The innate immune response induces signals that function in concert with antigens to stimulate the proliferation and differentiation of antigen-specific T and B lymphocytes. In addition to providing the initial defense against microbes, the innate immune response also sets in motion the adaptive immune response. The activation of lymphocytes requires two distinct signals, the first being antigen and the second being molecules that are produced during innate immune responses to microbes or injured cells (Fig. 1). This idea is called the two-signal hypothesis for lymphocyte activation. The requirement for antigens (so-called signal 1) ensures that the ensuing immune response is specific. The requirement for additional stimuli triggered by innate immune reactions to microbes (signal 2) ensures that adaptive immune responses are induced when there is a dangerous infection and not when lymphocytes recognize harmless antigens, including self antigens. The molecules produced during innate immune reactions that function as second signals for lymphocyte activation include costimulators (for T cells), cytokines (for both T and B cells), and complement breakdown products (for B cells).

Fig1. Stimulation of adaptive immunity by innate immune responses. Antigen recognition by lymphocytes provides signal 1 for the activation of the lymphocytes, and molecules induced on host cells during innate immune responses to microbes provide signal 2. In this illustration the lymphocytes are B cells, but the same principles apply to T lymphocytes. The nature of second signals differs for B and T cells and is described in later chapters.

The second signals generated during innate immune responses to different microbes not only enhance the magnitude of the subsequent adaptive immune response but also influence the nature of the adaptive response. A major function of T cell–mediated immunity is to activate macrophages to kill intracellular microbes and to induce robust inflammatory responses so that a sufficiently large army of phagocytes is called into a site of infection. When DCs or phagocytes encounter microbes, TLRs and other pattern recognition receptors stimulate the secretion of cytokines and induce on antigen-presenting cells the expression of costimulators, all of which promote T-cell activation. Thus, the innate immune response to microbes in macrophages stimulates the adaptive T-cell response that helps the macrophages to destroy such microbes.

By contrast, many extracellular microbes that enter the blood activate the alternative complement pathway, and some of the proteolytic products of complement activation enhance the production of antibodies by B lymphocytes. These antibodies opsonize the microbes and thereby promote their phagocytosis by neutrophils and macrophages, or kill the microbes by complement-dependent mechanisms. Thus, blood borne microbes induce an innate response (complement activation) that triggers the adaptive response that is designed to eliminate these extracellular pathogens.

Cytokines produced by cells during innate immune responses to microbes or cell injury stimulate the proliferation and differentiation of lymphocytes in adaptive immune responses. Examples of cytokines secreted during innate immune reactions acting on B cells, CD4+ T cells, and CD8+ T cells are given here. We have mentioned these cytokines previously and will discuss the details of their roles in lymphocyte responses in later chapters.

 • IL-12 is required for the differentiation of naive CD4+ T cells to the Th1 subset of effector cells and stimulates cytotoxic activity and IFN-γ secretion by CD8+ CTLs.

 • IL-1, IL-6, and IL-23 stimulate the differentiation of naive CD4+ T cells to the Th17 subset of effector cells.

• IL-25, IL-33, and TSLP stimulate the differentiation of naive CD4+ T cells to the Th2 subset of effector cells.

• IL-15 promotes the survival of memory CD8+ T cells.

• IL-6 promotes the survival of antibody-producing plasma cells.

Adjuvants are substances that need to be administered together with purified protein antigens to elicit maximal T cell dependent immune responses. Most work by stimulating innate immune responses at the site of antigen exposure that promote subsequent adaptive immunity. Adjuvants are useful in experimental immunology and in clinical vaccines. Many adjuvants in experimental use are microbial products that engage TLRs, such as killed mycobacteria and LPS. Aluminum, in the form of various salts, is the most commonly used adjuvant in human vaccines and may work by causing inflammasome activation. CpG, the ligand for TLR9, is used in some hepatitis B virus vaccines. Among their important effects, adjuvants activate DCs to express more MHC molecules that are part of the antigen (signal 1) that T cells recognize, increase the expression of costimulators (signal 2) and cytokines needed for T-cell activation, and stimulate migration of the DCs to lymph nodes where T cells are located.

اخر الاخبار

اخبار العتبة العباسية المقدسة

وسط أجواء عبادية.. المؤمنون يحيون ليلة الجمعة عند مرقد أبي الفضل العباس (عليه السلام)

شعبة الخطابة النسوية تطلق دورة تطويرية لتأهيل ملاكاتها التدريسية للدورات الصيفية

قسم الشؤون الفكرية يصدر كتابًا يناقش مناهج المستشرقين في تفسير القرآن الكريم

ضمن برنامج بالقرآن نحيا.. المجمَع العلمي يقيم محفلًا قرآنيًّا في كربلاء

المزيد

الآخبار الصحية

طريقة مبتكرة للكشف المبكر عن أمراض القلب والشرايين

منظمة الصحة تحذر من خطر إدمان الشباب لأكياس النيكوتين

خبراء يحذرون من عادة شائعة تهدد صحة الملايين

خبير يكشف 5 حقائق طبية صادمة وغير معروفة

المزيد

الآخبار التكنلوجية

الأولى في العالم.. الصين تجري تجربة رائدة في الفضاء باستخدام "جنين اصطناعي"

دراسة حديثة تفند ربط التستوستيرون بالمخاطرة لدى الرجال

ميتا تضيف وضع "المحادثة المخفية" إلى تطبيق "واتساب"

فوبيا المرتفعات ليست من الدماغ.. دراسة تكشف السبب

المزيد

مواضيع ذات صلة

Stages of T-Cell Maturation

Mechanisms that Limit Innate Immune Responses

Systemic and Pathologic Consequences of Inflammation

Immuno microscopy

V(D)J Recombination

Role of Macrophages in Tissue Repair

Ingestion and Killing of Microbes by Activated Phagocytes

Sequence of Events in Inflammation: Vascular Changes and Leukocyte Migration Into Tissues

Double Antibody Sandwich ELISA (DAS ELISA)

Enzyme Immunosorbent Assays

Antibody Structure and Function

Apoptosis in the Immune System