Allergies, DTH, and AIDS Flashcards
What are the types of Allergy responses?
Type 1: Ag causes crosslinking of Ab bound to Fc receptors on mast cells or basophils -> release of vasoactive mediators -> anaphylaxis: fever, asthma, hives, food allergies
Type 2: Ab target cells with antigen on the surface -> destruction by ADCC or complement - IgG or IgM
Type 3: Ab-Ag complexes induce complement and recruit neutrophils - Immune complex
Type 4: sensitized T cells release cytokines -> activate macrophages or cytotoxic T cells for direct damage
IgM/IgD class switching for which type of response?
IgG: TH1 intracellular
IgA: mucosal (pollen, worms) + some TH1
IgE: TH2 extracellular
What is the immune response to pollen?
IgE-Ag (pollen) on granulocytes cause granule releaseTH2 response
-Histamine: muscle contracts, the opening of veins, secretion of mucus (to build a barrier), cell chemotaxis
-same for Leukotrienes and prostaglandins but stronger
-Cytokines and Chemokines: IL-4, IL-13 more IgE production, IL-5 recruits eosinophils
What are the early and late allergic responses?
Early (minutes): Vasodilation, mucus, swelling bc IgE is already there, once the allergen is present it causes degranulation
Late (hours): release of Cytokines (IL-4, IL-5, IL-13) recruit neutrophils, eosinophils, and TH2 cells causing the swelling
Types of Allergies:
-Localized hypersensitivity: specific tissue (pollen airways)
-Food: allergens often stable to heat, acid, proteases -> smooth muscle contraction and gut vasodilation can cause vomiting
-Systematic: caused by injected allergen (bee sting, penicillin, seafood, nuts -> cause difficulties breathing bc contraction of smooth muscles, drop in blood pressure, anaphylactic shock -> need epinephrine to reverse that
Where do allergies come from?
Hypothesis: Exposure to some pathogens early in life provides better T cell balance -> if not exposed the body overreacts when a pollen comes in
For food allergies: starts in the skin, DC collects antigens and directs to Th cells -> B-cell switch to IgE -> IgE circulates in the blood -> upon second exposure IgE causes activation of ILC2, TH9, and TH2 to produce cytokines recruiting basophils and mast cells -> also gut inflammation, and symptoms
What are treatments for Type 1 hypersensitivity?
Antihistamines: blocking Histamin receptors
-Leukotriene antagonists
-Inhalation corticosteroids: inhibit the innate immune response in the airways
-Anti-IgE antibodies: prevent IgE from binding to mast cells
Desensitization immunotherapy
-by oral immunotherapy or allergy shots
-Repeated low-dose exposures may induce a Treg cell due to exposure in the anti-inflammatory environment (under self-background threshold)
-Treg induce a switch to TH1 response -> TH1 may also induce a switch to IgG + TH1 (IFN-gamma) inhibits TH2/IgE effects bc mast cells have Fc receptors for IgE and IgG -> IgG is useless for mast cell so they will be turned off -> less allergic reaction
Ab-Mediated (Type II) Hypersensitivity
IgG or IgM
-antibodies are generated against foreign targets found on cells (surface antigen)
-Type II Ab (IgG or IgM) -> induce ADCC and complement
-Example: Transfusion reactions
Immune Complex-Mediated (Type III)
Hypersensitivity
often IgG
-agglutinations of antigens, antibodies (often IgG), and complement factors C3a, C5a -> causing inflammation, no opsonization
-trigger release of inflammatory mediators and
vasoactive mediators -> neutrophils are coming from the blood vessels
*Vasculitis if in the blood vessel,
*Glomerulonephritis if in the kidney
* Arthritis if in joints (rheumatoid arthritis Ab bind Fc of Ab)
Example: Arthus reaction, immune complexes on site of entry
What are the antibodies that act in type 1-3 hypersensitivity?
Type I - IgE (allergies) -TH2 (mast cells, granulocytes)
Type II - IgG/IgM (red blood cell response) - TH1
Type III - IgG (immune complexes) - TH1
Type IV - T-cells and macrophages (takes longer) - TH1
What is an Arthus Reaction?
An inflammatory reaction induced by injection of an Ag, in someone with a high amount of Ab against the antigen
-Swelling and localized bleeding at the injection site (Peaks after) 4–10 hours
-Examples: insect bite (type III reactions), farmer’s lung from moldy hay
How is Delayed-Type (Type IV) Hypersensitivity (DTH) different from Type 1-3?
-Purely cell-mediated (T-cells) rather than Ab mediated
-Delayed bc it takes time for the T-cells to develop?
->recruitment of macrophages at the inflammation site
-Examples: Tuberculosis and poison ivy
How is DTH initiated?
-Sensitization: Initial exposure triggers the production of a T-cell response and memory cells
APC secrete IL-12 to TH1 cell -> IFN gamma (intracellular response)
-Often the CD4+ TH1 subset (M. tuberculosis -intracellular bacterial pathogen), it takes 1-2 weeks
-effector phase: Second exposure induces the production of TH1 inflammatory cytokines -> recruit macrophages -> prolonged activation of macrophages -> leads to granuloma formation
What happens if the antigen remains?
-exponential inflammatory responses
- can lead to destructive multinucleate giant cells and granulomas (f.e. in TB) surrounded by T-cells and macrophages
How can DTH be detected?
-by injecting a small amount of Ag under the skin
-positive when: If a red, slightly swollen, firm lesion
develops in 48–72 hours
-indicates that the person has sensitized TH1 cells against the Ag, but doesn’t tell if there is an active or the infection is overcome
How does Sensitization occur in Contact Dermatitis?
-Ag binds to Urushiol-modified proteins -> taken up by DC and carried to regional lymph node, and presented on MHC class II
-TH1-formation, TH1 cells return to the skin and release cytokines that activate macrophages
-Macrophages release inflammatory cytokines, lytic enzymes, and ROS causing tissue damagae
In class QUIZ:
MATCHING:
-Typ-1-D -> Cytotoxic T-cells
-Myasthenia gravis -> Neutralizing (Blocking) Ab
-Rheumatoid arthritis -> immune complex and
complement
-Systemic lupus -> Anti-DNA-Ab
Difference between primary and secondary Immunodeficiencies:
-Primary immunodeficiencies are genetic mutations (vary from mild to severe)
-> Severe combined immunodeficiency
(SCID) affects lymphocyte -> no T or B-cells, no adaptive immunity
-Secondary immunodeficiencies are are
acquired: Chemotherapy, steroid treatments, stress
What is HIV?
-The Retrovirus HIV-1 causes AIDS (acquired
immunodeficiency syndrome)
-Two RNA genomes and reverse transcriptase (RT) enzyme -> integrate cDNA into host cell chromosome
-spread through intimate contact with infected body fluids
How does the infection of HIV work?
- Binding on target cell CXCR4 or CCR5 + CD4
- Release of the viral RNA genome
- RT converts the 2 RNAs into cDNAs
- Integrase inserts cDNA into host cells chromosome
How does Cell tropism determine the cell target?
-Coreceptor expression dictates cell tropism (target cell)
-T-cell tropic strain use CXCR4 on T cells and M-cell tropics use CCR5 as co-receptor
-M-tropic variant is more predominant, as it infects DC at the site of infection -> then is passed to T-cells within secondary lymphoid organs
How is HIV activated in infected cells?
- Upon reactivation, the viral genome is converted to mRNA and exported to the cytoplasm (ssRNA transferred separately and will be packed into virion)
- Precursor proteins are cleaved by the protease into active fragments
- assemble with RNA genome to form new virions
What are the phases of HIV?
-Acute Phase: Spike in HIV levels in the blood, CD4 T cells decrease -> eventually brought under control by the production of Ab against HIV
-Asymptomatic phase: Gradual decrease in CD4+ T cells and increase in viral load -> can last years
-AIDS: Crash in CD4+ T-cell numbers and high levels of HIV in the blood
