Lecture 1- Hypersensitivity 1 Flashcards
The immune system is responsible for protection against
Infection and noninfectious agents
Failure of the immune system can lead to disease such as
immunodeficiency disease, auto immune disease and allergy.
Over activation of the immune system caused by
- infectious agents
- environmental substances
- or self antigen can lead to disease driven by hypersensitivity reactions
- Immunodeficiency is
- either primary (genetics) or secondary (HIV)
- Malnutrition is the major cause of immunodeficient
examples of harmful effects of the immune system
either:
- Organ specific diseases (tissue/cell damage)
- Change in function of organs (physiological change)
hypersensivity is defined as
“the antigen-specific immune responses that are either inappropriate or excessive and result in harm to host”
- ANTIGEN MEDIATED
- mechanisms underlying these aberrant immune responses are those employed by the host to fight infections
Hypersensitivity can be divided into 4 categories, each with a different mechanism for disease development.
Types of hypersensitivity reaction
- Type I – Immediate - Allergy- ~5mins
- Type II- Antibody mediated -5-12h
- Type III- Immune complex mediated – 3-8h
- Type IV- Cell medicated- Delayed 24-72h
- Hypersensitivity to exogenous antigens
- Non infectious substances (innocuous) e.g. allergies such as pollen, house mite, peanut etc
-
Infectious microbes
- Esp gram negative can drive abnormal response e.g. sepsis
- Drugs (penicillin)
Hypersensitivity to intrinsic antigens
-
Infectious microbes (mimicry)
- Microbe associates with self antigen and therefore body recognises self as foreign
- E.g. strep throat leading to endocarditis
-
Self antigens (auto-immunity)
- Persistent reaction because of persistence of antigen
Type I,II and III are all
antibody mediated
ttpe IV is
cell mediated
Type 1 hypersensitivity
-
Type I or immediate (Allergy)
- Environmental non- infectious antigens
- IgE
Type II hypersensitivity reaction
-
Type II or antiBody mediated
- IgG, IgM (insoluble antigen e.g. membrane bound)
type III hypersensitivity reactions
-
Type III or immune Complexes mediated
- IgG, IgM (soluble- binds to antigen in the blood stream- forming complex)
Type IV hypersensitivity reaction
-
Type IV or cell mediated (Delayed)
- Environmental infectious agents and self-antigens
difference between Type I, II and III
I- IgE
II - IgG, IgM (insoluble antigen e.g. membrane bound)
III - IgG, IgM (soluble- bind to antigen in the blood stream forming complex)
Common features of hypersensitivity reactions
- Sensitization phase
- Effector phase
Sensitization phase
First encounter with the antigen. Activation of APCs and memory effector cells. A previously exposed individual to the antigen is said to be “sensitized”
Effector phase
Pathologic reaction upon re-exposure to the same antigen and activation of the memory cells of the adaptive immunity
Will only have hypersensitive reaction outcome in effector phase
hypersensitivity type I also known as
allergy
outline Type I reaction (allergy)
Development of allergy specific antibodies resulting in mast cell degranulation.
Treatment for type I hypersensitivity reactions include:
- Allergen desensitisation
- Anti IgE antibody
- Antitistamine
- Leukotriene receptor antagonists
- Corticosteroids
outline Type 2 reaction
- Usually develops within 5-12 hr
- Involves IgG or IgM antibodies
- Targets cell bound antigens
- Exogenous: Blood group antigens, Rhesus D antigens
- Endogenous: self-antigens
- Induces different outcomes
- Tissue/cell damage
- Physiological change
Antibody binds with cell surface antigen to activate compliment resulting in cell and organ damage.
Examples of hypersensitivity type II reactions include:
- Haemolytic transfusion reactions
- Haemolytic disease of the newborn
- Myasthenia gravis
- Graves’ disease
- Autoimmune haemolytic anaemia (warm and cold)
- Immune thrombocytopenia Purpura
- Goodpasture’s syndrome
Mechanisms of tissue damage and physiological change caused by type II hypersensitivity reactions
Importance of the complement pathways
Deficiency in complement can lead to hypersensitivity
Type II Treatment options
Cell tissue damage
- Anti-inflammatory drugs e.g. oral prednisolone
- Plasmapheresis
- Splenectomy
- Intravenous immunoglobulin (IVIG)
Physiological change
- Correct metabolism
- Replacement therapy
An example of disease caused by type II hypersensitivity (IgM)
- Haemolytic transfusion reaction
Immune mechanism of haemolytic transfusion reaction
- Incompatibility in the ABO or rhesus D antigens
- Donor RBC destroyed by recipient’s immune system
- RBC lysis induced by type II hypersensitivity involving by the naturally occurring antibodies (IgM)
An example of disease caused by type II hypersensitivity (IgG)
Haemolytic disease of newborn
Haemolytic disease of newborn
Plasmapheresis therapy
Plasmapheresis is a process in which the liquid part of the blood, or plasma, is separated from the blood cells. Typically, the plasma is replaced with another solution such as saline or albumin, or the plasma is treated (i.e. self-antigens removed) and then returned to your body.
outline type III reactions
- Usually develops within 3-8 hr
- Involves immune complexes (IC) between IgG or IgM and antigens
- Can be cleared by the spleen
- Targets soluble antigens
- Foreign(Infection)
- Endogenous (self antigens)
- Tissue damage caused by the deposition of immune complexes in host tissues
Soluble antibody antigen complex forms causing immune complex to be deposited resulting in damage and disease development.
Key factors affecting IC pathogenesis
Complex size
- Small and large IC complexes cleared easily
- Intermediate IC tend to deposit in tissue meaning they aren’t cleared easily
- Cannot decrease persistence of self antigen
Host response
Local tissue factors
The persistence if the immunocomplex and deposition drives the disease. Common sites of damage are: Joints, Skin, small vessels and kidney – multisystem effects.
immune mechanism of Type III reactions
neutrophil adherence and degranulation causes tissue damage where intermediate antibody complexs have deposited
Examples of hypersensitivity type III reactions include:
- Rheumatoid arthritis
- Glomerulonephritis
- Systemic lupus erythematosus
Rheumatoid arthritis (self-antigen)
- Antigen = Fc portion of IgG (75%)
- Articular and extra-articular features
- Episodes of inflammation/remission
- Poor prognosis factors
- <30 year-old
- High-titre of RF
- Female
- DR4 allele
- Joint erosions
Glomerulonephritis (infectious)
- Bacterial endocarditis
- Hepatitis B infection
Systemic lupus erythematosus
- Antigen = Ds-DNA
- Most prevalent immune complexes disease
- Ratio female:male (9:1)
- 40-60% patients with cardiac, respiratory, renal, joint and neurological features
- Repeated miscarriage
- Every patient is unique!!!!!!
outline type IV reaction
- Usually develops within 24-72hr
- Involves lymphocytes and macrophages, Th1 t cells
- Different subtypes (clinical outcomes)
- exogenous
- endogenous
Mechanism of tissue destruction in type IV reaction
type IV exogenous response
Responses to exogenous antigens include:
- Contact hyperesensitivity
- Tuberculin hyperesensitivity
- Granulomatous hyperesensitivity
type IV endogenous response
-
Pancreatic Islet cells:
- Insulin-dependent diabetes mellitus
-
Thyroid gland:
- Hashimoto’s thyroiditis
-
Fc portion of IgG:
- Rheumatoid arthritis
Treatment options for type III and IV include
- Non-steroidal
- Corticosteroids (oral prednisolone)
- Second drugs as steroid-sparing agents (<10 mg oral steroid)
- Azathioprine
- Mycophenolate mofetil
- Cyclophosphamide
Monoclonal antibodies
- B Cells and T cells
- Cytokine network
- APCs
Contact hypersensitivity (type IV)
- Occurs 48-72 hr postexposure
- Epidermal reaction
- Requires endogenous proteins
- Examples
- Nickel
- Poison ivy
- Organic chemicals
Granulomatous hypersensitivity (IV)
- Occurs 21-48 days post-exposure
- Tissue damage (attempts to seal off infection)
- Examples:
- Tuberculosis
- Leprosy (tuberculoid)
- Schistosomiasis
- Sarcoidosis
tuberculin hypersensitity
difference between hashimotos disease (IV) versus Graves disease (II)
Hashimotos - involves lymphocytes and macrophages
- hypothyroidism- thryoid cell death
Graves- involves insoluble IgG and IgM
- hyperthryoidism- thyroud cell survival
