Download Chapter 16: Hypersensitive Reactions

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Lymphopoiesis wikipedia , lookup

Phagocyte wikipedia , lookup

Immune system wikipedia , lookup

Molecular mimicry wikipedia , lookup

Adaptive immune system wikipedia , lookup

Anaphylaxis wikipedia , lookup

Polyclonal B cell response wikipedia , lookup

DNA vaccination wikipedia , lookup

Cancer immunotherapy wikipedia , lookup

Psychoneuroimmunology wikipedia , lookup

Adoptive cell transfer wikipedia , lookup

Innate immune system wikipedia , lookup

Immunomics wikipedia , lookup

Immunosuppressive drug wikipedia , lookup

Allergy wikipedia , lookup

Transcript
Chapter 16: Hypersensitive Reactions
• Typically, inflammatory responses rid the body of Ag and
resolves the infection within days
• In some cases, the inflam response can have harmful
effects – even result in death!
-this type of IR is called ‘hypersensitivity’ or ‘allergy’
• Hypersensitive reactions develop during the course of
either:
– Humoral IR response or
– Cell-mediated IR response
Those reactions initiated by Ab or Ab-Ag complexes are
called Immediate Hypersensitivities
Those initiated by cell-mediated response are called Delayedtype Hypersensitivities
Gell and Coombs Classification
• Four categories of hypersensitivity were proposed
by G&C which recog differences in the effector
molecules generated.
They include:
• IgE mediated – Type I
• IgG mediated – Type II
• Immune complex mediated – Type III
• Cell mediated (DTH) – Type IV
General descriptions of the 4 types of hypersensitivity
Figure 16-1
IgE-Mediated (Type I)
Hypersensitivity
• Antibody class produced is different than the
normal 1° response
• IgE is produced vs an “allergen”(not vs parasite)
• IgE binds to mast cells/basophils  sensitized
• 2nd exposure to allergen cross-links IgE’s and
triggers degranulation of mast cells/basophils
• Effects may be systemic or localized depending..
Components of Type I Rxns:
1.
6.
3.
2.
Figure 16-2
4.
5.
Type I Rxns: 1. Allergens
• IgE produced in response to parasites, typically
• Atopic individuals produce IgE vs common
environmental Ag’s; genetic predisposition
• More susceptible to: hay fever, asthma, etc.
• Most rxns take place on mucus membranes
• Allergens are multi-antigenic; although only
several are allergenic (E and K fractions)*
• Allergenicity is a function of dose, sensitizing
route, possible adjuvant, and genetics**
Type I Rxns: 2. and 3. Reaginic Ab, Mast
Cells and Basophils
• IgE also called “reagin”, larger than typical Ig
due to extra H chain domain, low serum[c]
• IgE Fc binds to glycoprotein on Mast/Baso
• Baso’s – 0.5-1.0% of circ WBC; granulocytes!
• Mast’s – in conn tiss, near bv’s and lv’s
– Skin and mucus memb (esp resp & gi tracts)
– Upon activation, granules are released  effects!
Type I Rxns: 4. IgE Crosslinkage by
allergen
• Cross-linking 2 FcRI receptors initiates degranulation
of Mast/Basophils. This may occur several ways:
Typical trigger
Mast/Basophil Cell Activation and Degranulation
Type I Rxns:
5. Release of Pharmacologically
active agents
• Substances released from cell granules
• Substances act on: a) nearby tissue
b) 2° effector cells
• Substances (chemical mediators) are
categorized as either 1° or 2° :
• 1° are substances released from granules
• 2° are synthesized after activation or product(s) of
membrane destruction
Type I Hypersensitivity:
Main Bio effectors
1. Histamine – major portion of granules
- decarboxylation of histidine
-specific receptors (H1, H2, H3) on
target cells
*H1 - >permeability of b.v.’s
>contraction of intest/bronchial smooth muscles
>mucus secretion Goblet cells
H2
>vasc perm and vasodilation
-suppression of degran if bound to Mast/Baso – neg feedback
Type I Hypersensitivity:
Main Bio effectors
2. Leukotrienes and prostaglandins –
-produced from P-lipid breakdown
-longer lasting and more potent than histamine
as effector chemicals
-promote further contraction of smooth muscles
3.
Cytokines –
-various cytokines (IL-4,5,6, TNF-α) released from Mast/Baso
-attract neut’s/eosino’s
>IgE production from B cells
-TNF may contribute to systemic anaphylaxis
Type I Responses may be
Systemic or Localized
Systemic response (Anaphylaxis):
• occurs w/i minutes; symptoms include: difficult resp. BP drop,
smooth muscle contraction, massive edema
• Treat with epinephrine
Localized response (Atopy):
• Inherited; occurs in ~20%; rxn limited to target tissue
• often @ epithelial surfaces
Type I Rxns:
Localized allegic responses
1. Allergic rhinitis (hay fever) –
2. Asthma –
•
•
Early response
Late response
3. Food allergy 4. Atopic dermatitis (eczema) -
Type I Hypersensitivity:
Late-Phase Reactions
• Caused by pharmacologic/vasoactive mediators -> induce
local inflammation….causes tissue damage
• Occurs 4-6 hrs after initial rxn; can persist 1-2 days
• TNF-α and IL-1 increase CAM’s on endothelia  promote
tethering/migration of:
–
–
–
–
Neutrophils
Eosinophils
Monocytes
Basophils
Cytokines from Mast cells also
contribute!
• Eosino’s exhibit Fc receptors for IgE -> triggers degran.
• Neutro’s release lytic enzymes, PAF, leukotrienes
Type I Hypersensitivity:
Regulatory factors
• The following factors influence IgE response to allergens:
– Level of Ag dose
– Mode of antigen presentation
– Relative presence of TH1 and TH2 titres
• TH2’s release IL-3,4,5, and 10
• TH1’s release IFN-γ
• Atopic vs non-atopic individuals express qualitatively
different Type I responses to allergens…
– Atopic responses involve TH2  production of IgE from B cells
– Non-atopic responses involve TH1  production of IgM or IgG
Type I Hypersensitivity:
Detecting allergies
Skin tests- injections or scratchings
-Stim local Mast cells
-Produces P-K rxn (wheal and flare)
-Inexpensive and quick
-May sensitize one to new Ag’s
-May stim late-phase rxn in some
Immunoassays for serum IgE
-Radioimmunosorbent test (RIST)
-Radioallergosorbent test (RAST)
Immunoassays for IgE
RIST
RAST
Type I Hypersensitivity:
Treatment methods
Immunotherapy
• Antibody therapy
– Injected monoclonal antiIgE Ab binds free and mIgE
on B cells
• Hyposensitization
– Repeated injections of
allergen causes a shift in Ig
response
Drug treatments