Module 2

Epitope

Antigenic determinant site; the portion of an antigen to which antibodies bind.

Immunoglobulins

Another name for antibodies; 5 classes exist.

IgG

80% of all antibodies; resistance against viruses, bacteria, and bacterial toxins.

IgE

Attaches to mast cells and basophils; mediates the allergic response.

IgD

Receptor on B cell surfaces; binds antigens to sensitize the B cell.

IgM

First antibody secreted after antigen encounter; responsible for agglutination in blood type incompatibility.

IgA

Found in glandular secretions (mucus, tears, saliva, semen); attacks pathogens before they reach internal tissues.

MHC I

Present on all nucleated cells.

MHC II

Present on monocytes, macrophages, and dendritic cells (APCs).

Opsonization

Coating of pathogen surfaces (by C3b) that enhances phagocytosis.

Membrane attack complex (MAC)

C5b–C9 complex that inserts into a target cell membrane, creating pores that lyse the cell.

Hypersensitivity

Altered immunologic response to an antigen that causes disease or damage to the individual.

Type I hypersensitivity

IgE-mediated reactions.

Type II hypersensitivity

Tissue-specific reactions.

Type III hypersensitivity

Immune complex-mediated reactions.

Type IV hypersensitivity

Cell-mediated reactions.

Type I — prevalence

The most common allergic reactions.

Allergen

Small soluble protein, inhaled or ingested in low concentration, that elicits IgE production in susceptible subjects.

Atopic

Having predisposed sensitivity to environmental allergens.

Type I genetic linkage

Children of two allergic parents have a 50% chance of being allergic.

Type I mediation

Mediated by mast cells that release histamine and other cytokines.

Histamine — key actions

Increases vascular permeability, causes vasodilation, contracts bronchial smooth muscle.

Type I sensitizing exposure

Allergen diffuses through surface mucosa; dendritic cells present to TH2 and B cells; B cells become plasma cells producing IgE (via IL-4); IgE binds mast cells at Fc receptors.

Type I immediate re-exposure response

Type I longer-term response

Begins 8–12 hours, lasts 24–36 hours; mast cells generate leukotrienes, prostaglandins, and platelet-activating factor, causing further inflammation and local/systemic effects.

Type II — definition

Antibodies react to antigens fixed to the surface of body cells or specific tissues.

Type II mechanism

Cells damaged by normal immune mechanisms: complement activation, opsonization, phagocytosis, ROS, and leukocyte enzymes.

Complement-mediated cell destruction

IgG/IgM bound to a surface antigen activate the classical pathway → C3b opsonization, leukocyte attraction, MAC-mediated lysis.

Antibody-mediated cellular dysfunction

Type II mechanism where the cell is not destroyed — e.g., thyroid overstimulation in Graves disease, ACh receptor blocking in myasthenia gravis.

Type II example

Blood transfusion incompatibility.

Type III — definition

Ab-Ag complexes form in circulation, then deposit on cell surfaces.

Type III mechanism

Deposited complexes activate complement (C3b opsonization, C5a chemotaxis); neutrophils invade, attempt phagocytosis, and release lysozymes → vasculitis.

Why Type III is not tissue specific

Ab-Ag complexes attach to any tissue — blood vessels, glomerulus, synovial membrane, etc.

Systemic immune complex disorder

Ab-Ag deposit widely; triggered by food antigens, antibiotics, drugs, venoms (e.g., serum sickness).

Arthus reaction

Localized immune complex reaction, usually to an injected antigen (e.g., a vaccine), producing severe local inflammation.

Type IV — definition

Cell-mediated reaction; antibodies are NOT involved.

Type IV cells involved

TH1 cells, cytotoxic T cells, and macrophages.

Delayed hypersensitivity

Type IV reaction that peaks 48–72 hours after exposure.

Delayed Type IV mechanism

Antigen ingested by APC → presented to TH1 in lymph node → TH1 activated, releases cytokines (IL-2) → monocytes/macrophages recruited → release lysosomal enzymes and ROS.

Delayed Type IV examples

Poison ivy, TB skin test, contact dermatitis.

Tuberculin skin test (Mantoux)

Memory TH cells from prior TB exposure react to subcutaneous TB antigen, producing a delayed response.

Contact dermatitis

Allergen binds a skin protein, which is misidentified as foreign and presented to TH cells; lesions occur only at contact site.

Direct cell-mediated cytotoxicity

Helper T cells activate cytotoxic T cells, which destroy target cells via toxic cytokines and perforins (pore-forming agents).

Direct cytotoxicity examples

Viral infections (e.g., hepatitis) and autoimmune diseases (e.g., Type 1 diabetes).

Anaphylactic shock

Most severe Type I systemic reaction; massive vasodilation and increased capillary permeability cause circulatory collapse — life-threatening.

Anaphylaxis triggers

Insect bites/stings, foods, antibiotics; risk of death higher with pre-existing asthma.

Anaphylaxis treatment

Epinephrine (α1 vasoconstriction restores BP; β2 bronchodilation), IV fluids, corticosteroids, antihistamines.

Allergic rhinitis (hay fever)

Type I reaction with sneezing, itching, watery nasal discharge; treated with antihistamines, decongestants, nasal corticosteroids.

Desensitization therapy

Minute, increasing doses of antigen are injected over time to develop neutralizing IgG before IgE can bind.

Bronchial asthma

Chronic inflammatory disorder of the airways.

Asthma signs & symptoms

Recurrent wheezing, breathlessness, chest tightness, coughing — worse at night/early morning.

Extrinsic asthma

Type I response to environmental allergens (pollen, animal dander).

Intrinsic asthma

Non–Type I triggers: respiratory infections, cold air, emotional stress.

Asthma airflow obstruction

Widespread but variable; often reversible spontaneously or with treatment.

Asthma acute phase

10–20 minutes after exposure.

Asthma late phase

4–8 hours after exposure; involves edema and airway thickening from mucus.

Immunotolerance

Immunological control whereby an individual does not mount a detrimental immune response against their own tissues.

Autoimmune disease

Breakdown of immunotolerance; reactions occur via Type II, III, or IV mechanisms.

Molecular mimicry

Sequence similarity between foreign and self-peptides induces an immune response against own tissues.

Systemic lupus erythematosus (SLE)

Most common, complex, serious autoimmune disease; most common connective tissue disease.

SLE demographics

~1/2000; 90% women; peak 15–40 years.

SLE autoantibodies

Type III against nucleic acids, histones (hallmark), clotting proteins; Type II against erythrocytes, lymphocytes, platelets.

SLE manifestations

Butterfly rash, photosensitive rash, joint pain, fatigue, glomerulonephritis, pleurisy, carditis, hair loss.

SLE treatment

No cure; corticosteroids and NSAIDs for inflammation/pain; immunosuppressants for organ involvement.

HLA (Human Leukocyte Antigen)

MHC I genes on chromosome 6; unique to individuals; matched before transplantation.

Hyperacute rejection

Immediate rejection from pre-existing antibodies against graft vessel antigens — a Type III (Arthus) reaction.

Acute rejection

Days to months post-transplant; lymphocyte/macrophage infiltrate — a Type IV reaction.

Chronic rejection

Months to years post-transplant; slow organ failure from vessel damage and fibrosis; possibly weak Type IV.

Immunodeficiency

Failure of the immune system to function normally, causing increased infection susceptibility.

Primary immunodeficiency

Congenital; caused by genetic defect (rare).

Secondary immunodeficiency

Acquired; from cancer, infection, aging, malnutrition, etc. (much more common).

SCID

Severe Combined Immunodeficiency — few lymphocytes, no antibody, reduced thymus.

Bare lymphocyte syndrome

No MHC-I or MHC-II expression; cells cannot interact; death usually before age 5.

C3 deficiency

Most severe complement deficiency; increases risk of encapsulated bacterial infection (e.g., S. pneumoniae).

AIDS — characteristics

Profound immunosuppression, opportunistic infections, malignancies, wasting, CNS degeneration.

HIV transmission

Blood, semen, vaginal fluids, breast milk; NOT casual contact or insects.

HIV target

Destroys helper T cells (and macrophages), crippling both humoral and cell-mediated immunity.

HIV as retrovirus

RNA virus; reverse transcriptase converts RNA → DNA → inserted into host genome → new virions kill host cell.

HIV pathogenesis timeline

~10 years from infection to AIDS; ~99% of untreated progress to AIDS.

HIV treatment

Antiretroviral drugs suppress (do not eliminate) virus; treat secondary infections; no vaccine due to variability.

Kaposi's sarcoma

AIDS-associated viral-induced skin cancer; rare in general population.

Allergy

Hypersensitivity to environmental antigens.

Pruritus

Itching.

Urticaria

Localized pruritic skin disruption with wheals and hives.

Autoimmune response

Inappropriate immune response to tissues normally present in the body.

Alloimmune response

Immune response (within one species) to alternative forms of an antigen not in the recipient's body (e.g., ABO, Rh, transplant antigens).