Hypersensitivity Lecture

8/6/2019 Hypersensitivity Lecture

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Kuby IMMUNOLOGY

Sixth Edition

Chapter 15

Hypersensitivity Reactions

Copyright © 2007 by W. H. Freeman and Company

Kindt • Goldsby • Osborne





Type I Hypersensitivity Reaction





















Type I Hypersensitivity:

Systemic or Localized• Systemic (Anaphylaxis shock)

– Symptoms include: labored breathing, drop in

blood pressure, smooth muscle contraction, bronchiole constriction (suffocation)

• Localized

– Examples: Hay fever (allergic rhinitis), asthma(allergic or intrinsic), food allergies, atopic

dermatitis (eczema)





RIST

RAST











Generalized Type III Hypersensitivity

Reactions: Serum Sickness Occurs when antigen enters bloodstream,

circulating immune complexes form

Symptoms include:

– Fever

– Weakness

– Rashes

– And many others



1. Complement initiates

mast celldegranulation

2. Neutrophils are

chemotactically

attracted to the site

3. Neutrophils release

lytic enzyme after

failed attempts to

endocytose the

immune complex













Cell-Mediated Effector Responses



The primary domain of antibody protection liesoutside the cell.

If antibodies were the only agents of immunity,

pathogens that managed to evade them andcolonize the intracellular environment wouldescape the immune system.



The principal role of cell-mediated

immunity is to detect and eliminatecells that harbor intracellularpathogens.

Cell-mediated immunity also canrecognize and eliminate cells, such astumorcells,

that have undergone geneticmodifications so that they expressantigens not typical of normal cells.





Nonspecific cells include NK cells

and nonlymphoid cell types suchas macrophages, neutrophils, andeosinophils.





Cell-mediated immune responses can be dividedinto two major categories according to thedifferent effector populations that aremobilized.

One comprises antigen-specific cytotoxic T lymphocytes (CTLs)And

T wo nonspecific cells, such as natural killer(NK) cells and macrophages.

Effector Responses



General Properties of Effector T Cells

The three types of effector

T cells—CD4+,

TH1 and TH2 cells,

and CD8+ CTLs—

exhibit several properties





Effector T Cells Express a Variety

of Effector Molecules



Cytotoxic T Cells

Cytotoxic T lymphocytes, or CTLs, are generatedby immune activation of T cytotoxic (TC) cells.

These effector cells have lytic capability and arecritical in the recognition and eliminationof altered self-cells

(e.g., virus-infected cells andtumor cells) and in graft-rejection reactions.



In general,CTLs are CD8+ and are therefore classI MHC restricted,

Although in rare instances CD4+ class II–restricted T cells have been shown to function asCTLs.

Since virtually all nucleated cells in the bodyexpress class I MHC molecules,

CTLs canrecognize and eliminate almost any altered bodycell.



The CTL-mediated immune response can be

divided into two phases, reflecting differentaspects of the response.

The first phase activates and differentiates

naive TC cells into functional effector CTLs.

In the second phase, effector CTLsrecognize antigen–class I MHC complexes on

specific target cells,

which leads them to destroy the target cells.

Eff t CTL A G t d f CTL P



Generation of effector

CTLs.

Upon interaction with

antigen–class I MHCcomplexes on appropriate

target cells, CTL-Ps begin

to express IL-2 receptors

(IL-2R) and lesser amounts

of IL-2.

Proliferation anddifferentiation of antigen-

activated CTL-Ps generally

require additional IL-2

secreted by TH1 cells

resulting from antigen

activation and proliferation

of CD4+ T cells.

In the subsequent effector

phase, CTLs destroy

specific target cells.

Effector CTLs Are Generated from CTL Precursors









NK cells produce a number of immunologicallyimportant cytokines, they play important roles

in immune regulation and influence both innateand adaptive immunity.

IFN- production by NK cells can affect theparticipation of macrophages in innate immunityby activation of the phagocytic andmicrobicidal activities

NK activity is stimulated by IFN-, IFN-, andIL-12.



NK cells that peaks in about 3 days

NK cells are the first line of defense againstvirus infection, controlling viral replication during

the time required for activation, proliferation, anddifferentiation of CTL-P cells into functional CTLs atabout day 7.

Killing by NK Cells Is- Similar to CTL-MediatedKilling



Antibody-Dependent Cell-MediatedCytotoxicity



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Hypersensitivity Lecture

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