Week 3 Flashcards
Type I Hypersensitivity
- IgE mediated
- Onset within 1 hour
- Ie) anaphylaxis
Type II Hypersensitivity
- IgG/IgM or cytotoxic mediated
- Onset hours to days
- Ie) hemolytic anemia
Type III Hypersensitivity
- Immune complex mediated
- 1-3 weeks
- Ie) serum sickness or SLE
Type IV
- T cell mediated
- Onset days to weeks
- Ie) rash or SJS
Th 1 Cell-Mediated Allergens
- Contacted materials
- Plant leaves
- Industrial products made from plants
- Synthetic chemicals in industrial products
- Metals
IgE-Mediated Allergen
- Proteins
- Foods
- Plant pollens
- Drugs
- Insect products
- Mold spores
Atopic
- Genetic tendency to develop allergic disease
- Associated with heightened immune response to common allergens
- Inhaled/food allergens
- 1 atopic condition = more likely to develop another
Common Atopic Conditions
- Atopic asthma
- Allergic eczema
- Hay fever
Allergy March
- Natural history of atopic manifestation
- IgE antibody responses clinical symptoms persist over years/decades
- Spontaneously omit with age
First Exposure (Type I Reaction)
- Called sensitization
- Produce IgE Abs to the allergen
- Symptoms mild
Re-Exposure (Type I Reaction)
- Allergen binds IgE
- Activates mast cell
- Releases histamine & cytokines
- Allergic reaction - more severe reaction
First Exposure Process (Type I Reaction)
- Antigen presenting cell phagocytizes & processes antigen
- APC presents antigenic determinant to T cell
- IL-4 from T cell stimulates B cell
- B cell becomes plasma cell - secrete IgE
- IgE binds to mast cells, basophils, eosinophils
Upper Resp Tract Allergies
- Overproduction of mucus, sneezing, nasal congestion
- Rhinitis (hay fever)
Lower Resp Tract Allergies
- Bronchial smooth muscle contraction
- Asthma
Skin Allergen
- Local inflammation
- Urticaria - hives
Bloodstream Allergen
- Systemic inflammation
- Anaphylaxis
GI Allergen Ingestion
- Intestinal smooth muscle contraction - gastroenteritis (V/D)
- Systemic inflammation - allergen enters blood if it is rapidly absorbed - anaphylaxis
Anaphylaxis
- Medical emergency
- Life-threatening allergic reaction
- Injected directly into blood/rapid absorption
- Level of severity depends on level of previous sensitization
- Food allergies most common
Anaphylactic Shock
- Fast/slow HR
- Low BP
Epinephrine
- Temporary control of anaphylaxis
- Rapidly increased BP
- Causes vasoconstriction
Anaphylaxis Diagnosis
- Increased serum IgE levels
- Biopsy - GI related intolerances
- Skin prick/patch test
- Allergens show local inflammation at injection site when person is allergic
Desensitization Therapy
- Allergy shots - gradually increase dose
- Divert immune response from IgE tp IgG
- Different route of entry for allergen
- Long term treatment to decrease symptoms
Desensitization Risk
- Reactions possible
- Mild (local) few hours of injection
- Systemic reactions - 30 mins of injection
Type II Hypersensitivity Reaction
- Opsonization & phagocytosis
- Antibody dependent cellular cytotoxicity
- Complement activation
- Mediated by IgG or IgM antibodies
Cellular Cytotoxicity Process
IgG binds to surface antigen on infected cell NK then kill infected cell
Complement Activation Process
- IgG binds to complement
- Activating cell causing lysis
- Recruitment of neutrophils & monocytes
- Causing inflammation & tissue damage
Rh Factor
- Protein on red blood cells
- Inherited
- Most people Rh+
Rh Incompatibility
- Condition during pregnancy
- Rh+ father & Rh- mother
- Blood from baby (Rh+) crosses into blood stream from mom
- Mother creates Rh antibodies
- Antibodies don’t usually cause issues during 1st pregnancy
- More likely to cause problems in later pregnancies
- Rh antibodies cross placenta & damage fetal RBCs
- Leads to hemolytic anemia in baby
RohGAM Injection
- Given to pregnant women Rh-
- Immunoglobulin to prevent antibody formation against baby’s foreign antigen
Type III Hypersensitivity
- Immune complex mediated
- Mediated by formation insoluble antigen antibody complex
- Activate complement system
- Produce localized inflammation
- Produces damage when in contact in vessel lining/deposited in tissue
- Once deposited immune complexes illicit inflammatory response by activating complement
- Responsible for vasculitis, kidney damage
Type III Process
- Immune complexes deposited in wall of blood vessel
- Presence of immune complexes activates complement & attracts inflammatory cells (neutrophils)
- Enzymes release from neutrophils cause damage to endothelial cells from basement membrane
Post Streptococcal Glomerulonephritis
- Following streptococcal infection - group A (neptorgentic)
- Impacts nephriti and small vessels of kidneys
- Children 1-2 weeks after sore/strep throat, skin infection by strep impetigo
- Causes infiltration of leukocytes & proliferation of other cells in glomerulus
- Impairs capillary perfusion & glomerular filtration rate
Post Streptococcal Glomerulonephritis Complications
- Renal failure
- Acid/base imbalance
- Electrolyte Abnormalities
- Fluid volume overload
- Edema
- Hypertension
Post Streptococcal Glomerulonephritis Symptom Triad
- Hematuria (tea coloured)
- Edema
- Hypertension
Type IV Hypersensitivity
- Cell-mediated
- Delayed type hypersensitivity
- T-cells activated by antigens
- Occurs over 24-72hrs
- Previous exposure to antigen to mount immune response to 2nd exposure
Type IV Process
- Antigen introduced into subcutaneous tissue & processed by local antigen presenting cells
- Th1 effector cell recognizes antigen & release cytokines which act on vascular endothelium
- Recruitment of T cells, phagocytes, fluid, protein to site of antigen injection causes visible lesion
TB Skin Test
- Inactivated TB injected under the skin
- Previous exposure - develop local redness in 8-12 hrs
- Perivascular accumulation of CD4+ T cells, macrophages
- Local secretion of cytokines = increased vascular permeability
- Causing local redness & swelling
- Measure reaction of induration not surrounding redness
Normal Immune Response
- Invader (virus) enters body
- Lymphocytes create antibodies to fight invader
Autoimmune Disease
- Immune system creates antibodies that attack own cells
- Breakdown in immune system to differentiate between self & non-self
- Results in destruction of own cells/organs
- 5-10% of population
- Chronic with relapses & remissions
- Damage is progressive
Causes of Autoimmune Disease
- Foreign substance resembles bodily substance
- Normal body cells become altered
- Lymphocytes malfunction & make abnormal antibodies
Self Antigen or Autoantigen
Antigen expressed on your own cells
Autoreactive Cells
- T/B cells that bind to a self antigen
- BAD
Autoantibody
- Antibody that binds to a self antigen
- BAD
Self Tolerance
Ability of the immune system to recognize self-produced antigens as a non-threat while appropriately mounting a response to foreign substances
Central Tolerance
- Eliminating any developing T/B lymphocytes that are autoreactive
Thymus - T cells
Bone marrow - B cells
Peripheral Tolerance
Immunological tolerance developed after autoreactive T&B cells mature and enter periphery
Autoimmunity
- Result of loss of self-tolerance
- Inheritance of susceptibility genes
- Gender - women 5:1
- Trigger event: alter immune state
Trigger Event
Microbe shares immunological epitope with host
Environmental Factors
Promote activation of self-reactive lymphocytes
Autoimmunity Classification
Area of overlap of organ specific & systemic characteristics
Organ Specific
- Response targets antigen present in specific organ
- Graves disease
- Hashimoto’s thyroiditis
- T1D
- MS
Systemic Characteristics
- Antigen present at many different sites - involve multiple organs
- Rheumatoid arthritis
- Systemic scleroderma
- Systemic lupus erythematosus (SLE)
Graves Disease - Hyperthyroidism
- Immune system attacks thyroid - too much thyroid hormone produced
- Produce TSH receptor antibodies (TSI)
- Abs bind to TSH receptor
- Constant over secretion of T3, T4
Healthy Thyroid
- TSH secreted by pituitary
- TSH binds to TSH receptor on thyroid cells
- Stimulates release of thyroid hormones (T3, T4)
- Inhibit TSH production
Insulin-Dependent Diabetes Mellitus - Type I Diabetes
- Chronic autoimmune destruction of insulin producing beta cells in pancreas
- Autoreactive CTLs kill insulin-producing B-cells in pancreas
- Results in reduced insulin production, hyperglycemia
- Unknown what triggers inflammation in the pancreas
- Clusters in spring & fall
Multiple Sclerosis - MS
- Myelin sheath of nerve fibers in brain & spinal cord destroyed by autoreactive T cells
- Disrupts electrical signals & causes paralysis
- Unclear what triggers myelin damage & CNS inflammation
- Inflammatory process
Autoimmune Disease Treatments
- Treatment focus on mechanism
- Immunosuppression
- Plasmapheresis
- Block MHC with similar peptide
- Use antibodies that block B cells/T cells
- Disease specific treatments
Immunosuppression
- NSAIDS
- Prednisone
- Cyclosporin A
Plasmapheresis
- Remove antibodies
- Temporary fix
