Immunology -Vishy Flashcards
What are the layers of the epidermis from outermost–> innermost?
Stratum Corneum Stratum Lucidum Stratum granulosum Stratum spinosum Stratum basale
Where is Dsg1 found in the epidermis? What about Dsg 3? What diseases are associated with autoantibodies produced against these?
- Dsg3 is in the deep epidermis–> pemphis vulgaris (IgG)
- Dsg 1 is more in the superficial epidermis–> pemphis (IgG)
What is filaggrin responsible for? What results from a mutation in filaggrin?
fillaggrin is responsible for the terminal differentiation of the epidermis
-a mutation in fillagrin leaves the body more susceptible to bacterial and hypersensitivity reactions (atopic dermatitis)
What are the immune cells of the epidermis called? What is their function?
langerhans cells
-antigen presenting cells that phagocytose and pinocytose material to conjugate with MHC I or II and then enter lymphatic circulation to present to T cells
How are extracellular antigens processed for T cell recognition?
Extracellular anitgens –> endosome–> paired with MHC class II –> presented to CD4+T cells for recognition
How are intracellular antigens processed for T cell recognition?
Intracellular–> proteosome compartment –> antigenic peptide –> RER using TAP (transporter protein)
-conjugated with MHC I in the ER –> recognized by CD8 T cells
How many signals are required an antigen presenting cells to stimulate T cell proliferation?
2 signals:
1=Class II MHC on APC + TCR on T cell
2=
- ICAM-1 on APC presenting to LFA-1 on T cells
- B7-1/B7-2 on APC presenting to CD 28 on T cell
What happens after full activation of T cells? What can a person get if this does not occur?
after full activation, CD28 will disappear and CTLA 4 will appear.
- CTLA-4 will bind CD80/86 and inactivate the immune cells
- without inactivation, can get autoimmunity
What do Th1 cells secrete? Th2 cells? What are their functions?
Th1 cells secrete IL-2 and IFN-gamma –> important in neutophil and macrophages activation
Th2 cells secrete IL-4, IL-6 and IL-10. These stimulate B cells to produce certain classes of antibodies
What cytokines stimulates a T cell to exhibit a Th1 cell response? What cytokine stimulates a Th2 response?
IL-12 stimulates Th1
IL-10 stimulates Th2
What receptor is found on both basophil and mast cells? What does this bind to? Where are basophils and mast cells found?
Fc receptors on their surfaces bind to IgE
basophils are found in low numbers in the blood
Mast cells are in the dermis
What happens during the initial allergen encounter with an antigen? Subsequent allergen encounters?
- initial encounter: CD4 –> Th2 –> IL4 and IL5 produced ==> mast cells coated with IgE (bound by the Fc receptors)
subsequent: cross-linking of antigen to IgE on mast cells causes mast cell degranulation that releases vasoactive amines, cytokines, lipids
What types of physiological responses take place with a type I hypersensitivity reaction?
- constriction of bronchiole lumen
- vasoconstriction of the blood vessels
- endothelial vasodilation –> fluid loss and cell migration which causes urticaria
What are the 2 phases of atopic dermatitis? W T cell predominates in each phase? What type of infection is a person with more susceptible to in each phase?
acute:
- Th2 predominates–> produce IL4 and IL5. DCs produce IL-10.
- IgE and allergic reaction
- No INF gamma production=susceptible to bacterial infection of the skin
chronic
- CD4 Th1 predominates
- DCs produce IL12–> Th1 –> INF gamma produced (less susceptible to bacteria)
- Less plasmacytoid DCs=more susceptible to viral infections (less INF alpha and beta)
What molecule on T cells allow them to leave circulation and go to the skin? Where can these be found in atopic dermatitis?
CLA (cutaneous lymphocyte associated antigen)
can be detected in the dermis and epidermis
What type of hypersensitivity reaction is Goodpasture’s syndrome? What do the antibodies attack?
Type II hypersensitivity
antibodies attack the glomerulus basement membrane –> bind to type IV collagen in the basement membrane of blood vessels in kidneys and lungs –> fix complement
What are some other types of type II hypersensitivity reactions causing skin diseases?
- pemphigus vulgaris
- pemphigus foliaceus
- bullous pemphigoid
- linear IgA disease
What are the autoantibodies attacking in pemphigus vulgaris?
Dsg3 (in the base of the epidermis)
SEVERE
What are the autoantibodies attacking in pemphigus foliaceus?
Dsg 1 in the superficial dermis
Not as severe because the deeper parts of the skin are not exposed
What are the autoantibodies attacking in bullous pemphigoid? Where are these found in the epidermis?
BPAg1 and BPAg2 in the basal layer of the epidermis
does not expose the deeper skin when they pop==> not as bad as vulgaris
What are the autoantibodies attacking in Linear Immunoglobulin A disease? Where are these found?
BPAg2
in the basal layer ==> blisters form but no acantholysis
What is taking place in a type III hypersensitivity reaction?
-antibody (IgG) attaching to a soluble antigen forms complexes –> may deposit in blood vessels (vasculitis), synovial joints (arthritis), glomerular basement membrane (glomerulonephritis) and the choroid plexus
What type of hypersensitivity reaction is taking place in dermatitis herpetiformis? What is reacting to what?
type III hypersensitivity
produce IgA to gluten –> immune complex carried to different parts of the body and activates complement
What are the hallmarks of a type IV hypersensitivity reaction? What are some examples of this
TH cells that have been sensitized by an antigen develop a Th1 response ==> macrophage recruitment and activation (about 24 hours after repeat exposure) causing inflammation
-TB skin test, contact dermatitis, poison ivy
What type of immune cell is responsible for presenting the antigen to T cells? What determines if the person will develop an induration?
Langerhans cells
if the person was sensitized (previously exposed T cells) then the T cells will travel back to the skin and cause an induration
What is scleroderma?
autoimmune chronic multisystem fibrosis resulting in collagen deposits in different parts of the body
can present with Raynauds, difficulty swallowing from loss of esophageal motility, SOB, heartburn, renal failure and diarrhea (affects everything basically)
What is lupus? What are the common manifestations of lupus?
lupus: autoantibodies against histone proteins
- arthralgias and arthritis
- skin: malar and other rashes
- pleurtitis and pericarditis
- fetal loss (if preggo)
What is psoriasis? What immune cells are responsible for this reaction?
-autoimmune T cell disease causing thickening of the epidermis
- T cells activated==> release cytokines to trigger keratinocytes to replicate and proliferate
- T cells in the dermis and epidermis
What are the 3 proposed causes of psoriasis?
- streptococcal infeciton triggered
- super antigen theory –> triggers T cells
- no pathway with CTLA so get sustained T cell activation ==> excessive keratinocyte proliferation
Which of the following skin diseases is characterized by biphasic T cell responses during acute and chronic stages of the disease? A. scleroderma B. Dermatits herpetiformis C. atopic dermatitis D. IgA linear disease
C. atopic dermatitis
acute=more susceptible to bacteria
chronic=more susceptible to viral infecitons
A 60 year old male has complaints of hemoptysis and hematuria. Laboratory tests confirm the presence of antibodies against glomerular basement membrane protein. He is suffering from: A. Bullous pemphigoid disease B. Linear IgA disease C. SLE D. Goodpasture's syndrome
D. Goodpasture’s syndrome
Which of the following skin disease is considered a type I hypersensitivity reaction? A. Pemphigus vulgaris B. Pemphigus foliaceus C. Goodpastures syndrome D. Dermatitis herpetiformis E. Urticaria
E. Urticaria
(all others are type II reactions
