chapter 19: immunological disorders

immune system: overview

• fxn: protects human host from pathogens (invaders)

  • humoral immunity → B cells & antibodies

  • cell-mediated immunity (CMI) → T cells

antigens (Ag)

• non-self Ag: foreign/external antigen (pathogens, allergens)

• self Ag: body’s own cells/tissues

self-tolerance vs. loss of self-tolerance

• self-tolerance: immune system ignores your own tissues

• loss of self-tolerance: immune system attacks your own body (autoimmunity)

• immunosuppression: weakened immune system

  • d/t: HIV/AIDs, immunosuppressive drugs (organ transplant), chemotherapy

immune deficiencies

immune system partially or completely absent (affects humoral, CMI, or both)

• types:

  • primary (congenital): inherited, present since birth, d/t defective/missing genes

  • secondary (acquired): develop later in life (d/t HIV destroy CD4+ T cells, chemotherapy, immunosuppressive transplant drugs)

    • results in: weak or nonfunctional immune system, partial or complete immune deficiency

immune diseases

immune system present but abnormal

• exaggerated immune response: attacks non-self Ag, hypersensitivity (allergies)

• altered immune response: attacks self Ag, autoimmune disease

primary (congenital) immune deficiencies

• X-linked Infantile (Bruton’s) Agammaglobulinemia: defective B cells (↓ Ab’s) & humoral, mostly boys (X-linked), more bacterial infections, present CMI

• DiGeorge Syndrome (Thymic Aplasia): defective T cells & CMI, present humoral

• SCID (Severe Combined Immunodeficiency): defective stem cells (↓ B & T cells), defective humoral/CMI (complete deficiency)

  • ex. Bubble Boy disease

hypersensitivity: overview

• an exaggerated immune response to non-self antigens (allergens)

  • occurs when sensitized by previous exposure to non-self Ag’s (allergens → pollen, dust)

• exposure process:

  • first exposure → no harmful reaction → become sensitized (memory B cells form)

  • second exposure → same allergen triggers harmful immune response (allergic reaction; memory B cells → plasma cells → Ab)

• ACID (Anaphylactic, Cytotoxic, Immune Complex, Delayed Cell-Mediated)

  • types I-III: humoral immunity, B cells, Ab’s (rapid)

  • type IV: CMI, T_D cells (slow)

type I hypersensitivity (anaphylactic)

fast reaction (minutes after second exposure to non-self Ag’s)

• first exposure: IgE produced → IgE binds mast cells/basophils, no degranulation yet

• second exposure: allergen binds IgE → mast cells/basophils degranulate

  • released mediators:

    • histamine: ↑ capillary permeability (leaky)

    • leukotrienes: prolong smooth muscle contraction → airways narrow

• effects: (d/t neutrophils) edema, erythema, ↑ mucus, difficulty breathing

• ex: allergic reactions (seasonal allergies/asthma), anaphylactic shock (drug/insect venom)

localized vs. systemic anaphylaxis

• localized: d/t pollen, dust, smoke, foods, pet dander

  • sxs depend on entry route: sneezing, itchy eyes, runny nose

  • tx: antihistamines

• systemic (anaphylactic shock): medical emergency! d/t bee stings, drugs, peanuts, shellfish

  • effects: airway dialation needed, severe drop in BP, whole body affected

  • tx: epinephrine (EpiPen)

preventing allergies (skin testing & desensitization)

• skin test: inject allergen under skin, watch for inflammatory reaction

• desensitization: gradually inject increasing doses of allergen beneath skin

  • purpose: produce IgG → acts as a blocking antibody → binds allergen before IgE can (intercepts & neutralizes)

hypersensitivity type II (cytotoxic)

• involves non-self antigens bound on a fixed location or on cell surface

• IgG or IgM Ab’s target Ags on RBC or tissue cells

  • cell lysis is caused by complement activation or damage by macrophages

examples:

1. blood transfusion reactions (mismatching): ABO blood group system

2. hemolytic disease of the newborn: Rh blood group system

3. thrombocytopenic purpura & hemolytic anemia: drug-induced cytotoxic reactions

ABO blood group system

• transfusion reactions: ABO & Rh blood group systems mismatched between donor & recipient

• carbohydrate surface Ag on RBC → blood cell types

1. Type A blood: anti B Ab

2. Type B blood: anti A Ab

3. Type AB: no Ab (universal acceptor)

4. Type O: anti A and anti B (universal donor)

• ex. anti A + type A RBC → agglutination & hemolysis of RBCs (mismatching)

ABO blood group system: transfusion reactions

• type A:

  • donate to AB

  • receive from A, O

• type B:

  • donate to AB

  • receive from B, O

• type AB (universal acceptor):

  • donate to AB

  • receive from A, B, AB, O

• type O (universal donor):

  • donate to A, B, AB

  • receive from O

Rh blood group system

• Rh factor: antigen (Rh+) found on RBC surfaces

  • Rh+ person: no anti-Rh Ab’s

  • Rh- person: may possibly have anti-Rh Ab’s

• Rh- person will develop anti-Rh Ab’s only when immune system provoked

  • Rh+ donor blood to Rh- recipient → Rh- recipient will produce anti-Rh Ab’s

  • anti-Rh Ab’s will bind to Rh+ donor RBCs → mismatching → Rh+ donor RBCs damaged/lysed!

Hemolytic Disease of The Newborn (HDNB)

• Rh- female (but no anti-Rh ABs yet) → Rh+ fetus (1st pregnancy) → mom produce anti-Rh Ab’s AFTER birth (mixing of maternal & fetal circulation)

• mom’s anti-Rh Ab’s will attack 2nd Rh+ fetus (2nd pregnancy) → damageing fetal RBCs → HDNB

outcomes (newborn):

• 50% normal RBC count

• 25% moderate dz & require immediate tx

• 25% severe dz → stillborn/severe complications

prevention of HDNB

• prevention w/ RhoGAM (antibodies) inject into Rh- mom during 1st pregnancy or with 72 hours of delivery of Rh+ infant

  • artificial passive immunity

  • antibodies against mother’s anti-RH antibodies

drug-induced cytotoxic reactions

• target cell (PLT or RBC) coated w/ drug → drug-target cell complex

• Abs produced against drug → Abs bind drugs

• complement binds stem region of Abs → target cell destroyed! (exaggerated reaction to drug)

  • thrombocytopenic purpura

  • hemolytic anemia

thrombocytopenic purpura

• thrombocyte: platelets (target cell)

• “-penia”: low or decreased cell numbers

• purpura: purple color of skin (hemorrhaging d/t ↓ # PLTs)

hypersensitivity type III (immune complex) reactions

• involves non-self Ag’s circulating (not fixed) in blood

• formation of circulating immune complexes in serum w/ either excess Ag or excess Ab (IgG) present

• immune complexes lodge in basement membrances beneath cells → activates complement & attracts neutrophils → inflammation & tissue damage

  • arthus reaction: too many Ab made

  • serum sickness: not enough Ab made

serum sickness

• excess antigens → immune complexes form in presence of ↑ local concentration of injected serum Ag’s & ↓ circulating Ab concentration

• too little or few Abs formed

arthus reactions

• excess antibody → immune complexes form in presence of vaccine antigens & ↑ circulating antibody concentration

• too many Abs formed

hypersensitivity type IV (delayed cell-mediated) reactions

• delayed-type hypersensitivities

• CMI responses d/t T_D cells

• T_D cells release cytokines → attract macrophages → initiate tissue damage (inflammation)

  • tuberculin skin test

  • allergic contact dermatitis (not allergy)

“allergic” contact dermatitis

• chemicals combine w/ proteins in skin → produce immune response

• “allergic” response to poison ivy, cosmetics, metals, latex

• NOT HS type I reaction: delayed rxn, involves T_D cell (not IgE)

  • primary contact: make memory T cells (sensatization → no sxs)

  • secondary contact: many active T_D cells (sxs)

autoimmune diseases

• immune system responds to self-antigens → damage to organs

• autoimmunity: loss of self-tolerance

• affect any part of body; some more common than others

• some life-threatening but MOST are debilitating & require lifetime tx (NO CURE; yes management)

• origin largely unknown → result from genetic, environmental, lifestyle factors

• 80% women d/t ↑ hormone levels (esp during pregnancy)

  • ex. lupus, RA, MS