Allergy & Hypersensitivity Flashcards
Hypersensitivity
An immune disorder caused by an inappropriate response to antigens that are not necessarily pathogens
Hypersensitivity is an immune disorder only resulting from inappropriately vigorous innate immune response.
True or False?
False
Can be either immune and/or adaptive
Hypersensitivities are divided into —— categories that differ by
- 4
- the immune molecules and cells that cause them and by the way they induce damage
Allergy is a hypersensitivity disorder.
True or False?
True
Why some antigens induce allergy and others do not is still not fully understood. Some antigens that cause allergy appear to have —– ——- —–.
Intrinsic Protease Activity
Allergy definition
A damaging immune response by the body to a substance (allergen) to which it has become hypersensitive.
Allergy triggers unnecessary increases in ——— —— and ——– that lead to tissue damage with little benefit.
vascular permeability and inflammation
Local allergic responses
symptoms are restricted to the site where the antigen interacts with the body
Examples of local allergic response (3):
- asthma
- atopic dermatitis
- food allergies
Anaphylaxis
a system wide response that occurs if the same antigens (allergens) are more widely disseminated (eg: injected IV)
How quickly can anaphylactic shock be fatal?
Within 2-4 minutes of exposure to the antigen
Atopy
predisposition to an immune response against diverse antigens and allergens leading to overproduction of IgE, which leads to an increased likelihood of developing a hypersensitivity reaction.
Most frequent clinical manifestations of atopy (4):
- allergic bronchial asthma
- allergic rhinitis
- atopic dermatitis
- food allergy
Classification of hypersensitive reactions table
Type I hypersensitivity reaction:
- mediation?
- which type of immunoglobin and recognition?
- recognition of what?
- Which cells express which receptors and are the main mediators of allergy symptoms?
- How are signaling cascades initiated?
- Signalling results in?
- antibody mediated
- IgE recognise antigen via variable region
- IgE antibodies bind to one of two types of Fc receptors via their constant regions
- Mast cells, basophils and eosinophils (less likely) express a receptors known as FcεRI and are the main mediators of allergy symptoms
- Cross linking of FcεRI receptors by allergen/IgE complexes initiate signalling cascades that resemble those initiated by antigen receptors.
- signalling results in mast cell/basophil degranulation with the release of inflammatory mediators
What type of hypersensitivity is allergy?
Type I: antibody mediated (IgE)
Individuals without allergies generally produce IgE antibodies only in response to
Parasitic Infections
What does the allergen need in order to cause cross-linking? Example?
- multivalent: have multiple epitopes
- pollen
Type I hypersensitivity diagram:
General Mechanism of Type I hypersensitivity:
First exposure to the antigen allergen (A) triggers a standard immune response with the production of IgE. Re-exposure to the same allergen (B) triggers mast cell degranulation with the associated inflammatory responses.
degranulation and secretion of molecules diagram
1) first vasoactive amines released
2) proteases released
3) proteases cause tissue damage
4) leads to lipid mediators secreted
5) inflammation recruitment
where are the chemicals released in hours….
1) cytokines in late phase reaction
Insert graph degranulation and secretion of molecules: where are the chemicals released in hours….
1) cytokines in late phase reaction
Leukotrienes
- group of biologically active compounds, originally isolated from leucocytes.
- metabolites of arachidonic acid, containing three conjugated double bonds, act as mediators of inflammation
Prostaglandins
group of hormone like substances that participate in a wide range of body functions such as the contraction of blood vessels, control of blood pressure and modulation of inflammation.
The asthmatic response: Type I hypersensitivity (4):
- initial contraction of bronchial and tracheal smooth muscle is mediated by histamine, typically within minutes of release as a result of mast cell degranulation
- binding of histamine to the H1 receptors also increases vascular permeability and mucous secretion
- phospholipase released by degranulation initiates enzymatic breakdown of phospholipids in the plasma membrane leading to the release of leukotrienes and prostaglandins
- within 30-60 seconds, further bronchoconstriction is triggered, together with further increased vascular permeability and mucous secretion
How much more active are leukotrienes and prostaglandins than histamine?
1000 fold more active than histamines
In humans, leukotrienes are thought to contribute significantly to the ——— ———- and —— – – ——– seen in asthmatics.
Prolonged bronchospasm
Build up of mucous
Type I hypersensitivity: asthma:
What facilitates the influx of neutrophils, eosinophils and T helper cell
Cytokines released from mast cells increase the expression of adhesion molecules on endothelial cells.
Histamine acts on (2):
- endothelial cells
- smooth muscle
Cytokine recruits inflammatory cells during Type I hypersensitivity response leading to
Injury of epithelium which initiates repair mechanism, leading to thickening of basement membrane hence damages the airway
diagram from early and late responses in asthma
Type II hypersensitivity response:
- involved —— ——— destruction of cells by —– Three mechanisms used to trigger destruction of the antigen/allergen
- results in
- involve antibody mediated destructions of cells by antibody classes other than IgE, IgG or IgM
- Three mechanisms:
1) activation of the complement cascade
2) antibody - dependent cell mediated toxicity (ADCC)
3) antibody bound to target cell attracts and activates phagocytic cells that kill by the process known as opsonisation - Results in tissue damage
Type II hypersensitivity response: Activation of complement cascade as a method of destruction of cell:
Certain antibody isotypes (mainly IgM,IgG) possess structural elements in their Fc domain that initiate the complement cascade. Results in the formation of Membrane Attack Complex, which punches holes in the cell to which antibody is bound.
Type II hypersensitivity response: Antibody - dependent cell-mediated cytotoxicity (ADCC) as a method of destruction of cell:
Antibodies attach to antigens on a target cell via the variable domain, whilst the antibody Fc domain binds to the Fc receptor on cytotoxic cells; antibody acts as a bridge and the target cell is destroyed
Type II hypersensitivity response: Opsonisation as a method of destruction of cell:
Antibody bound to the target cell can act as an “opsonin” enabling phagocytic cells with Fc or C3b (complement) receptors to bind and phagocytose the antibody-coated cell
Type II hypersensitivity: antibody mediated diagram:
- C3b increases susceptibility to phagocytes
ADCC stands for
Antibody-dependent cell-mediated cytotoxicity
What receptor in Type II hypersensitivity?
FC gamma R
Clinical Manifestation of Type II Hypersensitivity diagram:
Drug induced haemolytic anaemia
Type III hypersensitivity response:
- extensive immune complexes of antibody and antigen can’t always be cleared by phagocytes, either because of peculiarities of the antigen itself, or disorders in phagocytic machinery
- uncleared immune complexes can induce degranulation of mast cells and inflammation triggered by complement activation and attraction and activation of neutrophils at the site of the immune complex.
- immune complexes can be deposited in tissues and capillary beds where they induce more innate immune activity, vasculitis and tissue damage
Vasculitis is
blood vessel inflammation
Depositions of immune complexes of antibody and antigen in the kidney can lead to
glomerulonephritis
kidneys become inflamed and have problems filtering waste from the blood
Deposition of immune complexes of antibody and antigen in the joints
arthritis
Type III hypersensitivity response: immune complex mediated:
When may Type III hypersensitivity be self-limiting?
If the antigen in the immune complex is derived from an infectious organism or limited in terms of quantity
May be cleared spontaneously without intervention
When is Type III hypersensitivity not self-limiting?
If the antigen in the immune complex is a self-antigen, the immune complex will never be cleared from the site where the antigen is expressed.
Diseases resulting from type III hypersensitivity table:
Type IV hypersensitivity:
- mediated
- aka
- requires
- cell mediated
- aka Delayed-type hypersensitivity (DTH)
- requires T cells to be sensitised to antigen and subsequent re-exposure results in cytokine production, inflammation and the recruitment of macrophages
When do symptoms appear in Type IV hypersensitivity (cell-mediated)?
24-48 hours after re-exposures (hence the name delayed-type)
Examples of Type IV hypersensitivity (cell mediated):
- contact dermatitis
- granulomas associated with tuberculosis
- graft rejection
Type IV hypersensitivity: sensitisation phase:
- initial contact with antigen by APC triggers activation, clonal expansion and differentiation of T helper cells bearing appropriately shaped TCRs.
- Activated T cells secrete cytokines
- takes 1-2 weeks to complete
- process resembles normal adaptive immune response
Type IV hypersensitivity: sensitisation phase diagram
Don’t need to know types of T cell till 2nd year
Type IV hypersensitivity: effector phase:
- upon re-exposure to antigen, the sensitised T cell produces a variety of cytokines and chemokines
- which attract and activate macrophages and other non-specific inflammatory cells
- activated macrophages are professional APCs so this perpetuates the immune response
- typically symptoms occur 24-48 hours after re-exposure
Type IV hypersensitivity: Effector Phase Diagram:
Both TNF and IFN activate macrophages (cytokines)
Inducers of Type IV hypersensitivity table
Arthus Reactions are triggered by?
and an example of which type of hypersensitivity?
- triggered by insect bites or inhalation of fungal or animal proteins
- Type III
Clinical investigation of coughing:
- hypersensitivity reactions (Type I allergies) are a common cause of coughing but it is important to consider that a cough may be a symptom of serious disease (hypersensitivity mediated or otherwise)
- can also be triggered by medication, idiopathic causes or psychogenic in origin
Red Flags associated with coughing (10)
