Hypersensitivity Flashcards
What are hypersensitivities?
Maladaptive immune responses toward harmless foreign substances or self antigens that occur after tissue sensitisation:
- Immediate
- Delayed
- Autoimmunity
Mechanism of allergies?
- Exposure to allergen
- APCs present processed allergen to Th cells
- Th cells stimulate B cells to produce IgE antibodies
- IgE interacts with mast cells
- Upon subsequent exposure to the same allergen, IgE molecules on mast cells bind the antigen and stimulate the mast cell to release histamine and serotonin
- These chemical mediators then recruit eosinophils which mediate allergic responses.
What do Type I hypersensitivity reactions involve?
IgE antibody against soluble antigen, triggering mast cell degranulation.
For susceptible individuals, describe the first exposure to an allergen in a Type I hypersensitivity reaction?
A first exposure to an allergen activates a strong TH2 cell response. APCs process allergen and present it to Th2 cells.
- Th2 cells release cytokines interleukin (IL)-4 and IL-13 which activate B cells specific to the same allergen
- This results in clonal proliferation, differentiation into plasma cells, and antibody-class switch from production of IgM to production of IgE.
- IgE binds to mast cells by Fc regions mast cells
- Mast cells are primed or a subsequent exposure and the individual is sensitised to the allergen.
During subsequent exposures to allergens in Type I reactions, what happens?
- Allergens bind to multiple IgE molecules on mast cells, cross-linking the IgE molecules.
- This cross-linking of IgE activates the mast cells and triggers degranulation (histamine, serotonin and bradykinin)
- The chemical mediators released by mast cells collectively causing allergy symptoms
What is the effect of histamine?
- Mucus secretion in nasal passages
- Tear formation from lacrimal glands, promoting the runny nose and watery eyes of allergies.
- Itching and sneezing
- Smooth muscle contraction
- Increases vascular permeability
Etc etc
Examples of localised type I hypersensitivity reactions?
Hay fever rhinitis, hives, asthma
Examples of systemic type I hypersensitivity reactions?
anaphylaxis or anaphylactic shock.
What are late-phase reactions in Type I hypersensitivities?
may develop 4–12 hours after the early phase
What are late-phase reactions in type I mediated by?
eosinophils, neutrophils, and lymphocytes that have been recruited by chemotactic factors released from mast cells
What does activation of eosinophils, neutrophils, and lymphocytes in late-phase type I reactions lead to?
Leads to the release of more chemical mediators that cause tissue damage and late-phase symptoms
What are late-phase symptoms?
swelling and redness of the skin, coughing, wheezing, and nasal discharge.
There is evidence that the IgE produced during type I hypersensitivity reactions is actually meant to counter what?
helminth infections
Allergy-induced asthma:
a) Cause?
b) Signs and symptoms?
a) Inhalation of allergens
b) Constriction of bronchi, laboured breathing, coughing, chills, body aches
Anaphylaxis:
a) Cause?
b) Signs and symptoms?
a) Systemic reaction to allergens
b) Hives, itching, swelling of tongue and throat, nausea, vomiting, low blood pressure, shock
Hay fever:
a) Cause?
b) Signs and symptoms?
a) Inhalation of mould or pollen
b) Runny nose, watery eyes, sneezing
Hives:
a) cause?
b) signs and symptoms?
Raised, bumpy skin rash with itching; bumps may converge into large raised areas
Depending on the cytokines they synthesise and secrete, what can CD4+ helper T cells (Th) be divided into?
Type I helper T lymphocytes (Thl) and type II helper T cells (Th2).
Both derived from Th
What are the most effective regulators of Th cell differentiation?
Cytokines
Which cytokines are secreted by Th1?
IFN-γ，IL-2, IL-3, TNF-α, TNF-β
Characteristic cytokine of Th1?
IFN-γ
Which cytokines are secreted by Th2?
IL-4, IL-10, IL-5, IL-9, IL-13
Characteristic cytokine of Th2?
IL-4
Role of Th1 cells?
- Stimulate cellular immune response
- Participate in the inhibition of macrophage activation
- Stimulate B cells to produce IgM, IgG1
Role of Th2 cells?
- Stimulates humoral immune response
- Promotes B cell proliferation and induces antibody production (IL-4).
- It can also induce the differentiation and proliferation of mast cells (IL-3, IL-4), and the differentiation and proliferation of eosinophilic leukocytes (IL-5).
Effect of IL-4?
- Promotes B cell proliferation and induces antibody production
- Induces differentiation and proliferation of mast cells
Effect of IL-5?
differentiation and proliferation of eosinophilic leukocytes
Under normal circumstances, describe the balance of Th1/Th2?
Are in a balanced state
What happens once the Th1/Th2 balance is thrown off?
Diseases
What can over expression of Th2 lead to?
inappropriate immune responses, leading to diseases such as allergies and asthma
What can over expression of Th1 lead to?
autoimmune diseases such as rheumatoid arthritis and multiple sclerosis
What does histamine (and other chemical mediators released by mast cells) recruit?
eosinophils, neutrophils, basophils and lymphocytes
What do type II hypersensitivity reactions involve?
IgG and IgM antibodies directed against cellular antigens, leading to cell damage mediated by other immune system effectors.
What are type II hypersensitivity reactions also known as?
cytotoxic hypersensitivities
What are type II hypersensitivity reactions mediated by?
IgG and IgM
In type II reactions, what i effect of antibodies binding to cell-surface antigens or matrix-associated antigens on basement membranes?
Either:
1) Activate complement, resulting in an inflammatory response and lysis of the targeted cells
or
2) can be involved in antibody-dependent cell-mediated cytotoxicity (ADCC) with cytotoxic T cells.
If the targeted antigen is a self-antigen in type II reactions, what is this known as?
autoimmune disease
Antibodies may bind to naturally occurring, but exogenous, cell-surface molecules such as antigens associated with blood typing found on red blood cells (RBCs) in type II reactions.
What does this lead to?
1) coating of the RBCs by antibodies
2) activation of the complement cascade
3) complement-mediated lysis of RBCs
4) opsonization of RBCs for phagocytosis
What are 2 examples of type II hypersensitivity reactions involving RBCs?
- haemolytic transfusion reaction (HTR)
2) haemolytic disease of the newborn (HDN)
What type of reactions are antibody-initiated responses against blood cells?
Type II
What occurs during haemolytic transfusion reaction (HTR)?
IgG and IgM bind to antigens on transfused RBCs, targeting donor RBCs for destruction
Signs and symptoms of haemolytic transfusion reaction (HTR)?
Fever, jaundice, hypotension, disseminated intravascular coagulation, possibly leading to kidney failure and death
What occurs during haemolytic disease of the newborn (HDN)?
IgG from mother crosses the placenta, targeting the fetus’ RBCs for destruction
Signs and symptoms of haemolytic disease of the newborn (HDN)?
Anaemia, oedema, enlarged liver or spleen, hydrops (fluid in body cavity), leading to death of newborn in severe cases
What are the the four blood types based on?
the presence or absence of surface glycoproteins “A” and “B” (antigens)
Describe the dominance of ABO blood types
The alleles for A and B blood types are codominant to each other, and both are dominant over blood type O.
What antigens does a person with type AB blood express on the surface of RBCs?
Those with a genotype of AB have type AB blood and express both A and B glycoprotein antigens on the surface of their RBCs.
What antigens does a person with type O blood express on the surface of RBCs?
lack A and B glycoproteins on the surface of their RBCs (none)
Blood type A:
a) what antibodies produced?
b) What antigens on RBC?
a) Produces anti-B antibodies
b) A antigen
Can receive O and A blood
Blood type B:
a) what antibodies produced?
b) What antigens on RBC?
a) produces anti-A antibodies
b) B antigen
Can receive O and B blood
Blood type AB:
a) what antibodies produced?
b) What antigens on RBC?
a) no antibodies produced
b) A and B antigens
Can receive all blood types (universal recipient)
Blood type O:
a) what antibodies produced?
b) What antigens on RBC?
a) Anti-A and Anti-B
b) no antigens
Can receive O
What can a transfusion with an incompatible ABO blood type lead to?
a strong, potentially lethal type II hypersensitivity cytotoxic response called hemolytic transfusion reaction (HTR).
Describe a hemolytic transfusion reaction (HTR)
If a person with type B blood receives a transfusion of type A blood, their anti-A antibodies will bind to and agglutinate the transfused RBCs.
In addition, activation of the classical complement cascade will lead to a strong inflammatory response, and the complement membrane attack complex (MAC) will mediate massive hemolysis of the transfused RBCs.
Leads to haemolytic anaemia.
What are the second most frequently described RBC antigens?
Rh antigens
Cells are classified as Rh+ or Rh-
Which cells stimulate class switching from IgM to other antibody classes?
Th2 cells
What type of reaction can Rh factor incompatibility between mother and fetus cause?
a type II hypersensitivity hemolytic reaction, referred to as hemolytic disease of the newborn (HDN)
What are the only antibodies that can cross the placenta?
IgG
Describe what happens during hemolytic disease of the newborn (HDN)
- If an Rh− woman carries an Rh+ baby to term, the mother’s immune system can be exposed to Rh+ fetal red blood cells.
- The Rh+ fetal RBCs will activate a primary adaptive immune response in the mother, and anti-Rh factor IgG antibodies will be produced and can cross placenta
- In most cases, the first Rh+ baby is unaffected by these antibodies
- If a subsequent pregnancy with an Rh+ fetus occurs, the mother’s second exposure to the Rh factor antigens causes a strong secondary antibody response that produces larger quantities of anti-Rh factor IgG.
- These antibodies can cross the placenta from mother to fetus and cause HDN, a potentially lethal condition for the baby.
Of what antibody class are anti-B and anti-A antibodies?
IgG or IgM
