Organs and Tissues of the Immune System

 Organs and Tissues of the Immune System

• Based on function, the organs and tissues of the immune system can be divided into primary or secondary lymphoid organs and tissues.

• The primary organs and tissues are where immature lymphocytes mature and differentiate into antigen sensitive B and T cells.
• The THYMUS is the primary lymphoid organ for T cells, and the BONE MARROW is the primary lymphoid tissue for B cells.
• The secondary organs and tissues serve as areas where lymphocytes may encounter and bind antigen,
• which triggers their proliferation and differentiation into fully active,antigen-specific effector cells.

• The SPLEEN is a secondary lymphoid organ, and
• LYMPH NODES AND MUCOSAL-ASSOCIATED TISSUES (GALT- gut-associated lymphoid tissue, and SALT-skin-associated lymphoid tissue) are secondary lymphoid tissues.

Primary Lymphoid Organs and Tissues

• THYMUS - Primary Lymphoid Organs :
• The thymus is a highly organized lymphoid organ located above the heart.
• Precursor cells from the bone marrow migrate into the outer cortex of the thymus, where they proliferate.
• As they mature, about 98% die.This is due to a process known as thymic selection in which T cells that could recognize and respond to the host (self) are destroyed.
• The remaining 2% move into the medulla of the thymus where they mature and subsequently enter the bloodstream.

• These T cells recognize and respond to the myriad of foreign nonhost substances, collectively referred to as "nonself:'
•   In mammals, the bone marrow is the site of B-cell maturation.
• Like thymic selection during T-cell maturation, a selection process within the bone marrow eliminates nonfunctioning B cells and those that recognize and respond against self.
• Remaining B cells mature in the bone marrow and subsequently enter the bloodstream.

Secondary Lymphoid Organs and Tissues

Secondary lymphoid organ: (SPLEEN & LYMPH NODES)

SPLEEN (Secondary lymphoid organ)

• The spleen is the most highly organized secondary lymphoid organ.
• It is a large organ located in the abdominal cavity that functions to filter the blood and trap blood-borne particles to be assessed for foreignness by phagocytes.
• Macrophages and dendritic cells are present in abundance, and once trapped by splenic macrophages or dendritic cells, a pathogen is phagocytosed, killed, and digested.
• The resulting antigens are presented to lymphocytes, activating a specific immune response.

LYMPH NODES (Secondary lymphoid organ)

• Lymph nodes lie at the junctions of lymphatic vessels, where

macrophages and dendritic cells trap particles that enter the lymphatic system.

• If a particle is found to be foreign, it is then phagocytosed and degraded,
• and the resulting antigens are presented to lymphocytes.

Secondary Lymphoid Tissues : (SALT & MALT)

• Lymphoid tissues are found throughout the body as highly organized or loosely associated cellular complexes.
• Some lymphoid cells are closely associated with specific tissues such as skin (skin-associated lymphoid tissue, or SALT) and

  mucous membranes (mucosal-associated lymphoid tissue, or MALT).

• SALT and MALT are good examples of highly organized lymphoid tissues that feature macrophages surrounded by specific areas of B and T lymphocytes and sometimes dendritic cells.
• Loosely associated lymphoid tissue is best represented by the bronchial- associated 

• lymphoid tissue (BALT), because it lacks cellular partitioning. The primary role of theselymphoid tissues is to efficiently organize leukocytes to increase interaction between the innate and the adaptive arms of the immune response.
• Thus, the lymphoid tissues serve as the interface between the innateresistance mechanisms and adaptive immunity of a host.

 

Cells, tissues and organs of the immune system

•       Cells of the immune system
• tissues of the immune system
• organs of the immune system

  Cells of the immune system

        leukocytes

Mast cells

Granulocytes

Basophils,

Eosinophils,

        Neutrophils

Monocytes

Macrophages

Dendritic cells

Lymphocytes

T- Lymphocytes

        B- Lymphocytes

NK cell

Lymphocytes. T cells, B cells, and natural killer, or NK, cells.

 

Lymphocytes

• Lymphocytes are the major cells of the adaptive immune system.
• Lymphocytes can be divided into three populations:

                     1) T cells,

                     2) B cells, and

                     3) natural killer, or NK, cells.

• B and T lymphocytes differentiate from their respective

lymphoid precursor cells and

• leave the bone marrow in a kind of cellular stasis-not

actively replicating like other somatic cells .

• These cells are said to be naive.

 T- lymphocytes or T cells

• Lymphocytes destined to become T lymphocytes or T cells leave the bone marrow and

mature in the thymus gland.

• They can remain in the thymus, circulate in the blood, or reside in lymphoid organs such as the lymph nodes and spleen.
• Naïve T cells require a specific antigen to bind to a specific, membrane bound receptor (the T-cell receptor) to signal the continuation of replication.
• The now "activated" T cells differentiate into effector cells and memory cells.

     1. EffectorT cells include the

• T-helper cells (TH) ,
• cytotoxic lymphocytes (CTLs),
• natural killer T cells, or
• T-regulatory cells,
• that respond to a myriad of antigens by producing and secreting cytokines .
• The cytokines secreted from effector T cells control specific responses directing theactions of other host cells.

     2. Memory cells are quiescent, only to become activated T cells upon a subsequentexposure to the antigen.

• They provide a faster, heightened response.

B lymphocytes or B cells

• After B lymphocytes or B cells reach maturity within the bone marrow,
• they also circulate in the blood and
• disperse into various lymphoid organs where they await to become activated.
• The activated B cell becomes more ovoid.
• Its nuclear chromatin condenses, and numerous folds of endoplasmic reticulum become more visible.
• A mature, activated B cell is called a plasma cell.
• Plasma cells secrete large quantities of antibodies .
• Activated B cells also produce memory cells that are primed to act upon subsequent exposure to antigen

Natural killer (NK) cells

• Natural killer (NK) cells are a small population of large,

non phagocytic granular lymphocytes that play an important role in innate immunity.

• The major NK cell function is to attack and destroy
• malignant cells and
• cells infected with microorganisms, such as viruses and intracellular bacteria;
• however, NK cells do not recognize antigen.
• They recognize their targets in one of two ways
• First, NK cells survey somatic cells for a specific membrane-bound protein,known as the class I major histocompatibility complex (MHC) protein.

• Normal healthy host cells express class I MHC proteins on the cell surface, andNK cells bear a receptor that recognizes MHC class I.

• When NK cells encounter host cells with altered or missing class I MHC proteins, as sometimes happens during intracellular infection and oncogenesis, the aberrant cells are destroyed.
• NK cells also recognize and eliminate infected and malignant cells, expressing what are called stress, or shock, proteins on their surface.

• Finally, because NK cells have receptors for antibodies, they can also attack cells that are opsonized by antibodies. This process is called antibody dependent cell-mediated cytotoxicity (ADCC) and causes the death of the target cell.

• In all cases, attack by the NK cell results in the release of

pore-forming, perforin proteins and enzymes called granzymes.

• Together the perforins and granzymes induce target cell to commit suicide (apoptosis) .

• Unlike T and B cells, NK cells do not exhibit memory responses to target cells, thus they are considered part of the innate immune response.

GRANULOCYTES,types of granulocytes

 

  granulocytes

• Granulocytes have irregularly shaped nuclei with two to five lobes.
• Their cytoplasm has granules that contain reactive substances that kill microorganisms and enhance inflammation.

  Three types of granulocytes exist:   1. Basophils                                                                                   

                                                            2.Eosinophil

                        

                                                            3. Neutrophils 

1. Basophils  

•        Basophils (Greek basis, base, and philein, to love) have irregularly shaped nuclei with two lobes.
• The granules contain histamine and other substances similar to those in mast cells.
• However, basophils arise from a different cellular lineage
• basophils tend to infiltrate specific tissue sites rather than circulate through the bloodstream.
• Basophils are also important in the development of allergies and hypersensitivities

 2.Eosinophil

• Eosinophils have a two lobed nucleus connected by a slender thread of chromatin.
• Eosinophil granules contain hydrolytic enzymes (nucleases,

glucuronidases, and peroxidases), and major basic protein.

• It circulate in low numbers and migrate from the bloodstream into tissue spaces, especially mucous membranes, when recruited by soluble chemotactic mediators.
• They are important in the defense against protozoan and helminth parasites, mainly by releasing enzymes, cationic peptides and reactive oxygen species into the extracellular fluid.
• These molecules damage the parasite's plasma membrane, killing it.
• Eosinophils also play a role in allergic reactions, as they have granules that contain histaminase and aryl sulphatase, down regulators of the inflammatory mediators histamine and leukotrienes, respectively.
• Thus their numbers circulating in the bloodstream often increase during

allergic reactions, especially type l hypersensitivities

 3.Neutrophils 

• Neutrophils are highly PHAgocytic cells with a nucleus that has

three to five lobes connected by slender threads of chromatin .

• Because of the irregularly shaped nuclei, neutrophils are also called

polymorphonuclear neutrophils, or PMNs.

• Neutrophils have inconspicuous organelles known as primary and secondary granules.
• Primary granules contain peroxidase, lysozyme, defensins, and various hydrolytic
• enzymes
• secondary granules have collagenase, lactoferrin, cathelicidins, and lysozyme. 
• These enzymes and other molecules help digest foreign material after it is phagocytosed.
• Neutrophils also use oxygen-dependent and oxygen-independent Pathways that generate additional antimicrobial substances to kill ingested microorganisms.
• Mature neutrophils leave the bone marrow and circulate in blood so they can rapidly migrate to a site of tissue damage and infection, where they become the principal phagocytic and microbicidal responders.
• Neutrophils have toll-like pattern recognition receptors (PRRs), as well as receptors for antibodies and complement proteins, so that PAMPs and opsonize particles,respectively, can be more readily phagocytosed.
• PRRs bind to specific patterns that characterize microbial macromolecules and that their binding upregulates transcription pathways for phagocytosis
• Neutrophils have a limited life span that shotens upon activation of the phagocytic
• processes.

Physical and chemical barrier .Defence of innate resistance

     - potential microbial pathogen invading a human host immediately confronts a vast array of innate defense mechanisms.

     -  Although the effectiveness of an individual mechanism may not be great, collectively they are formidable.

         Many direct factors (age, nutrition, physiology, fever, genetics) and indirect factors (personal hygiene, socioeconomic status, living condition) contribute in some degree to all host-microbe relationships.

- At times, they favor the establishment of the microorganism; at other times, they provide the host some measure of general defense.

 Physical and mechanical barriers along with host secretions are the host's first line of defense against pathogens. e.g.,

1. Skin

2. Mucous membranes

3. Epithelia of the respiratory

4. Gastrointestinal, and

5. Genitourinary systems

1. SKIN

- Intact skin contributes greatly to innate host resistance because it is a

very effective mechanical barrier to microbial invasion.

- Its outer LAyer consists of thick, closely packed cells called Keratinocytes, which produce Keratins- Scleraproteins (insoluble proteins) that are the main components of hair, nails, and the outer skin cells.

- These outer skin cells shed continuously, removing microorganisms that manage to adhere to their surface.

- The skin is slightly acidic (around pH 5 to 6) due to sebum, secretions from sweat glands, and organic acids produced by commensal staphylococci & high concentration of sodium chloride and is subject toperiodic drying.

2. MUCOUS MEMBRANES

- The mucous membranes of the eye (conjunctiva) and the respiratory, digestive, and urogenital systems withstand microbial invasion because the intact stratified epithelium and mucus form a protective covering that resists penetration and traps microorganisms.

- Many mucosal surfaces are bathed in specific antimicrobial secretions. For example, cervical mucus, prostatic fluid, and tears are toxic to many bacteria.

- The conjunctiva that lines the interior surface of each eyelid and the expose surface of the eyeball is a good example of how a mucous membrane functions to provide chemical as well as physical protection from microorganisms.

- It is kept moist by the continuous flushing action of tears from the lacrimal glands.

- Tears contain large amounts of lysozyme, lactoferrin, and other antimicrobial chemicals.

Lysozyme:

lyses bacteria by hydrolyzing the β(1-4) bond connecting N-acetylmuramic acid(NAG) and N-acetylglucosamine

(NAM) of the bacterial cell wall peptidoglycan especially inGram-positive bacteria.

Lactoferrin:

- Tears and other mucous secretions also contain significant amounts of the iron-binding protein lactoferrin.

- Lactoferrin is released by activated phagocytic cells called macrophages and polymorphonuclearleukocytes (PMNs).

- It sequesters iron from the blood plasma, reducing the amount of iron available to invading microbial pathogens thereby limiting their ability to multiply.

Lactoperoxidase:

- mucous membranes produce lactoperoxidase,

- catalyzes the production of superoxide radicals, a reactive oxygen species that is toxic to many microorganisms.

3. Respiratory System

- The average person inhales at least eight microorganisms a minute, or 10,000 each day.

- Once inhaled, microorganism must first survive and penetrate the air- filtration system of the upper and lower respiratory tracts.

- Airflow in these tracts is very turbulent, microorganisms are deposited on the moist, sticky mucosal surfaces. Microbes lArger tHAn 10 µm usually are trapped by hairs and cilia lining the nasal cavity.

- The cilia in the nasal cavity beat toward the pharynx, so that mucus with its trapped microorganisms is moved toward the mouth to be expelled

 - Humidification of the air within the nasal cavity causes many microorganisms to swell, and this aids phagocytosis.

- Microbes sMAller THAn 10 µm (i.e., most bacterial cells) pass through nasal cavity and trapped by the mucociliary blanket that coats the mucosal surfaces of lower respiratory system.

- The trapped microbes are transported by ciliary action the

mucociliary escalator-that moves them away from the lungs.

- Coughing and sneezing reflexes clear the respiratory system of microorganisms by expelling air forcefully from the lungs through the mouth and nose, respectively.

- SAlivAtion also washes microorganisms from the mouth and nasopharyngeal areas into the stomach.

- Microorganisms that succeed in reaching the alveoli of the lungs encounter a population of specialized cells called alveolar macrophages that ingest and kill most inhaled microorganisms by phagocytosis.

4. Gastrointestinal Tract

- Most microorganisms that reach the stomach are killed by the acidic gastric juice (pH 2-3): mixture of

hydrochloric acid + proteolytic enzymes + mucus.

- However, some microorganisms and their products

(e.g., protozoan cysts, HeliCOBACTER pylori, Clostridium spp., and staphylococcal toxins) can survive the stomach acidity.

- Organisms embedded in food particles may be protected from gastric juice and reach the small intestine and damaged by pancreatic enzymes, bile, enzymes in intestinal secretions, and the GALT( Gut associated lymphoid tissue) system.

  Peristalsis and the normal shedding of columnar epithelial cells act in concert to purge intestinal microorganisms.

- In addition, the normal micro biota of large intestine is extremely important in preventing the establishment of pathogenic organisms.

- E.g., metabolic products (e.g., fatty acids) of many normal microbiota in the intestinal tract prevent unwanted microorganisms from becoming established.

- Other normal microbiota outcompete potential pathogens for attachment sites and nutrients.

-       The mucous membranes of the intestinal tract contain cells called Paneth cells - produce lysozyme , peptides called cryptidins- are toxic for some bacteria, as they form membrane channels that result in cell lysis.

5. Genitourinary Tract

- Kidneys, ureters, and urinary bladder of mammals are sterile in normal condition.

- Urine within the urinary bladder also is sterile.

- However, in both males and females, a few bacteria are usually

present in the distal portion of the urethra.

- The factors responsible for this sterility are complex. In addition to removing microbes by flushing action, urine kills some bacteria due to its low pH and the presence of urea and other metabolic end products (e.g., uric acid, fatty acids, mucin, enzymes).

- Portions of the kidney are so hypertonic that few organisms can

survive there.

- In males, the anatomical length of the urethra (20 cm) provides distance barrier that excludes microorganisms from the urinary bladder.

- In females, short urethra (5 cm) is more readily traversed by

microorganisms;

- This explains why urinary tract infections are 14 times more

common in females than in males.

- The vagina has another unique defense.

- Under the influence of ESTROGENS,

- Vaginal epithelium produces increased amounts of glycogen that is degrade to form lactic acid by acid- tolerant LACTOBACIllus ACIdophilus bacteria.

- Normal vaginal secretions contain up to 108 of these bacteria per ml.

- Thus an acidic environment (pH 3-5) unfavorable to most other organisms for establishment.

- Cervical mucus also has some antibacterial activity.

Innate resistance overview & immunity,immunity meaning,what is immunity,humoral immunity,herd immunity

       To establish an infection, an invading microorganism must first overcome many surface barriers, such as

 - skin, degradative enzymes, and mucus,

 - that have either direct antimicrobial activity or 

 - inhibit attachment of the microorganism to the host.

 - Because neither the surface of the skin nor the mucus- lined body cavities are ideal environments for the vast majority of microorganisms, 

 -  Most pathogens, or disease-causing microorganisms, must breach these barriers and reach underlying tissues to cause disease.

         However, any microorganism that penetrates these barriers encounters two levels of host defenses:

1. Innate resistance mechanisms and
2. Adaptive immune response.

- Animals (including humans) are continuously exposed to microorganisms that can cause disease.

- Fortunately animals are equipped with an immune system that usually protects against adverse consequences of this exposure.

- The immune system is composed of widely distributed proteins, cells, tissues, and organs that recognize foreign substances, including microorganisms.

- Together they act to neutralize or destroy them, maintaining host integrity.

            

                 immunity

           Immunity: (Latin immunis, free of burden) refers to the general ability of a host to resist infection or disease.

- Immunology is the science focused on immune responses to foreign substances and how these responses are used to resist infection.

- It includes the distinction between "self" and "nonself" and all the biological, chemical, physiological, metabolic, and physical aspects of the immune response.

- There are two fundamentally different yet complementary components of the mammalian immune response.

1. The first component arises by virtue of being a vertebrate animal.Vertebrates have evolved to express unique features that inherently protect against invasion by foreign substances. Some of these features are physical and act as barriers.

2. chemical in nature and directly kill or inhibit invaders.

- Still other features result when specialized cells recognize generic yet highly conserved chemical motifs (expressed on bacteria, fungi, and viruses) and initiate processes to engulf and degrade the foreign substance.

- These features are collectively called the innate resistance

mechanisms.

- The second component of the mammalian immune response is much more sophisticated, being directed by highly specialized cells that can respond to specific invaders through

- receptor-mediated capture events,

- be programmed to "remember" their encounters with foreign substances,

- amplify individual responses, recruiting other components of the host immune system to eliminate or reduce the threat posed by the invader.

Innate resistance mechanisms, also known as

- nonspecific resistance and

- innate, nonspecific, or

- natural immunity,

- is the first line of defense against any foreign material, including microorganisms, encountered by the host.

- It includes general mechanisms inherited as part of the innate structure and function of each animal (such as skin, mucus, and constitutively produced antimicrobial chemicals such as lysozyme).

- Innate resistance mechanisms defend against foreign invaders equally and to the same maximal extent each time a foreign invader is encountered.

Adaptive immune response, also known as

- Acquired or

- Specific immunity, defends against a particular foreign agent.

- The effectiveness of adaptive immune responses increases on repeated exposure to foreign agents such as viruses, bacteria, or toxins; that is to say, adaptive responses have "MEMORY.

- ANTIGEN: Substances recognized as foreign that provoke immune responses

Also known as immunogens (immunity generators).

- The presence of foreign antigens causes specific cells to replicate and manufacture a variety of proteins that function to protect the host. One such cell, the B cell, produces and secretes glycoproteins called ANTIBODIES.

- Antibodies bind to specific antigens and inactivate them or contribute to their

elimination.

- Other immune cells become activated to destroy host cells harboring intracellular  destroy host cells harboring intracellular pathogens, such as viruses.

- Innate resistance mechanisms and the adaptive immune responses work

together to eliminate pathogenic microorganisms and other foreign materials.

 -innate systems react immediately upon initial exposure to foreign

substances,

- multiple bridges occur between the two immune system components .

- variety of cells function in both innate and adaptive immunity, These cells are known as the white blood cells, or leukocytes.

- White Blood cell development occurs in the bone marrow of mammals during the process of hematopoiesis.

- Leukocytes function in the innate system, whereas others are part of a specific immune response.

- Some are important because they link the innate arm of the immune system to the adaptive.

- The leukocytes form the basis for immune responses to invading microbes and foreign substances. Many of these cells reside in specialized tissues and organs. Some tissues and organs provide supportive functions in nurturing the cells so that they can mature and respond correctly to antigens.