Autoimmunity - Beaty Flashcards
Major issues that cause hypersensitivity:
4 types
STII
- Susceptibility - often associated with inheritance of particular genes
- Triggers - by exogenous environmental antigens (microbiral and non microbial) or endogenous self antigens.
- Imbalance - between normal immune response + their limiting control mechanisms
- Injury - poor control
Immediate Hypersensitivity is probably an ___ hypersensitivity process. It is a rapid immunological reaction that occurs from previous ____, triggered by binding of antigen to ___ on mast cells.
Immediate Hypersensitivity is probably an innate hypersensitivity process. It is a rapid immunological reaction that occurs from previous sensitization, triggered by binding of antigen to IgE on mast cells.
Some Clinical Presentations of Type I Rxns are:
ABAF
Anaphylaxis - fall in BP, causing vascular dilations, airway obstruction
B - Bronchial asthma - airway obstruction caused by bronchial smooth muscle hyperactivation. Inflammation and tissue injury caused by late phase reaction
A - Allergic rhinitis and sinusitis (hay fever) - increased mucus secretion, inflammation of uppe rairways.
F- Food allergies - Increase perstalsis due to contraction of intestinal muscles.
ABAF are clinical presentations of a type ___ hypersensitivity rxn:
Anaphylaxis - fall in BP, causing vascular dilations, airway obstruction
B - Bronchial ashma - airway obstruction caused by bronchial smooth muscle hyperactivation. Inflammation and tissue injury caused by late phase reaction
A - Allergic rhinitis and sinusitis (hay fever) - increased mucus secretion, inflammation of uppe rairways.
F- Food allergies - Increase perstalsis due to contraction of intestinal muscles.
ABAF - Type I hypersensitivity Rxn
Anaphylaxis - fall in BP, causing vascular dilations, airway obstruction
B - Bronchial ashma - airway obstruction caused by bronchial smooth muscle hyperactivation. Inflammation and tissue injury caused by late phase reaction
A - Allergic rhinitis and sinusitis (hay fever) - increased mucus secretion, inflammation of uppe rairways.
F- Food allergies - Increase perstalsis due to contraction of intestinal muscles.
Type I is initiated by the introduction of an ___. It stimulates the ___ responses and __ production in genetically susceptible people. It causes sensitization of __ cells. These __ cells get coated with ___. __ (cytokine) activates eosinophils. The next time you are exposed to the antigen, __ gets crosslinked and activates the ___ cells. ___ (cytokine, enhances IgE production and stimulated epithlieal cell mucus secretion.
Type I is initiated by the introduction of an allergen. It stimulates the Th2 responses and IgE production in genetically susceptible people. It causes sensitization of mast cells. These mast cells get coated with IgE. IL-5 (cytokine) activates eosinohils. The next time you are exposed to the antigen, IgE gets crosslinked and activates the mast cells. IL-13 (cytokine, enhances IgE production and stimulated epithlieal cell mucus secretion.
Many local type I HSR have __ well defined phases:
- ___ rxn occurs within 5-30 minutes and increase ___, ___ permeability and increases ___ leakage.
- ___ rxn occurs 2-24 hours after exposure, characterized by tissue damage and eosinophis, neutrophils, basophils, monocytes and ___ infiltration.
Many local type I HSR have 2 well defined phases:
- Immediate rxn occurs within 5-30 minutes and increase vasodilation, vascular permeability and increases vascular leakage.
- Late rxn occurs 2-24 hours after exposure, characterized by tissue damage and eosinophis, neutrophils, basophils, monocytes and Th infiltration.
In type 1 HSR, re-exposure to the same antigen leads to cross-linking of surface bound ___ molecules, which causes ____ of the pre-senstizied __ and __ cells. Released mediators initiate the immediate phase of the HSR, which manifests as immediate edema, erythema and pruritis.
- Immediate phase is __, because the products released by degranulation have been pre-synthesized by inflammatory cells.
- Late phase results in the synthesis and release of ___ acid metabolites (leukotrienes and prostaglandins).
The role of eosinophils in the late stage is to:
- ____ and ___ the inflammatory response
- Liberate major basic proteins and eosinophil cationic protein which are toxic to epithelial cells.
- Activate __ cells.
In type 1 HSR, re-exposure to the same antigen leads to cross-linking of surface bound IgE molecules, which causes cross-linking of the pre-senstizied basophils and mast cells. Released mediators initiate the immediate phase of the HSR, which manifests as immediate edema, erythema and pruritis.
- Immediate phase is rapid, because the products released by degranulation have been pre-synthesized by inflammatory cells.
- Late phase results in the synthesis and release of arachodonic acid metabolites (leukotrienes and prostaglandins).
The role of eosinophils in the late stage is to:
- Amplify and sustain the inflammatory response
- Liberate major basic proteins and eosinophil cationic protein which are toxic to epithelial cells.
- Activate mast cells.
In Type I HSR, preformed mediators contained within the __ cell, and ___ granules are released within minutes of the ___ exposure. In contrast, lipid mediators (notably, ____) are synthesized during sequential reactions and released hours after initial exposure to antigen.
In Type I HSR, preformed mediators contained within the mast cell, and basophil granules are released within minutes of the allergern exposure. In contrast, lipid mediators (notably, leukotrienes) are synthesized during sequential reactions and released hours after initial exposure to antigen.
Type II HSR is an ___ response. It is ___ ___ cytotoxicity.
It is all about ___ cells! It connects to antigens via __ and ___. These activate the ____ system, which calls upon ___, a powerful anaphylatoxin. They also call upon neutrophils which release ____. The ___ kill not only the pathogen, but also ___ cells. It also induces ___, which neutralizes the pathogen.
Type II HSR is an antibody response. It is antibody dependent cytotoxicity.
It is all about killing cells! It connects to antigens via IgG and IgM. These activate the classical complement system, which calls upon C5a, a powerful anaphylatoxin. They also call upon neutrophils which release ROS’s.The ROS’s kill not only the pathogen, but also host cells. It also induces opsonization, which neutralizes the pathogen.
There are two categories of pathogensis in a type II HSR:
1.
2.
- Cytotoxic - antibodies bind and destroy the cell via variety of mechanism, like opsonization, phagocytosis, complement mediated inflammatory response and tissue damage.
- Non-cytotoxic - antibody binds and interferes with normal host function.
What are some consequence of the non-cytotoxic pathogenesis of type II HSR?
Myasthenia gravis - anti-AcH receptor antibodies bind post synaptic AcH receptors
Graves disease - anti TSH receptor antibodies bind and stimulate TSH receptors
Other examples
Rheumatic fever, Pernicious anemia, goodpasture disease, autoimmune hemolytic anemia.
There are THREE ways that AB’s can create a type II HSR:
What are the three ways?
- Opsonization - phagocytosis
- Inflammation - induce AB deposition into your tissues like in collagen or the basement membrane. This elicits an inflammatory response which increases neutrophils, and directs tissue injury.
- Cellular dysfunction - antibody against a particular receptor such as in Graves Dieases (turns on thyroid hormones by binding to TSH receptor) and Myasthenia Gravis (causes paralysis because it binds to the post synaptic AcH receptors.
Type ___ HSR involves the immune-complex. The circulating antigen-antibody complexes deposit on surface of blood vessels, activate the complement system and cause tissue destruction.
III
In the type III HSR, the immune complex consists of an antigen and antibody. This activates the complement system. Usually, these AB’s are __ or ___, which activate the classical complement system and turn on C5A. C5a calls upon neutrophils and these neutrophils release ROS’s that hurt the host.
In the type III HSR, the immune complex consists of an antigen and antibody. This activates the complement system. Usually, these AB’s are IgG or IgM, which activate the classical complement system and turn on C5a. C5a calls upon neutrophils and these neutrophils release ROS’s that hurt the host.
What HSR rxn causes Lupus?
Type III HSR - causes nephritis, skin lesions and arthritis.
What HSR causes rheumatoid arthritis?
Type III HSR
Which HSR causes Poststreptococcal glomerulonephritis?
Type III HSR
Antigen-antibody complexes produce damage by eliciting inflammation at sites of deposition. What type of HSR is this?
III
What is the pathogenesis of a type III HSR? (3 steps)
- Formation of immune complex - usually there is a trigger that causes an antibody production that cross reacts with antigen
- Deposition of immune complex - typically gets deposited in the wall of blood vessel
- Inflammation and tissue injury –> vasculitis
Three steps of Type III HSR:
- Formation of __ __ - usually there is a trigger that causes an antibody production that cross reacts with antigen
- ___n of immune complex - typically gets deposited in the wall of blood vessel
- Inflammation and tissue injury –> ___
- Formation of immune complex - usually there is a trigger that causes an antibody production that cross reacts with antigen
- Deposition of immune complex - typically gets deposited in the wall of blood vessel
- Inflammation and tissue injury –> vasculitis
What is going on here?
This is acute vasculitis. It is a result of a Type III HSR. When you look at a biopsy of a patient with type III HSR, you will see this. The pink part on the rim is the immune complex. Of course, this interferes with the natural function of the blood vessel and activates an immune response, causing tissue damage and leads to FIBRNOID NECROSIS in the artery.
___ is a result of a Type III HSR. When you look at a biopsy of a patient with type III HSR, you will see this. The ____ interferes with the natural function of the blood vessel and activates an immune response, causing tissue damage and leads to ____ NECROSIS in the artery.
Acute vasculitis is a result of a Type III HSR. When you look at a biopsy of a patient with type III HSR, you will see this. The vasculitis interferes with the natural function of the blood vessel and activates an immune response, causing tissue damage and leads to Fibrinoid NECROSIS in the artery.
What type if HSR is this?
Type IV (Delayed Type Hypersensitivity)
These are your CD4’s reacting and causing a cytokine storm.
A patient comes to your clinic with an enlarged thyroid. Her T3, T4 and free thyroxine is low, but her TSH is elevated. What does she have? What type of antibody would she be positive for? Why does this thyroid look nodular?
She has a hyPOthyroidism. This could be from Hashimoto’s disease. She is posititve for an antithyroglobulin antibody that was doing all the damage.
The thyroid looks nodular because there are lymphoid folicles and thyroid follciesl in one tissue –> autoimmune disease.
What is wrong with this thyroid?
Infiltration of B lymphocytes. This is why it is enlarged. There are germinal centers mainly involving B cell proliferation.
This patient has hypothyroidism –> HASHIMOTO’S THYROIDITIS.
This is a type IV HSR
What type of HSR is Hashimoto Disease?
Type IV
It is initiated by autoreactive T cells, but B cells are also involved. Activation of CD8 T cells cause destruction of thyrocytes, Recruitment of macrophages is another effect of the helper Th cell, which produced inflammatory cytokines within thyroid tissue.
A women has swollen knees, organomegaly, and a butterfly looking rash on her face. She was anemic, and had proteinuria. She also had RBC casts in the tubules of her kidneys.
She had a positive VDRL test, but was negative for the antitreponemal antibodies.
She was positive for ANA - (anti-nuclear antigen antibody)
She also has Smith antibodies and anti-ds-DNA antibodies
What does she have?
SLE - Type III
Very systemic
A patient has a malar rash on the face, and exposure to sunlight accentuates erythema on arm. There is also a deposition of immunoglobulin and complement along dermoepidermal junction.
What does she have?
SLE
