Four types of hypersensitivity

• type I- allergic
• type II- cytotoxic
• type III- immune complex
• type IV- cell mediated

Examples of type I allergic reactions

• asthma
• eczema
• hives/urticaria
• food allergies

MOST EXTREME IS ANAPHYLAXIS!!!!!!!!

1. Th2 cells respond to specific antigen
2. primed Th2 cells secrete IL-4
   1. cause isotype switching in B cell to produce IgE
3. IgE binds to high affinity FcεRI on mast cells and basophils
4. results in sensitized mast cells and basophils that can be triggered very quickly

1. subsequent allergen exposure cause cross- linking of igE on tissue mast cells and basophils
2. degranuation of mast cells, basophils in two ways
   1. immediate phase- release contents of preformed granules
   2. late phase- release newly synthesized mediators

• histamine
• heparin (anticoagulant)
• chemotactic factors (attract neutrophils, eosinophils)
• trypase (cleave peptides, activate remodeling)

• increase muscle contraction (bronchoconstriction)
• increase vascular permeability
  • rapid fluid movement
  • increase secretion by nasal, bronchial, gastric glands

• hives (from dermal vasodilation, vessel permeability)
• bronchospasm in lung
• rhinnorhea

• leukotrines
• platelet activating factor (PAF)
• prostaglindins
• cytokines
  • TNF-α
  • IL-5

• function- prolonged constriction of smooth muscle and vascular permeability
• clinical effects- continued bronchial hyperresponsiveness → asthma

Fuction of Platelet activating factor

• aggregation of platelets
• bronchoconstriction

• PGD2- increase vascular permeability and smooth muscle contraction(increase airway reactivity)
• PGE2- increase vascular permeability and increase pain

• TNF alpha- induce local inflammation by upregulating endothelial expression of leukocyte adhesion molecules
• IL-5- promote production of eosinophils by bone marrow

• release cationic granule protines
• release enzymes
  • eosinophil peroxidase → tissue remodeling

• result of persistant tissue inflammation due to persistant leukocyte recruitment and activation

Process of anaphylaxis

• bronchoconstiction due to lung swelling (thromboxanes, PAF)
• asphyxiation due to swelling of throught
• systemic shock due to massive drop in bp (increase vasodilation, vascular permeability via PG's, NO) associated with fluid mobility
• vomit
• elevated HR to attempt to compensate

Treatment for allergic reactions

• avoid allergen
• antihistamine
• antileukotrine
• desensitization
• allergy shots (IgE to IgG shift)

shortness of breath

coughing

wheezing

• excess mucus secretion
• submucosal anti-inflammatory infiltrate with lymphocytes and eosinophils
• smooth muscle cell hyperplasia
• thick basement membrane

• exposure to increasing amounts of allergen induce shift from Th2 to Th1 priming
• the goal is to trick the body into thinking the allergen is a part of oneself and to stop mounting an allergic response to it
• it will result in body becoming tolerant to it and making more Th1 IgG immune response to allergen rather than IgE response

• expose to increasin amounts of allergen
• induce desensitization or exhaustion of allergen-specific T cells and B cells

• opsonize cells and activate complement cascade
• recruit neutrophils, macrophages that cause tissue damage
• Ab's bind to normal cell receptors and interfere with their function

• Grave's disease
• Myasthenia gravis
• Goodpasture's disease
• thrombocytopenia
• type II diabetes
• acute rhematic fever

• cause- antibody is anti-TSH receptor
• clincal symptoms
  • hyperthyroidism
  • "bulging eyes"
  • enlarged thyroid
  • heat intolerance
  • palpitations
  • weight loss

• cause- Ab against ACh receptor which keeps ACh from binding
• clinical symptoms
  • muscle weakness
  • droopy eyes
  • paralysis

Cause and clinical signs of Goodpasture's disease

• cause- Ab's against basement membrane of the alveoli in lung and kidneys
• clinical symptoms
  • nephritis
  • lung hemorage
  • on path slide: Ab deposits

• drugs bind to RBC and platelets
• Ab generated against drug will bind to host cells and induce their killing

• mother is Rh neg and first child is Rh positive, leading to her buidling up IgG's to the child
• upon the second pregnancy, if she has a Rh positive child, her Ab's cross the placenta and react with fetal RBC's leading to hemolytic anemia

Process of type III hypersensitivity

1. Ag:Ab conmplexes bind FcγRIII on tissue mast cells
2. release proinflammatory factors
3. recruit macrophages, neutrophils to tissue site

• lupus
• rheumatoid arthritis
• serum sickness
• post streptococcal glomerular nephritis

• local (arthus rxn)- in skin following vaccine or local infection
• systemic (serum sickness)- example is anti-venom antidote, anti-venom, anti-lymphocyte (treatment: stop drug)

• fever
• swollen lymph nodes
• painful and swollen joints
• rashes

• cause- Ag is dsDNA, other nuclear proteins, Smith
• clinical symptoms
  • butterfly facial rash
  • vasculitis
  • nephritis
  • arthritis

• cause- cross rxn of Fc portion of IgM, IgG
• symptoms- painful, swollen joints

• fever
• rash
• vasculitis
• arthralgias

• streptococcal cell wall Ag's deposit into glomerular basement membrane
• show as nephritis and bumpy lumpy deposits

Different forms of Type IV hypersensitivity

• delayed type
• contact

• Th1 cells stimulated by antigen loaded macrophages
• Th1 activate macrophages to secrete proinflammatory facdtors, leading to local tissue inflammation

Ex: PPD TB skin test

Process of contact hypersensitivity

• CD4 mediated
  1. small reactive molecules (ex: metals) form hapten complexes with host proteins
  2. complexes taken up by APC and presented with MHC II to stimulate Th1 cells
  3. Th1 cells secrete IFNγ and TNF to activate macrophages
• CD8 mediated (most common: poison ivy)
  1. chemical cross into cytoplasm of host cells and modify host proteins so they appear forein
  2. these proteins presented to surface of host cell with MHC I
  3. CD8 cells stimulated to kill these "foreign looking" cells

• IDDM
• Multiple schlerosis
• contact dermititis

• cause- Ag is myelin basic protein
• symptoms
  • progressive demyelination
  • blurred vision
  • paralysis

• cause- Ag could be nickel, poison ivy
• symptoms
  • rash
  • vesicles
  • itchiness