The Body's Defense Systems

• Disease-causing microorganisms like viruses, bacteria, fungi, and parasites, as well as other toxic substances constantly threaten the body.
• The body employs multiple lines of defense to counter these threats.

First Lines of Defense

• The skin and mucous membranes act as physical barriers preventing harmful substances from entering.
• Skin's epidermis consists of tightly bound cells impenetrable to microorganisms unless injured.
• Mucosae are easier to breach than skin, but structural and physiologic factors help prevent microorganism entry.
• Mucus protects mucosal surfaces of the respiratory, digestive, and genitourinary tracts.
• Cilia in some epithelial cells help move and eliminate toxic substances.
• Tears and saliva contain antibacterial substances, including lysozymes, that fight off pathogenic microorganisms.

When First Line of Defense Fails

• The body unleashes an army of cells, triggering two defense systems: inflammatory response and immune response.

Inflammatory Response (Non-Immune Response; Inflammation)

• Immediate, localized process starting within minutes of tissue damage or entry of a microorganism or foreign antigen.
• Effector cells primarily include phagocytes (neutrophils and macrophages).
• Other cells assisting phagocytes include eosinophils, basophils, mast cells, NK cells, and T-cells.
• The cells destroy invading organisms and foreign antigens destroy organisms through phagocytosis or by releasing toxic substances.
• Chemical mediators are released that attract or facilitate the entry of phagocytes and other cells into the injured area.
• The inflammatory response is triggered in various ways, including invading microorganisms producing chemotaxins that attract phagocytes, or detection of foreign organisms by the complement system.
• The complement system consists of over 20 plasma proteins produced by the liver that form an enzyme cascade.
• It is involved in both inflammatory and immune responses.
• In inflammation, the complement system gets spontaneously activated in the presence of microorganisms or foreign substances.
• Activation of the complement system during inflammation leads to the production of chemotaxins, marking of bacteria for phagocytosis, and releasing cytokines.
• Activated phagocytes (neutrophils and macrophages) gather in the injured area within minutes.
• They engulf and digest invading microorganisms or other foreign elements.
• They also release cytokines and chemical mediators to attract and activate other cells.
• Antigen-presenting cells (APCs) with limited phagocytic activity process the antigens they have digested.
• APCs attach antigen parts on their surface for presentation to T-cells, the first step in the immune response.
• Effector cells can initiate a primary immune response, which is then turned on almost simultaneously with the inflammatory response.
• If the threat is not eliminated by the inflammatory response, the immune response takes over.
• Cytokines and other mediators cause swelling, redness, heat, and pain.
• Interleukin-1, a cytokine produced by activated macrophages, can cause fever by entering the bloodstream and affecting the hypothalamus.
• The hypothalamus responds by increasing body temperature.

Immune Response (Immunological Response)

• More powerful than the inflammatory response.
• Mounting a new antigen takes more time than inflammation because it is not innate and must be developed.
• It is antigen-specific, meaning it must be developed for every foreign substance.

Antigens Vary in Size and Composition

• From amino acids to large antigenic systems (bacteria, viruses, fungi, parasites, and toxins).
• Lymphocytes are the primary effector cells, supported by a variety of other cells.
• The body contains about two trillion lymphocytes, capable of conferring immunity against as many as 10 to the 7th power different antigens.
• Lymphocytes are classified into three types based on their antigen receptors.
• B-cells have B-cell antigen receptors (BCR).
• T-cells carry T-cell antigen receptors (TCR).
• NK cells carry natural cytotoxicity receptors (NCR).
• Lymphocytes have other surface markers or receptors, including the CD3 molecular complex on all T-cells for signal transmission via the T-cell receptor (TCR).
• T-cells have either CD4 or CD8 markers.
• CD4 markers (CD4+ T-cells) differentiate into helper T-cells (Th cells).
• CD8 markers (CD8+ T-cells) differentiate into cytotoxic or suppressor T-cells.
• NK cells are CD3-positive as well.

Two Types of Immune Responses

• Humoral and cell-mediated, each conferring humoral immunity and cell-mediated immunity, respectively.
• Both types are activated as soon as an antigen enters the body.
• One type predominates, depending on the nature of the antigen.

Humoral Immunity (Antibody-Mediated Immunity; AMI)

• Mediated by antibodies, which are substances synthesized by plasma cells.
• Primarily the function of B-cells.
• Antibodies bind to antigens, triggering their production, and neutralize or eliminate them.
• Some pathogens have molecules to enter cells, which are then Parasitized.
• Antibodies bind with these molecules to prevent the pathogen from invading the cells.
• Antibody attachment immobilizes bacteria and protozoans.
• Antibodies pinpoint antigens to phagocytes.
• Phagocytes then phagocytose the pathogens, facilitated by the complement system.
• Humoral immunity is important in containing viral and bacterial infections.
• Immunity conferred by vaccines is also this type.

Cell-Mediated Immunity (CMI)

• Not mediated by antibodies.
• Primarily the function of T-cells.
• Effector cells are mainly cytotoxic T-cells (Tc cells).
• T cells eliminate antigens inside cells and protect cells from antibodies, especially virus-infected cells and cells with intracellular bacteria.
• T-cells destroy cells harboring microorganisms, cancer cells, and foreign cells.
• T cells can destroy target cells by inducing apoptosis, releasing proteins from cytoplasmic granules.
• Cellular immunity is also responsible for delayed hypersensitivity reactions and tissue/organ transplant rejection.

Development of an Immune Response

• Entry of a new antigen elicits a primary immune response.
• Subsequent entries elicit a secondary response.
• Primary Immune Response: designed to eliminate the new antigen and produce memory lymphocytes.
• It has a long induction phase (several days to weeks), involving multiple cell types.
• The primary immune response steps: antigen recognition, lymphocyte activation, and effector phase.

Antigen Recognition

• APCs present antigens on their surface for CD4+ T-cells.
• Naive CD4+ T cells (mature cells from bone marrow) only differentiate into T-cells when presented an antigen by an APC.
• B-cells do not react unless activated by cytokines produced by helper T-cells (Th cells).
• Naive CD8+ T-cells do not differentiate into Tc cells unless activated by APCs or helper T-cells (Th cells).
• Endothelial and NK cells can present antigens to T-cells.
• Professional APCs deliver two signals: antigen and co-stimulatory needed to activate CD4+ T-cells, including macrophages, dendritic cells, and B-cells.
• Macrophages are effector cells that engulf antigens by phagocytosis, process them, and attach fragments on their surface for presentation to T-cells.
• Dendritic Cells (DCs): APCs with branched projections from lymphoid and other tissues.
• They are the most potent of the APCs with a limited capacity for phagocytosis, but attach antigenic materials to surfaces for naive CD4+ T-cells.
• Two categories of DCs: Myeloid-related (mDC) and lymphoid-related (pDC).
• Langerhans cells in the epidermis are examples of mDCs.
• Lymphoid-related DCs are found in lymphoid tissues, and likely share a lineage with lymphocytes.
• B-cells can act as APCs when antigens bind to their receptors, when they release cytokines, and by phagocytosing, processing, and attaching parts of the antigen to the surface.
• Despite presenting the antigen a naive B-cell won't get activated it it interacts and receives a signal from a T cell.

Lymphocyte Stimulation

• Naive CD4+ T-cells proliferate and differentiate into various cell types when presented antigens by APCs with co-stimulators.
• They become T cells that synthesize necessary cytokines for cell-mediated immunity, for humoral immunity, and for inflammatory processes.

Effector Phase

• T cells in humoral immunity encounter naive B-cells with the same new antigen, interact, and release cytokines to activate the B-cells.
• Activated B-cells proliferate, and plasma cells then differentiate and produce antibodies.
• Memory B-cells carry the antigen image and effect secondary immune responses.
• Some antigens are T-cell independent and activate naive B-cells on their own.
• In cellular immunity, T-cells secrete cytokines to stimulate CD8+ T-cells to proliferate.
• After proliferation, CD8+ T-cells differentiate into cytotoxic T-cells (Tc cells), memory T-cells, and suppressor T-cells.
• T cells are effector cells of cellular immunity.
• Memory T-cells, like memory B-cells, effect secondary immune responses.
• Sometimes a primary cellular immune response can be brought about without the help of T cells, as antigens are directly presented by APCs to CD8+ T-cells.
• Suppressor T-cells (Ts cells) regulate activity of B-cells and other T-cells.
• Once the offending antigen has been eradicated, remaining antigenic-specific cells, except memory cells, undergo apoptosis.

Secondary Immune Response

• Re-exposure to an antigen elicits it
• It has a short induction phase.
• Memory B-cells or T-cells remember the specific antigen encounter, allowing rapid division and differentiation into effector cells.
• The response is so effective that the pathogenic microorganisms are eliminated before the person manifests any symptoms.
• As in the primary response, antigenic-specific cells apoptose, except for memory cells, once the offending antigen in the secondary immune response has been eradicated.

Abnormal Immune Responses

• the immune response is vital to survival but it sometimes goes awry.
• Overwhelming reaction causes allergic reactions which are occasionally fatal.
• The immune defense system can sometimes fails to distinguish between self and non-self antigens, leading to autoimmune diseases.

Components of the Lymphoid System

• Lymphoid tissues and organs concerned with the immune response.
• Lymphoid tissue is where the parenchyma consists mainly of lymphocytes
• Lymphoid organs refer to organs that are primarily made up of lymphoid tissue.
• The stroma of lymphoid tissues and organs (except the thymus) consists of reticular fibers and cells.
• Lymphoid tissues and organs are classified into central (primary) and peripheral (secondary) types.
• Central Lymphoid Organs: bone marrow and thymus
• Peripheral Lymphoid Tissues: Lymph nodes, spleen and mucosa-associated lymphoid tissue (MALT)

Central Lymphoid Organs

• The bone marrow and the thymus where stem cells transform into mature and immunocompetent, but naive, lymphocytes.
• They are released through the blood or lymph into peripheral tissue.
• Mucosa-associated Lymphoid Tissue (MALT): the tonsils and other non-encapsulated lymphoid tissues in the gastrointestinal, respiratory, and genitourinary tracts.
• Peripheral Lymphoid Tissues: Are responsible for immune responses and generating lymphocytes that participate in these responses.

Lymphoid Tissue

• Exists in diffuse or nodular forms

Diffuse Lymphoid Tissue

• When lymphocytes are evenly dispersed and is a part of not only lymphoid organs but also of most connective tissue.
• Especially prominent in the lamina propria and submucosa of the gastrointestinal, respiratory, and genitourinary tracts.
• T-cells comprise most of the cells in diffuse lymphoid tissue, though there is also a small amount of B-cells, plasma cells, and dendritic cells.
• Is loose when lymphocytes are few and far apart
• Is dense where lymphocytes are numerous and close.

Nodular Lymphoid Tissue

• (Lymphoid nodule; Lymphoid follicle; Lymphatic follicle)
• Lymphoid tissue where clustered lymphocytes form masses called lymphoid nodules.
• Lymphocytes are mainly B-cells.
• A scattering of T cells, dendritic cells, and macrophages are also present.
• Lymphoid nodules begin only at birth.
• Nodules are interspersed in areas of dense, diffuse lymphoid tissue.
• Nodules are typically found in some lymphoid organs (spleen and lymph nodes) and in the lamina propria and submucosa of the gastrointestinal, respiratory, and genitourinary tracts.
• Nodules can occur singly or in aggregates, as in Peyer's patches in the ileum.
• Two Types of Lymphoid Nodules: Primary and Secondary

Secondary Nodule

• Lymphocytes react to an antigen
• Regions: Germinal Center and Corona
• Germinal Center (Reaction Center): central area which is a pale central area populated mainly by activated B – cells.
• Following exposure to an antigen, the cells undergo proliferation and functional differentiation.
• Corona: darker peripheral region contains younger lymphocytes that are actively dividing; larger and have more abundant cytoplasm
• Older lymphocytes are pushed to the periphery as new cells are produced in the germinal center.

Primary Nodule

• Lymphocytes in the nodule area are idle or resting.
• They do not have a germinal center.

Thymus

• Derived from the third branchial (pharyngeal pouch).
• Moves caudally during development and ends up in the superior mediastinum.
• At birth, weighs 10-35 g.
• Size increases during childhood.
• Attains its maximum weight (30-50 g) at puberty.
• Then gradually involutes to connective tissue among the elderly.
• Thymus involutes in individuals under stress, illness, or radiation.
• This involution may be followed by an almost complete regeneration.
• Transforms T stem cells into mature, competent, and self-tolerant, albeit naïve, T cells.
• Produces cytokines that regulate T cell function in thymus and other lymphoid tissues/organs.
• T lymphocytes populate the thymus.

Histologic Organization of the Thymus

• The adult thymus is composed of two pyramidal lobes fused together.

• Each of the two lobes of the thymus is enclosed by a capsule, a dense irregular connective tissue.

• The trabeculae divide the lobes incompletely into lobules of unequal sizes

• Thin strands of connective tissue from the trabeculae form secondary septa within the gland.

• A thymic lobule exhibits a peripheral, darker-staining region (cortex) that surrounds a central lighter (medulla) in LM preparation.

• the Cortex is darker than the medulla because its cells are more numerous and closely packed to each other.

• The trabeculae don't extend deep enough to separate the medulla of adjacent lobules, which interconect.

• Thymic lobules' stroma unlike that of other lymphoid tissues because it is mainly of stellate epitheloid cells (epithelial reticular cells), and a few connective cells.

• Epithelloid cells resemble the reticular cells but arise from endoderm and do not produce reticular fibers; have cytoplasmic processes joined by desmosomes.

• Epithelloid cells produce most of the thymic cytokines, likewise thymocytes also produce cytokines

• Some epitheloid cells (nurse cells) envelop multiple young lymphocytes.

• Nurse cells promote proliferation and differentiation of lymphocytes.

• New T stem cells that settle in the peripheral part of the cortex outer cortex transform into lymphoblasts and proliferate

• they mature and move towards the medulla.

• When they reach the medulla, they are mostly small lymphocytes.

• their stay in the cortex, the T-cells acquire their receptors.

• Those that are unable to do so die by apoptosis and are devoured by macrophages.

• In the medulla, the small lymphocytes aren't as numerous as in the cortex.

• APCs (thymic interdigitating dendritic cells are among the parenchymal cells in the medulla

• these cells prevent autoimmunity by presenting self-antigens to enable the T-cells to recognize "self" antigens.

• T-cells, that react with the antigens, are induced to undergo apoptosis, and their remnants are phagocytosed by macrophages.

• Only 10-30% of lymphoctytes survive and leave the thymus as mature, immunocompetent, and "self-tolerant", albeit naive, T-cells.

• Mature T-cells join enter blood or lymphatic vessels in the thymic medulla.

• Some T-cells go to the spleen before going to the blood.

Blood Vessels of the Thymus

• A rich blood supply comes from branches of the internal thoracic, anterior intercostal, and inferior thyroid arteries.
• Arteries ramify and travel within the trabeculae and septa.
• At the corticomedullary boundary, the arteries give off capillaries that supply the cortex while main arterial branches continue into the medulla and break up.
• In the cortex, capillaries anastomose, are drained by postcapillary venules; they unite proceed to the medulla where they unite with the postcapillary venules that drain the medullary capillaries to form bigger venules.

Blood-Thymus Barrier

• Cortical capillaries are closely related with the epitheloid cells

• It prevents antigens in the capillaries from contacting T-cells.

• It consists of:

• continuous Endothelial cells

• Their thick basal lamina;

• epitheloid cells and sheet with the help of desmosomes to adjacent cells.

• Perivascular space isolates the endothelium from the epitheloid cells.

• Medulla of the thymus: No blood-thymus barrier, for that T-cells are simply simply phagocytose the antigens who enter the area

• There are no afferent lymphatic vessels, and lymph collected by efferent capillaries starts as blind tubes.

• The lymphatic capillaries unite to form progressively bigger vessels (that follow the veins through the capsule)

Lymph Node

• A bean-shaped organ that is an encapsulated collection of lymphoid tissue.
• There are 500 to 600 nodes in the body
• Nodes are positioned along lymphatic vessels and depend on their location
• They are important for lymphocytes and various functional types.
• They are filters for matter and microorganisms present in the lymph.

Macrophages filter through lymph

• These organs' placement is strategically in many parts of the body.
• They are present in the axillary region side of the neck along the neck along the abdominal vessels etc.
• Nodes become swollen and tender when an infection is present.
• A node has an indented area called the hilus.
• Efferent and blood vessels leave and enter the organ there.
• Afferent lymph channels enter the node on its convex surface.

Histologic Organization of the Lymph Node

• Lymph node is encased by a capsule, a dense irregular connective structure that gives off the incomplete that creates a reticular stroma.

• Lymph node parenchyma is divided into the cortex.

• Indistinct boundary between the cortex and medulla.

• The outer layer is mainly lymphoid nodules by dense tissue whereas the inner contains no nodules and consists of lymphocytes.

• The interdigitating dendritic cells are in the T-cell-rich areas (deep cortex) exhibit nuclei and interdigitate.

• The medulla is lighter-staining and is arranged to form call medullary cords and sinuses.

• B-cells and plasma cells is what the cords consist of.

Lymphatic Vessels of the Lymph Node

• Vessels ramifiy and give smaller branches enter te convex surface.
• Afferent lymphatic vessels are provided with one-way backflow valves.
• The subcapsular are right undeneath the capsule that connect in travecular.
• Travecular-Carry into medullary sinuses and the several efferent channels.

Blood Vessles of the lymph node

• Blood eneters, the trabecular supplies both the cords and the medulla, forms capillary.
• This blood-lymphocyte interaction ensures interaction.
• Lymph leave to recirculatory pool.

Spleen

• The largest (7 cm x 12 cm) lymphoid organ in the body.
• located in upper quadrant near the stomach.
• Like the lymph nodes, is an important part of the body's immune defense system.
• The organ that the lymphocytes differentiate in when activated by bloody antigens
• Is also filtered.
• Destroys and collects foreign substances.
• old red blood cells and platelets are destroyed
• acts as a storage area

Hystrilic Org

• Not vital and adult removes the organs that are more susceptible
• the capsule contains layers of tissue
• The tissues contains ligaments.

Parechyma of the Spleen

(splenic pulp)

• Contains the white pulp and forms a bulk

• White- Lymphoid nodules

• Dence tissue, which functions to sleeves the vessels.

• Red pulp

• Contains cords for reticular fluid.

• blood accounted for

Blood Vsseels of the spleen

• supplied by celia

• divided the hilus.

• arities are formed by tissue

• At the boundary the main arities get branches.

• A small muscular artery that is not connective.

Lymph vessels of the spleen

• spleen has no vessels (efferent vessels, capillaries) unitive and the blood flows

Lymphoid

• MALT

• Consists of loose tissue

• BALT

• forms in lymph

MALTs generates antibodies

Tonsils

• Forms a ring

• Paired are covered in a capsule.

• pharynegeal

Respiratory system

• Human utilze o2 to procress the metabolic activities.

• O2 deivers carbon from the cells

• to deliver o2 and from blood.

• In blood and inahaled

• Internal reps in tissues

• fucntiion the system only.

Component Organs

consists.

• paired to transfer lungs the lungs

• Nose

• hoolow with two spaces

• anterior and postier

• nasals

Respiratory

• Ciliated epith that lies with the portion, system.

• The epithelim that rest on the basal laminar:

• clilitated columner that is the most abundant.

• the epithemlial brush

• Small celles that are fimilat to nuero celss.

• the top of the ribinate refwffered.

• Olfactiorily

ParaNasal Snusis

• which are named according which are bone, bone
• which contian few glands
• Direction celss

Pharynx

• which consist of the esophougs.

• conssts

Larynx

• three and tree

trechea

• walls four sall
• elastic and mait nod

Lungs

• luns
• thracic
• vessle linin

The vessels the bronchial or directly the area aorta