Immunopathology II (H.R) Flashcards
What are hypersensitivity rxns❓
Here, an organism responds to a renewed contact with an antigen that it already knows and to which it is hypersensitive
Describe the 4 hypersensitivity rxns and their effectors using the Gell and Coombs classification
Type I
Description: Immediate rxn
Effector: IgE antibodies
Type II
Description: Cytotoxic rxn
Effector: IgG and IgM antibodies
Type III
Description: Immune complexes
Effector: IgG and IgM antibodies
Type IV
Description: Delayed rxn (48hrs)
Effector: T cells
What do Type I, II and III hypersensitivity rxns have in common❓
What is the mediator of Type IV hypersensitivity rxn❓
- Mediated by Antibodies/Plasma cells
2-6hrs after exposure
- T-cell and macrophages
24-36hrs after exposure
List the examples of allergens that can cause type I hypersensitivity rxns
Tree, grass, weed pollens
Cat/animal dander antigens
Dust/mite/fecal/pellet antigens
Mold spores
What makes individuals susceptible to Type I hypersensitivity rxn❓
The propensity to make strong Th2 responses and make IgE antibodies against allergens
- What are the other names for type I hypersensitivity rxn❓
2. What is it characterized by❓
- Anaphylactic rxn
IgE allergy
IgE hypersensitivity rxn - IgE production
Describe the pathogenesis of Type I hypersensitivity rxn
Allergen inhalation/ingestion/injection ⬇️ Production of local chemokines *eotaxin ⬇️ Recruitment of Th2 cells ⬇️ Th2 secrete cytokines that are responsible for hypersensitivity rxn
IL-4: produces IgE
IL-5: activates eosinophils
IL-13: secretes mucus
⬇️
IgE is implanted on FcR of mast cells and basophils
⬇️
Priming of mast cell occurs
⬇️
Cross linking of IgE Fc on surface of mast cells on 2nd exposure
⬇️
Mast cell is stimulated and releases all its products (degranulates)
*eotaxin recruits eosinophils
Describe the function of:
IL-4
IL-5
IL-13
In Type I hypersensitivity rxns
IL-4: stimulates B cells to undergo heavy-class switching to IgE
IL-5: activated eosinophils
IL-13: stimulates mucus secretion
In Type 1 hypersensitivity rxn, the complement system isn’t activated
True or false❓
Which other hypersensitivity rxn mimics this❓
True
Type II (ADCC) Type IV H. R
List the cells that express FceRI (Fc portion of the E heavy chain on IgE)
Mast cells
Basophils
Eosinophils
What are the primary and secondary mediators of hypersensitivity rxns❓
What do they cause❓
1. Primary mediators: •Histamine •Serotonin •NCF, ECF •Proteases
Cause:
•Vasodilation
•Bronchoconstriction
2. Secondary mediators: •Leukotrienes •Prostaglandins •PAF •Cytokines
Cause:
•Lead to inflammation
List the consequences of the mediators of Type I hypersensitivity rxn
⬆️vascular permeability
⬆️glandular secretion
Smooth muscle contraction
Edema
Inflammatory cell attraction
List the mediators that cause:
- Chemotaxis
- Vasoactivity
- Smooth muscle spasms
In type I hypersensitivity rxn
Chemotaxis:
LTB4
ECF
NCF
Vasoactivity: Histamine PAF LTC4, D4, E4 Neutral protease PGD2
Smooth muscle spasms: Histamine LTC4, D4, E4 PG PAF
Mention some important medical conditions that fall into Type I hypersensitivity rxns and their symptoms
- Penicillin/Bee sting allergy (systemic anaphylaxis)
Symptoms: Acute asthma Laryngeal edema Diarrhea Urticaria Shock
- Food allergies/Allergic rhinitis/Hay fever (local anaphylaxis/atopy)
Symptoms:
Asthma
Hives
- What are the other names for type II hypersensitivity rxn❓
- What is it characterized by❓
Cytotoxic rxn
IgG/IgM immunoglobulins
Describe the pathogenesis of Type II hypersensitivity rxn
•Complement-dependent cytotoxicity: Ag/Ab rxn ⬇️ Complement pathway (classical pathway) is activated ⬇️ Cell lysis
eg Transfusion rxns
Autoimmune hemolytic anemia
Erythroblastosis fetalis
Goodpasture’s syndrome
•Antibody-dependent cell-mediated cytotoxicity:
Low conc of IgG/IgE (parasitic) coat target cells
⬇️
Inflammatory cells bind to FcE receptors
⬇️
Cell lysis
🚫phagocytosis
Eg Transplant rejection
Immune rxns against neoplasms/parasites
•Anti-receptor antibodies:
IgG antibody is directed against receptors in target cells
⬇️
Complement-mediated destruction of the receptors
⬇️
Functional derangement
🚫cell injury
Eg Mysthenia graves (anti ACh receptor)
Graves’ disease (anti TSH receptor/TSI)
Pernicious anemia
- What are the other names for type III hypersensitivity rxn❓
- What is it characterized by❓
- Immune complexes
2. Ag-Ab complexes
Describe the pathogenesis of Type III hypersensitivity rxn
⬆️Circulating, soluble immune complexes containing IgG/IgM antibody ⬇️ Deposition in tissues 🚫removal by mononuclear phagocytes ⬇️ Activation of complement
*C3b and C5a attracts neutrophils and are used up
Is serum complement increased or reduced in:
- Complement-dependent, Type II H.R
- Immune complex, Type III H. R
- Serum complement ⬆️ in type II complement dependent H. R
2. Serum complement ⬇️ in type III H. R
Which H. R is sometimes classified as TYPE V❓
Antireceptor antibodies, Type II H. R
What are the differences between Complement-dependent (Type II H.R) and Immune complex (Type III H. R)❓
- Serum complement ⬆️ in type II complement dependent H. R
Serum complement ⬇️ in type III H. R
- The Ag is not an intrinsic component of the target cells in Type III H. R
Mention some important medical conditions that fall into Type III hypersensitivity rxns
Systemic immune complex:
Glomerulonephritis
Serum sickness
Vasculitis
Local immune complex/Arthus rxn:
Pneumonitis/Farmers lung
SLE Polyarteritis nodosa Rheumatoid arthritis Lupus nephropathy Post-streptococcal GNs
What is Arthus rxn❓
Injection/local transplant of antigen in the presence of preformed Ab ⬇️ Ag-Ab binding ⬇️ Formation of immune complexes locally ⬇️ Precipitation in vessel walls ⬇️ Fibrinoid necrosis and thrombosis ⬇️ Ischemic injury
What is Serum Sickness❓
Systemic deposition of Ag-Ab complexes in multiple sites (esp kidneys, heart, joints)
What are the three phases of systemic immune complex disease❓
- Formation of Ag-Ab complexes in the circulation
- Deposition in various tissues
- Inflammatory rxn
What is the striking characteristic of SLE❓
Malar rash-immune complex deposition
What happens in PAN❓
Generalized immune complex disease involving small and medium sized arteries
- What are the other names for type IV hypersensitivity rxn❓
- What is it characterized by❓
- Mediated/Delated Type
- T-cell and macrophage mediated
🚫antibody
🚫complement system
Describe the pathophysiology of Type IV, Delayed-type and Immune inflammation H. R
Display of peptides by APCs (dendritic cells)
Production of cytokines by APCs* Production of IL-2 by APCs** Production of IL-1, 6, 23 by APCs*** ⬇️ Recognition by naive CD4+ cells ⬇️ Secretion of IL-2 ⬇️ Proliferation of T cells
Differentiation to Th1/Th17* Differentiation of CD4+ T cells to Th1 subset** Differentiation to Th17*** ⬇️ Repeated exposure to antigen ⬇️ Th1 secretes IFN-gamma ⬇️ Inflammation Phagocytosis ⬇️ Removal of offending agent
Rxn of CD4+ T cells are seen in delayed type H.R and immune inflammation
True or false❓
Which cells are involved in cell-mediated cytotoxicity❓
True
CD8+ T cells
In Type IV H. R, Th17 cells secrete which cytokines❓
IL-17
IL-21 (amplifies Th17 response)
IL-22
The tuberculin rxn is a type of DTH (Type IV), what happens in this rxn❓
Intracutaneous injection of purified protein derivative/tuberculin
⬇️
Accumulation of CD4+ T cells and macrophages around venules (perivascular cuffing)
⬇️
Cytokine-mediated endothelial activation
⬇️
Macrophages become epithelioid cells/granuloma
Reddening and induration of site 8-12 hrs
Peaks 24-72 hrs
Subsides
Contact dermatitis is evoked by contact with urushiol (antigenic component of poison ivy or poison oak)
True or false
True
Describe the pathophysiology of Type IV, Cell-Mediated H. R
Th1 cells recognize antigenic peptide on APC
Secrete IFN-gamma (inflammatory rxns)
CD8+ CTLs kill antigen-bearing target cells
Fas ligand (apoptosis)
Perforins, granzymes and serglycin (enter through endocytosis)
Perforin facilitates the release of granzymes from the complex
Granzymes cleave and activate caspases which cause apoptosis of target cells
Antibodies and complement play no role in Delayed type H. R
True or false
True
Mention some important medical conditions that fall into Type IV, Cell-Mediated hypersensitivity rxns
Granuloma diseases (mycobacteria, fungi)
Tuberculin skin rxns
Contact dermatitis
Tumor rejection
Graft rejection
Type 1 diabetes
Reactions against viruses
What are the the substances that could trigger contact dermatitis❓
Poison ivy (catechols)
Nickel
Formaldehyde
Latex
Chromium
Dyes in clothing and cosmetics
In CTL (Cytotoxic T-lymphocyte mediated responses),
- Class I HLA molecules play a role
- Cytokines are not involved
True or false
Rxns with this mode include
True
Neoplasia cell lysis
Transplant rejection
Virus-infected cell lysis
