh-positive baby's RBCs
• Drug-induced hemolytic anemia: Some drugs bind to RBC surface, triggering antibody attack

Type III — Immune Complex

Mechanism: Antigen + antibody form immune complexes (clumps) → complexes deposit in tissues (joints, kidneys, blood vessel walls) → complement activates at the deposit site → inflammation and tissue damage.

• SLE: Complexes deposit everywhere (kidneys, joints, skin, brain)
• Serum sickness: Reaction to foreign proteins (antivenom, some drugs)

Type IV — Delayed / Cell-Mediated

Mechanism: No antibodies involved — this one is all T cells. Sensitized T cells encounter the antigen → release cytokines → recruit macrophages → inflammation peaks at 24–72 hours.

• Contact dermatitis: Poison ivy, nickel allergy, latex reaction
• TB skin test (PPD/Mantoux): Read at 48–72 hours because Type IV takes time
• Transplant rejection: T cells attack the foreign organ

Systemic Lupus Erythematosus (SLE)

The Analogy

SLE is like a rogue demolition crew that can't read blueprints — it tears down the building it was supposed to protect. It can hit any organ system, which is why SLE is called the "great imitator" — it mimics dozens of other diseases.

The Mechanism

• Type III hypersensitivity — body makes antibodies against its own DNA and nuclear components
• Immune complexes deposit in kidneys, joints, skin, brain, heart, lungs
• Chronic inflammation damages every tissue they settle in
• Characteristic ANA (antinuclear antibody) test is positive

The Clinical Connection

• Butterfly (malar) rash: Red rash across nose and cheeks — triggered or worsened by sunlight
• Kidney involvement (lupus nephritis): The #1 cause of death in SLE patients
• Joint pain: Mimics rheumatoid arthritis but usually non-deforming
• Flares and remissions — stress, sunlight, and infection trigger flares
• More common in women of childbearing age (9:1 female-to-male ratio)

Rheumatoid Arthritis (RA)

The Mechanism

• Autoimmune attack on the synovial membrane (the lining inside joints)
• T cells activate → inflammatory cytokines released → synovium thickens (pannus formation) → cartilage and bone erode over time
• Symmetric joint involvement (both hands, both knees — not just one side)

The Clinical Connection

• Morning stiffness > 1 hour (vs. osteoarthritis stiffness <30 min)
• Affects small joints first: fingers (MCP, PIP joints), wrists
• Swan-neck and boutonniere deformities in advanced disease
• Rheumatoid factor (RF) positive in ~80% of patients

Selective IgA Deficiency

The most common primary immunodeficiency. IgA is the antibody that guards your mucosal surfaces — the mouth, nose, gut, and lungs. Without it, those front doors are unlocked.

• Recurrent respiratory and GI infections (sinusitis, pneumonia, diarrhea)
• Many patients are asymptomatic — other antibodies partially compensate
• Transfusion risk: Can have anaphylaxis to blood products containing IgA because their body sees IgA as foreign

DiGeorge Syndrome

Chromosome 22q11.2 deletion → thymus fails to develop → T cells can't mature. No mature T cells means no cell-mediated immunity.

• CATCH-22: Cardiac defects, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia (missing parathyroids) — chromosome 22
• Recurrent viral and fungal infections (T cells normally fight these)
• Low calcium → tetany, seizures (parathyroid glands also fail to develop)

HIV / AIDS

HIV specifically targets and destroys CD4+ T helper cells — the generals that coordinate the entire immune army. Without them, the rest of the immune system falls apart.

• CD4 count: Normal = 500–1,500 cells/μL
• AIDS defined: CD4 < 200 cells/μL OR development of an AIDS-defining illness (Pneumocystis pneumonia, Kaposi sarcoma, etc.)
• HIV is a retrovirus — uses reverse transcriptase to insert its DNA into the host T cell
• Progressive decline: acute infection → clinical latency (years) → AIDS

Leukemia — Cancer of the Blood-Forming Cells

The bone marrow produces massive numbers of immature, non-functional WBCs that crowd out normal blood cells. The patient ends up with high WBC counts but a broken immune system — plus anemia (low RBCs) and thrombocytopenia (low platelets) because the marrow is full of useless blasts.

Lymphoma — Cancer of the Lymphatic System

Unlike leukemia (bone marrow), lymphoma starts in the lymph nodes. The lymphocytes become malignant inside the lymphatic tissue.

Anemia of Acute Blood Loss

• Cause: Sudden hemorrhage — trauma, surgery, ruptured aneurysm
• Signs: Tachycardia, hypotension, cool/clammy skin, decreased urine output
• Key point: Hematocrit drops only after IV fluids dilute the remaining blood — initial labs can look falsely normal
• Treatment: Stop the bleeding, IV fluids, blood transfusion

Anemia of Chronic Blood Loss

• Cause: Slow, ongoing bleeding — GI ulcers, heavy menstrual periods, colon cancer
• Over time, iron stores deplete → evolves into iron-deficiency anemia
• Patient often doesn't realize they're bleeding (occult blood in stool)
• Treatment: Find and fix the bleeding source + oral iron supplementation

Iron-Deficiency Anemia

The most common anemia worldwide. Not enough iron → not enough hemoglobin → RBCs are small and pale (microcytic, hypochromic).

• Symptoms: Fatigue, pallor, brittle nails (koilonychia/spoon nails), pica (craving ice, dirt, starch)
• Labs: Low ferritin (iron stores), low serum iron, elevated TIBC (body is hungry for iron)

Pernicious Anemia

Can't absorb vitamin B12 because the stomach lacks intrinsic factor (a protein the stomach makes specifically to grab B12 in the gut). Without B12, RBCs grow too large and can't divide properly → macrocytic (megaloblastic) anemia.

• Symptoms: Fatigue + neurological changes (paresthesia, balance problems, memory loss) — B12 is needed for nerve myelin
• Key distinction: The neuro symptoms are what separate B12 deficiency from folate deficiency (both cause macrocytic anemia, but only B12 deficiency causes neuro damage)
• Treatment: IM B12 injections for life (oral B12 won't help because the absorption problem is in the gut)

Sickle Cell Anemia

A single gene mutation produces abnormal hemoglobin S (HbS) instead of normal hemoglobin A. Under low-oxygen conditions, HbS polymerizes and forces the RBC into a rigid crescent (sickle) shape.

• Autosomal recessive: Both parents must carry the gene (carriers have sickle cell trait and are usually asymptomatic)
• Sickled RBCs: Rigid → get stuck in small vessels → vaso-occlusive crisis (severe pain, organ damage)
• Triggers for sickling: Dehydration, infection, cold, high altitude, stress (anything that lowers O₂)
• Complications: Stroke, splenic sequestration, acute chest syndrome, chronic organ damage
• Treatment: Hydroxyurea (increases fetal hemoglobin, which resists sickling), pain management, hydration, blood transfusions

Hemolytic Anemia & Erythroblastosis Fetalis

Hemolytic anemia = RBCs are destroyed faster than the bone marrow can replace them. Causes include autoimmune reactions, infections, toxins, and mechanical damage (prosthetic heart valves).

Hemolytic Disease of the Newborn (Erythroblastosis Fetalis)

• Rh-negative mother carrying an Rh-positive baby
• First pregnancy usually fine. At delivery, fetal blood mixes with maternal blood → mom produces anti-Rh antibodies (sensitization)
• Second Rh-positive pregnancy: mom's antibodies cross the placenta → attack fetal RBCs → hemolysis → jaundice, anemia, hydrops fetalis
• Prevention: RhoGAM (Rh immunoglobulin) given at 28 weeks and within 72 hours after delivery — prevents mom from making antibodies
• Newborn treatment: Phototherapy (breaks down bilirubin from hemolysis), exchange transfusion in severe cases

Immune Thrombocytopenic Purpura (ITP)

Autoimmune destruction of platelets — the immune system makes antibodies that tag platelets for destruction by the spleen.

• Symptoms: Petechiae (pinpoint purple dots), purpura (larger purple patches), easy bruising, mucosal bleeding (gums, nosebleeds)
• Often follows a viral infection in children (post-viral ITP — usually self-limiting)
• Key: Platelet count is very low, but PT/aPTT are normal (the clotting factors work fine, there just aren't enough platelets)
• Treatment: Corticosteroids (suppress immune attack), IVIG, splenectomy in refractory cases

Hemophilia

Genetic deficiency of clotting factors. The platelets work, but the coagulation cascade breaks because a key factor is missing.

• Hemophilia A: Missing Factor VIII (most common — ~80% of cases)
• Hemophilia B (Christmas disease): Missing Factor IX
• X-linked recessive — almost exclusively affects males (mothers are carriers)
• Symptoms: Prolonged bleeding after minor cuts, hemarthrosis (bleeding into joints — most characteristic), deep tissue/muscle bleeds
• Labs: Prolonged aPTT, normal PT, normal platelet count
• Treatment: Replace the missing factor (recombinant Factor VIII or IX), desmopressin (DDAVP) for mild Hemophilia A

Hyperlipidemia

• Elevated cholesterol and/or triglycerides in the blood
• LDL ("bad" cholesterol): Delivers cholesterol INTO artery walls → plaque buildup
• HDL ("good" cholesterol): Removes cholesterol FROM artery walls → protective
• Treatment: Statins (HMG-CoA reductase inhibitors) are first-line — lower LDL by 30–50%

Hypertension

Persistent BP ≥ 130/80 mmHg (per 2017 ACC/AHA guidelines). Called the "silent killer" because most people have no symptoms until organ damage occurs.

• Primary (essential) HTN: ~95% of cases — no identifiable cause (genetic + lifestyle)
• Secondary HTN: Caused by renal disease, endocrine disorders, or medication
• Target organ damage: Heart (LV hypertrophy, CHF), brain (stroke), kidneys (nephrosclerosis), eyes (retinopathy)
• Treatment: Lifestyle first (DASH diet, Na <2,300 mg/day, exercise, weight loss). Medications: ACE inhibitors (-prils), ARBs (-sartans), beta-blockers (-olols), calcium channel blockers (-dipines), thiazide diuretics

Atherosclerosis

Chronic, progressive buildup of lipid-laden plaques (atheromas) inside arterial walls. This is the underlying cause of most heart attacks and strokes.

• Pathophysiology: Endothelial injury → LDL infiltrates → macrophages eat LDL → become foam cells → fatty streak → fibrous plaque → complicated plaque (calcification, rupture risk)
• Consequences: Angina, MI (heart attack), stroke, peripheral arterial disease (PAD), aortic aneurysm
• Risk factors: Smoking, diabetes, hypertension, hyperlipidemia, family history, obesity, sedentary lifestyle

Deep Vein Thrombosis (DVT)

Blood clot forms in a deep vein, usually in the legs. The big danger: the clot breaks loose and travels to the lungs → pulmonary embolism (PE) — a life-threatening emergency.

Virchow's Triad (3 causes of clot formation)

1. Stasis — blood flow slows down (bed rest, long flights, post-surgery immobility)
2. Endothelial injury — damage to the blood vessel wall (surgery, trauma, IV catheters)
3. Hypercoagulability — blood clots too easily (cancer, pregnancy, oral contraceptives, genetic clotting disorders)

• Symptoms: Unilateral leg swelling, warmth, redness, calf pain (positive Homans' sign is unreliable but still tested on exams)
• Diagnosis: Doppler ultrasound, D-dimer blood test
• Treatment: Anticoagulation (heparin → warfarin or DOACs)

Varicose Veins

• Superficial veins become dilated and tortuous because the one-way valves inside the vein fail
• Blood pools in the veins (venous insufficiency) instead of returning to the heart
• Risk factors: Prolonged standing, pregnancy, obesity, family history
• Complications: Venous stasis ulcers (typically at the medial malleolus/inner ankle), edema, thrombophlebitis
• Treatment: Compression stockings, leg elevation, sclerotherapy or surgery for severe cases