A hypersensitivity reaction is the immune system overreacting or misfiring against something it shouldn't — and there are four distinct ways that can happen, remembered by the mnemonic ACID.

ACID:

• A — Allergic (Type I)
• C — Cytotoxic (Type II)
• I — Immune complex (Type III)
• D — Delayed (Type IV)

Type I — Allergic:

The first time you meet an allergen, your body makes IgE antibodies against it, and those IgE molecules attach themselves to the surface of mast cells and basophils — this priming step is called sensitization, and by itself it causes no symptoms. The problem happens on re-exposure: the allergen comes back, binds to two nearby IgE molecules at once (cross-links them), and that cross-linking triggers the mast cell to dump its contents — degranulation. This releases histamine and other mediators within minutes, which is why Type I reactions are so fast.

Type II — Cytotoxic:

Here, an antibody (IgG or IgM) attacks an antigen that is sitting directly on the surface of a cell — your own cell, or a foreign one like a transfused red blood cell. Complement, phagocytes, and NK cells are recruited to destroy that cell. Because it takes time to mount that antibody attack and recruit the killing machinery, onset is hours to days.

Some Type II autoantibodies don't destroy the cell at all — instead they attach to a hormone or neurotransmitter receptor sitting on the cell surface and either turn its activity up or down. That's exactly what's going on in two of this type's prototype diseases: in Graves disease the antibody over-activates the receptor, and in myasthenia gravis the antibody blocks it — opposite effects, but both are still Type II, because in each case the antibody is attacking a receptor sitting on the cell surface.

Type III — Immune complex:

This is the one students most often confuse with Type II, so hold the picture carefully: here the antibody and antigen are not attached to any cell. Instead they find each other while floating free in the bloodstream, clump together into immune complexes, and only afterward deposit into tissue — commonly the kidneys, joints, skin, and blood vessels. Once lodged there, they trigger complement and draw in neutrophils, which is what causes the local damage. Because it depends on how much complex forms and where it lands, onset is variable. One more thing worth memorising in the book's own words: **Type III is not organ specific. The complexes form in the blood, so they land wherever the circulation happens to drop them — most often as inflamed blood vessels in the skin, kidney or lung. That is the cleanest way to keep Type II and Type III apart: Type II has a target; Type III does not. (Your book names two patterns — serum sickness when it's body-wide, the Arthus reaction** when it stays local to the skin.)

Type IV — Delayed:

This type has no antibody involved at all. Instead, T cells (both CD4+ and CD8+) directly recognize the antigen, release cytokines, and recruit macrophages to the site. Because it depends on T cells mobilizing rather than a fast antibody reaction, it takes 24–72 hours to show up — hence "delayed." (Your slides 29 and 46 say 48–72. Know both; the textbook's window is the wider one.)

Type I mediators and what each one does:

• Histamine → widens blood vessels (vasodilation) and makes them leakier (increased vascular permeability)
• Leukotrienes → tighten the airways (bronchoconstriction)
• Prostaglandins → drive inflammation
• All of them together → more mucus. This is the one that actually blocks the airway, and it's why an allergic attack makes someone wheeze and struggle to breathe rather than just producing a runny nose. Hold onto it — it comes back in asthma, in unit 4.

The mechanism chains, spelled out in order — this is the part worth memorizing as a sequence:

Type I:

1. Antigen enters the body
2. A B-cell recognizes it
3. The B-cell matures into a plasma cell
4. The plasma cell produces IgE
5. IgE coats a mast cell (this is sensitization)
6. On re-exposure, the mast cell degranulates
7. Histamine is released

Type II:

1. Antibodies attach to an antigen sitting on a cell surface
2. Complement is activated
3. The cell wall is attacked
4. The cell lyses (bursts)
5. The debris is cleared by phagocytosis

Type III:

1. Antibodies bind antigens while both are free in the blood
2. Immune complexes form
3. The complexes deposit in vessels or tissues
4. Complement is activated at that site
5. Neutrophils arrive and try to eat the complexes — they are the main cell in Type III
6. They cannot engulf them properly, so they spill their lysosomal enzymes into the surrounding tissue instead
7. That spill is what does the damage

Type IV:

1. A macrophage presents the antigen
2. A T-lymphocyte becomes sensitized to it
3. Lymphokines are released
4. Inflammation and cell lysis follow
5. Tissue destruction results

Granuloma formation: sometimes the T cells and macrophages in a Type IV reaction can't fully get rid of the antigen. When that happens, they wall it off inside a granuloma instead — a strategy that contains the antigen but can itself cause organ dysfunction if the granuloma grows or sits somewhere that matters.

Each hypersensitivity type has its own signature diseases, and this course makes two deliberate classification calls that you should reproduce exactly as given, even if they feel surprising.

Why symptoms vary so much within Type III: the mechanism is the same everywhere (complexes form in blood, then deposit), but where they happen to land determines what you see clinically.

Where Type III complexes deposit determines the symptoms:

Treatment for each hypersensitivity type follows logically from its mechanism — calm the mediator, stop the antibody attack, or suppress the immune cells doing the damage.

Anaphylaxis treatment algorithm (high yield — know this cold):

1. Manage exposure — remove the allergen; assess airway, breathing, and circulation
2. Confirm anaphylaxis — any ONE of: (a) acute onset with skin/mucosal involvement plus respiratory distress, low blood pressure, or GI symptoms; (b) two or more symptoms rapidly after a likely exposure; (c) reduced blood pressure after a known allergen
3. Give epinephrine IM in the anterolateral thigh immediately — 0.3 mg for adults and children over 25 kg; 0.15 mg for children 5–25 kg. Repeat every 5–15 minutes as needed. Position the patient supine with legs elevated. These come from your eDapt Week 1 module — you confirmed that yourself. Chapter 48 covers anaphylaxis but gives no dose and no route, and they are in none of your slides, key points or recordings, so eDapt is where they live. Nobody here has a copy of eDapt to read, so the numbers are not double-checked against anything — but they match standard practice.
4. Activate emergency response
5. Monitor continuously — vitals, supplemental oxygen, IV normal saline, and CPR if indicated
6. Document the allergen and the patient's response

HIV works by hijacking the very cells that are supposed to organize the immune response, then rewriting the host's own genetic instructions so it can keep replicating.

HIV is an RNA retrovirus that primarily infects CD4+ T cells — the cells that direct and coordinate the rest of the immune response. Once inside a host cell, HIV uses an enzyme called reverse transcriptase to convert its RNA into DNA (the reverse of the normal DNA-to-RNA direction, which is where the name comes from). That new DNA is then integrated into the host's own genome, which lets the virus replicate within host cells.

The downstream chain of damage:

1. CD4+ T cells are progressively depleted
2. This causes loss of cell-mediated immunity
3. Which leads to opportunistic infections and malignancies

AIDS is the diagnosis given once the CD4 count drops below 200 cells/mm³, or once the person develops an AIDS-defining illness — either one is sufficient.

Antiretroviral therapy (ART) works by targeting different stages of the HIV life cycle described above (for example, blocking reverse transcriptase or integration) to suppress replication and let the immune system recover.

The three stages, in order.

1. ACUTE HIV — about 2 to 4 weeks in (your module says 2-3). Flu-like, or nothing at all. Viral load is sky-high and they're highly contagious.
2. CLINICAL LATENCY — quiet years. The virus keeps copying itself, CD4 counts creep down, usually no symptoms. How long: the textbook says 10 to 11 years untreated, or decades on good treatment. Your module says "a year or more", which badly undersells it — go with the book.
3. AIDS — CD4 drops below 200, or an opportunistic infection or certain cancers appear. Whichever comes first.

SLE starts with the immune system losing the ability to tell 'self' from 'not-self,' and everything else follows from that one failure.

In one sentence: loss of self-tolerance leads to autoantibodies against the body's own nuclear material, those autoantibodies form immune complexes that deposit in tissues, and the result is multi-organ inflammation.

The chain in more detail:

1. T cells fail to distinguish self from non-self
2. This triggers inflammatory cytokines
3. Which activates B cells
4. Activated B cells produce autoantibodies

The autoantibodies produced — especially ANA (antinuclear antibody) — bind to the body's own nuclear material and form immune complexes, which then deposit in tissue. That deposition activates complement and recruits neutrophils, producing inflammation, vasculitis, tissue damage, and scarring.

Diagnosing SLE relies on antibody tests that each play a different role — one to screen, one to confirm, and one that indirectly measures how much immune-complex damage is happening.

SLE symptoms touch nearly every organ system, and most of them trace back to the same Type III immune-complex mechanism — except the blood findings, which are Type II.

SLE treatment is layered — a foundational drug nearly everyone takes, something stronger for active flares, and escalation only when organs are threatened.

• NSAIDs — for mild joint pain and serositis
• Antimalarials (hydroxychloroquine) — foundational therapy for nearly all patients
• Corticosteroids — the mainstay for flares; a higher dose acutely, then tapered down
• Immunosuppressives — azathioprine, mycophenolate, cyclophosphamide, used for organ-threatening disease
• Biologics — belimumab
• Lifestyle and support — sun protection (because of photosensitivity), regular monitoring, a healthy lifestyle

SLE has no cure — it follows a lifelong pattern of exacerbations (flares) and remissions, which is why treatment is about controlling flares rather than curing the disease.

Graves is the Type II example where the antibody doesn't kill the cell — it jams the switch ON.

An antibody sits on the thyroid's ON button and holds it down.

Normally the pituitary controls the thyroid with TSH — press the button, get thyroid hormone. In Graves, an antibody (TSI, also called TSAb or TRAb) binds that same button and presses it constantly. The gland swells (goiter) and pumps out T3 and T4.

How they test for it.

• TSH — low.
• T3 and T4 — high.
• TRAb / TSI — looks for the antibody itself.
• Iodine uptake scan — the thyroid is greedy for iodine, so it lights up bright and evenly all over. That even, high pattern says Graves.
• Ultrasound — big gland with lots of blood flow. Your deck nicknames it the “thyroid inferno”.

How they treat it.

• Methimazole — the usual first drug. Fewer side effects, so it's preferred for most people.
• PTU — the one used in pregnancy. This comes from your eDapt module, which you confirmed. If a question gives you a pregnant patient with Graves, PTU is the answer. The reason: methimazole carries a risk to the baby early on, so the usual first choice gets swapped for PTU. (Standard practice narrows this to the first trimester and then switches back to methimazole — but your own course says "pregnant women", so don't let the extra detail argue you out of PTU.)
• Beta blockers — don't touch the thyroid at all. They just calm the racing heart and palpitations while the other drugs work.
• Radioactive iodine (I-131) — kills the gland off. No surgery needed.
• Surgery (thyroidectomy) — take the gland out.

Two signs that only happen in Graves: eyes bulging forward (exophthalmos), and thick, lumpy, discoloured skin on the shins (pretibial myxedema). Someone whose overactive thyroid is caused by lumps in the gland instead won't have either.

Alloimmunity is when the immune system attacks tissue from another person of the same species — a different problem from autoimmunity, where it attacks itself.

• Transfusion reactions — caused by ABO incompatibility, which is exactly why blood typing and cross-matching before a transfusion are essential. Type O is the universal donor and Type AB is the universal recipient, because people with Type AB blood don't have anti-A or anti-B antibodies of their own.
• Transplant rejection — the recipient's immune system attacks the donor tissue as foreign, in three patterns — see the table below.
• Hemolytic disease of the newborn (Rh incompatibility) — see the mechanism below

The three patterns of transplant rejection:

Hemolytic disease of the newborn — also called hemolytic disease of the fetus and newborn (HDFN) or erythroblastosis fetalis — step by step:

1. An Rh-negative mother is exposed to Rh-positive fetal blood
2. Her immune system produces anti-Rh antibodies in response
3. In any later pregnancy with an Rh-positive baby she makes those antibodies faster and in greater amounts, and they cross the placenta
4. They destroy the fetal red blood cells
5. The newborn presents with jaundice and anemia

This is also classified as a Type II reaction — the antibody is attacking an antigen sitting directly on the fetal red blood cells. Prevention is RhoGAM (Rh immunoglobulin), given to Rh-negative mothers so their immune system never mounts that anti-Rh antibody response in the first place.

Your body stops invaders in three stages. Each one takes over when the one before it is broken through.

1. BARRIERS — keep it out.

Walls and washes. Physical ones are solid surfaces: skin, the linings of your mouth and gut. Mechanical ones move things out: tiny hairs (cilia) sweeping, plus coughing, sneezing, peeing, vomiting. Biochemical ones are fluids that trap and kill: mucus, sweat, saliva, tears, earwax.

None of this cares what the invader is. It blocks everything the same way. Your normal gut and skin bacteria count here too — they crowd out the harmful ones.

2. INFLAMMATION — contain it and kill it.

If something gets through, this kicks in within minutes. Still not fussy about what it is — it reacts the same to anything.

• Neutrophils arrive first. They roll to the edge of the blood vessel (margination), squeeze out through the wall (diapedesis), then eat the invader (phagocytosis). Remember the order — it gets asked.
• Macrophages eat too, and shout for help by releasing cytokines.
• Mast cells dump histamine, then make more chemicals — including PAF.
• Three protein systems switch on together: complement, clotting, kinin. Three. Not four — PAF is not one of them, even though your module lists it there.
• Complement does more than leak fluid: it tags bacteria so phagocytes grab them (opsonization), and it can drill holes straight through them.

3. ADAPTIVE IMMUNITY — remember it.

Now it gets specific. A macrophage or dendritic cell eats the invader and shows a piece of it to a CD4+ helper T cell — like handing over a mugshot.

That helper T cell is the conductor. It switches on killer (CD8+) T cells, macrophages, and B cells — and B cells turn into factories pumping out antibodies aimed at that exact invader.

The core question that separates these two is simple: was the immune system ever normal? If it was built defective, it's primary; if it was normal and then damaged, it's secondary.

Cancer-induced immunodeficiency (covered explicitly in this course) — three separate ways cancer suppresses immunity:

• Chronic inflammation from the malignancy itself suppresses adaptive immunity, by activating immunosuppressive cells and promoting new blood vessel growth (angiogenesis) that feeds the tumor
• Advanced cancer creates acidic local conditions and releases metabolites that directly inhibit immune cell function
• Cancer treatments themselves are immunosuppressive — corticosteroids, antirejection medications, chemotherapy, radiation

CVID is the primary (congenital) immunodeficiency that often goes unrecognised for years, because it can start in childhood or in adulthood — that spread is exactly what makes it easy to miss.

• It is the most common symptomatic primary immunodeficiency — the textbook says that plainly, without limiting it to adults
• Low IgG, plus low IgA and/or IgM → the body mounts a poor antibody response overall. B-cell counts are normal in CVID — that's what separates it from Bruton agammaglobulinemia, where B cells are nearly absent (under 2%).
• It has two peak ages when it shows up: once before age 10, and again between 30 and 40. Do not assume it is adults-only — the textbook gives both peaks
• About 90% of patients have recurrent infections — sinopulmonary (otitis, sinusitis, and pneumonia, most often from S. pneumoniae and H. influenzae) and GI infections — plus an increased risk of autoimmune disease and cancer (lymphoid, skin, and GI). Interstitial lung disease is also a significant cause of illness and death in CVID.
• Treatment: IVIG replacement therapy