1) Hypersensitivity Reactions Flashcards
(21 cards)
Define Hypersensitivity
Antigen Specific immune response that are either inappropriate or excessive and result in harm to host.
List some exogenous antigens which can cause hypersensitivity
> Non infectious Substances
Infectious Microbes => Sepsis
Drugs => Penicillin
List some endogenous antigens which can cause hypersensitivity
> Infectious Microbes (Mimicry)
> Self antigens (Auto - immunity)
List the different types of Hypersensitivity Reactions
Type I (Immediate) => Allergy (IgE)
Type II => Antibody Mediated (IgG)
Type III => Immune Complex Mediates (IgG)
Type IV (Delayed) => Cell Mediated
What are the two phases that leads to Hypersensitivity Reactions ?
> Sensitisation Phase
- 1st encounter with the antigen
- Activation of APCs and memory effector cells.
Effector Phase
- Pathological reaction upon re exposure to the same antigen and activation of memory cells of the adaptive immunity
How does Type 2 Hypersensitivity Reactions cause different outcomes.
> Tissue / Cell Damage
> Physiological Change
Tissue / Cell Damage > Complement Activation - Cell Lysis - Neutrophil Recruitment (C3a / C5a) - Opsonisation (C3b) > Antibody Dependent Cell Cytotoxicity (NK Cell)
Physiological Changes > Receptor Stimulation - Graves' Disease > Receptor Blockade - Myasthenia Gravis
Give an Example of disease caused by Type II Hypersensitivity (IgM)
> Immune Mechanism
Haemolytic Transfusion Reaction
=> Shock, Kidney Failure, Circulatory Collapse and Death
Immune Mechanism:
> Incompatibility of ABO or Rhesus D Antigen
> Donor RBC is destroyed by recipient Immune System by Naturally occurring IgM
Give an Example of disease caused by Type II Hypersensitivity (IgG)
> Immune Mechanism
Haemolytic Disease of New born Disease
Immune Mechanism:
> Rh + Father and Rh - Mother first child is Rh+ (Sensitisation Phase)
> During Delivery Antigens from fetus can enter maternal blood
> Anti Rh Antibodies are produced
> If Mother becomes pregnant again with another Rh+ Fetus, antibodies will cross the placenta and damage fetal RBC
Treatment => RhoGam Immunoglobulin administer 72 hours after birth of first child
List the Therapeutic Approaches for Type II Hypersensitivity
1) Anti inflammatory Drugs
- Complement Activation
2) Plasmapheresis
- Circulating Antibodies and Inflammatory Mediators
3) Splenectomy
- Opsonisation
4) IV Immunoglobulin
- IgG Degradation
5) Graves’ - Anti thyroid medication
6) Myasthenia Gravis - Pyridostigmine - Acetylcholiesterase inhibitor
What serious complication can occur in Haemolytic Disease of the Newborn ?
Kernicterus - Permanent Neurological Damage in the babies that survive
What test can you carry out to diagnose HDN ?
Coombs Test
What key factors can affect IC Pathogenesis ?
> Complex Size
- Small and Large ICs cleared
- Intermediate size ICs
> Host Response
- Low affinity Antibody
- Complement Deficiency
> Local Tissue Factors
- Haemodynamic Factors
- Physiochemical Factors
How does Type III Hypersensitivity cause damage in patients ?
Immune complexes between IgG and IgM and antigens. Deposited in Host tissue -Joints -Kidney -Small Vessels -Skin
Outline the immune mechanism of Type III hypersensitivity ?
1) Intermediate sized Immune Complex deposited in the tissue
2) Complement Activated
3) Neutrophil Chemotaxis
4) Neutrophil adherence and degranulation
List 3 Examples of diseases caused by type III hypersensitivity
Rheumatoid Arthritis (Self Antigen)
Glomerulonephritis (Infectious)
SLE
What are some common symptoms of SLE
Systemic:
- Low Grade Fever
- Photosensitivity
Physiological
- Fatigue
- Loss of Appetite
Mouth Ulcers Muscle Aches Butterfly Rash Inflammation of Pleura and Pericardium Arthritis Poor Circulation
What does Type IV hypersensitivity involve ?
Lymphocytes and Macrophages
Give examples of diseases which is caused by Type IV hypersensitivity to Exogenous Antigens
Contact Hypersensitivity: > 48 - 72 hours post exposure - Nickel - Poison Ivy - Organic Chemicals > Epidermal Reaction
Granulomatous Hypersensitivity > 21-48 post exposure - TB - Leprosy - Schistosomiasis - Sarcoidosis > Tissue Damage
Give examples of disease caused by Type IV Hypersensitivity to Endogenous Antigens
- Pancreatic Islet Cells => Insulin Dependent DM
- Thyroid Gland => Hashimoto’s
- Fc portion of IgG => RA
What therapy is used to treat Type III and IV ?
Anti inflammatory drugs - Non Steroidals - Corticosteroids (Predisnolone) - Steroid Sparing Agents: > Azathioprine > Mycophenolate Mofetil > Cyclophosphamide
MAB
Outline the features of Myasthenia Gravis
> Signs and Symptoms
> Pathophysiology
> Treatment
Signs and Symptoms:
> Muscle Paralysis
> Ptosis
> Diplopia
Pathophysiology
> AchR - Antibodies are produced which circulate the blood, which binds to Nicotinic Receptors on the muscle end plates
> This prevents Ach from binding and thus no Depolarisation of muscle end plates
Treatment:
> Pyridostigmine - Acetylcholinesterase inhibitor that binds to Acetylcholinesterase and thereby reduces binding and degradation of Ach at the muscle end plate and thus increases concentration prolonging its action