Lecture 17 (10A) - Hypersensitivity Flashcards Preview

Basic Immunology > Lecture 17 (10A) - Hypersensitivity > Flashcards

Flashcards in Lecture 17 (10A) - Hypersensitivity Deck (51):

Immune reactions in the body have by-stander effects on normal tissues

neutrophils gobble up and kill bacteria, but they also secrete toxic molecules
- free radicals
- tissue-degrading enzymes (elastase, collagenase)
- cytokines
- chemokines
- defensins
--> cell death of healthy cell
--> tissue damage

• toxins that kill bacteria also kill normal cells (get inflammation)


Immunological hypersensitivity

hypersensitivity to innocuous antigens causes diseases
• Gell and Coombs classification still useful
• eg coeliac disease (hypersensitive to gluten)
• calssified immune response by what cause them - 4 types


Type I hypersensitivity

immediate hypersensitivity
• allergies AKA atopy
• hay fever (allergic rhinitis) and nasal allergies
• allergies increasing in developed world


CD4 T cells can differentiate along 2 pathways


presented IL-12 by APC
--> Th1
makes IFNγ, TNFα
--> excess macrphage activation, tissue damage

presented IL-4 by mast cell
--> Th2
makes IL-4, IL-5, IL-10
--> IgE, allergies
(IL-4 drives differentiation of B cells to make IgE - so allergic T cells = Th2)


T cells tell B cells what type of antibody to make

• T cells make IFNγ = class switching from IgM to IgG2 or IgG3
• T cells make IL-4 = class switching from IgM to IgG2 or IgE


Class switching to IgE is driven by

• IL-4 causes looping out of DNA
• get VDJ + IgE


Serum IgE is often raised in allergies, but

• you can be allergic with normal IgE
• you can be not allergic with high IgE

• allergic patients don't always have high levels of IgE


IgE secreted into serum binds to

surface of mast cells in tissues
• IgE molecule has FcεRI binding site, and mast cell has FcεRI receptor
• lungs, airways, skin, gut
• so it is sequestered on mast cells in tissues
• sucks IgE out of serum and puts on cells


Mast cells have lots of granules containing

pre-formed mediators
• flow cyto into mast cells
• high side scatter because lots of granules


What happens when IgE on a mast cell binds an antigen (allergen)?

• allergen in, binds and cross links IgE
• granules pop out of mast cell = immediate hypersensitivity

• Fcε signals to the cell to release granules


Mast cells release

histamines when the allergen is encountered
• also release serotonin
• allergic = take antihistamines
• very bioreactive to cells in the tissues --> mast cells with no granules left


Mast cell mediators

• make blood vessels leaky - edema
• vasodilation
• cause smooth muscle contraction
• urticaria


Symptoms of immune response
(anaphylaxis = severe allergic response)

• anaphylaxis
• loss of consciousness
• hives
• swelling of tongue, inability to swallow
• rapid swelling of throat tissues
• need epinephrine so muscles relax and can breathe


The sting of anaphylaxis

• anaphylaxis is the medical term for an allergic reaction
• the only treatment to an allergic reaction is the use of epinephrine and other treatments
- epinephrine can be self-injected or administered by a doctor
• often intravenous fluids, oxygen, and other treatments are necessary as well
• it is very important to call for medical assistance immediately


Interleukin-5 (IL-5)

draws eosinphils into tissues and blood


Eosinophils - stain with dye

eosin - and granues show up
• granules toxic to cells


Lung has no

exit - only 1 way in/out


Type I hypersensitivity is involved in some kinds of

asthma (allercig asthma)
• walls thinner, need steroids to relax it


Summary of an allergic Type 1
immediate hypersensitivity

1. antigen (allergen) crosses mucosal lining
2. onto APC
3. through TCR induced to TH2 cell
4. releases IL-4 -->
5. makes B make IgE
6. bind to mast cell
7. cross links
8. release of granules


Skin prick testing

inject suspected allergen into skin-wheal and flare reaction
• put an antigen in sin, have IgE and mast cells --> get reaction
--> skin swelling like happens in airways


How do you treat allergies?
(type I)

1. avoidance
2. anti-histamines, mast cell stabilizers
3. omaluzimab-anti-IgE
4. antigen-specific desensitization
- dose they can tolerate goes up, give small amount of antigen, try to induce tolerance
- immunosuppression mediated by regulatory/suppressor T cells
(T cells suppress IgE responses)


Type 1

antibody mediated hypersensitivity (IgE)
• type II is also antibody-mediated (IgM, IgG)
• type III is also antibody-mediated (IgG)


Type II hypersensitivity reactions

• also quick but not mediated by IgE
• mediated by Igm and IgG natural antibodies in serum
• also antibody-mediated


Type II
Type O blood has natural antibodies to

A and B
but no A and B antigens


Type II
Type O+ Rhesus negative

universal donor of red cells



have A antigens
have B antigens
Rh cells


Blood type O

antigen - no A or B
antibodies - anti-A and anti-B


Blood A blood type

antigens - A
antibodies - anti-B


Blood B blood type

antigens - B
antibodies - anti-B


Blood AB blood type

antigens - A and B antigens
antibodies - no a or B antibodies


When red blood cells with eg group A antigens on their membranes are mixed with plasma containing antibodies to group A

the antibodis cause the blood cells to clump, or agglutinate
(give wrong type, get clumps of RBC - fingers fall off - because make antibodies against)


Hemolytic transfusion reaction

• donor - blood type A
• recipient - type O with anti-A antibody
--> severe intravascular hemolysis
1. transfusion
2. agglutination and complement binding
3. hemolysis


Type II hypersensitivity

Rh+ father with RH- mother carrying her first RH+ fetus
• Rh atigens from the developing fetus can enter the mother's blood during deilvery
• in response to the fetal Rh antigens, the mother will produce anti-Rhh antibodies
• if the woman becomes pregnant with another Rh+ fetus, her anti-Rh antibodies will cross the placenta and damage fetal blood cells

baby Rh+
mothers Rh- --> make anti-rhesus antibodies
next baby --> kill baby's RBC (anemia)


Type III hypersensitivity

• mediated by IgG antibodies and their specific antigen which form immune complexes
• when they form in the skin after injection of the Ag-Arthus reaction
• when they form in the blood and deposit in the kidneys and joints - serum sickness

• also antibody-mediated - IgG
• immune complex in skin - artnus, blood --> kidneys - serum sickness


Type III hypersensitivity
antibodies in equilibrium with

• antibodies in equilibrium with antigen
• polyvalent antibody - multivalent antigen

• big agglutination (immune complex), antigen + antibody structure


Type III forms

immune complex
• antigenic determinant sites on antigen, antibody binds

• IgG antibody as 2 arms/binding sites


Immune complex disease

Immune complex disease

drug reactions
• allergies to penicillin and sulfonamides

infectous diseases
• poststreptococcal glomerulonephritis
• meningitis
• hepatitis
• mononucleosis
• malaria
• tyrpanosomiasis

• can make antibodies against antibodies


Type III hypersensitivity forms immune complex deposition by

• immune complex sticks to vessels
• neutrophils come


Phases of Type III hypersensitivity

Phase I - immune complex formation
• antigen in circulation, B cell to plasma cell to antibody, antigen-antibody complex

Phase II - immune complex deposition
• inflammatory cell makes cytokines

Phase III - complex-mediated inflammation
• complement, neutrophil attacks the complexes, neutrophil lysosomal enzymes


Type III hypersensitivity reactions
immune complex glomerulonephritis

1. deposition of immune complexes
2. activation of complement
3. chemotactic attraction and activation of PMNs (neutrophils)
4. release of proteases and oxygen radicals with tissue damage (neutorphil act)


Type IV hypersensitivity

delayed type hypersensitivity
• 24-48 hours to manifest, mediated by T cells and macrophages
• only not mediated by antibodies
• T cell makes INF, TNF
blood monocyte --> increase adhesion


Examples of DTH
(Type IV)

• manatoux reaction to PPD for TB
• poison ivy
• nickel sensitivity

• intradermal injection
• measure the tiameter


Delayed hypersensitivity can do

a lot of damage


Type IV
normal lung vs lung with TB

• macrophage in tissues (eg TB)
• T cells recognize, bring macrophages
• in and lung destroyed
• TB aka consumption


Type IV

macrophages wall off bacteria


Type IV
poison ivy elicits

DTH reactions


When antigen is injected into the skin, different hypersensitivities

happen at different rates
skin swelling
• type I high at 3 hours
• type III high at 8-10 hours
• type IV high between 12-24


Type I hypersensitivity - summary

anaphylactic type
• mediator IgE bound to basophils/mast cells
• mechanism - mediator release
• examples - anaphylaxis, allergic dermatitis, drug and vaccine reactions, parasite reactions


Type II hypersensitivity - summary

antibody dependent cytotoxic
• mediator - IgG/IgM directed cytotoxicity or dysyfunction
• mechanism - cytotoxicity mediated by complement or NK cell
• expamples - autoimmune hemolytic anemia, infections hemolytic anemia (anaplasmosis, babesiosis, EIA), myasthenia gravis (dysfunction)


Type III hypersensitivity - summary

• immune complex type
• mediator - IgG and IgM
• mechanism - immune complexes deposited with activation of complement and mediator release
• examples - immune complex glomerulonephritis, immune complex vasculitis, extrinsic allergic alveolitis


Type IV hypersensitivity - summary

• cell mediated
• mediator - CD4+ and CD8+ T-cells
• mechanism - cell mediated immunity with lymphokine mediated effects and CD8-mediated cytotoxicity
• examples - tuberculosis, contact dermatitis, transplant rejection