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Justin Cabrera P.6 Lymphatic/Immune system - Coggle Diagram
Justin Cabrera P.6
Lymphatic/Immune system
Major functions of the Lymphatic & Immune systems
Lymphatic system
T and B lymphocytes share common development and steps in their life cycles
Lymphocyte development, maturation, and activation
Maturation
Lymphocytes are “educated” in a 2-3 day process and mature in primary lymphoid organs (B cells in bone marrow and thymus)
Educated for 2 reasons
Immunocompetence
lymphocytes must be able to recognize only 1 specific antigen
B or T cells display only one unique type of antigen receptor on surface when mature so bind only one specific antigen
Self-tolerance
lymphocytes must be unresponsive to own antigens
Seeding secondary lymphoid organs and circulation
Exported from primary lymphoid organs (bone marrow and thymus) to “seed” (colonize) secondary lymphoid organs (lymph nodes, spleen, etc.)
Increases chance of encounter with antigen
Immunocompetent B and T cells not yet exposed to antigen are called naive
Origin
both lymphocytes originate in red bone marrow
Antigen encounter and activation
Lymphocyte is selected to differentiate into active cell by binding to its specific antigen
clonal selection
If correct signals are present, lymphocyte will complete its differentiation into active cell
Naive lymphocyte’s first encounter with antigen triggers lymphocyte to develop further
Proliferation and differentiation
Most clones become effector cells that fight infections
A few remain as memory cells
Able to respond to same antigen more quickly second time it is encountered
B and T memory cells and effector T cells circulate continuously
Once selected and activated, lymphocyte proliferates
Forms army of exact copies of itself
Referred to as clones
Antigen receptor diversity
Genes, not antigens, determine which foreign substances the immune system will recognize
Huge variety of receptors: gene segments are shuffled around, resulting in many combinations
Lymphocyte Education during Maturation
T cells mature in thymus under negative and positive selection pressures
Immune system
provides resistance to disease
a functional system rather than organ system
Made up of two intrinsic systems
Innate
Adaptive
Innate and adaptive defenses are intertwined
Innate defenses do have specific pathways for certain substances
Innate responses release proteins that alert cells of adaptive system to foreign molecules
Both release and recognize many of the same defensive molecules
Passive V. Active Immunity
Active and Passive Humoral Immunity
Passive humoral immunity
occurs when ready-made antibodies are introduced into body
B cells are not challenged by antigens; Immunological memory does not occur
Protection ends when antibodies degrade
Two types of passive humoral immunity
Artificially acquired
injection of serum, such as gamma globulin
Protection immediate but ends when antibodies naturally degrade in body
Naturally acquired
antibodies delivered to fetus via placenta or to infant through milk
Active humoral immunity
occurs when B cells encounter antigens and produce specific antibodies against them
Two types of active humoral immunity
Artificially acquired
formed in response to vaccine of dead or attenuated pathogens
Naturally acquired
formed in response to actual bacterial or viral infection
Cells involved in the immune system and their functions
Phagocytes
white blood cells that ingest and digest (eat) foreign invaders
Macrophages
develop from monocytes and are chief phagocytic cells; most robust phagocytic cell
Neutrophils
most abundant phagocytes, but die fighting; become phagocytic on exposure to infectious material
Natural Killer (NK) Cells
Attack cells that lack “self” cell-surface receptors
Kill by inducing apoptosis in cancer cells and virus-infected cells
Nonphagocytic, large granular lymphocytes that police blood and lymph
an kill cancer and virus-infected cells before adaptive immune system is activated
Secrete potent chemicals that enhance inflammatory response
lymphocytes
T lymphocytes (T cells)
B lymphocytes (B cells)
Antigen-presenting cells (APCs)
Do not respond to specific antigens
Play essential auxiliary roles in immunity
Engulf antigens and present fragments of antigens to T cells for recognition
3 Major types
B cells
Present antigens to helper T cell to assist their own activation
Do not activate naive T cells
Macrophages
Present antigens to T cells, which not only activates T cell, but also further activates macrophage
Also trigger powerful inflammatory responses and recruit additional defenses
Activated macrophage becomes phagocytic killer
Widely distributed in connective tissues and lymphoid organs
Dendritic cells
Phagocytize pathogens that enter tissues, then enter lymphatics to present antigens to T cells in lymph node
Key link between innate and adaptive immunity
Most effective antigen presenter known
Found in connective tissues and epidermis
Act as mobile sentinels of boundary tissues
Helper T (TH) cells
Activate both humoral and cellular arms
Once primed by APC presentation of antigen, helper T cells
Secrete cytokines that recruit other immune cells
Induce T and B cell proliferation
Help activate B cells and other T cells
Play central role in adaptive immune response
Without TH, there is no immune response
Specific Effector T Cells
Activation of CD8 cells
CD8 cells require TH cell to become activated into destructive cytotoxic T cells
Cause dendritic cells to express co-stimulatory molecules required for CD8 cell activation
Amplification of innate defenses
Activate macrophages, leading to more potent killers
Mobilize lymphocytes and macrophages and attract other types of WBCs
Amplify responses of innate immune system
Activation of B cells
Stimulate B cells to divide more rapidly and begin antibody formation
Helper T cells interact directly with B cells displaying antigen fragments bound to MHC II receptors
Cytotoxic T (TC) cells
Activated TC cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize
Activated TC cells target
Virus-infected cells
Cells w/ intracellular bacteria or parasites
Cancer cells
Foreign cells (transfusions or transplants)
Directly attack and kill other cells
Deliver lethal hit using two mechanisms
TC cell releases perforins and granzymes by exocytosis
stimulates apoptosis
TC cell binds specific membrane receptor on target cell and stimulates apoptosis
Regulatory T (TReg) cells
Important in preventing autoimmune reactions
Humoral response and cellular response
Humoral Immune Response
When B cell encounters target antigen, it provokes humoral immune response
Antibodies specific for that particular antigen are then produced
Activation and Differentiation of B Cells
B cells are activated when antigens bind to surface receptors, cross-linking them
Triggers receptor-mediated endocytosis of cross-linked antigen-receptor complexes (clonal selection), leading to proliferation and differentiation of B cell into effector cells
Most clone cells become plasma cells, antibody-secreting effector cells
Antibodies circulate in blood or lymph, binding to free antigens, marking them for destruction by innate or other adaptive mechanisms
Secrete specific antibodies at rate of 2000 molecules per second for 4 to 5 days, then die
Clone cells that do not become plasma cells become memory cells
Provide immunological memory
Mount an immediate response to future exposures to same antigen
Cellular immune Response
Some T cells directly kill cells; others release chemicals that regulate immune response
T cells are more complex than B cells both in classification and function
T cells provide defense against intracellular antigens
cells infected with viruses or bacteria, cancerous or abnormal cells, foreign (transplanted) cells
Two populations of T cells
CD8 cells
Also become memory T cells
become cytotoxic T cells (TC) that are capable of destroying cells harboring foreign antigens
CD4 cells
usually become helper T cells (TH) that can activate B cells, other T cells, and macrophages; direct adaptive immune response
Some become regulatory T cells, which moderate immune response
Also become memory T cells
Helper, cytotoxic, and regulatory T cells are activated T cells
Naive T cells are simply termed CD4 or CD8 cells
Antigen presentation is vital for activation of naive T cells and normal functioning of effector T cells
Activation and Differentiation of T Cells
T cells can be activated only when antigen is presented to them
Activation is a two-step process
Co-stimulation
Complete T cell activation requires T cell to also bind to one or more co-stimulatory signals on surface of APC
Antigen binding
TCR must recognize both MHC and foreign antigen it displays
Binding of TCR to complex triggers multiple intracellular signaling pathways that start T cell activation
T cell antigen receptors (TCRs) bind to antigen-MHC complex on APC surface
Both occur on surface of same APC
Both are required for clonal selection of T cell
Proliferation and differentiation
Primary T cell response peaks within a week
T cell apoptosis occurs between days 7 and 30
Activated T cells are a hazard because they produce large amounts of inflammatory cytokines
Could result in hyperplasia or cancer if not cleared from system
T cells that are activated enlarge and proliferate in response to cytokines
Differentiate and perform functions according to their T cell class
Memory T cells remain and mediate secondary responses
Cytokines
Mediate cell development, differentiation, and responses in immune system
Include interferons and interleukins
Interleukin 1 (IL-1) is released by macrophages and stimulates T cells to
Synthesize more IL-2 receptors
Release interleukin 2 (IL-2)
Chemical messengers of immune system
IL-2 is a key growth factor, acting on same cells that release it and other T cells
Encourages activated T cells to divide rapidly
Other cytokines amplify and regulate innate and adaptive responses
Example: gamma interferon—enhances killing power of macrophages
Disorders associated with the Immune system
Pus
creamy yellow mixture of dead neutrophils, tissue/cells, and living/dead pathogens
Abscess
collagen fibers are laid down, walling off sac of pus; may need to be surgically drained
Some bacteria, such as tuberculosis bacilli, resist digestion by macrophages and remain alive inside
Bacteria may remain inactive forever, or if person’s immunity decreases, may break free, become activated, and cause disease
Can form tumorlike growths called granulomas—area of infected macrophages surrounded by uninfected macrophages and outer capsule
Immunodeficiency
congenital or acquired conditions that impair function or production of immune cells or molecules
Severe combined immunodeficiency (SCID) syndrome
genetic defect with marked
deficit in B and T cells
Treatment: bone marrow transplants
Defective adenosine deaminase (ADA) enzyme allows accumulation of metabolites lethal to T cells; fatal if untreated
Hodgkin’s disease
an acquired immunodeficiency that causes cancer of B cells, which depresses lymph node cells and thus leads to immunodeficiency
Acquired immune deficiency syndrome (AIDS)
Characterized by severe weight loss, night sweats, and swollen lymph nodes
Symptoms begin when immune system collapses
No cure for AIDS found; four major classes of antivirals in combination help but can fail as virus becomes resistant
Opportunistic infections occur, including Pneumocystis pneumonia and Kaposi’s sarcoma
Human immunodeficiency virus (HIV) cripples immune system by interfering with activity of helper T cells
HIV is transmitted via body fluids: blood, semen, and vaginal secretions
HIV can enter the body via:
Blood transfusions
blood-contaminated needles
sexual intercourse and oral
sex
mother to fetus
HIV destroys TH cells, thereby depressing cellular immunity
Autoimmune disease
results when immune system loses ability to distinguish self from foreign
Autoimmunity
production of autoantibodies and sensitized TC cells that destroys body tissues
Ex:
Myasthenia gravis: impairs nerve-muscle connections
Multiple sclerosis: destroys white matter myelin
Rheumatoid arthritis: destroys joints
Graves’ disease: causes hyperthyroidism
Type 1 diabetes mellitus: destroys pancreatic cells
Systemic lupus erythematosus (SLE): affects multiple organs
Glomerulonephritis: damages kidney
Treatment of autoimmune diseases
Anti-inflammatory drugs, such as corticosteroids
Blocking cytokine action
Suppress entire immune system
Blocking co-stimulatory molecules
Hypersensitivities
immune responses to perceived (otherwise harmless) threat that cause tissue damage
Immediate hypersensitivity(acute (type I) hypersensitivities (allergies))
Activated IgE against antigen binds to mast cells and basophils
Later encounter with same allergen causes flood of histamine release from IgEs, resulting in induced inflammatory response
Initial contact with allergen is asymptomatic but sensitizes person
Histamines causes vasodilation and leakiness of the vessels, leading to symptoms of runny nose, itchy hives, or watery eyes
Asthma can occur if allergen is inhaled
Antihistamines are needed to control
begin in seconds after contact
with allergen, antigen that causes allergic reaction
Systemic response is anaphylactic shock
Vasodilation results in low blood volume, which could cause circulatory collapse
Treatment: epinephrine
Bronchioles constrict, making breathing difficult
Usually seen with injected allergens (example: bee sting)
Allergic reactions can be local or systemic
Innate(natural) immune defenses and Adaptive(acquired) immune defenses
Innate (nonspecific) defense system
Constitutes first and second lines of defense
Second line of defense: antimicrobial proteins, phagocytes, and other cells
inhibit spread of invaders; inflammation most important mechanism
first line of defense: external body membranes
skin and mucosae
stop attacks by
pathogens
Surface Barriers
skin and mucous membranes, along with their secretions
Enzymes
lysozyme of saliva, respiratory mucus, and lacrimal fluid kills many microorganisms; enzymes in stomach kill many microorganisms
Acid
acidity of skin and some mucous secretions inhibits growth; called acid mantle
Mucin
sticky mucus that lines digestive and respiratory tract traps microorganisms
Keratin is resistant to weak acids and bases, bacterial enzymes, and toxins
Physical barrier to most microorganisms
Mucosae provide similar mechanical barriers
If breached by nicks or cuts trigger the internal second line of defense that protects deeper tissues
Respiratory system
Cilia of upper respiratory tract sweep dust- and bacteria-laden mucus toward mouth
Mucus-coated hairs in nose trap inhaled particles
2nd line tools
Inflammatory response
macrophages
mast cells
WBCs
inflammatory chemicals
Antimicrobial proteins
interferons and complement proteins
Natural killer (NK) cells
Phagocytes
Fever
Many second-line cells have pattern recognition receptors that recognize and bind tightly to structures on microbes, disarming them before they do harm
Inflammation
Benefits
Alerts adaptive immune system
Sets the stage for repair
Disposes of cell debris and pathogens
Prevents spread of damaging agents
triggered whenever body tissues are injured
Injuries can be due to trauma, heat, irritating chemicals, or infections by microorganisms
4 cardinal signs
Swelling
Pain
Heat
Redness
Potential 5th; impairment of function
Stages of inflammation
Vasodilation and increased vascular permeability
Phagocyte mobilization
If inflammation is due to pathogens, complement is activated; adaptive immunity elements arrive
Neutrophils flood area first; macrophages follow
Inflammatory chemical release
Chemicals are released into ECF by injured tissues or immune cells
Ex: histamine released by mast cells
Kinins, prostaglandins (PGs), cytokines and if pathogens are involved, complement
Many attract phagocytes to area
All make capillaries leaky
All cause vasodilation of local arterioles
Adaptive (specific) defense system
Third line of defense attacks particular foreign substances
takes longer to
react than innate
specific defensive system that eliminates almost any pathogen or abnormal cell in body
Characteristics of adaptive immunity
It is systemic: not restricted to initial site
It has memory: mounts an even stronger attack to “known” antigens (second and subsequent exposures)
It is specific: recognizes and targets specific antigens
Two main branches of adaptive system
Cellular (cell-mediated) immunity
Lymphocytes act against target cell
Indirectly—by releasing chemicals that enhance inflammatory response; or activating other lymphocytes or macrophages
Directly—by killing infected cells
Humoral (antibody-mediated) immunity
Bind temporarily to target cell
Mark for destruction
Antibodies, produced by lymphocytes, circulate freely in body fluids
Adaptive immune system involves three crucial types of cells
Antigen-presenting cells (APCs)
Two types of lymphocytes
T lymphocytes (T cells)
cellular immunity
B lymphocytes (B cells)
humoral immunity
Antigens & Antibodies
Antigens
substances that can mobilize adaptive defenses and provoke an immune response
Targets of all adaptive immune responses
Most are large, complex molecules not normally found in body (nonself)
Characteristics
Can be a self-antigen
Contain antigentic determinants
Can be a complete antigen or hapten (incomplete)
Self-Antigens: MHC Proteins
One set of important self-proteins are group of glycoproteins called MHC proteins
Contain groove that can hold piece of self-antigen or foreign antigen
T lymphocytes can recognize only antigens that are presented on MHC proteins
Coded by genes of major histocompatibility complex (MHC) and unique to each individual
all cells are covered with variety of proteins located on surface that are not antigenic to self, but may be antigenic to others in transfusions or grafts
Antibodies(Immunoglobulins (Igs))
proteins secreted by plasma cells
Capable of binding specifically with antigen detected by B cells
Grouped into one of five Ig classes
Basic antibody structure
Variable (V) regions at one end of each arm combine to form two identical antigen-binding sites
Four chains consist of:
Two identical light (L) chains
Two identical heavy (H) chains with hinge region at “middles”
Overall T- or Y-shaped antibody monomer consists of four looping polypeptide chains linked by disulfide bonds
Stems make up constant (C) regions
Antibody classes
Five major classes
IgD
IgG
IgA
IgE
IgM
Antibody targets and functions
Antibodies do not destroy antigens; they inactivate and tag them
Form antigen-antibody (immune) complexes
Defensive mechanisms used by antibodies
Complement fixation
When several antibodies are bound close together on same antigen, complement-binding sites on their stem regions are aligned
Main antibody defense against cellular antigens (bacteria, mismatched RBCs)
Precipitation
Complexes precipitate out of solution
Precipated complexes are easier for phagocytes to engulf
Soluble molecules (instead of cells) are cross-linked into complexes
Agglutination
Allows for antigen-antibody complexes to become cross-linked into large lattice-like clumps
Process referred to as agglutination
Neutralization
Antibodies block specific sites on viruses or bacterial exotoxins
Prevent antigens from binding to receptors on tissue cells
Simplest, but one of most important defensive mechanism
Antigen-antibody complexes undergo phagocytosis
Summary of antibody actions
Antigen-antibody complexes do not destroy antigens; they prepare them for destruction by innate defenses
Antibodies go after extracellular pathogens; they do not invade solid tissue unless lesion is present
Recent exception found: antibodies can act intracellularly if attached to virus before it enters cell
Recent exception found: antibodies can act intracellularly if attached to virus before it enters cell
Purpose and examples of First, Second and Third line of defense
2nd line tools
Inflammatory response
macrophages
mast cells
WBCs
inflammatory chemicals
Antimicrobial proteins
interferons and complement proteins
Natural killer (NK) cells
Phagocytes
Fever
Many second-line cells have pattern recognition receptors that recognize and bind tightly to structures on microbes, disarming them before they do harm
Constitutes first and second lines of defense
Second line of defense: antimicrobial proteins, phagocytes, and other cells
inhibit spread of invaders; inflammation most important mechanism
first line of defense: external body membranes
skin and mucosae
Surface Barriers
skin and mucous membranes, along with their secretions
Enzymes
lysozyme of saliva, respiratory mucus, and lacrimal fluid kills many microorganisms; enzymes in stomach kill many microorganisms
Acid
acidity of skin and some mucous secretions inhibits growth; called acid mantle
Mucin
sticky mucus that lines digestive and respiratory tract traps microorganisms
Keratin is resistant to weak acids and bases, bacterial enzymes, and toxins
Physical barrier to most microorganisms
Mucosae provide similar mechanical barriers
If breached by nicks or cuts trigger the internal second line of defense that protects deeper tissues
Adaptive (specific) defense system
Third line of defense attacks particular foreign substances
takes longer to
react than innate
specific defensive system that eliminates almost any pathogen or abnormal cell in body
Characteristics of adaptive immunity
It is systemic: not restricted to initial site
It has memory: mounts an even stronger attack to “known” antigens (second and subsequent exposures)
It is specific: recognizes and targets specific antigens
Artificial vs. Naturally acquired immunity
Artifical
formed in response to vaccine of dead or attenuated pathogens
injection of serum, such as gamma globulin
Protection immediate but ends when antibodies naturally degrade in body
Naturally
formed in response to actual bacterial or viral infection
antibodies delivered to fetus via placenta or to infant through milk
Location of Lymphatic organs and their functions
Red Bone Marrow
RBCs, WBCs, and platelets are created
commonly found in flat bones
Thymus
anterior to ascending aorta and posterior sternum
makes WBCs called T cell lymphocytes
Spleen
Cleanse blood & removes aged/defective RBCs
store platelets, iron, and monocytes
Tonsils
part of soft tissue masses in back of throat
prevent germs and intrusion of bacteria into the body
Peyer's Patch
Clusters of subepithelial, lymphoid follicles w/ intestine
immune system recognizes & destroys pathogens
Appendix
lower right abdomen
Maturation of B Cell lymphocytes