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Flashcards in Immunopathologies Deck (67)
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1

What is meant by Type I Immunopathology?

• Type 1 = symptoms/pathology b/c of IgE. TH2 mediated events are seen along with IgE caused problems. Think ALLERGIES

2

How common is auto-immunity in the population you will be practicing in?

• Pretty common. About 5-8% of people you see will have an autoimmune problem

3

Why will you often see IgE problems in conjunction with TH2 responses?

• The Tfh cell that helps B cell switching to IgE is closely related to TH2 cell so there is some overlap there

4

What is meant by Type II Immunopathology?

• Type 2 - Antibody-mediated tissue damage that is NOT IgE (IgG,M,A). Also can be antibody-mediated inappropriate STIMULATION

5

What is meant by Type IV Immunopathology?

• Type 4 - CTL/TH-cell recognition of self as non-self. Pathologic outcomes of normal T-cell responses.

6

There are four final/underlying mechanisms for immune mediated disease (originally 5) that correlate to what terminology we use today?

• Type 1 - Type IV immunopathology
• Type 1 = symptoms/pathology b/c of IgE. TH2 mediated events are seen along with IgE caused problems. Think ALLERGIES
• Type 2 - Antibody-mediated tissue damage that is NOT IgE (IgG,M,A). Also can be antibody-mediated inappropriate STIMULATION
• Type 3 - Immune COMPLEX mediated tissue damage. Not just antibody perfectly binding self antigen but complexes of antibody and complement initiating inflammation and tissue damage
• Type 4 - CTL/TH-cell recognition of self as non-self. Pathologic outcomes of normal T-cell responses.

7

What is meant by Type III Immunopathology?

• Type 3 - Immune COMPLEX mediated tissue damage. Not just antibody perfectly binding self antigen but complexes of antibody and complement initiating inflammation and tissue damage
• Associated with inflammation in endothelium of VESSELS in particular (complex deposition on endothelial ECM)

8

What are some treatments for Myesthenia Gravis?


• Make residual AchR more effective with neostimine-related drugs
• IVIg (anti-autoantibody)
• Immunosuppression
• Thymectomy IN A SUBSET of patients where thymus is enlarged b/c of TH cell reaction against intrathymic mm cells

9

What is meant by "stimulatory hypersensitivity in type II immunopathology?

• When an antibody is directed against self tissue in such a way as to inappropriatly STIMULATE a cellular response…that is what stimulatory hypersensitivity is
• Best example is Graves disease (LATS = long activating thyroid stimulator)
• Antibody-anti-TSHR (thyroid stimulating hormone receptor)
• The end result is hyperthyroidism

10

How is Myesthenia Gravis illustrative of type II immunopathology?

• Mediated by Antibody against alpha subunit of AchR
• Ach necessary for muscle contraction so if receptor is targeted by Antagonist Ab, less muscle use, leading to increased muscle atrophy
• The antibody to AchR also results in neutrophilic and compliment-mediated tissue damage (direct tissue damage)

11

Specific tissue damage in Type II immunopathology is mediated by what?

• A targeted humoral response
• Must have Ab anti-self Ag in type II

12

What type of immunity makes chronic type III immunopathology steadily worse?

• T-cell mediated immunity

13

What is compliment-mediated damage in the context of type II immunopathology?

• MAC or opsonization
• Autoimmune hemolytic anemia is a good example
• Phagocytosis increases because of opsonization
○ Autoimmune thrombocytopenia purpura is a good example
• Release of lysosomal enzymes at self tissue
○ Myesthenia gravis and Goodpasture syndrome are examples

14

What is meant by "neutralization" as a way of direct tissue damage in the context of type II immunopathology?

• Human (self) protein is rendered inactive b/c of antibody binding it (just like a toxin is neutralized normally)
• EXAMPLE - IFN-gamma is targeted by self-reactant antibody and is not allowed to function properly
○ Can result in disseminated non-TB mycobacterial infections
• You are made immunodeficient by Ab directed against self antigen

15

How do Antibodies lead to tissue damage when directed against self Ag?

• Neutralization
• Compliment-mediated damage
• "Stimulating hypersensitivity" (Graves Disease)

16

What does Aire have to do with MG?

• MG = myesthenia gravis
• Thymic version of the alpha subunit of AchR doesn't get expressed (Aire mediated) then there is no way to negatively select self-reactive T-cells
• They get activated against AchR and direct Bcells to make Ab to it

17

What's the autoimmunity in Graves Disease?

• Result = hyperthyroidism…Ab against hormone receptor
• The Ab recognition leads to stimulatory hypersensitivity
• Increases the thyroid growth pathway

18

How is Rheumatic heart Disease a classic type II immunopathology example?

• Ab cross-reaction btw. Group A streptococcus M-protein Ag and endothelium of heart tissue
• Leads to pericardial effusion
• Leads to heart tissue destruction (neutrophil mediated)

19

What's up with Goodpasture syndrome?

• Auto-Ab to lung/kidney basement membranes
• Endothelial cells of capillaries build themselves on this C.T. network
• Type IV collagen is the specific Ag here
• Persistant glomerulonephritis (Ab causing neutrophil and compliment action)
• Pneumonitis and pulmonary hemorrhage
• First disease PROVEN to be self-Ab mediated

20

What is Dressler syndrome?

• "Post cardiac injury syndrome"
• Mediated by Ab to heart Ag after MI
• Some people get it to show symptoms, others have Ab but no symptoms
• Treated with immunosuppression

21

How was Goodpasture disease proven to be antibody mediated?

• Took tissue of dead patient and isolated Ab
• Gave that Ab to chimp…chimp developed goodpasture syndrome

22

What's up with ATP (Autoimmune Thromobycytopenic Purpura?)?





• Increased bleeding b/c of rapid platelete destruction in spleen
• Autoantibodies lead to destruction of plateletes (opsonized)
• See it in young healthy people post viral infection
• See it in old people with other autoantibody problems
• See it in systemic drug reactions (targeting drug bound cells)

23

What is the leading cause of hypothyrodism (not Hyper)?

• Hashimoto Disease, autoantibody against thyroglobulin, thyroid peroxidase
• Inflammation and tissue destruction is result
• Ab, compliment, neutrophils and T-cell mediated damage
• AITD = autoimmune thyroid disease = combo of Hashimoto and Graves

24

How might release of sequestered Ag cause a problem?

• Not normally present to be recognized
• Some other pathology is what allows for release of Ag and recognition
• This can snowball as more and more sequestered Ag is realeased b/c of tissue destruction
• Best example is sterility in mumps patients (males) because of reactivity against sperm antigen that is normally sequestered

25

Can neonates or fetuses have self-reactive Ab?

• Unfortunately, yes. The mother in MG or SLE can have ab that recognizes baby's tissues

26


What is the hybrid (foreign + self) Ab formation theory all about?

• B-cell has surface IgG that recognizes SELF
○ Normally this self recognition would lead to NO T-cell help and really no big deal
• HOWEVER, if that self Ag that is B-cell recognized is in complex with FOREIGN something (drug, or bacteria)
• Ingestion and presentation by MHC II is random for peptide selection and recognition of self can lead to presentation of foreign by MHC II
• Normal T-cell response will activate the self-reactive B-cell
• You now have a proliferating, activated self-reactive B-cell

27

Can self-reactive B-cell make anti-self IgG with no T-cell involvement?

• Nope, class switching is Th cell mediated
What is meant by emergence of forbidden clones?
• A self-reactive T-cell will escape selection somehow and mediate autoimmunity

28

What is meant by Delayed Type Hypersensitivity?

• "older term" = T-cell mediated events that are considered undesirable or injurious
• The new term is type IV immunopathology
• The only immunopatholgoy that does not require the action/presence of B-cells

29

What are 4 classic examples of type IV immunopathology?

• Rejection of allografts
• GvHD (Graft-vs-host disease (reverse of allograft rejection)
• PPD skin test positive result
• Contact dermatitis (poison ivy)
• (bonus) tumor immunity

30

Why isnt' there a huge painful reaction to the first urushiol exposure?

• Urushiol = molecule in poision ivy that causes the reaction
• By the time the immunization phase has completed and Th1 and Th17 phenotype have proliferated, the antigen has been washed away or diluted to the point of not illiciting that response