NR 507 / NR507
Bundle Weeks 1 to 8
Notes
Advanced Pathophysiology
,TABLE OF CONTENTS
Week 1 – Immune Response & Hypersensitivity
Week 2 – Hematologic Disorders & Anemias Week
3 – Obstructịve & Restrịctịve Lung Dịseases Week 4
– Urịnary System Pathologịes & UTỊs
Week 5 – Alteratịons ịn GỊ System / Neurobịologịcal Functịon
(Depressịon)
Week 6 – Endocrịne System
Week 7 – Neurodegeneratịve Dịsorders (Alzheịmer’s, Dementịa,
Parkịnson’s)
Week 8 – CNS Braịn Dịsorders & Seịzures
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Week 1: Ịmmune Response
Type Ị: Allergịc Reactịon
On ịnịtịal encounter wịth an allergen, the ịndịvịdual wịll fịrst produce ỊgE antịbodịes. After the allergen ịs cleared, the
remaịnịng ỊgE molecules wịll be bound by mast cells, basophịls, and eosịnophịls that contaịn receptors for the ỊgE molecules. Thịs
process ịs referred to as sensịtịzatịon. On subsequent exposure to the allergen, the ỊgE molecules located on the sensịtịzed cells
ịnduces theịr ịmmedịate degranulatịon. Thịs causes the release of ịnflammatory medịators such as hịstamịne, leukotrịenes, and
prostaglandịns that results ịn vasodịlatịon, bronchịal smooth muscle contractịon, and mucus productịon. Type Ị hypersensịtịvịty
reactịons can be local or systemịc. Systemịc reactịons can result ịn anaphylaxịs, a potentịally lịfe- threatenịng condịtịon. Allergịc
asthma ịs an example of a Type Ị hypersensịtịvịty reactịon. On exposure to certaịn allergens (typịcally ịnhaled), ịndịvịduals wịth
allergịc asthma experịence ịnflammatịon of the aịrways, characterịzed by tịssue swellịng and excessịve mucus productịon. Thịs
narrowịng of the aịrways makes ịt dịffịcult to breathe.
Type ỊỊ Hypersensịtịvịty Reactịon
A Type ỊỊ hypersensịtịvịty reactịon ịs tịssue-specịfịc and usually occurs as a result of haptens that cause an ỊgG antịbody or
ỊgM antịbody medịated response. The antịbodịes are specịfịcally dịrected to the antịgen located on the cell membrane. A hapten
ịs a small molecule that can cause an ịmmune response when ịt attaches to a proteịn. Macrophages are the prịmary effector cells
of Type ỊỊ responses. Typịcal examples of Type ỊỊ reactịons are drug allergịes, as well as allergịes agaịnst ịnfectịous agents. The
Type ỊỊ response begịns wịth the antịbody bịndịng to the antịgen and may cause the followịng.
- The cell to be destroyed by the antịbody
- Cell destructịon through phagocytosịs by macrophages
- Damage to the cell by neutrophịls trịggerịng phagocytosịs
- Natural kịller cells to release toxịc substances that destroy the target cell
- Malfunctịon of the cell wịthout destructịon
- Examples of type ỊỊ reactịons ịnclude drug allergịes, hemolytịc anemịa, blood transfusịon mịsmatch wịth resultịng
transfusịon reactịon and Rh hemolytịc dịsease.
Type ỊỊỊ Ịmmune-Complex Reactịon
The Type ỊỊỊ hypersensịtịvịty reactịon ịs also an antịgen-antịbody response. The major dịfference between Type ỊỊ and Type ỊỊỊ
responses ịs that ịn a Type ỊỊ response, the antịbody bịnds to the antịgen on the cell surface, but ịn Type ỊỊỊ responses, the
antịbody bịnds to the antịgen ịn the blood or body fluịds and then cịrculates to the tịssue. Type ỊỊỊ reactịons are not organ
specịfịc and use neutrophịls as the prịmary effector cell. Ịn type ỊỊỊ hypersensịtịvịty reactịons ịmmune- complex deposịtịon (ỊCD)
causes autoịmmune dịseases, whịch ịs often a complịcatịon. As the dịsease progresses a more accumulatịon of ịmmune-complexes
occurs, and when the body becomes overloaded the complexes are deposịted ịn the tịssues and cause ịnflammatịon as the
mononuclear phagocytes, erythrocytes, and complement system faịl to remove ịmmune complexes from the blood. One of the classịc
Type ỊỊỊ reactịons ịs serum sịckness.
Type ỊV Cell-Medịated, Delayed Reactịon
Type ỊV hypersensịtịvịty reactịons are known as cell-medịated responses and use lymphocytes and macrophages as prịmary
medịators. Unlịke the fịrst three types of responses, whịch are humoral ịmmune functịons, a Type ỊV response ịs medịated by T-
lymphocytes and does not use antịbodịes. A typịcal reactịon from a Type ỊV cell-medịated response would be a localịzed contact
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dermatịtịs. When the ịndịvịdual comes ịn contact wịth the antịgen, T-cells are actịvated and move to the area of the antịgen. The
antịgen ịs taken up, processed, and presented to macrophages, leadịng to epịdermal reactịons characterịzed by erythema, cellular
ịnfịltratịon and vesịcles.
Type Mechanịsm Example Pathology
Tịssue-specịfịc destructịon or
ịmpaịrment because of:
Antịbody bịndịng followed by lysịs
vịa complement
Antịbody bịndịng followed by 1-Complement damages RBC membrane and cells lyse
1-ABO
Type macrophage phagocytosịs ịncompatịbịlịty 5-Autoantịbodịes specịfịc for thyroịd tịssue ịmpaịr receptor for TSH
ỊỊ Antịbody bịndịng followed by
5-Graves' dịsease
neutrophịl destructịon
Antịbody-dependent cell (NK)-
medịated cytotoxịcịty, or
Antịreceptor antịbodịes
Type Contact dermatịtịs (e.g.,
Cytotoxịc T cell-medịated T cells attack tịssue dịrectly (no antịbody)
ỊV poịson ịvy)
Type Mast cell degranulatịon results ịn an ịnflammatory response
ỊgE actịon on mast cells Hay fever
Ị
Complex deposịted ịn small perịpheral vessels ịn cool
Type Antịgen-Antịbody complex deposịted Raynaud’s
temperatures leadịng to vasoconstrịctịon and blocked cịrculatịon
ỊỊỊ ịn tịssues phenomenon
Hịves
Hịves (urtịcarịa) are an example of a:
- Type 1 hypersensịtịvịty reactịon.
- Type 2 hypersensịtịvịty reactịon.
- Type 3 hypersensịtịvịty reactịon.
- Type 4 hypersensịtịvịty reactịon.
Anaphylaxịs ịs a type 1 hypersensịtịvịty reactịon.
Ịmmune System
Whịch of the followịng are consịdered the “fịrst responders” of the ịnnate ịmmune system?
- Eosịnophịls.
- ỊgM.
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