MIIM - Immunopathology I - Week 5 Flashcards
What is a possible disadvantage of immune activation in response to an infectious agent?
Damage to the body’s cells
Define immunodeficiency, and name three outcomes.
Failure of all or part of the immune system.
-recurrent infections
-overwhelming infections
-opportunistic infections
Name three abnormal or unwanted responses. Name two mechanisims by which it can occur.
Allergies
Autoimmune diseases
Graft rejection
-hypersensitivity and inflammation can cause them
Define primary immunodeficiency. Describe two possible causes, and ita rarity.
Inherent congenital defect in the immune system
-either genetic or caused by the intrauterine environment
-rare
Define secondary immunodeficiency.
External agents or alterations in other body systems that compromise the immune system.
Name 6 predisposing factors to secondary immunodeficiency.
Age
Malnutrition
Tumours
Cytotoxic drugs / irradiation
Other diseases (diabetes)
Infections (malaria, HIV)
In the eye, what are diseases found often due to?
Re-activation of latent infections
How many types of hypersensitivities are there?
4
Describe type I hypersensitivity, including what its first phase is, and what it is followed by (2), including its rarity, and possible symptoms (4). Name the later 2 phases.
Sensitisation, followed by Response.
Response include:
Local - rhinitis, bronchoconstriction, conjunctivitis
Systemic - anaphylaxis
Responses both have an immediate and a delayed phase
What are two other names for type I hypersensitivity.
Allergy and atopy
Name one general and three common causes of type I hypersensitivity.
Inocuous environmental antigens like pollen, house dust, and many foods
Consider type I hypersensitivity. What antibodies are produced and in response to what? What happens to these antibodies? What is this called? What happens with subsequent induction of type I hypersensitivity?
IgE antibodies are produced in response to an inocuous antigen (the allergen).
They bind to local mast cells.
After subsequent exposure to the allergen, they can bind to the mast cell-bound IgE antibodies, and result in the symptoms of allergy.
Which adaptive immune system signal is responsible for the sensitisation phase of type I hypersensitivity? What does it result in, and the production of what, by which cell? What is the mediator cytokine? Describe the process briefly.
Signal 3
It results in the differentiation of cells to TH2 cells. This will stimulate B cells to produce IgE antibodies to the allergen. The mediator cytokine is IL-4.
The CD4 TH2 cell is stimulated by a phagocytic cell, and in turn, stimulates B cells, which eventually produce the antibodies.
Define elicitation.
Subsequent allergen exposure leads to mast cell degranulation.
Consider elicitation. What kind of compounds are released, and how quickly? Order them (~5) into three time categories. Describe why the slowest response is so.
30 - 45 secs:
Histamine
Tryptase
10 - 30 mins:
Prostaglandins
Slow:
Cytokines
IL-4*
*Late respons edue to eosinophil and T cell activation
There are many types of allergic responses. What is it dependent on? What are the four main responses?
It is tissue dependent.
Main responses are:
-vasodilation
-vasopermeability
-smooth muscle contraction
-fluid secretion
Name two allergic responses in the GI tract and two symptoms it can cause.
Responses:
-increased fluid secretion
-increased peristalsis
Symptoms:
-diarrhoea
-vomiting
Name two allergic responses in the skin and three symptoms it can cause.
Responses:
-increased fluid secretion
-vasodilation
Symptoms:
-swelling
-itching
-urticaria (hives)
Name two allergic responses in the airway and four symptoms it can cause.
Responses:
-decreased bronchial diameter
-increased mucus
Symptoms:
-nasal blockage
-coughing
-phlegm
-athsma
Name two allergic responses in the blood vessels and three symptoms it can cause.
Responses:
-increased blood flow
-increased permeability
Symptoms:
-increased tissue fluid (oedema)
-increased cell infiltrate
-anaphylactic shock
Give four examples of type I hypersensitivity in the eye.
Allergic (seasonal) conjunctivitis
Vernal keratoconjunctivitis
Giant papillary conjunctivitis
Atopic keratoconjunctivitis
Name 6 possible treatment options for allergic conjunctivitis.
Avoiding the allergen
Cold compresses
Artifical tears, topical anti-histamines
Mast cell stabilisers
Vasoconstrictors
NSAIDs
Corticosteroids
What effect does histamine have on goblet cells?
It induces excessive cell mucus production
In severe cases, what is vernal keratoconjunctivitis associated with and what can it lead to? What cell is involved?
Corneal ulceration, leading to opacification.
Eosinophils are involved.
What occurs with increased frequency of vernal keratoconjunctivitis?
Ocular infection
Name 5 treatment options for vernal keratoconjunctivitis.
Mucolytics
Mast cell stabilisers
Corticosteroids
Cy A
Aspirin
In type II hypersensitivity, what two antibodies are involved and what do they react with?
IgG and IgM
They react with host cell antigens.
Name the two outcomes of type II hypersensitivity, what it leads to, and how it occurs.
Cytotoxicity - resulting in cell lysis and tissue injury.
-occurs due to complement activation and phagocyte activation, resulting in oxygen radical release.
Collectively this results in cell death.
Functional modification - antibodies bind to tissue receptors.
Name two examples of type II hypersensitivity in the eye.
Cicatricial pemphigoid
Myasthaenia gravis
Briefly describe how cicatricial pemphigoid occurs.
Antibodies target B4 integrin on the conjunctival epithelium. They are deposited on the basement membrane.
Name 5 symptoms associated with cicatricial pemphigoid.
Chronic blistering
Scarring
Severe ocular dryness
Eyelid and eyelash abnormalities
What is the prognosis for cicatricial pemphigoid like?
Poor
Is the treatment of cicatricial pemphigoid easy? Name 6 treatment options.
Is difficult.
Systemic corticosteroids
Blister cleaning
Immunosuppressives
Eyelash removal
Tear flim management
Surgery
Briefly describe why myasthaenia gravis occurs (2).
Autoantibodies against ACh receptors inhibit receptor function, reducing the number of ACh receptors.
Complement components induce cell destruction and loss of muscle function.
Name 4 symptoms of myasthaenia gravis in the eye.
Ptosis
Poor levator and EOM muscle function
Difficulty in sustaining gaze
Diplopia
Type III hypersensitivity is a what mediated hypersensitivity?
Immune complex mediated hypersensitivity
What two antibodies are involved with type III hypersensitivity?
IgG and IgM
Describe in x steps how type III hypersensitivity occurs.
-Immune complexes are formed every time antibody meets antigen
-IgG and IgM containing complexes activate the complement cascade and become coated with C3b
-Phagocytes express C3b receptors, so they normally remove those complexes from the tissue/circulation
-When immune complexes bind erythrocytes, they are carried to the spleen and liver, where they are removed by macrophages
-In Type III hypersensitivity, complexes are not cleared, and persist
-Complexes that persist tend to be small and form in antigen excess
-These complexes deposit in blood vessel walls where, when aggregated, trigger the complement cascade
What toxins does type III hypersensitivity generate? Which phagocytic cell is activated? Does this type result in mast cell degranulation?
Generates anaphylotoxins
Activates neutrophils
Results in mast cell degranulation
True or false
Type III hypersensitivity doesnt induce macrophage cytokine release.
False, it does
True or false
Type III hypersensitivity DIRECTLY activates platelets and basophils.
True
Does type III hypersensitivity lead to cell damage and tissure injury?
Yesd
Name 6 examples of type III hypersensitivity in ocular disease.
Cicatricial pemphigoid
Steven Johnsons syndrome
Several forms of uveitis
Sarcoidosis
Retinal vasculitis
Scleritis
What type of hypersensitivity is type IV hypersensitivity?
Cell mediated: delayed type
What is the main cause of type IV hypersensitivity?
Persisting antigen-specific T cells (CD4 or CD8)
Describe what normally happens without type IV hypersensitivity and how its different with type IV hypersensitivity.
Normally, macrophages which have engulfed microorganisms are stimulated to kill them by helper T cells.
When the organism, or stimulating agent persists, macrophages and T cells accumulate at the antigen site in large numbers and result in pathology.
Describe, in four steps, the sensitisation phase of type IV hypersensitivty. Describe the consequence of a persisting antigen.
Uptake and degradation of the allergen by APCs
Presentation to Th1 cells in the lymph node (co-stimulation)
Memory Th1 cells migrate to the site
Activation of Th1 cells in lymphoid tissue
-normally the antigen is removed. If it persists, activated macrophages and T cells accumulate
How long does the response phase of type IV hypersensitivity take?
24 - 72 hours
Why would accumulating macrophages and Th1 cells be damaging? Describe what they release that results in this (9).
Increased oxygen radicals
Increased nitric oxide
Increased cyto/chemokines
Mononuclear cell recruitment
Marcrophage differentiation
Granuloma formation
Inflammatory cytokines
Epithelioid cell recruitment
Damage caused by excess cytotoxic T cell activation
Name 7 stimuli for type IV hypersensitivity in the eye.
Irritants like cosmetics/detergents
Metals
Resins
Topical antibiotics
Antihistamines
Infectious agents
What suppresses type IV hypersensitivity in the anterior chamber? What cell generation is suppressed? What two factors result in this suppression?
Can it be overcome (1)?
Anterior chamber associated immune deviation
Suppresses the generation of Th1 cells, due to the production of T-reg cells and TGFβ.
It can be overcome, as in graft rejection.
