case 1 everything u need skidididipapa , except that osteopathic thing.

What is a hypersensitivity reaction?

It is an excessive or misdirected immune response that damages the host's own tissues instead of protecting them.

What are the two triggers of hypersensitivity?

Foreign antigens (allergens, microbes) and self-antigens (autoimmunity due to failure of self-tolerance).

What happens on first exposure to an allergen?

First exposure causes sensitization — no symptoms occur, but the immune system is primed to respond.

What happens on re-exposure to an allergen?

Re-exposure triggers the actual hypersensitivity reaction, which worsens with each subsequent exposure.

Which hypersensitivity types are antibody-mediated?

Types I, II, and III are all antibody-mediated; only Type IV is T-cell-mediated.

Type I hypersensitivity is mediated by which antibody?

IgE — it is the only hypersensitivity type that uses IgE.

Type II hypersensitivity is mediated by which antibodies?

IgG and IgM directed against antigens fixed on cell surfaces or the extracellular matrix.

Type III hypersensitivity is caused by what?

Circulating immune complexes (IgG or IgM bound to soluble antigens) that deposit in vessel walls and tissues.

Type IV hypersensitivity is mediated by what?

CD4+ T cells (Th1/Th17) and CD8+ cytotoxic T lymphocytes — no antibody is involved.

Why is Type IV called "delayed-type hypersensitivity"?

Because it takes 24-72 hours for circulating memory T cells to migrate to the site and secrete enough cytokines to cause a visible reaction.

If you see "antibody complex deposits" in a question, what type is it?

Always Type III — it is the only hypersensitivity type where antigen-antibody complexes deposit in tissues.

What are the key players in Type I hypersensitivity?

Th2 cells, IgE antibodies, mast cells, basophils, and eosinophils.

What other names are used for Type I hypersensitivity?

It is also called immediate hypersensitivity, allergy, or atopy; the triggering antigens are called allergens.

When is serum IgE normally elevated?

Serum IgE is normally very low, but becomes elevated in atopic (allergic) individuals and in helminthic (worm) infections.

Where are mast cells located in the body?

Mast cells are found in
connective tissue under the skin,
mucosal linings, and
all vascularized tissues except the CNS and retina.

Where are basophils found?

Basophils circulate in the blood and can traffic into tissues during inflammation.

Step 1 of Type I sensitization: What happens on first allergen exposure?

Injured epithelial cells release alarm cytokines — IL-25, IL-33, and TSLP — which activate Th2 cells and Tfh cells.

Step 2 of Type I sensitization: What do Tfh cells do?

Tfh cells secrete IL-4 and IL-13, which cause B cells to class-switch and produce large amounts of IgE antibodies.

Step 3 of Type I sensitization: What happens to the newly made IgE?

IgE binds tightly to high-affinity FcεRI receptors on the surface of mast cells and basophils — this is called "sensitization."

Step 4 of Type I — re-exposure: What triggers degranulation?

When the allergen re-enters the body, it cross-links the IgE already sitting on the mast cell, triggering immediate degranulation.

What is the immediate phase of Type I hypersensitivity?

Within minutes of re-exposure, mast cells release pre-formed histamine, causing rapid vasodilation, vascular leakage (edema), and smooth muscle contraction.

What does histamine do in a Type I reaction?

Histamine binds smooth muscle receptors causing contraction and endothelial receptors causing increased vascular permeability and vasodilation.

What is the late-phase reaction in Type I hypersensitivity?

Hours after histamine release, mast cell cytokines (TNF, IL-4) recruit eosinophils (driven by IL-5), which cause chronic tissue damage.

What are the three waves of mast cell mediators after degranulation?

Wave 1 (seconds): preformed histamine and proteases.
Wave 2 (minutes): newly synthesized leukotrienes and prostaglandins.
Wave 3 (4-6 hours): newly synthesized cytokines and chemokines.

Which mast cell mediator is most potent for bronchoconstriction?

Leukotriene D4 (LTD4) — is more potent than histamine at causing bronchoconstriction.

What are cysteinyl leukotrienes (CysLTs) and what do they do?

CysLTs (LTC4, LTD4, LTE4) are lipid mediators synthesized from arachidonic acid that cause bronchoconstriction, mucus hypersecretion, and capillary leakage.

What cytokine drives eosinophil proliferation and survival in the late phase?

IL-5 — produced by Th2 cells and ILC2s — is the master regulator of eosinophil production and survival.

What do Th2 cells produce and what does each cytokine do?

IL-4 drives IgE class switching;
IL-5 drives eosinophil activation;
IL-13 causes mucus production and airway remodeling.

What are alarmins and which cells release them?

IL-25, IL-33, and TSLP are "alarm" cytokines released by injured epithelial cells that push the immune system toward a Th2/allergic response

What is the filaggrin mutation and what does it cause?

Filaggrin is a protein that maintains the skin barrier; its mutation breaks down the barrier, allowing allergen entry and causing atopic dermatitis (eczema).

What is the atopic march?

Children with eczema progress to food allergies and then asthma — having all three is called the atopic triad.

What is anaphylaxis?

The most dangerous Type I reaction — systemic allergen exposure (bee sting, penicillin, peanuts) causes body-wide mast cell degranulation, leading to fatal BP drop and laryngeal edema.

What is the evolutionary purpose of the IgE/mast cell system?

It evolved to kill large helminthic parasites (worms) and destroy venomous toxins — not to react to harmless allergens.

What is the hygiene hypothesis?

Early exposure to infections, siblings, rural environments, and daycare protects against developing asthma by promoting Th1 responses and preventing Th2 skewing.

What is an atopic individual?

A person with a genetic predisposition to generate exaggerated IgE responses to common environmental antigens.

How is Type I hypersensitivity treated clinically?

Antihistamines (ideally taken before allergen exposure) block histamine receptors; epinephrine is used for anaphylaxis.

What are clinical diseases caused by Type I hypersensitivity?

Allergic rhinitis (hay fever), food allergies, bronchial asthma, atopic dermatitis (eczema), and anaphylaxis.

What defines Type II hypersensitivity?

IgG or IgM antibodies bind directly to antigens fixed on cell surfaces or the extracellular matrix, causing organ-specific damage.

Is Type II hypersensitivity systemic or organ-specific?

It is almost always organ-specific because antibodies target a specific tissue antigen.

What are the 3 mechanisms of tissue injury in Type II hypersensitivity?

(1) Complement activation → inflammation;
(2) opsonization and phagocytosis;
(3) abnormal cellular function (antibody acts as agonist or antagonist at a receptor).

How does complement cause damage in Type II hypersensitivity?

IgG1/IgG3 activate the classical complement pathway → C3a and C5a recruit neutrophils → neutrophils release ROS and proteases → tissue destruction.

How does opsonization cause damage in Type II hypersensitivity?

Antibodies coat cells (e.g., RBCs, platelets) and macrophages in the spleen recognize and
phagocytose these antibody-tagged cells.

What is the non-cytotoxic mechanism in Type II hypersensitivity?

Antibodies bind to cellular receptors and
either activate them (agonist) or
block them (antagonist) without killing the cell.

Graves' disease: What is the autoantigen and what happens?

Antibodies act as agonists at the TSH receptor, continuously stimulating it and causing hyperthyroidism regardless of pituitary feedback.

Graves' disease: What are the clinical features?

Heat intolerance, weight loss, nervousness, goiter, bulging eyes (exophthalmos), and elevated thyroid hormones.

Why doesn't negative feedback shut off thyroid hormone production in Graves' disease?

Because the autoantibodies continuously stimulate the TSH receptor independent of TSH levels or pituitary signals.

Can Graves' disease affect a newborn?

Yes — IgG antibodies cross the placenta and can cause transient neonatal hyperthyroidism.

Myasthenia Gravis: What is the autoantigen and what happens?

Antibodies block and downregulate the acetylcholine receptor at the neuromuscular junction, impairing neuromuscular transmission and causing muscle weakness.

Myasthenia Gravis: Who is most commonly affected?

Young women or older men — muscle weakness is the hallmark, and it can progress to paralysis and respiratory failure.

Myasthenia Gravis: How is it treated?

Plasmapheresis removes the autoantibodies;
Eculizumab (anti-C5) blocks complement;
efgartigimod (FcRn inhibitor) accelerates IgG degradation.

Goodpasture Syndrome: What is the autoantigen?

Antibodies target type IV collagen in the basement membranes of both the kidneys and lungs.

Goodpasture Syndrome: What are the classic symptoms?

Hemoptysis (lung hemorrhage) followed by
hematuria (glomerulonephritis)
classically affects young male smokers.

Goodpasture Syndrome: How is it treated?

Plasmapheresis to remove autoantibodies plus immunosuppression (glucocorticoids).

Autoimmune Hemolytic Anemia (AIHA): What happens?

Antibodies target Rh blood group antigens on RBCs → opsonization → macrophages in the spleen phagocytose and destroy the RBCs → anemia.

Immune Thrombocytopenic Purpura (ITP): What happens?

Antibodies target platelet GPIIb-IIIa → opsonization → macrophages destroy platelets →
thrombocytopenia and excessive bleeding.

Why is the spleen important in AIHA and ITP?

The spleen is the primary site where macrophages phagocytose antibody-coated RBCs and platelets — splenectomy is therapeutic.

Pernicious Anemia: What is the mechanism?

Antibodies neutralize intrinsic factor, preventing vitamin B12 absorption in the gut →
megaloblastic anemia.

Rheumatic Fever: What is the mechanism?

Antibodies made against streptococcal bacteria accidentally cross-react with cardiac muscle antigens (molecular mimicry) →
myocarditis and arthritis.

Rheumatic Fever: What is the classic history?

A child with recent strep throat (pharyngitis) develops fever, joint pain, and signs of myocarditis 2-4 weeks later.

Erythroblastosis Fetalis: What is it?

A Type II cytotoxic reaction where maternal anti-Rh IgG crosses the placenta and destroys Rh+ fetal RBCs, causing fetal hemolytic anemia.

Erythroblastosis Fetalis: When does it occur?

It occurs in a second or later pregnancy when an Rh− mother has been sensitized by a prior Rh+ fetus.

Pemphigus Vulgaris: What happens?

Antibodies target epidermal cadherin (a cell adhesion protein), causing loss of cell-cell adhesion →
severe skin blistering (bullae).

How is Type II hypersensitivity treated?

Corticosteroids (reduce inflammation),

Plasmapheresis (remove autoantibodies),
Splenectomy (AIHA/ITP), and
biologics like rituximab (deplete B cells).

What defines Type III hypersensitivity?

IgG or IgM antibodies bind to soluble antigens in the bloodstream, forming circulating immune complexes that deposit in vessel walls.

Is Type III hypersensitivity systemic or organ-specific?

It is almost always systemic because immune complexes travel in the blood and deposit throughout the body.

How do immune complexes cause damage after deposition?

The Fc regions of deposited antibodies activate complement → C3a and C5a recruit neutrophils →
neutrophils release ROS and proteases →
vasculitis, thrombosis, and ischemia.

Where do immune complexes preferentially deposit and why?

They deposit in high-pressure filtration areas — mainly the renal glomeruli and joint synovium — because blood is filtered under pressure there.

What are the symptoms of Type III hypersensitivity?

Vasculitis, glomerulonephritis (causing hematuria/proteinuria), and arthritis — often occurring together.

What is serum sickness?

A systemic Type III reaction to injected foreign proteins (horse serum, drugs like rituximab, antivenom) causing fever, rash, arthritis, and nephritis.

What is the Arthus reaction?

A localized Type III reaction where subcutaneous antigen injection in a pre-immunized person causes local immune complex formation →
cutaneous vasculitis and tissue necrosis at the injection site.

What is Farmer's Lung?

A Type III reaction where inhaled antigens (e.g., fungal spores from moldy hay) form immune complexes that deposit at the alveolar-capillary interface causing lung inflammation.

SLE: What type of hypersensitivity and what are the key autoantigens?

Type III — autoantibodies against self-nuclear antigens (DNA, histones, snRNP) form immune complexes that deposit everywhere.

SLE: What are the classic clinical findings?

Butterfly (malar) rash, glomerulonephritis, arthritis, and systemic vasculitis — it is the classic multiorgan Type III disease.

Post-Streptococcal Glomerulonephritis: What happens?

Anti-streptococcal antibodies form complexes with bacterial antigens that deposit in the glomeruli →
nephritis and hematuria following a strep infection.

PAN and Type III: How is Hepatitis B involved?

In 30% of PAN cases, HBsAg-anti-HBsAb immune complexes deposit in medium-sized vessel walls → vasculitis.

How is Type III hypersensitivity treated?

The mainstay is
broad anti-inflammatory and
immunosuppressive therapy, predominantly corticosteroids.

What is the key distinguishing feature of Type III vs. Type II?

In Type II, antibodies target FIXED antigens on cells or tissue;
Type III, antibodies target SOLUBLE antigens in the blood, forming circulating complexes.

What defines Type IV hypersensitivity?

It is the only hypersensitivity type mediated entirely by T cells (no antibody involved) —
also called delayed-type hypersensitivity (DTH).

Why is Type IV called "delayed"?

It takes 24-72 hours for circulating memory T cells to home to the site of antigen challenge, recognize the antigen, and secrete enough cytokines to cause a visible reaction.

What are the two mechanisms of tissue injury in Type IV hypersensitivity?

(1) CD4+ Th1 cells secrete IFN-γ → activate macrophages →
tissue destruction via ROS and lysosomal enzymes.
(2) CD8+ CTLs recognize self-antigens on MHC I →
kill target cells via perforin and granzyme.

How does Th17 contribute to Type IV hypersensitivity?

Th17 cells secrete IL-17, which recruits neutrophils to the site of inflammation, adding to tissue destruction.

What does a biopsy of a DTH reaction show?

Perivascular cuffing — an accumulation of CD4+ lymphocytes and macrophages surrounding blood vessels — with dermal edema and fibrin deposition.

What is the PPD (tuberculin) skin test and what type of reaction is it?

It is a Type IV DTH reaction — purified mycobacterial protein is injected into the skin, and a positive result (induration) appears within 48 hours in a person with prior TB exposure.

What causes the induration in a PPD test?

CD4+ memory T cells migrate to the injection site, secrete IFN-γ, activate macrophages, and the accumulation of these cells causes the visible firm swelling.

What are classic examples of Type IV hypersensitivity diseases?

Type 1 diabetes,
multiple sclerosis,
rheumatoid arthritis,
Crohn's disease, c
ontact dermatitis (poison ivy, nickel), and
chronic TB granuloma.

Type 1 Diabetes: What is the mechanism?

CD4+ and CD8+ T cells recognize pancreatic beta-cell antigens → CD8+ CTLs kill beta cells → loss of insulin production.

Multiple Sclerosis: What is the mechanism?

Pathogenic T cells specific for myelin proteins cause demyelination in the CNS →
sensory and motor dysfunction.

Multiple Sclerosis: Is the T cell response pro- or anti-inflammatory?

Pro-inflammatory — T cells CAUSE the demyelination; they do NOT reduce inflammation (a common wrong-answer trap).

Rheumatoid Arthritis: What is the mechanism?

Pathogenic T cells specific for unknown synovial joint antigens drive inflammation → cartilage and bone erosion in joints.

Contact sensitivity (poison ivy/nickel): What is the mechanism?

Chemicals act as haptens, binding to skin proteins to create neoantigens → T cells attack these modified proteins →
blistering rash appears 24-72 hours after exposure.

What is epitope spreading in Type IV autoimmune disease?

As T cells destroy host tissues, new hidden self-proteins are released → immune system creates new autoreactive clones → the autoimmune attack spreads to more targets over time.

Why are Type IV autoimmune diseases typically chronic and progressive?

Because long-lived memory T cells continuously respond to self-antigens that can never be fully cleared from the body.

What is a superantigen and what does it cause?

Microbial toxins (e.g., staph enterotoxins) that bypass normal antigen processing, binding directly to MHC II and TCR to activate massive numbers of T cells simultaneously → cytokine storm → septic shock (toxic shock syndrome).

How is Type IV hypersensitivity treated?

TNF antagonists, IL-6 blockers, IL-17/IL-23 blockers, JAK inhibitors, costimulation blockade (abatacept), and corticosteroids to reduce T cell-driven inflammation.

What is autoimmunity?

An inappropriate immune response against the body's own self-antigens, caused by a failure of self-tolerance.

What is self-tolerance?

The immune system's normal state of unresponsiveness to self-antigens, induced by exposure to self-antigens during lymphocyte development.

Which hypersensitivity type does NOT cause autoimmune disease?

Type I — it is driven by IgE against external allergens, not self-antigens.

What is central tolerance and where does it occur?

The deletion of self-reactive lymphocytes in central lymphoid organs —
B cells in the bone marrow, T cells in the thymus
(negative selection in the medulla).

What is AIRE and why is it critical?

AIRE (Autoimmune Regulator) is a transcription factor expressed only in medullary thymic epithelial cells that allows the thymus to display virtually any self-protein, enabling negative selection of autoreactive T cells.

What happens when a T cell binds self-antigen too strongly during negative selection?

It undergoes apoptosis (clonal deletion).