Immunology Exam 3

Type I hypersensitivity

Allergen exposure → body makes IgE

IgE sticks to mast cells & basophils

Next exposure → allergen binds IgE on mast cells/basophils → histamines releases (degranulation)

causes: sneezing, swelling, wheezing, etc

🕐first and fast

Type I Hypersensitivity reactions:

Phase II Activation - Early phase symptoms

Skin: Redness & swelling

Histamine: dilates small blood vessels and increases permeability → redness, swelling, itching

Respiratory tract: bronchoconstriction → wheezing/asthma

Histamine: contracts smooth muscle in bronchioles → wheezing, shortness of breath

GI tract: Cramping, diarrhea, nausea

Smooth muscle contraction + fluid secretion in intestines → pain, diarrhea, nausea

Systemic: ⬆ vascular permeability → hypotension, anaphylactic shock

Anaphylaxis

Type I sensitivity

Rapid, life-threatening severe allergic reaction

Triggers: allergens such as bee stings, peanuts, shellfish, or medications

Cause: widespread activation of mast cells → release of histamines and other mediators

-vasodilation (low bp)

-airway constriction

-swelling, hives, nausea

Type I Hypersensitivity reactions:

Phase II Activation - Late phase symptoms

Secondary mediators (newly made in mast cells & basophils)

Cytokines (IL-5, IL-4, IL-3, TNF-a)

stronger and longer lasting than histamine → late phase symptoms

Eosinophilic infiltration

Eosinophils enter allergen site

stimulate IL-5 from Th2 cells

release toxic proteins + enzymes → tissue injury & symptoms

Clinical consequences

Chronic inflammation → tissue remodeling

Type I hypersensitivity

Allergic Rhinitis (hay fever)

Most common atopic condition

Symptoms: sneezing, running nose, congestion, itchy nose/eyes

Triggers: pollen, mold, dust mites, animal dander

Complications: sinusitis, otitis media, sleep disturbances

Type I hypersensitivity

Allergic asthma

Triggered by inhaled → bronchoconstriction, mucus, edema

Symptoms: Wheezing, breathlessness, cough, sputum

Pathophysiology: ⬆ airway resistance → trapped air, “panting”

Type I hypersensitivity

Food allergy

Common triggers: milk, eggs, nuts, soy, wheat, fish, shellfish

GI symptoms: Cramps, vomiting, diarrhea

Systemic spread: Hives, angioedema, asthma, anaphylaxis

Type I hypersensitivity

Skin reactions

Uricaria (hives): itchy wide reaction

Angioedema: Deep swelling in skin

Atopic dermatitis (eczema): chronic itchy rash (asthma & rhinitis)

Latex allergy

Type I hypersensitivity

Testing

Allergen specific IgE testing

Total IgE

measured by capturing the antibody with an anti IgE bound to a solid phase. A second anti IgE immunoglobulin with an enzyme label is used to produced a visible reaction

Antigen specific IgE

measured by using solid phase antigen to capture patient antibody. then a second antibody, enzyme labeled anti IgE immunoglobulin is added. this combined with any bound IgE to produce a visible reaction in the presence of substrate

Type II hypersensitivity reactions

Antibodies (IgG or IgM) bind to antigens on cell surfaces or tissues

Effects of the antibodies

• Cellular destruction

-Classic complement actionation → MAC attack

-Opsonization and engulfment

-Antibody directed cellular cytotoxicity (ADCC)

• Function of the cell can be inhibited

• Function of the cell increased above normal limits

CYTOTOXIC!

Type II hypersensitivity

Transfusion reactions

Antibodies (IgM or IgG) bind to RBC antigens → hemolysis

Anti-A & Anti-B antibodies are formed naturally

Acutehemolytic (minutes-hours)

cause: Preformed IgM antibodies (usually anti- A or anti-B in ABO mismatch)

Mechanism: IgM strongly activates complement → RBC lyse inside blood vessels (Iintravascular hemolysis)

Delayed hemolytic (days-weeks)

cause: IgG antibodies (Rh, kell, duffy, kidd) from prior exposure (transfusion, pregnancy)

Mechanism: IgG coats donor RBCs → removed by macrophages in spleen/ liver (extravascular hemolysis)

Type II hypersensitivity

hemolytic disease of the fetus and newborn (HDFN)

First pregnancy

Rh- mother exposed to Rh+ fetal RBCs (late gestation or delivery)

Primary response: B cells make mostly IgM (does not cross placenta)

baby born healthy

Maternal memory B cells (MB) also produced

Second pregnancy

(Rh+ baby)

Secondary response: memory B cells make IgG anti rh

IgG crosses placenta

Destroy fetal RBCs → HDFN

Solution: Mother given anti-Rh (RhIg) at 28 weeks

-future Rh+ babies are safe

Type II hypersensitivity

Autoimmune hemolytic anemia

Autoantibodies target patient’s own RBC

Symptoms: fatigue, weakness, pallor, fever, jaundice

Hemolysis: usually extravascular (spleen/liver), sometimes intravascular

Warm

antibody: IgG (reacts at 37C, body temp)

Causes: drugs may act as haptens, infections

Cold

antibody: IgM (reversible upon warming)

Hemolysis: complement mediated, mostly extravascular (liver)

Causes: post infection

Chronic: lymphomas, waldenstrom, SLE

Type II hypersensitivity

Goodpasture syndrome

Autoantibodies target the basement membrane in kidney glomeruli and lung alveoli → complement → tissue damage

Type II hypersensitivity

Hashimoto’s disease

Autoantibodies attack thyroid → chronic inflammation and gradual thyroid destruction. leads to hypothyroidism

Type II hypersensitivity

Myasthenia Gravis

Autoimmune disorder where antibodies block or destroy acetylcholine receptors at the neuromuscular junction.

Causes fluctuating muscle weakness

Type II hypersensitivity

Type I diabetes mellitus

Autoantibodies attack the pancreatic B cells lead to absolute insulin deficiency

Testing for Type II hypersensitivity

Direct antiglobulin test (DAT)

-direct coombs test

Detects IgG or complement already bound to patient’s RBCs in vivo

-Patient RBCc are incubated with Coombs reagent (anti human, AHG)

-Contains antibodies against human IgG and complement (C3b, C3d)

Indirect Antiglobulin test (IAT)

Indirect coombs test

Detects free IgG antibodies in patient serum that could bind RBC antigens

-Used for antibody screening, crossmatching, prenatal Rh testing

Type III hypersensitivity reactions (add more info)

Caused by IgG or IgM binding to soluble antigen, forming circulating immune complexes

• Immune complexes deposit in tissues (joints, kidneys, vessels)

• Complement activation (classical) + inflammation → tissue damage

⭐️Imagine an immune complex as 3 things stuck together:

antigen - antibody - complement

Type III hypersensitivity reactions

Arthus reaction

seen after some vaccine boosters

Antigen injected intradermally binds circulating IgG → immune complex formation

complexes deposit in dermal vessels → activate complement

-Neutrophils recruited, mast cells in skin degranulate

Redness & swelling (3-8 hrs)

-can progress to hemorrhagic necrosis

Type III hypersensitivity reactions

Serum sickness

Caused by immune complex formation after passive immunization with animal serum

Antibodies form against foreign proteins → complexes deposit in tissue → complement activation, inflammation

• 7-21 days after exposure

Symptoms: fever, rash, joint pain, lymphadenopathy, nausea/vomiting

Course: Usually self limiting; more severe with repeat exposure

Type III hypersensitivity reactions

Systemic lupus erythematosus (SLE)

Autoantibodies against self nuclear antigens (DNA, histones)

Immune complexes deposit in skin, joints, kidneys → rash, arthritis, nephritis

Type III hypersensitivity reactions

Rheumatoid arthritis (RA)

IgM autoantibodies against IgG (rheumatoid factor)

Immune complexes in synovium joints → chronic joint inflammation and damage

Type III hypersensitivity reactions

Others

Vaccines (foreign proteins): rare (boosters for tetanus, diptheria)

venom: Bee, wasp stings

Drugs: penicillin, sulfonamides

Infections: Viral hepatitis, group A strep

Type III hypersensitivity

Testing

Autoimmune disease specific tests

SLE & RA: detects antinuclear antibodies (ANA)

-methods: indirect immunofluorescence, ELISA, multiple assays

Complement levels (C3, C4)

Type IV hypersensitivity

Mediated by T cells (Th1 helper cells especially), not antibodies

Antigen sensitized Th1 cells releases cytokines that recruit and activate macrophages, leading to delayed inflammation and tissue damage

🕐Days before response

Type IV hypersensitivity reactions

Intracellular pathogens

Contact antigens

Transplants

Type IV hypersensitivity reactions

Contact dermatitis

Type IV hypersensitivity reactions

Hypersensitivity pneumonitis

Type IV hypersensitivity reactions

Tuberculosis and Granulomas

Type IV hypersensitivity reactions

Skin testing for delayed hypersensitivity

Indirect immunofluorescence (IIF / FANA Test)

FANA test patterns

Crithidia luciliae Test (IIF for anti dsDNA)

Ouchterlony Test

Sjögren’s syndrome

Systemic sclerosis (SSc)

Inflammatory Myopathies

Granulomatosis with Polyangiitis (Wegner’s Granulomatosis)

Anti neutrophil cytoplasmic Antibodies (ANCA)

Hashimoto’s Thyroiditis

Grave’s disease

Type 1 diabetes mellitus (T1DM)

Celiac Disease

Autoimmune hepatitis

Primary biliary cholangitis (PBC)

Multiple sclerosis

Myasthenia Gravis

Anti glomerular basement membrane disease (Goodpasture’s Syndrome)