Receptor interaction Following the exposure to microorganisms, several mediators of innate immunity are recruited to the site of infection (Table 1). The first step that takes place is attachment, which involves binding of the surface molecules of microorganisms to the receptors on the cells of innate immunity.

Table1. Differences between innate and acquired immunity.

Microbial Surface Molecules

They are the repeating patterns of conserved molecules which are common to most microbial surfaces; called Microbes-associated molecular patterns (MAMPs). Examples of MAMPs include peptidoglycan, lipopolysaccharides (LPS), teichoic acid and lipoproteins present on bacterial surface.

Pattern Recognition Receptors (PRRs)

These are the molecules present on the surface of host cells (e.g. phagocytes) that recognize MAMPs. They are generally conserved regions, encoded by germ line genes.

1. Toll-like receptors (TLRs) are classical examples of pattern recognition receptors, named after the fruit fly (Drosophila); the main receptor for inducing innate immunity
2. Signals generated following binding of TLRs to MAMPs activate transcription factors that stimulate expression of genes encoding cytokines and enzymes, which are involved in several antimicrobial activities of cells of innate immunity.

components of innate immunity

There are several mediators of innate immunity. They exert antimicrobial activities by various mechanisms as described below. Some of these mediators are not purely part of innate immunity; they often act as bridge between innate and acquired immunity (e.g. complements and macrophages).

Anatomical and Physiological Barriers

1. Anatomical barriers such as skin and mucosal surfaces have a spectrum of antimicrobial activities (Table 2)
2. Physiological barriers that contribute to the innate immunity are the body temperature, pH and various soluble secretory products of mucosa (Table2).

Table2. Role of barriers in innate immunity.

Phagocytes

 Phagocytes such as neutrophils, macrophages including monocytes are the main components of innate immunity. They are rapidly recruited to the site of infection. Phagocytosis involves three sequential steps— (1) engulfment of microbes and subsequent hosting in phagosome, (2) fusion of lysosome with phagosome to form phagolysosome and (3) microbial killing.

Natural Killer (NK) Cells They are a class of lymphocytes that kill virus infected cells and tumor cells.

Other Rare Classes of Lymphocytes

T and B lymphocytes are the chief mediators of acquired immunity. However, there are several rare types of lymphocytes that share the features of both acquired and innate immunity, e.g.

1. γδ T cells (also called intraepithelial lymphocytes): They are present in epithelial lining of skin and mucosa
2. NK-T cells: They are present in epithelium and lymphoid organs
3.  B-1 cells: They are found mostly in the peritoneal cavity and mucosal tissues
4. Marginal-zone B cells: They are present at the edges of lymphoid follicles of spleen.

Mast Cells

They are present in the epithelial lining of the respiratory and other mucosa.

1. They are activated by microbial products binding to toll like receptors or by IgE antibody dependent mechanism, following which;
2. They release abundant cytoplasmic granules rich in histamine, prostaglandins and cytokines that initiate inflammation and proteolytic enzymes that results in killing of bacteria.

Dendritic Cells

They respond to microbes by producing numerous cytokines that initiate inflammation. They also serve as vehicle in transporting the antigen(s) from the skin and mucosal sites to lymph nodes where they present the antigen(s) to T cells. Hence, dendritic cells serve as a bridge between innate and acquired immunity.

Complement Pathways

 Alternative and mannose binding pathways are the chief mediators of innate immunity.

1. Alternative complement pathway is activated in response to bacterial endotoxin whereas the mannose binding pathway is stimulated by mannose carbohydrate residues on bacterial surface.
2. Following activation, the complements mediate various biological functions such as (refer Chapter 13):

• Lysis of the target microbes (by forming pores on the microbial surfaces)
•  Stimulate inflammation (by secreting inflammatory mediators)
• Stimulate acquired immunity: Complements are another bridge between innate and acquired immunity.

Inflammatory Response

 Inflammation is defined as the biological response of vascular tissues to harmful stimuli, such as microorganisms or other foreign substances. The major events that take place during an inflammatory response following a microbial entry are as follows (Fig. 1):

1. Vasodilation due to release of vasoactive substances from the damaged tissues
2. Leakage of plasma proteins through blood vessels Recruitment of phagocytes (e.g. neutrophils) to the site of inflammation—phagocytes undergo the following steps—(1) margination (adherence to the endothelium), (2) rolling on endothelium, (3) extravasation (moves out of the blood vessels), (4) chemotactic migration to the inflammation site
3. Engulfment of microbes and dead material by the phagocytes
4.  Destruction of the microbes. Inflammation is not always protective in nature,

sometime, it may produce injurious consequences to host tissues in the form of hypersensitivity reactions.

Fig1. Major events in an inflammatory response.

Normal Resident Flora

 Normal resident flora lining intestinal, respiratory and genital tract exert several antimicrobial activities.

1. They compete with the pathogens for nutrition
2. They produce antibacterial substances.

Cytokines

In response to the microbial antigens, dendritic cells, macrophages, and other cells secrete several cytokines that mediate many of the cellular reactions of innate immunity such as:

1. Tumor necrosis factor-α (TNF-α)
2.  Interleukin-1 (IL-1), IL-6, IL-8, IL-12 and IL-16
3. Interferons (IFN-α, β) and
4.  Transforming growth factor (TGF-β).

Acute Phase Reactant Proteins (APRs)

They are the proteins synthesized by liver at steady concentration, but their synthesis either increases or decreases exponentially during acute inflammatory conditions. Though liver is the primary site, APRs can also be synthesized by various other cells such as endothelial cells, fibroblasts, monocytes and adipocytes.

1. Positive APRs: They are the proteins whose levels increase during acute inflammation. Examples include:

• Serum amyloid A
•  C-Reactive protein
• Complement proteins—complement factors (C1 C9), factor B, D, and properdin
• Coagulation protein, e.g. fibrinogen, von Willebrand factor
•  Proteinase inhibitors, e.g. α-1 antitrypsin
•  α1 acid glycoprotein
•  Mannose binding protein
• Haptoglobin
• Metal binding proteins, e.g. ceruloplasmin.

1. Negative APRs: They are the proteins whose levels are decreased during acute inflammation; thus creating a negative feedback that stimulates the liver to produce positive APRs. Examples of negative APRs include albumin, transferrin and antithrombin
2. Role of APRs: They have a wide range of activities that contribute to the host defense

• APRs have various antimicrobial and anti-inflammatory activities (e.g. complement factors)
• Metal binding proteins can chelate various metals such as iron, copper, etc. making them unavailable for the bacteria.

اخر الاخبار

اخبار العتبة العباسية المقدسة

المفارز التطوعية: نقدم خدماتنا الطبية للزائرين على مدار اليوم بدعم العتبة العباسية المقدسة

فرقة العباس (عليه السلام) تقدم خدمة الاستفتاءات الشرعية لزائري الأربعين

منظومة تبريد العتبة العباسية المقدسة تتخطى حاجز 5 آلاف طن خلال زيارة الأربعين

عبر موكب الباقيات الصالحات.. مجمع العفاف النسوي يقدم خدمات متنوعة لزائرات الأربعين

المزيد

الآخبار الصحية

حجم جزء محدد من الجسم يعكس الصحة العامة ومخاطر الأمراض

تفشي عدوى بكتيرية بفرنسا يحتمل ارتباطها بنوع من الجبن الطري

دراسة حديثة تكشف ما تفعله الشاشات بـ"قلوب الأطفال" !

متلازمة المبنى المريض.. هكذا يتحول تكييف الهواء إلى خطر صحي ؟؟

المزيد

الآخبار التكنلوجية

كيف تتعامل مع حرارة الطقس أثناء القيادة؟

لماذا يجب عليك إيقاف تكييف السيارة قبل إطفاء المحرك؟

دراسة تكشف سببا محتملا وراء زيادة خطر إصابة الأطفال بالتوحد

تشيلي.. العثور على متحجرة حيوان ثديي صغير من زمن الديناصورات

المزيد

مواضيع ذات صلة

Immunologic Manifestations of Viral, Rickettsial, and Mycoplasmal Diseases

Immunologic Manifestations of Fungal Diseases

The Structure of Antibodies

Myelomas and Monoclonal Antibodies

Telling the Difference Between Foreign and Self

The Basic Adaptive Immune Response

The Immunoglobulin Domain and Variations

Deficiencies of the Immune Response

Hypersensitivity

Cytokines

Complement Deficiencies and Pathogen Evasion

Complement Pathways