5. Cutaneous-Associated Lymphoid Tissue

The skin is an important anatomic barrier to the external environment, and its large surface area makes this tissue important in nonspecific (innate) defenses. The epidermal (outer) layer of the skin is composed largely of specialized epithelial cells called keratinocytes. These cells secrete a number of cytokines that may function to induce a local inflammatory reaction. In addition, keratinocytes can be induced to express class II MHC molecules and may function as antigen-presenting cells. Scattered among the epithelial-cell matrix of the epidermis are Langerhans cells, a type of dendritic cell, which internalize antigen by phagocytosis or endocytosis. The Langerhans cells then migrate from the epidermis to regional lymph nodes, where they differentiate into interdigitating dendritic cells. These cells express high levels of class II MHC molecules and function as potent activators of naive TH cells.

The epidermis also contains so-called intraepidermal lymphocytes. These are similar to the intraepithelial lymphocytes of MALT in that most of them are CD8⁺ T cells, many of which express γδ T-cell receptors, which have limited diversity for antigen. These intraepidermal T cells are well situated to encounter antigens that enter through the skin and some immunologists believe that they may play a role in combating antigens that enter through the skin. The underlying dermal layer of the skin contains scattered CD4⁺ and CD8⁺ T cells and macrophages. Most of these dermal T cells were either previously activated cells or are memory cells.

Figure. Comparison of the circulation patterns of the regular circulatory and lymphatic systems. The movement of lymphatic flow is in one direction (green) from lymph capillaries to collecting vessels and ducts to large lymphatic trunks to subclavian veins to the heart. The flow of blood on the other hand, is cyclic, with blood continuously fl owing through arteries to capillaries to veins to the heart and back around. With this combined system the lymphatics can collect excess tissue fluid and return it to the bloodstream. The two systems can also participate together in surveillance of the tissues for foreign invaders. Note: The lymphatic flow (green) is shown on only one side to keep the comparison uncluttered.

Lecture 1.4 Major populations of immunocompetent cells

Adaptive Immunity and Cells of Immune System

Plan:

Introduction

1. The Adaptive Immune System Requires Cooperation Between Lymphocytes and Antigen-Presenting Cells

2. Humoral Immunity But Not Cellular Immunity Is Transferred with Antibody

3. Antigen Is Recognized Differently by B and T Lymphocytes

4. B and T Lymphocytes Utilize Similar Mechanisms To Generate Diversity in Antigen Receptors

5. The Major Histocompatibility Molecules Bind Antigenic Peptides

6. Complex Antigens Are Degraded (Processed) and Displayed (Presented) with MHC Molecules on the Cell Surface

7. Antigen Selection of Lymphocytes Causes Clonal Expansion

8. The Innate and Adaptive Immune Systems Collaborate, Increasing the Efficiency of Immune Responsiveness

Introduction

Adaptive immunity is capable of recognizing and selectively eliminating specific foreign microorganisms and molecules (i.e., foreign antigens). Unlike innate immune responses, adaptive immune responses are not the same in all members of a species but are reactions to specific antigenic challenges.

Adaptive immunity displays four characteristic attributes:

• Antigenic specificity

• Diversity

• Immunologic memory

• Self/nonself recognition

The antigenic specificity of the immune system permits it to distinguish subtle differences among antigens. Antibodies can distinguish between two protein molecules that differ in only a single amino acid. The immune system is capable of generating tremendous diversity in its recognition molecules, allowing it to recognize billions of unique structures on foreign antigens. Once the immune system has recognized and responded to an antigen, it exhibits immunologic memory; that is, a second encounter with the same antigen induces a heightened state of immune reactivity. Because of this attribute, the immune system can confer life-long immunity to many infectious agents after an initial encounter. Finally, the immune system normally responds only to foreign antigens, indicating that it is capable of self/nonself recognition. The ability of the immune system to distinguish self from nonself and respond only to nonself molecules is essential, for, as described below, the outcome of an inappropriate response to self molecules can be fatal.

Adaptive immunity is not independent of innate immunity. The phagocytic cells crucial to nonspecific immune responses are intimately involved in activating the specific immune response. Conversely, various soluble factors produced by a specific immune response have been shown to augment the activity of these phagocytic cells. As an inflammatory response develops, for example, soluble mediators are produced that attract cells of the immune system. The immune response will, in turn, serve to regulate the intensity of the inflammatory response. Through the carefully regulated interplay of adaptive and innate immunity, the two systems work together to eliminate a foreign invader.