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Immunology of the Skin
Terms in this set (64)
List four things that the skin secretes that aids in defense against organisms from entering the body
What is the function of sebum secreted by the sebaceous glands of the skin?
Maintains a LOW pH, which prevents colonization of bacteria
TRUE or FALSE: Defensins degrade the peptidoglycan layer on the surface of gram positive bacteria
FALSE, that is LYSOZYME
TEST/TEST: What are the two major layers of the skin? Which one of these layers is made up of 4 layers? What separates these two major layers?
1) Epidermis (outer)
- Contains 4 layers
2) Dermis (inner)
The two are separated by a BASEMENT MEMBRANE
TEST: What are the four layers of the epidermis, from most superficial to deep?
1) Stratum corneum (most SUPERFICIAL)
2) Stratum granulosum
3) Stratum spinosum
4) Statum basale
List three cells contained within the dermis that contribute to innate defense mechanisms of the skin
1) Keratinocytes (KCs)
2) Dendritic cells (DCs)
3) Mast Cells (MCs)
AGAIN: What maintains a low pH of the skin to prevent colonization by bacteria?
AGAIN: What is the outermost layer of the epidermis that serves as a physical barrier?
TEST: In the stratum corneum, there are _______ (types of cells) that are locked together by ______, acting as a glue. What are two major proteins contained within this "glue"?
In the stratum corneum, there are KERATINOCYTES that are locked together by DESMOSOMES, acting as a glue.
Two major proteins within demosomes:
1) Desmoglein 3
2) Desmoglein 1
TEST: In terms of location, what is the difference between Desmoglein 3 and Desmoglein 1?
Desmoglein 3 = BASAL part of epidermis
Desmoglein 1 = SUPRABASAL region
______ is a protein involved in the terminal differentiation of the epidermis. What are some conditions that arise when there are mutations in this protein?
Mutations can result in:
- Atopic dermatitis
- Allergic asthma
- Increased rates of sensitization to allergens
What is one cytokine that has been shown to be a marker for defects of skin barrier function? List two skin conditions that this cytokine has been associated with.
THYMIC STROMAL LYMPHOPOIETIN (TSLP)
- Allergic skin inflammation
- Development of ASTHMA in patients with atopic dermatitis
TRUE or FALSE: Thymic stromal lymphopoeitin is derived from keratinocytes
RECALL: What is the main function of dendritic cells?
ANTIGEN PRESENTING CELLS to initate the ADAPTIVE immune response
TEST: In the epidermis, the dendritic cells are classified as _______ cells
LANGERHANS cells = DCs of the epidermis!
TEST: What are four subsets of dendritic cells?
1) LCs (Langerhans, or EPIDERMAL DCs)
2) Dermal DCs
3) Plasmacytoid DCs (PDCs)
4) Infiltrating inflammatory dendritic epidermal cells (IDECs)
Which dendritic cell type is the most critical and effective at processing and presenting foreign antigens?
LCs (Langerhans, or epidermal DCs)
TEST: Which two dendritic cell types express more costimulatory molecules than LCs? Which of these produce IFN-alpha and IFN-beta?
- PDCs also produce large amounts of IFN-alpha and IFN-beta
TRUE or FALSE: IFN-alpha and IFN-beta protect against bacterial infections
FALSE, interferons play a role against VIRAL infections
TEST: What cell is the most important cellular player in the induction of allergies? What is released from these cells, and what triggers the release?
- Release HISTAMINES
- Trigger: Cross-linking of IgE bound to the FCeRI on the surface of mast cells
RECALL: What are the two signals required between the APC and T-cells to trigger T-cell activation?
Signal 1) CD4 or CD8 receptors on the T cell binding to the respective MHC receptors on APC (CD4 to MHC II, CD8 to MHC I)
Signal 2) Co-stimulatory molecule binding (B7-1 and B7-2 on APC to CD28 on T-cell as an example)
- Note: B7 = CD80/86
RECALL: List some of the costimulation signals needed for T-cell activation
- CD28 on T cell and B7 (CD80/86) on APC
- CTLA-4 on T cell and B7 (CD80/86) on APC (inhibitory)
- LFA-1 on T cell and ICAM-1 on APC
- CD2 on T cell and LFA-3 on APC
RECALL: What happens to the T cell if they only had MHC binding to the TCRs (CD4 or CD8) and no other signal?
RECALL: What happens to the T cell if there is MHC binding to the TCR, as well as CD28 binding to CD80/86 on the APC?
PROLIFERATION and DIFFERENTIATION!
RECALL: Besides CD28 on T cells, what can CD80/86 on APCs bind to on T cells that can trigger cell-cycle arrest?
This is the INHIBITION pathway of T-cell activation and is critical to many regulatory processes
RECALL: What are two granules released by cytotoxic T-cells that induce apoptosis in the target cells?
1) Perforins (generate transmembrane pores)
2) Granzymes (enter and trigger apoptosis)
TEST/TEST/RECALL: List the four major types of hypersensitivity reactions
Type I) Anaphylactic and atopic, First and Fast, involves IgE
Type II) Cytotoxic (antibody mediated), involves IgM and IgG binding to FIXED antigens on the foreign cell SURFACE --> COMPLEMENT activation or ADCC
Type III) SOLUBLE antibody-antigen complexes that activate COMPLEMENT
Type IV) Delayed type, CELL mediated
AGAIN: What is the main difference between type II and type III hypersensitivity reactions?
Type II involves antibodies binding to FIXED antigens (on the cell surface)
- Possible LOCAL effect
Type III involves antibodies binding to SOLUBLE antigens
- Possible SYSTEMIC effect as these soluble Ag:Ab complexes are found in CIRCULATION
AGAIN: Which hypersensitivity reaction is the only cell-mediated reaction and not antibody-mediated?
TEST: In type I hypersensitivity reactions, Ig__ binds to ____ on mast cells which cause _______ and release of _____ and _____, both of which enhance vascular permeability and cause smooth muscle contractions
In type I hypersensitivity reactions, IgE binds to CD23 (FceR1) on mast cells which cause DEGRANULATION and release of HISTAMINE and HEPARIN
TEST: List two common examples of type I hypersensitivity reactions
1) Hives (urticaria)
2) Atopic dermatitis
AGAIN: Atopic dermatitis usually involves polymorphisims of the ______ gene
TEST: What are the two phases of atopic dermatitis? In each of these phases, there is a ______ T-cell response. Describe this response.
There is a BIPHASIC T-cell response:
- Acute: Th2 CD4 T cell dominant
- Chronic: Th1 CD4 T cell dominant
TEST: In the acute phase of atopic dermatitis, which interleukin is released from langerhans cells? What does this induce?
IL-10 (ACUTE phase)
- Induces differentiation of CD4 cells to the Th2 lineage -> IL-4 and IL-5 release --> ANTIBODY production by B cells
TEST: In the chronic phase of atopic dermatitis, which interleukin is released from langerhans cells? What does this induce?
IL-12 (CHRONIC phase)
- Induces differentiation of CD4 cells to the Th1 lineage --> IFN-gamma
TEST/TEST: In acute phase of atopic dermatitis, there is an increased susceptibility to (viral/bacterial) infections. Why?
How is this different from the chronic phase of atopic dermatitis?
Acute phase, there is an increased susceptibility to BACTERIAL infections
- Less IFN-gamma production (since that is induced by IL-12 in the chronic phase), which is important to the synthesis of antimicrobial peptides
In the CHRONIC phase, there is INCREASED IFN-gamma but there is also DECREASED plasmacytoid DCs (PDCs), which produce IFN-alpha and IFN-beta
- This leads to increased susceptibility to VIRAL infections
RECAP: List which T-cell and IFN/Interleukin is produced by the acute and chronic phases of atopic dermatitis and what kind of infections each phase is susceptible to
- T- cell = CD4 Th2
- IL-4 and IL-5
- Susceptible to BACTERIAL infections (lack of IFN-gamma)
- T cell = CD4 Th1
- Susceptible to VIRAL infections (lack of PDCs making IFN-alpha and IFN-beta)
RECALL: In type II hypersensitivity reations, Ig__ or Ig__ binds to antigens and activates the complement system by the _____ pathway
IgM or IgG --> Complement activation by the CLASSICAL pathway
List some common diseases caused by type II hypersensitivity reactions
- Goodpasture's syndrome (anti-GBM)
- Pemphigus vulgaris
- Pemphigus foliaceus
- Bullous pemphigoid
- Linear IgA dermatosis
Pemphigus comprises a group of autoimmune ______ disorders that are examples of type ___ hypersensitivity reactions. Which type is most severe?
Pemphigus = Autoimmune BLISTERING disorders, examples of type II hypersensitivity reactions
- Most severe = Pemphigus VULGARIS
TEST: In pemphigus vulgaris, there are autoantibodies to _______ in the ______ of the keratinocytes.
This results in ________ which is absent in bullous pemphigoid, making it good for distinguishing between the two.
DESMOGLEIN-3 in the DESMOSOMES of the keratinocytes
This results in ACANTHOLYSIS (separation of epidermal cells) which is absent in bullous pemphigoid, making it good for distinguishing between the two
TEST: Unlike pemphigus vulgaris, there are autoantibodies to _______ in pemphigus foliaceus
The primary lesion of pemphigus foliaceus is a flaccid _____
TRUE or FALSE: Pemphigus foliaceus is much more benign than pemphigus vulgaris
TRUE, since desmoglein-1 (involved in folicaeus) is much more superficial in the epidermis!
TEST: What autoantibodies are involved in the pathogenesis of bullous pemphigoid?
Autoantibodies to Hemidesmosomal BP antigens BP230 (BPAg1) BP180 (BPAg2)
- IgG mediated
TEST: What autoantibodies are involved in the pathogenesis of linear IgA dermatosis?
Autoantibodies to BPAg2 (BP180)
- IgA mediated
AGAIN: What is the main difference between bullous pemphigoid and IgA dermatosis?
Bullous pemphigoid: Autoantibodies to BPAg1 (BP230) and BPAg2 (BP180), IgG mediated
Autoantibodies to BPAg2 only, IgA-mediated
RECAP: List what there are autoantibodies to in each of the following type II hypersensitivity skin disorders:
- Pemphigus vulgaris
- Pemphigus foliaceus
- Bullous pemphigoid
- IgA dermatosis
Pemphigus vulgaris: Desmoglein-3
Pemphigus foliaceus: Desmoglein-1
Bullous pemphgoid: BPAg1 and BPAg2 (IgG)
IgA dermatosis: BPAg2 (IgA)
TEST: What is one common skin example of a type III hypersensitivity reaction?
TEST/TEST: Dermatitis Herpetiformis is associated with what common GI disorder?
CELIAC SPRUE (Gluten sensitive enteropathy, or GSE)
TRUE or FALSE: Dermatitis herpetiformis is mediated by IgE antibodies to gluten, leading to complement activation
FALSE, it is mediated by IgA to gluten which are deposited in blood vessels
What is the mnemonic to remember the major manifestations of type IV hypersensitivity reactions?
- Transplant rejections
- TB skin tests
- Touching (contact dermatitis, like POISON IVY)
RECALL: Describe how a TB skin test is an example of type IV hypersensitivity reactions
Mycobacterial antigens --> forearm --> presented by DCs and macrophages to MEMORY T-cells (hence, delayed type) --> cytokine release --> INDURATION
TEST: What skin disorder is characterized by excessive fibrosis and collagen deposition? What are the two types of this disorder, and what is the main antibody association between the two?
1) DIFFUSE - Associated with Scl-70 Ab (anti-DNA topo I)
2) LIMITED - Associated with Anti-Centromere Ab
List some of the manifestations of scleroderma (either diffuse or limited)
- PUFFY and TAUT skin
- Absence of wrinkles
- GI disturbances (dysphagia, heartburn)
- Joint manifestations (polyarthralgia or mild arthritis)
- Cardiopulmonary manifestations (lung fibrosis)
- Renal crisis
RECALL: What syndrome is associated with limited scleroderma? What are some manifestations of this syndrome?
Raynaud phenomenon - (hypopigmented or hyperpigmented due to fibrosis of blood vessels)
RECALL: What rash is very characteristic of SLE?
BUTTERFLY rash (both cheeks, but spares nose and lips)
What skin disorder is characterized by sharply demarcated erythematous plaques with silvery scales?
PSORIASIS (hyperkeratosis, or thickening of the epidermis)
TEST: What two genes are associated with psoriasis?
PSORS1 and PSORS2
RECALL: In the dermis, CD__ T cells predominate, while in the epidermis, CD__ T cells predominante
Dermis: CD4 T cells
Epidermis: CD8 T cells
Psoriasis is suggested to be a (T/B) cell mediated autoimmune disease, and more specifically a ___ dominant disease
- Th1 dominant disease
Briefly describe how psoriasis is a T-cell mediated autoimmune disease
In developing psoriatic plaques, there is an influx of activated CD4 cells and in resolving psoriatic plaques, an influx of activated CD8 cells predominate
CD4 --> APCs and MHC II --> Th1 releasing IL-2 and IFN-gamma, and Th2 releasing IL-4, IL-5, and IL-10
CD8 --> APCs and MHCI
List some of the cytokines that has been characterized in a psoriatic lesion
What are three possible causes of psoriasis?
1) Super-antigens (nonspecific polyclonal T-cell activation)
2) Sustained T-cell stimulation (loss of CTL4 inhibition pathway)
3) Streptococcal infection
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