CH. 21: The Immune System Flashcards
What is the lymphatic system?
An extensive network of one-way lymphatic vessels, lymphatic tissues and organs
What is the function of the lymphatic system?
Return of excess fluid (3 liters/day)
Defense against disease using lymphocytes at the lymph nodes
Transportation of absorbed fats by lymphatics moving filtered proteins to the venous fluids (too big for capillaries)
Return of filtered proteins because filtered proteins cannot return back into the capillaries so they are returned through the venous fluids via lymphatics
No unique functions of its own (has to work with other systems)
What are lymph and its components?
An interstitial fluid that moves into lymphatic capillaries due to pressure gradient during the capillary exchange
-15% of fluid does not get reabsorbed back into the capillaries
-Blood is not returned as much as it was filtered out, so it goes through the lymphatic vessels
Components:
-Water & dissolved solutes
-Few proteins
-Foreign materials (cellular debris, pathogens, metastasized cancer cells)
What are lymphatic capillaries and its components?
Are initial lymphatics located at the terminal end of the lymphatic system
Components:
-Blind-ended
-Intertwined with the capillary bed
-Interspersed throughout areolar connective tissue except in red bone marrow and CNS
-Absent in avascular tissue
What is the structure of lymphatic capillaries?
Larger than capillaries
Lack of a basement membrane
Possess free-edged overlapping endothelial cells serving as one-way mini valves to allow fluid into the capillary
Anchoring filaments hold the endothelial cells in place to prevent lymphatics from collapsing due to excessive interstitial fluid hydrostatic pressure (HPif)
What happens when you move lymph into lymphatics?
The pressure drives function where interstitial fluid hydrostatic pressure (HPif) forces fluid between endothelial cells, and internal hydrostatic pressure forces endothelial cells together preventing fluid outflow to ECF
Escaped proteins, cellular debris, & pathogens are shunted to lymphatics because the openings are larger than capillary pores (following the direction of bulk flow)
What are lymphatic vessels and their components?
Vessels that are formed by the convergence of the lymphatic capillaries
Superficial lymphatics are adjacent to superficial veins, and deep lymphatic vessels are adjacent to both deep arteries and veins
Posses all 3 vessel tunics and one-way valves
Lacks a pump so it relies on the skeletal and respiratory pump to drive pulsatile movement of blood in nearby arteries. The rhythmic contraction of lymphatic smooth muscle also helps with lymph flow
What are lymphatic trunks and their components?
They form the union of lymphatic vessels and are named for the region of the body from which they collect lymph
Paired Trunks (right & left)
-Jugular: head and neck
-Subclavian: upper limbs, breasts, & superficial thoracic wall
-Bronchomediastinal: deep thoracic structures
-Lumbar: lower limbs, pelvis, and abdominopelvic wall
Unpaired Trunks
-Intestinal: most abdominal structures
What are lymphatic ducts and their components?
They are where lymph empties into the venous circulation
Consists of right lymphatic duct and thoracic duct
What are the components of the thoracic duct?
Larger of the two ducts and is responsible for the rest of the body extending from the left subclavian and jugular veins and consist of the cisterna chyli at the end of the duct
Cisterna Chyli
-Receives from vessels that drain the small intestine, intestinal trunk, and from lumbar trunk
-Lipid-rich lymph (chyle)
What are primary lymphatic structures?
Involved in the formation and maturation of lymphocytes
Includes the red bone marrow and thymus
What are secondary lymphatic structures?
House lymphocytes and other immune cells following their formation
Provide the site where an immune response is initiated
Includes the lymph nodes, spleen, tonsils, lymphatic nodules, and MALT
What are red bone marrow and its components?
They are found in between trabeculae in selected portions of spongy bone
In adults, it includes flat bones of the skull, vertebrae, ribs, sternum, ossa coxae, and proximal epiphysis of the humerus & femur
Responsible for hematopoiesis:
-T-cells: must migrate from bone marrow to thymus to complete maturation
-B-cells: mature in the bone marrow
What are the thymus and its components?
Composition:
-Lobules are composed primarily of the epithelium to secrete hormones (thymopoietin & thymosins) that participate in T-cell maturation
-Infiltrated with T-cells at various stages of maturation
The most important function is early in life and continues to grow until puberty and regresses into adulthood (thymic tissue is replaced by adipose tissue)
What is the structure of the thymus?
Two fused lobes surrounded by a connective tissue capsule
Extensions of the capsule (trabeculae) subdivide the lobes into lobules
Lobules are arranged by the outer region (cortex) and inner region (medulla)
Blood-thymus barrier prevents entry of bloodborne pathogens into the cortex and premature activation of the immature T-cell
What is the difference between macrophages, dendritic cells, and immune cells within the secondary lymphatic structures?
Macrophages - phagocytize foreign substances
Dendritic Cells - capture antigens & bring them to the lymph nodes
Immune cells - are enmeshed within a reticular extracellular matrix
How are the secondary lymphatic structures are organized?
Organized into either an organ or an aggregate of lymphatic nodules in the presence/absence of a dense irregular CT capsule
Complete CT capsule = organ
-Lymph nodes and spleen
Incomplete or absent capsule = other lymphatic structure
-Tonsils, MALT, and diffuse lymphatic nodules
What are lymph nodes and their components?
Clusters that receive lymph from selected body regions or individually throughout the body
-Most are embedded in CT and not readily observed
-Large clusters are found near the body surface in the axillary, inguinal, and cervical regions
Functions to filter the lymph before it returns to the bloodstream
-Macrophages in the node destroy microorganisms and other cellular debris to prevent them from entering the bloodstream
-Monitor for the presence of antigens and mount attacks against them
What is the lymph node structure?
Capsule
Outer cortex
Inner medulla
Cortical and Medullary sinuses
What are the components of the capsule of the lymph node?
It is a dense fibrous enclosure made of trabeculae
Trabeculae
-connective tissue strands that extend from the capsule to divide the node into compartments
What are the components of the outer cortex of the lymph node?
It is the activation and proliferation site of lymphocytes that is divided into the lymphatic nodules
Lymphatic Nodule
-Composed of reticular fibers
-Activation/proliferation site for B-cells in inner germinal centers
-Outer mantle zone contains T-cells, macrophages, and dendritic cells
What are the components of the inner medulla of the lymph node?
It is the center of most portion of the node
Consists of medullary cords
-CT extension from the lymphoid tissue of the cortex
-Supports B-cells, T-cells, and macrophages
What are the components of the sinuses in the lymph node?
The lymph capillary system allows the lymph to be exposed to the cells in the node that is lined with macrophages
Includes cortical and medullary sinuses
How does lymph flow through the nodes?
- Afferent Lymphatic Vessels
-Numerous - Sinuses (cortical and medullary)
-Macrophages remove foreign debris
-Lymphocytes come into contact with foreign debris and become activated
-Cortical Sinus initiates B-cell activation and proliferation
-Medullary Sinus is where B-cells & T-cells enter the circulation to sites of infection - Efferent Lymphatic Vessel
-Only one per many afferent vessels because lymph flows slow down in the node to allow the cells within the node to be exposed longer to the lymph and perform their protective function
-Originates from the hilum
Lymph nodes move through a series of nodes (in a cluster) and the same lymph is repeatedly screened for unwanted materials
What is the spleen and its components?
It is the largest lymphatic organ that is responsible for fighting any invading germs in the blood
Located:
-On the left side of the abdominal cavity
-Curves around the anterior aspect of the stomach
-Lies lateral to left kidney
-Posterolateral side (diaphragmatic surface) lies against the diaphragm
The medial side is concave and contains the hilum (blood vessels and nerves)
What is the spleen strcuture?
CT capsule
Trabeculae responsible for subdividing spleen into white and red pulp
Populated with lymphocytes and macrophages
What is the structure of the white pulp of the spleen?
Spherical structures of T-cells, B-cells, & macrophages resiting on reticular fibers
Each structure surrounds a branch of the splenic artery (central artery)
Involved in immune function of the spleen
What is the function of the red pulp in the spleen?
Surrounds white pulp
Consists of B-cells, macrophages, erythrocytes, and platelets residing on splenic cords consisting of reticular fibers (platelet reservoir)
Splenic sinuses are associated with red pulp for permeable capillaries to drain into small venules
What are the functions of the spleen?
Immune surveillance and response by having macrophages remove debris and foreign matter (white & red pulp)
Is a blood cleanser by extracting aged and defective RBCs and platelets from circulation (red pulp)
Is a reservoir for platelets (red pulp)
Responsible for erythrocyte production in the fetus during the first 5 months of development
What is the direction of flow of the spleen?
- Splenic artery
- Central arteries (white pulp)
- Sinusnoids (red pulp)
- Venules
- Splenic vein
What are the tonsils and their components?
They are the simplest lymphatic organs with incomplete connective tissue capsule
Three Pairs of Tonsils:
-Pharyngeal
-Palatine
-Lingual
Functions to help protect against ingested or inhaled foreign substances
What are the three pairs of tonsils?
Pharyngeal
-Posterior wall of the nasopharynx
-Also referred to as adenoids
Palatine
-Posterolateral region of the oral cavity
Lingual
-Posterior third of the tongue
What is the structure of the tonsils?
Tonsillar Crypts
-Invaginated outer edges
-Increases surface to entrap bacteria and particulate matter
-Presents antigens to the lymphocytes for heightened immunity
Lymphatic Nodules
-Contain loosely scattered lymphocytes and some contain germinal centers
What is lymphatic nodules?
They are small oval clusters of lymphatic cells with incomplete/absent CT capsules (some have an extracellular matrix)
Diffuse lymphatic nodules are scattered and found within every body organ
Function to localized to destroy bacteria and generate “memory” T cells for long-term immunity
What is MALT?
Mucosa-associated lymphatic tissues (MALT) are located within lamina propria of the mucosa of the GI, respiratory, genital, and urinary tract
If located in the small intestine, they are called Peyer patches
Functions to defend against foreign materials in mucosal membranes
What are the components of the right lymphatic duct?
Responsible for the upper right quadrant of the body
Receives lymph draining from the right:
-Head & neck (jugular)
-Upper limb (subclavian)
-Thorax
What are infectious agents and their categories?
Organisms that cause damage to the host organism (pathogenic)
Categories:
-Bacteria
-Viruses
-Fungi
-Protozoans
-Multicellular parasites
What are bacterias and their components?
They are prokaryotic, microscopic, single-celled organisms enclosed in a capsule
They are named based on the shape
-Spherical (cocci)
-Rod-like (bacilli)
-Coiled (spirilla)
Certain kinds produce a disease (can be extracellular or intracellular parasites or produce enzymes or toxins). Some examples are:
-Tuberculosis
-Syphilis
-Lyme disease
-Salmonella
-Anthrax
What are viruses and their components?
They are NOT a cell but is composed of DNA or RNA with a protein capsid. They are obligate intracellular parasite and uses cells to replicate. It ultimately kills the infected cells
Examples:
-Common cold
-Influenza
-Polio
-Chickenpox
-Herpes
-HIV
What are fungi and their components?
They are eukaryotic cells with cell walls. They produce spores and release proteolytic enzymes. These include mold, yeasts, and multicellular fungi
Examples:
-Superficial (ringworm, athlete’s foot)
-Mucosal (vaginal yeast infections)
-Internal (histoplasmosis)
What are protozoans and their components?
They are eukaryotic cells without a cell wall and could be either intracellular or extracellular parasites
Examples:
-Malaria
-Toxoplasmosis
-Giardiasis
-Amoebiasis
What are multicellular parasites and their components?
They are nonmicroscopic parasites that live in the host and use nutrients provided by the host
Examples:
-Tapeworms
-Flukes
-Hookworms
-Pinworms
What are prions and their components?
Small infectious proteins that cause disease in nervous tissue and are spread by consuming infectious meat
Examples:
-Bovine spongiform encephalopathy (mad cow disease)
What is the immune system and the defense components?
It provides resistance to disease by including immune cells, plasma proteins, and cytokines (hormone-like chemicals)
Intrinsic Defense Components:
-Innate Immune Component is non-specific and fast
-Adaptive Immune Component is specific and slow
What are the primary locations of immunocytes?
Most leukocytes are not circulating in the blood so they are found at either:
-Lymphatic tissue
-Select organs
-Epithelium of the skin and mucosa
-Connective tissue
What types of immunocytes are found in the lymphatic tissues?
T-cells, B-cells, macrophages, & NK cells in secondary lymphatic structures
What types of immunocytes are found in select organs?
Specifically named macrophages in specific tissues
Permanent Resident = fixed macrophages
Migrating Macrophage = wandering macrophages
What types of immunocytes are found in the epithelium of the skin and mucosa?
Dendritic cells (from monocytes) are phagocytic cells that engulf pathogens and then migrate to lymph tissue to present antigens
What types of immunocytes that are found in the connective tissue?
Mast cells are abundant in skin and mucosa or respiratory, GI, and urogenital tract
What are cytokines and their components?
They are small soluble proteins produced by immune cells. They function to:
-Means of communication between cells
-Control development and behavior of effector cells
-Regulate inflammatory response
-Serve as a weapon of destruction
In the mode of action, they are:
-Released by a cell to bind to a receptor on the target cell to activate a signal cascade
-Can be an autocrine, paracrine, or endocrine signal
Relatively short half-lives
What are the four classes of cytokines?
Interleukins (ILS) regulate immune cells
Tumor Necrosis Factors (TNFs) destroy tumor cells
Colony-Stimulating Factors (CSFs) stimulate leukopoiesis
Interferons (INFs) are anti-viral and pro-inflammatory agents
What is innate immunity?
They are born defenses to protect against non-specific substances
It prevents entry of potentially harmful substances which is the 1st line of defense (external) through skin and mucosal membranes
It responds non-specifically to a wide range of harmful substances after entering the body as the 2nd line of defense
-Cellular (activities of neutrophils, macrophages, and NK cells)
-Chemical (interferons and complement)
-Physiological (inflammation and fever)
How does the skin prevent the entry of pathogens?
Epidermis is a heavily keratinized epithelial membrane acting as a physical barrier to most microorganisms
Mucosa is structurally modified to trap and move invading particles away from the internal environment. They also produce acids and enzymes
Secrete a variety of antimicrobial substances
-IgA: binds to foreign particles
-Lysozyme, Defensins, & Dermicidin: antibacterial and antifungal substances
-Sebum: biotoxic and creates a low pH that inhibits bacterial growth
Mucus traps microorganisms to prevent them from spreading
Other pathogen removals:
-Skin slough off
-Saliva washes materials away and contains antibacterial enzymes
-Lacrimal fluids
-Urine
What are the phagocytic cells of innate defense and their function?
Neutrophils
-The most abundant type of leukocyte and is the first to arrive during an inflammatory response
Macrophages
-Derived from monocytes and arrive at the site of injury after the inflammatory response begins and remain
-Reside in tissues as fixed or wanderers
Both are phagocytes where they engulf and degrade unwanted substances
What are the steps of phagocytosis?
Adherence
Engulfing the particle
Lysosomal digestion
Exocytosis of degraded residue
What occurs in adherence of phagocytosis?
The particle to be ingested needs to be recognized and then adhered to by the phagocytes
Some particles are not easily identified, so complement proteins can adhere to the foreign particles to mark it for destruction (opsonization)
What occurs in the engulfment of phagocytosis?
Phagocytes release their chemicals into the surrounding environment if the particles are too large
What occurs in the lysosomal digestion of phagocytosis?
Enzymatic digestion of the foreign particle
Cells can also introduce free radicals to help destroy the particles that are resistant to the standard enzymes
Increase acidity and osmolarity to promote specific protease activity
Neutrophils can release molecules (defensins) to pierce the pathogen’s membrane
What are the proinflammatory immunocytes and their function?
Basophils circulate in the blood and mast cells reside in CT of the skin, mucosa, and various organs
They are pro-inflammatory, chemical-secreting cells that promote inflammation through:
-Histamine to promote vasodilation and capillary permeability
-Heparin as an anticoagulant
-Eicosanoids as lipids that promote inflammation
What are natural killer cells and their components?
They are large granular lymphocytes for immune surveillance. They look for “self” markers or lack of the proper markers to target and destroy the cell
They are NOT phagocytic but induce apoptosis in target cells. Secrete chemicals to enhance inflammatory response:
-Perforin creates holes in cell membranes
-Granzymes initiates apoptosis
What is the function of eosinophils?
They are weakly phagocytic against parasitic worms
They attach to parasites and release their chemicals to kill and destroy the parasite
Other functions:
-Participate in immune response associated with allergy/asthma
-Phagocytose antigen-antibody complexes
What are antimicrobial proteins and their function?
They enhance the innate defense response
Consists of:
-Interferons for non-specific defense against viral infection
-Complement to mediate several defense mechanisms
What are interferons and their components?
They are used to help prevent the spread of viruses and are released from infected cell
They bind to receptors on neighboring cells, preventing them from becoming infected, and trigger the synthesis of enzymes that destroy viral RNA and DNA to inhibit the synthesis of viral proteins
They also mobilize the immune system (macrophages and NK) to destroy virally infected cells
Three types:
-alpha (leukocytes) for inflammation reduction
-beta (fibroblasts) for inflammation reduction
-gamma (lymphocytes)
What are complement proteins and their components?
They are a group of approximately 30 plasma proteins that are normally inactive in the bloodstream
They are continuously produced by the liver
They account for approximately 10% of serum proteins
Identify as “C” + a number
What are the pathways for complement activation?
Classical Pathway
-Complement binds to antigen-antibody (Ag-Ab complex)
Alternate Pathway
-Complements binds directly to bacterial polysaccharide coat/fungal cell wall and DOES NOT require antibody
What are the complement defense mechanisms?
Opsonization
Inflammation
Cytolysis
Elimination of Immune Complexes
What occurs in the opsonization of complement defense mechanisms?
It is the binding of complement to a bacteria or cell to enhance phagocytosis using a bind protein (opsonin)
It makes it easier to identify the substance to be engulfed
What occurs in the inflammation of complement defense mechanisms?
It activates mast cells and basophils and attracts neutrophils and macrophages
What occurs in the cytolysis of complement defense mechanisms?
Formation of the membrane attack complex (MAC) from C5-C9
Creates holes in the plasma membrane to compromise cell
What occurs in the elimination of immune complexes of complement defense mechanisms?
It links Ag-Ab to erythrocytes which carry complex to the liver/spleen for removal & destruction
Erythrocytes act as a transporter and continue to circulate
Why does inflammation occur? What are its benefits?
Occurs in response to physical trauma, intense heat, irritation, or infection
Benefits:
-Prevent the spread of damaging agents to nearby tissues
-Disposal of cellular debris and pathogens
-Prepares area for repair
What occurs in chemical release?
Release of chemicals by inflammatory and chemotactic factors
Accomplished through damaged tissue, basophils, and mast cells, or infectious organisms
What occurs in vascular response?
Occurs in response to inflammatory chemicals
Includes:
-Vasodilation
-Increased capillary permeability
-CAM expression within endothelium to attract leukocytes
What occurs in leukocyte recruitment?
Margination
-Use of CAMs to arrest leukocyte flow through blood vessels
Diapedesis
-Cells exit blood stream by squeezing between endothelial cells
Chemotaxis
-Migration of cells to site of injury following the chemical trail
What occurs when plasma proteins migrate to injury?
Immunoglobulins and complement
Clotting proteins walls off injuries and prevents the spread of microbes
Kinins increase capillary permeability, promote endothelial CAM production, and stimulate pain receptors
What are the cardinal signs of inflammation?
Redness
-Due to increased blood flow resulting in increased oxygen and nutrients to the area
Heat
-Due to increased blood flow resulting in increased metabolic activity within the area
Swelling
-Due to increased fluid out of capillaries (limiting movement) resulting in decreased use of area and dilutes potential pathogen
Pain
-Due to stimulation of nociceptors by mechanical stimulation of swelling and chemical stimulation of kinins (limiting movement) resulting in decreased use of area
Loss of Function
-Occurs in severe cases of inflammation resulting in decreased use of area
What is a fever? What are its benefits?
It is an abnormally high body temperature (pyrexia)
The body’s thermostat (hypothalamus) is reset in response to pyrogens
-Interferons and interleukins toxins are released by infectious agents
-Secreted by leukocytes and macrophages
Benefits:
-Inhibits bacterial and viral production
-Promotes interferon activity and adaptive immunity activity
-Accelerates tissue repair (increased metabolic activity)
-Promotes immune cell migration (increased CAM expression)
What are the stages of a fever?
Onset
-Vasoconstriction in the skin to prevent heat loss
-Shivering produces heat through muscle contraction
Stadium
-Increased metabolic rate promotes the elimination of harmful substances
-Liver & spleen sequester key minerals (Zn and Fe) to slow microbial reproduction
Defervescence
-Temperature returns to its normal set point
-Hypothalamus (without pyrogens) promotes heat shedding
Cycles until the pathogen is removed
What is adaptive immunity?
Specific defense against specific infections and is systemic
Has a delayed response and memory (frequent exposure = stronger)
What are the 2 subcategories of adaptive immunity?
Cell-Mediated (cellular)
-Lymphocytes are responsible for immune response
Antibody-Mediated (humoral)
-Free antibodies target and mark foreign material for destruction
-Mediated through B-cells
What are antigens?
Substances that can be recognized by the immune system
They are large and complex and bounded by an antibody or a T-cell
What are foreign antigens?
They are not naturally found within the body
Usually recognized and bound by the adaptive immune system (unless with highly repetitive microstructures)
What are self antigens?
Molecules produced by the body
Are not normally recognized and bound by the adaptive immune system
What is autoimmunity antigens?
When self antigens are recognized as foreign and an immune response is initiated
What are epitopes?
Known as antigenic determinants where the specific portions of the antigen that is recognized by the immune system
The more chemically complex an antigen is, the more immunogenicity it has
What is an immunogen?
An antigen that induces an immune response
What is immunigenicity?
The degree an antigen can induce an immune response
Dependent on:
-Degree of foreignness
-Size
-Complexity
-Quantity
What is hapten?
Small molecules that are reactive but not immunogenic where it has the ability to reach with activated lymphocytes and antibodies release by the immunogenic reaction
Require a carrier molecule to bind it to trigger an immune response
What are the antigen receptors?
A portion of the receptor complex that lies on the cell’s surface and is composed of TCR and BCR
TCR (T-cell receptor):
-Antigen must be processed and presented by another cell requiring a co-receptor molecule that helps T-cell interaction with APC (antigen-presenting cell)
BCR (B-cell receptor):
-Contacts antigens directly
What is difference between T-helper cell and cytotoxic T cell?
T-helper cell (Th)
-Activate B cells and other immune cells
-Possess CD4
Cytotoxic T-cells (Tc)
-Release chemicals that attack other cells
-Possess CD8
What is antigen presentation?
Display of an antigen on the cell surface and enables T-cells to see antigens
Requires physical attachment of the antigen to a specialized self surface protein (MHC)
What are the 2 cell types that present antigens?
All nucleated cells:
-Includes all cells in the body except RBCs & APCs
Antigen-Presenting cells (APCs):
-Any immune cell that functions to communicate the presence of an antigen to TH and TC cells (includes dendritic cells, macrophages, and B-cells)
What are MHC proteins?
Glycoproteins that are genetically determined and display small peptides to help mobilize the immune system
-Healthy Cells = peptides are partially degraded self-proteins
-Infected Cells = peptides include partially degraded non-self proteins
Continuously produced in RER, loaded with peptide and embedded within plasma membrane
What are the 2 categories of MHC proteins?
MHC Class I:
-Found on all nucleated cells including APCs
MHC Class II:
-Found only on APCs
How are MHC Class I proteins formed?
1) MHC class I molecules are synthesized by the RER and peptide fragments attached to MHC class I molecules
2) MHC class I molecules are shipped by the endomembrane system through the Golgi and then to the plasma membrane
3)MHC class I molecules with bound foreign antigens are displayed
How are MHC Class II proteins formed?
1) MCH class II is synthesized by the RER of the APC
2) MHC class II molecules are shipped by the endomembrane system through the Golgi to the plasma membrane
3) Phagocytosis of exogenous antigen
4) MHC class II molecules and foreign antigen are displayed within the plasma membrane
What are the significant steps of the life of lymphocytes?
Formation, activation, and effector response of T- and B- cells
What happens in formation of lymphocytes?
It is the maturation process that occurs in the primary lymphatic structures (thymus and red bone marrow)
It becomes specialized to recognize only one specific foreign antigen
What happens in the activation of lymphocytes?
It occurs in the secondary lymphatic structures (lymph nodes, spleen, tonsils, MALT)
It leads to replication after exposure to the antigen
What happens in the effector response in lymphocytes?
The specific action to eliminate the antigen at the site of infection
-T-cells leave a secondary structure and migrate to the site of infection
-B-cells stay in secondary structures and produce antibodies
What is the T-cell formation?
It originates in the red bone marrow as immature T-cells where it possesses a unique TCR via the unique gene-shuffling mechanism
Immature T-cells migrate to the thymus to mature through the two-fold maturation process. It is tested to see if it can bind to or recognize the antigen on MHC molecule. It then results in T-cell selection
What is T-cell selection?
It occurs in the thymus to see if TCR can recognize an MHC protein or self-antigens
98% of maturing T-cells are eliminated through this process and the remaining 2% are functional cells to recognize MHC
What is positive T-cell selection?
A test to see if TCR can bind to and recognize an MHC protein
Thymic epithelial cells present MHC proteins to T-cells
If TCR cannot bind to MHC protein = apoptosis
What is negative T-cell selection?
A test to see if TCR recognizes self-antigens
Thymic dendritic cells present self-antigens via MHC class I and II proteins to T-cells
If the TCR recognizes self-antigen = apoptosis
What happens in T-cell differentiation & migration
T-cells differentiate into either T-helper cells or cytotoxic T-cells requiring a selective loss of either CD4 or CD8
-Loss of CD4 yields CD8 cell (Tc)
-Loss of CD8 yields CD4 cell (Th)
What happens in B-cell development?
Occurs in the red bone marrow where different cell surface proteins are involved to be tested to determine if BCR detects self-antigen (negative selection)
Migration to secondary lymphatic structures to finish the maturation process where the final steps produce an immunocompetent and naive B-cell
What happens if BCR detects self-antigen?
Clonal Deletion: apoptotic removal of B-cell
Receptor Editing: BCR is reconfigured and re-rested to produce a less auto-reactive BCR
Anergy: change in B-cell not the BCR (no longer capable of generating an adaptive response)
Ignorance: ignores and continues to mature
What is lymphocyte activation?
Contact between the lymphocyte and the antigen it recognizes occurring in the secondary lymphatic structures (depending on the point of entry of antigen):
-Ag in blood = spleen
-Ag in skin = dendritic cells to lymph node
-Ag in respiratory = respiratory, GI, urogenital via MALT or tonsils
What is clonal selection and expansion?
Recognition yields proliferation and differentiation to produce more of the same cell to respond to that antigen
What happens in the 1st stimulation in the activation of T-helper cells?
Direct physical contact between an APC and the T-helper cell (Ag is presented via MHC class II)
Antigen inspection:
-TCR binds MHC class I protein
-CD4 stabilized interaction
-If no recognition, disengagement
-If recognition, contact is maintained
What happens in the 2nd stimulation in the activation of T-helper cells?
T-helper cells begin to secrete cytokines (interleukin-2)
Cells proliferate and differentiate to produce 2 types of T-helper cells:
-Activated Th helper cell produces more IL-2
-Memory Th cells for later
What happens in the 1st stimulation in the activation of T-cytotoxic cells?
Direct contact between the cytotoxic T-cells and an infected cell (antigen is presented via MHC class I on infected cell)
Antigen Inspection:
-TCR binds MHC class I
-CD8 stabilizes the interaction
-If no recognition = disengagement
-If recognition = contact is maintained
What happens in the 2nd stimulation in the activation of T-cytotoxic cells?
IL-2 from T-helper cells binds to IL-2R on cytotoxic T-cells
Cells proliferate and differentiate to produce two types of cytotoxic T-cells:
-Activated cytotoxic T-cells
-Memory cytotoxic T-cells for later
What happens in the 1st stimulation in the activation of B-cells?
Free antigen binds to BCR
B-cell engulfs, processes, & presents antigen via MHC class II to present to T-helper cells
What happens in the 2nd stimulation in the activation of B-cells?
Activated T-helper cells release IL-4 (paracrine fashion) that activates B-cells
B-cells proliferate and differentiate to produce 2 types of B-cells:
-Plasma cells (produces double Abs)
-Memory B-cells (retain BCR and survive for years)
What is the T-helper cell effector response?
Both activated and memory-cytotoxic T-cells migrate to the site of infection after several days of exposure
Continue to release cytokines:
-Activate B-cells, cytotoxic T-cells, macrophages, and NK cells
What is the T-cytotoxic effector response?
Both activated and memory-cytotoxic T-cells migrate to the site of infection after several days of exposure
Destroy infected cells displaying antigens by releasing cytotoxic chemicals:
-Granzymes induce cell death by apoptosis (Fas/FasL)
-Perforins form holes in the cell membrane increasing permeability
What is the B-cell effector response?
Antibodies are the effectors of humoral immunity
Produced by plasma cells that remain in lymph nodes for 5 days and then later released into the bloodstream
What are antibodies?
They mark antigens and facilitate their destruction by other immune cells
They are immunoglobins with 5 major classes 15 prescription
What is the structure of antibodies?
Y-shaped and soluble
4 polypeptide chains (2 heavy and 2 light chains)
Variable regions contain the Ag binding site Binding through weak interactions
Constant Region: Contain Fc region determines biological function and elimination
What is the IgG class of antibodies?
Major class (75-85%) of all antibodies
Blood, lymph, CSF, serous of all
Able to cross the placental barrier and participates in all functions described
What is the IgM class of antibodies?
Pentamer is mostly found in blood
Effective at agglutination and binding complement
Responsible for mismatched blood transfusion
What is the IgA class of antibodies?
Found in areas exposed to the environment for protection on respiratory and GI tract
Dimer in secretions
Prevents pathogens from adhering to epithelial cells
Effective at agglutination
What is the IgD class of antibodies?
Acts as NCR to serve as a maturity signal for B-cells
What is the IgE class of antibodies?
Low rate of synthesis
Plays a role in allergies and parasitic infections to cause produce release in basophils and mast cells (attract eosinophils)
What does the binding of the antigen-binding site of an antibody with antigen cause?
Neutralization:
-Covers an antigenic determinant of a pathogen to make them ineffective
Agglutination:
-Causes cells to clump together to protect from bacteria or foreign RBCs
Precipitation:
-Causes the antigen to settle out of the solution
-Ag-Ab complex can be eliminated b phagocytic cells
What does the exposed Fc portion following antigen binding by antibody promote?
Complement Fixation:
-Fc region of IgG & IgM bind complement proteins to activate the classical complement pathway
Opsonization:
-Fc region of IgG causes opsonization while neutrophils and macrophages have receptors for Fc regions
Activation of NK Cells:
-Fc region of IgG can activate NK cells to release cytotoxic chemicals to result in apoptosis (antibody-dependent cell-mediated cytotoxicity)
What is immunological memory?
Activation of adaptive immunity requires physical contain between antigen and lymphocyte
What is the first exposure of immunological memory?
Lag time includes Ag detection, activation, proliferation, and differentiation from 3 to 6 days
Lower titer from 1 to 2 weeks of initial exposure. Produces IgM then IgG
What is the second exposure of immunological memory?
Lag time is shorter
Higher titer rise within days of exposure and more IgG than IgM
What is active immunity?
Obtained from a direct encounter with a pathogen/foreign substance
Natural - directly exposed to an antigen/infectious agent
Artificial - occurs through a vaccine
What is passive immunity?
Obtained through another individual and lasts as long as the presence of the antibody (no memory cells)
Natural - transfer of antibodies between mother and child
Artificial - transfer of antibody-containing serum or antibodies from one individual to another
What is a titer?
The concentration of Abs in circulation against the Ag
