Pathology - Immunity & Hypersensitivity

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Immunity
Natural (non-specific) immunity:
Inherited & do not depend on ___ ___
(a) First line of defense: ___ (skin), ___ in trachea and bronchi, nasal and gastric ___
(b) Second line of defense: ___, complement and ___ cells

Acquired (specific) immunity:
Specific response following exposure to a particular ___

previous exposure
mechanical; cilia; secretions
lysozymes; phagocytic

antigen

Essential features of immune system

- Specificity: for one particular ___
- Diversity: can recognize different ___
- Memory: to ___ antigens, responsible for rapid, higher and persistent ___ ___ response
- Recruitment: by releasing ___ that recruit & activate other defense mechanisms

antigen
antigens
previous; secondary immune
cytokines

Harmful Immune Reactions Immunopathology

Three groups of diseases:
(1) ___ (as anaphylaxis)
(2) ___ (as SLE)
(3) ___ deficiency (congenital or acquired)

hypersensitivity
autoimmune
immunologic

Hypersensitivity
Allergy
- Abnormal exaggerated immune ___ resulting in tissue injury
- Four types on the basis of mechanism of ___:
Type I: ___ (anaphylactic)
Type II: ___
Type III: ___ complex
Type IV: cell-mediated ___

reactions
injury
immediate
cytotoxic
immune
hypersensitivity

Type I: Immediate (___) Reaction Mechanism:
- 1st exposure to allergen stimulates ___ --> binds to mast cell and blood ___
- On subsequent exposure, the allergen reacts with the fixed ___ --> degranulation of ___ cells -->
release of ___ and others

ANAPHYLACTIC
IgE; basophils
AB; mast; histamine

Activation of mast cell & the potent inflammatory mediators released

Clinical Types:
(1) Atopy
- ___ form (affecting one organ) e.g. ___ (hives), allergic ___, ___ asthma
- Response to ingested or inhaled ___ allergens
- Affects ___% of population
- Strong ___ PREDISPOSITION

local; urticaria; rhinitis; bronchial
environmental
10
FAMILIAL

Bronchial asthma, high power Numerous ___ are prominent.

eosinophils

(2) Anaphylaxis
- Systemic from --> release of ___ amines into circulation e.g. peripheral circulatory ___, shock, ___, even death
- Follows injection of allergens e.g. ___, drugs (___)

vasoactive; failure; hypotension
serum; penicillin

Drug-induced urticaria: ___
Large, urticarial ___ on the face, neck, and trunk with ___ in the periorbital region.

penicillin
wheals; angiodema

Type II: Cytotoxic Reaction & Antibody-mediated Reaction

Mechanism:
Specific antibody (___ or ___) reacts with cell membrane antigen, activates the complement resulting in cell ___

IgG; IgM; lysis

Clinical types
1. Transfusion reaction due to ___ ___: AB in ___ serum reacts against antigen on transfused RBCs
2. ___ incompatibility:
Maternal AB to fetal RBC antigen (___) cross the placenta (___)
3. Autoimmune hemolytic anemia: ___ to RBCs

BLOOD INCOMPATIBILITY; recipient
Rh; Rh; IgG
autoantibodies

Type II hypersensitivity. Antibody- and ___-mediated red blood cell lysis due to complement activation and the formation of the ___ membrane attack complex (MAC).

complement; C5b-9

4. Myasthenia gravis:
Autoantibodies against ___ receptors at neuromuscular junction, compete with acetylcholine for the acetylcholine ___, inhibiting synaptic transmission leading to profound muscle ___.

5. Graves' disease:
Autoantibodies to ___ ___ hormone receptors on ___ cells -->  stimulation of cells

acetylcholine; receptors; weakness

thyroid stimulating; follicular

___ antireceptor antibodies in Graves disease and myasthenia. The binding of the antibody to the ___ receptor in Graves disease results in ___, whereas the ___ of synaptic transmission in myasthenia gravis leads to profound muscle weakness.

Non-cytotoxic; TSH; hyperthyroidism; inhibition

6. Goodpasture's syndrome:
- Formation of AB (___) to antigens common in ___ & pulmonary ___ membranes
- AB reacts with basement membrane antigen --> activates ___ resulting in:
- Lung: hemorrhage, ___, fibrosis
- Kidney: glomerulonephritis, ___, failure

IgG; glomeruli; basement
complement
necrosis
fibrosis

Antibody against ___ basement membrane antigens in Goodpasture disease. The binding of antibody to antigens of basement membrane activates complement, thereby recruiting ___ leukocytes and provoking tissue ___.

glomerular; polymorphonuclear; injury

Type III: immune Complex Reaction

Mechanism:
- Reaction of AB (___ or ___) with antigen results in the formation of ___ immune complexes
- ___ of immune complexes in various tissues
- ___ of complement --> acute ___ and tissue damage

IgG; IgM; soluble
deposition
activation; inflammation

Arthus phenomenon...

Type III
Clinical types:
(1) Systemic form:
- ___ sickness
- rheumatoid arthritis
- systemic ___ ___
(2) Local form:
- ___ that develops 6-8 hours after inhalation of moldy hay (___ lung) or moldy cheese (___ ___ lung)

serum
lupus erythematosus
pneumonitis; Farmer's; Cheese maker's

One form of hypersensitivity pneumonitis is known as farmer's lung because the farmer inhales ___ ___ in moldy hay that set off the reaction.

thermophilic actinomyces

Lung, hypersensitivity pneumonitis, microscopic
This is an example of hypersensitivity pneumonitis that can occur when there is an inhaled organic dust that produces a ___ type ___ hypersensitivity (Arthus) reaction from antigen-antibody complexes. There are no major ___ complications.

localized; III; long-term

Type IV: Cell Mediated Hypersensitivity
Type IV is mediated by ___ cells rather than antibodies

Mechanism:
Includes 2 types of reactions
1- DTH: ___ hypersensitivity:
- Reaction is mediated by ___ cells (antigen-specific ___ T cells)

2-T cell-mediated ___:
- Release of ___ for activation of CD8 and ___ for activation of macrophages

T
delayed-type
CD4; memory

cytotoxicity
IL-2; y-interferon

Granulomas, which are typical of type ___ hypersensitivity, consist of ___ cells, ___ cells, and ___.

IV; epithelioid; giant; lymphocytes

Type IV
Clinical types:
(1) ___ dermatitis
(2) Killing of ___ and ___-infected cells
(3) ___ rejection

contact
tumors; virus
transplant

Immune Mechanism of Tissue Injury

Summary:
Immune responses (___ or cellular) to ___ (exogenous or endogenous) cause tissue damaging ___ reactions:

Type I: Humoral AB (___) binds to antigens, releases vasoactive ___ from ___ cells & blood ___.

humoral; antigens; hypersensitivity

IgE; amines; mast; basophils

Type II: Humoral AB (___, ___) binds to antigen on cell surface, activates complement --> cell ___

Type III: Humoral AB (IgG, IgM) binds to antigen forming ___ immune complexes --> activates complement --> attracts ___ --> release of ___ enzymes --> tissue damage

Type IV: Antigen-specific ___ memory cells recruit & activate ___ and ___ --> tissue damage

IgG, IgM; lysis

soluble; neutrophils; neutrophilic

CD4; CD8; macrophages

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