1.  Reflexive neurovascular responses

2.  Innate immune responses which produce acute inflammation

3.Delayed onset adaptive immune response that is dedicated to recognizing and disposing of invading foreign antigens

T lymphocytes

1. Name three main subtypes

2. Describe role with Langerhans cells

1.  There are three main subtypes: Helper T cells (facilitate immune reactions); Cytotoxic T cells (kill infected cells); and Suppressor T cells (regulate other lymphocytes).  Surface receptors help to categorized subtypes: Helper T cells usually have the CD4 receptor and Cytotoxic “Killer” T cells usually have the CD8 receptor. 

2.  They circulate through normal skin amongst other areas.  Langerhans cells present antigens in the lymph nodes to T lymphocyte.  Such antigen presentation induces the expression of cutaneous lymphocyte antigen (CLA), the T cell skin homing receptor.  These activated T cells then reach the skin via blood vessels to participate in the immune response.

1. Langerhans cell

2. T lymphocyte

3. B lymphocyte

4. Mast cell

5. Keratinocyte

6. Macrophage

7. Neutrophil

No, not found in normal skin.  Present in some disease states such as cutaneous B cell lymphoma.

A normal resident in the dermis along with the macrophage.  Their major constituents and functions are very similar to basophils.  Mast cell degranulation results in the release of histamine and other vasoactive mediators which induce the immediate hypersensitivity response. (characteristically asthma, allergic rhinitis, and urticaria) and anaphylactic shock

Plays an important role in the innate immune system, functions as an antigen presenting cell, has phagocytizing properties, releases inflammatory mediators

Phagocytizing properties, releases many inflammatory mediators

a.     Rubor – Redness (erythema)--due to increased blood flow

b.    Calor – Warmth

c.     Tumor - Swelling / Induration

d.    Dolor – Pain, itching [pruritus], burning, tenderness

1.  What is a requirement for dermatographism/Triple response of Lewis? 

2.  What are the three stages to the triple response of lewis?

I.    A critically important requirement for development and subsidence of the Lewis Triple Response is the presence of a functional cutaneous circulation

2.  Three stages

a.     The rapidly formed (3-10 seconds) red spots (erythema)--mechanism is capillary dilatation from endogenous histamine like substances released in the localized region of mild injury

b.    The "flare" or expanding reddening response due to neighboring cutaneous arteriolar dilatation from localized post synaptic antidromic nerve impulses (axon reflex).

c.     The formation of wheals within the reaction sites due to increased vascular permeability in the dilated region.

1.  What does the innate immune response recognize?

2. What are some examples of PAMPs?

3.  Which cells are professional antigen-presenting cells?

1.  Recognize a few, highly conserved structures present in large groups of microorganisms. 

                                          i.        Pathogen-associated molecular patterns are produced only by microbial pathogens, and not by their hosts.

                                         ii.        The structures recognized by the innate immune system are usually essential for the survival or pathogenicity of microorganisms.

                                        iii.        Pathogen-associated molecular patterns are usually invariant structures shared by entire classes of pathogens. For example, all gram-negative bacteria have lipopolysaccharides, and therefore, the lipopolysaccharide pattern-recognition receptor of the host can detect the presence of virtually any gram-negative bacterial infection.

2. Bacterial lipopolysaccharide, peptidoglycan, lipteichoic acids, mannans and clucans, and bacterial DNA

3.  Macrophages, dendritic cells, and B cells

1. Signal induces co-stimulators, cytokines, and chemokines, which recruit and activate antigen-specific lymphocytes and initiate adaptive immune responses

2.  The signals induced on recognition by the innate immune system control the activation of adaptive immune responses because the adaptive immune system responds to a pathogen only after it has been recognized by the innate immune system

Adaptive Immunity

1.  Describe the repertoire of receptors

2.  Describe the capacity to recognize antigens

3.  What is a problem with a diverse antigen recognition?

4.  When is the adaptive immune response harmful?

1.     The random generation of a highly diverse repertoire of antigen receptors allows the adaptive immune system to recognize virtually any antigen

2.    The adaptive immune system has a tremendous capacity to recognize almost any antigenic structure, but because antigen receptors are generated at random, they bind to antigens regardless of their origin - bacterial, environmental, or self.

3.     The price of this diversity is the inability to distinguish foreign antigens from self antigens

4.    Activation of the adaptive immune response can be harmful to the host when the antigens are self or environmental antigens, since immune responses to such antigens can lead to autoimmune diseases and allergies.

T cell activation

1.  What does a T cell receptor bind to on an antigen-presenting cell?

2.  What is the second signal required for activation?

3.  What happens in the absence of the second signal?

4.  What controls the expression of the co-stimulatory signal?

1.       T cells use their antigen receptors to recognize a ligand in the form of a peptide bound to an MHC class II molecule on the surface of an antigen-presenting cell.

2.      However, the recognition of the peptide-MHC ligand by the antigen receptor is not sufficient to activate T cells. T cells require at least two signals to become activated: one is the complex of a peptide and an MHC molecule, and the other is a co-stimulatory signal mediated by, for example, the CD80 and CD86 molecules on the surface of the antigen-presenting cell.

3.       Recognition of an antigen in the absence of CD80 or CD86 molecules leads to permanent inactivation or apoptosis of the T cell.

4.      The expression of CD80 and CD86 molecules on the surface of the antigen-presenting cell is controlled by the innate immune system.

Certain memory T cells appear to remember the anatomical site where they first encountered antigen. Specifically, there is an identifiable subgroup of memory T cells with the ability to circulate preferentially to the skin.

These memory T cells, identified by a marker known as cutaneous lymphocyte antigen (CLA), are generated in lymph nodes draining skin and are recruited back to the skin during inflammation.

Cutaneous T-cell lymphoma

Graft-versus-host disease

Allergic contact dermititis

Psoriasis

Atopic dermatitis

Alopecia areata

Vitiligo

Drug-related eruptions

• IgE is bound to the surface of mast cells via Fc receptors.  
• Upon binding antigen (pollen, food, etc.), the IgE molecules group together and become cross-linked which causes mast cell degranulation and release of inflammatory mediators (histamine, prostaglandins, leukotrienes, etc.).  
• The response occurs within minutes and can range from skin urticaria to anaphylaxis.  There is also a delayed component that is recognized.  In addition, other factors besides IgE can cause mast cell degranulation.

• Antigens on target skin cells or structures attracts antibodies.  In turn, killer T cells and complement activation are induced and produce cytotoxic effects.  This can lead to lysis of keratinocytes and intraepidermal blisters.  
• Other examples of type II reactions are hemolytic anemia, transfusion reactions, vitiligo, and certain autoimmune reactions.

• In the blood, antigen and antibodies form immune complexes. 
  
• These immune complexes are deposited in the walls of vessels, especially the small vessels of the skin. 
  
• Vascular damage results as these immune complexes induce complement, platelet aggregation, and lysosomal enzyme release from polymorphs. 
  
• This reaction is seen in systemic lupus erythematosus and dermatomyositis, microbial infections such as infective endocarditis.

• Antigen is presented to T cells by antigen presenting cells (APC).  
• Released cytokines activate T cells and amplify the reaction by recruiting more T cells and macrophages to the site of action.  
• Tissue damage results which is maximal at 48-72 hours.
  
• This reaction is seen in allergic contact dermatitis, and the tuberculin reaction to intradermally administered antigen.  Leprosy, poison ivy reaction, and tuberculosis are granulomatous variants of the Type IV reaction.

A highly selective form of "cell suicide" with characteristic morphological and biochemical features: chromatin condensation, formation of apoptotic bodies, and DNA fragmentation by activation of endonucleases.

Ultraviolet exposure causes a number of adverse consequences for the immune system including suppression of cutaneous immune responsiveness and immunologic unresponsiveness to cutaneous tumors. Local mechanisms for these effects include depletion of resident Langerhans, Thy1+ and dendritic epidermal T cell populations. Systemic mechanisms include production of suppressor T-cells and release of soluble immunosuppressive factors such as cis-urocanic acid, tumor necrosis factor-alpha, interleukin-1, prostaglandins, and interleukin-10.

1. Reflexive neurovascular response to mechanical trauma

2. Radid-acting innate immune response that produces acute cutaneous inflammation

3. A delayed-onset adaptive immune response dedicated to recognizing and disposing of foreign antigens

Select the correct answer

a. Atopic dermatitis is a B-cell mediated disease

b. Innate and Adaptive immunity differ only in the rapidity of response

c. Lymphocytes phagocytize bacteria

d. Innate immunity can respond only to a finite number and type of antigens

Select the correct answer which describes the Triple Response of Lewis

a. Pain, warmth, erythema

b. Erythema, wheal and flare

c. Dolor, calor, and discharge

d. Recognition, adaptation, and response

Select the true statement

a. Mast cells release histamine

b. Dendritic cells contain keratin filaments

c. Allergic contact dermatitis is a Type I hypersensitivity reaction.

d. UV radiation enhances the cutaneous immune system.