11-immunopathology part 1

8/10/2019 11-Immunopathology Part 1

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Immunity

Natural (non-specific) immunity:

Inherited & do not depend on previous exposure

(a) First line of defense: mechanical (skin), cilia in

trachea and bronchi, nasal and gastric secretions

(b) Second line of defense: lysozymes, complement

and phagocytic cells

Acquired (specific) immunity:

Specific response following exposure to a particular

antigen

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Essential features of immune system

- Specificity: for one particular antigen

- Diversity: can recognize different antigens

- Memory: to previous antigens, responsible

for rapid, higher and persistent

secondary immune response

- Recruitment:by releasing cytokines that recruit

& activate other defense mechanisms

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Harmful Immune Reactions

Immunopathology

Three groups of diseases:(1) Hypersensitivity (as anaphylaxis)

(2) Autoimmune (as SLE)

(3) immunologic deficiency (congenital or

acquired)

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Hypersensitivity

Allergy- Abnormal exaggerated immune reactions resulting

in tissue injury

- Four types on the basis of mechanism of injury:

Type I: immediate (anaphylactic)

Type II: cytotoxicType III: immune complex

Type IV: cell-mediated hypersensitivity

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Type I: Immediate (Anaphylactic) Reaction

Mechanism:

- 1st

exposure to allergen stimulates IgEbinds tomast cell and blood basophils

- On subsequent exposure, the allergen reacts with

the fixed AB degranulation of mast cells

release of histamine and others

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Activation of mast cell & the potent inflammatory mediators

released

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Clinical Types:

(1) Atopy- Local form (affecting one organ) e.g. urticaria

(hives), allergic rhinitis, bronchial asthma

- Response to ingested or inhaled environmentalallergens

- Affects 10% of population

- Strong familial predisposition

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Bronchial asthma, high power

Numerous eosinophils are prominent.

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(2) Anaphylaxis

- Systemic from release of vasoactive amines

into circulation e.g. peripheral circulatory failure,

shock, hypotension, even death

- Follows injection of allergens e.g. serum, drugs(penicillin)

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Drug-induced urticaria: penicillin

Large, urticarial wheals on the face, neck, and trunk withangiodema in the periorbital region.

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Type II: Cytotoxic Reaction

& Antibody-mediated Reaction

Mechanism:

Specific antibody (IgG or IgM) reacts with cell

membrane antigen, activates the complement

resulting in cell lysis

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Clinical types

Transfusion reaction due to blood incompatibility:

AB in recipient serum reacts against antigen ontransfused RBCs

Rh incompatibility:Maternal AB to fetal RBC antigen (Rh) cross the

placenta (IgG)

Autoimmune hemolytic anemia:

Autoantibodies to RBCs

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Type II hypersensitivity.

Antibody- and

complement-mediated red

blood cell lysis due tocomplement activation and

the formation of the C5b-9

membrane attack complex

(MAC).

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Myasthenia gravis:

Autoantibodies against acetylcholine receptors

at neuromuscular junction, compete withacetylcholine for the acetylcholine receptors,

inhibiting synaptic transmission leading to

profound muscle weakness.

Graves disease:

Autoantibodies to thyroid stimulating hormone

receptors on follicular cells stimulation of cells

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Noncytotoxic antireceptor antibodies in Graves disease and

myasthenia. The binding of the antibody to the TSH receptor

in Graves disease results in hyperthyroidism, whereas the

inhibition of synaptic transmission in myasthenia gravis leads

to profound muscle weakness.16


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Goodpastures syndrome:

- Formation of AB (IgG) to antigens common

in glomeruli & pulmonary basement membranes

- AB reacts with basement membrane antigen

activates complement resulting in:- Lung: hemorrhage, necrosis, fibrosis

- Kidney: glomerulonephritis, fibrosis, failure

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Antibody against glomerular basement membrane antigens inGoodpasture disease. The binding of antibody to antigens of

basement membrane activates complement, thereby recruitingpolymorphonuclear leukocytes and provoking tissue injury.

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Type III: immune Complex Reaction

Mechanism:- Reaction of AB (IgG or IgM) with antigen results

in the formation of soluble immune complexes

- deposition of immune complexes in various tissues

- Activation of complement acute inflammation

and tissue damage

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Arthus phenomenon


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Clinical types:

(1) Systemic form:

- serum sickness

- rheumatoid arthritis

- systemic lupus erythematosus

(2) Local form:

- pneumonitis that develops 6-8 hours after

inhalation of moldy hay (Farmers lung) ormoldy cheese (Cheese makers lung)

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

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Lung hypersensitivity pneumonitis microscopic


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Lung, hypersensitivity pneumonitis, microscopic

This is an example of hypersensitivity pneumonitis that canoccur when there is an inhaled organic dust that produces alocalized type III hypersensitivity (Arthus) reaction from

antigen-antibody complexes. There are no major long-termcomplications.

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Type IV: Cell Mediated Hypersensitivity

Type IV is mediated by T cells rather than antibodies

Mechanism:

Includes 2 types of reaction

1- DTH: Delayed-type hypersensitivity:

- Reaction is mediated by CD4 cells (antigen-

specific memory T cells)

2-T cell-mediated cytotoxicity:

- Release of IL-2 for activation of CD8 and y-

interferon for activation of macrophages 26


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Granulomas, which are

typical of type IVhypersensitivity, consist

of epithelioid cells, giant

cells, and lymphocytes.

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Clinical types:

(1) contact dermatitis

(2) Killing of tumors and virus infected cells

(3) Transplant rejection

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Contact Dermatitis


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Contact Dermatitis


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Immune Mechanism of Tissue Injury

Summary:Immune responses (humoral or cellular) to antigens

(exogenous or endogenous) cause tissue damaging

hypersensitivity reactions:

Type I: Humoral AB (IgE) binds to antigens,

releases vasoactive amines from mast cells &

blood basophils.

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Type II: Humoral AB (IgG, IgM) binds to antigen on

cell surface, activates complement cell lysis

Type III: Humoral AB (IgG, IgM) binds to antigen

forming soluble immune complexes

activates complement attracts neutrophils

release of neutrophilic enzymes tissue

damage

Type IV: Antigen-specific CD4 memory cells

recruit & activate CD8 and macrophages

tissue damage32

11-immunopathology part 1

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