OBJ - Introduction to Hypersensitivity

Question 1

Compare the major distinguishing features between innate versus adaptive immunity.

Answer 1

Innate
Nonspecific, same response to everything
Barriers, phagocytes, complement & NK cells

Adaptive
Specific/targeted
Cell-mediated immunity
B lymphocytes -> antibodies
T Lymphocytes -> CD4+ & CD8+

Question 2

Compare and contrast the 4 types of hypersensitivity and give examples of each.

Answer 2

Excessive response to an antigen

*Imbalance between effector mechanisms and control mechanisms or inappropriate targeting (self antigens)

*Exogenous (foreign) antigens-dust, pollen, food, drugs, microbes, chemicals, blood products
Autologous antigens-AUTOIMMUNITY

*Susceptibility genes-HLA and non-HLA

Types I - Immediate
Types II - Antibody mediated
Types III - Immunity complex-mediated
Types IV - Cell mediated

Question 3

Types I - Immediate Hypersensitivity

Answer 3

Hallmark - Production of IgE antibodies

Disorders:
Allergy, asthma, allergic rhinitis, conjunctivitis Hives/uticaria, Anaphylaxis

Mechanism: 
Activation of T2 helper cell & antibody class switching -> IgE

MEDIATORS OF TYPE I RESPONSE

• CD4+ T helper cell subtype: “Th2 cell”
• IL-4 promote switching of B cells from IgM to IgE production and further Th2 development
• IL-5 induce expansion and activation of eosinophils
• IL-13 promote switching of B cells from IgM to IgE production and stimulate mucus secretion by epithelial cells

Immediate: vasoactive amines
1) Degranulate (histamine, proteases, ECF/NCF)
2) Membran Phospholipids (AA pathway)
Late Phase: cytokines/inflammatory response
3) Cytokine secretion
-> immediate release from mast cells & later recruits inflammatory cells

Symptoms:
vascular dilation, edema, smooth muscle contraction, mucus production, inflammation

EOSINOPHILS - late phase
*Eosinophil chemotactic factor (ECF) produced by mast cells recruit eosinophils to tissue site.
*IL-5 produced by Th2 cells promote growth and activation of eosinophils.
*Secrete major basic protein and eosinophil
cationic protein toxic to epithelial cells
*Produce leukotriene C4 and platelet
activating factor (PAF) that directly activate
mast cells

Question 4

Types II - Antibody mediated Hypersensitivity

Answer 4

IgG & IgM production

• Antibodies IgG & IgM bind to antigen on cell surface (either intrinsic (auto antigen) or exogenous (foreign) [e.g. drug] that attaches to cell surface)
• Specific antibody binding to cell surface antigen results in injury to cell via variety of potential mechanisms

Disorders:
Autoimmune hemolytic anemia (Fetal Rh attack), Good pasture syndrome (Table 4-3)

Mechanism:
1) Opsonization/phagocytosis )Fetal Rh factor)
2) Complement & Fc receptor mediated inflammation (Good pasture - Kidney & lung functions)
degranulation of mast cells
3) Antibodies bind to ACh receptor & stimulate/block signaling
(block = Myasthenia Gravis; stimulate = Graves disease/hyperthyroidism)

Symptoms:
variety - see Table 4-3

Question 5

Types III - Immunity Complex-mediated

Answer 5

• Soluble antigen & free floating complex, activates complement & inflammatory cascade

Disorders:

• Vasculitis, lupus, glomerulonephritis
• Lots of “-itis”es

Mechanism:

• Antibody binds to circulating antigens to form immune complex
• Immune complexes deposit in preferred tissue sites and elicit inflammatory response:
  - Blood vessel wall (vasculitis)
  - Glomeruli (glomerulonephritis)
  - Joints (arthritis)
• Immune complex activates complement to recruit neutrophils; mechanism of injury similar regardless of tissue site
• Large IC (Immuno Complex) - rapidly cleared because so big/obstructive
• Small - poorly cleared, circulate, & deposit in tissues (filters); deposit inflammatory mediators -> causing inflammation

Symptoms:
Abnormal & location specific Inflammation

Question 6

Types IV - Cell mediated Hypersensitivity (Delayed type Hypersensitivity - DTH)

Answer 6

T Cells gone awry

Disorders: Contact dermatitis/poison ivy, MS, DM1, TB

Mechanism:
- CD4+ T cells react to foreign or self-antigens and differentiate into:
-Th1 cells (IFN-γ TNF-α); macrophage activation
-Th17 cells (IL-17, IL-22): neutrophils activation
- CD4+ T cells recruit CD8+ T cells [cytotoxic T
lymphocytes (CTL)]

2 Types:

1) DTH = CD4 mediated
S/s: Contact dermatitis

2) Cellular cytotoxicity = CD8 mediated
S/s: CD8+ attacking own cells (MS = myelin sheath, DM1 = Islet cells )

• Type I diabetes mellitis: T cells react with antigens of pancreatic islet β cells (insulitis)
• Multiple sclerosis: T cells react with antigens in CNS myelin (perivascular inflammation in white matter and demyelination)
• Rheumatoid arthritis: T cells react with antigens in joint synovium (chronic arthritis)
• Contact sensitivity: T cells react with antigens of poison ivy and poison oak (dermatitis with blisters)

Question 7

Atopic vs Non-Atopic allergy

Answer 7

Atopic allergy 
- Th2 cells and IgE 
- Genetically determined (HLA and non-HLA 
genes implicated) 
- Family history in 50% 

Non-atopic allergy
- do not involve Th2 cells or IgE
- triggered by temperature extremes and exercise
- mast cells abnormally sensitive to stimuli
- Non-IgE Mast cell secretagogues
C5a and C3a
codeine and morphine
mellitin (in bee venom)
heat, cold, sunlight, exercise
*desensitization/allergy testing NOT helpful

Question 8

Granuloma Tissues

Answer 8

Walled off in giant cell; not gotten rid of
macrophages activated
TB, Sarcoidosis, funghi