Lymphatic, Immune System Flashcards
What are the functions of the lymphatic system?
Collect excess interstitial fluid that results from fluid exchange in the capillary beds and return it to the blood
Removes proteins and other particles that are too large to be taken up by the capillaries (glycerides)
Takes excess fluid through lymph nodes (can elicit immune response)
Recycles interstitial fluid while monitoring it for infection, reroutes low-solubility fat digestates around small capillaries of intestine and into large veins of neck
Where does lymph circulate to?
Through lymphatic vessels, eventually dumping into the thoracic duct and vena cava
Is lymphatic system an open or closed system?
Lymphatic system is an open system
Fluid enters at one end and leaves at the other
contrast to closed circulatory system
How do substances enter the lymphatic system?
Insterstitial fluid flows between overlapping endothelial cells
large particles push their way between cells into the lymph
Once inside, large particles cannot push their way out
Lymph capillaries are like tiny fingers protruding into tissues
What factors affect interstitial pressure and what is it normally?
Typically interstitial fluid has slightly negative gauge pressure
Lymph flow increases when interstitial pressure rises towards zero
Blood pressure, plasma osmotic pressure, interstitial osmotic pressure, and permeability of capillaries affect interstitial pressure
How is fluid propelled through lymph vessel valves?
Have valves to prevent backflow
Smooth muscle in walls of larger lymph vessels contract when stretched
Lymph vessels may also be squeezed by adjacent skeletal muscles, body movements, and arterial pulsations (lymph flow greater in active individual)
Where does the lymph system empty?
Empties into large veins at thoracic duct and right lymphatic duct (right arm and head)
Lymph Nodes
Part of lymphatic system, filter lymph through
Contain large quantities of lymphocytes
Filter and trap particles and site of stimulation of lymphocytes to respond to pathogens
What is the purpose of the immune system?
Protect human body from toxins and from invasion by other organisms, including bacteria, viruses, fungi, and parasites
What are the two strategies immune cells use to accomplish primary goals of immune system?
- Phagocytose (‘eat’) dangerous material
2. Secrete effector molecules that have downstream functions
What are the two main interconnected branches of the immune system?
- Innate immunity: non-specific and quick, providing generalized protection from most intruding organisms and toxins
- Adaptive / Acquired immunity: develops more slowly and only after the body has experienced the initial attack, provides protection against specific organisms or toxins (B-cell mediated and T-cell mediated)
What are some cellular and non-cellular defenses that innate immunity includes?
- Skin as barrier to organisms and toxins
- Stomach acid and digestive enzymes to destroy digested organisms / toxins
- Phagocytotic cells: neutrophils and macrophages
- Chemicals in the blood
What happens when tissues are injured?
Inflammation
Functions to “wall-off” affected tissue and local lymph vessels from rest of the body, impeding spread of infection
Includes dilation of blood vessels, increased permeability of capillaries, swelling of tissue cells, migration of granulocytes and macrophages to inflamed area
What are some causative agents of inflammation?
Histamines, prostaglandins, and lymphokines are released by tissues
What is one way innate immune cells can recognize foreign invaders?
Pathogen-Associated Molecular Patterns (PAMPs)
Innate immune cells look for molecules that are expressed by pathogens, but not by humans
E.g. many gram-negative bacteria express a carbohydrate called lipopolysaccharide or LPS. LPS alone could send a person into septic shock
Phagocytes
Many of earliest responders to pathogens, ingest (‘eat’) dangerous substances and destroy them
Local Macrophages: phagocytotic giants that can engulf as many as 100 bacteria
Neutrophils
Monocytes: arrive and mature to become macrophages
Neutrophils
Arrive to injured or infected site after macrophages, stored in bone marrow until needed. Move towards infected areas drawn by chemical signals. Slip between endothelial cells of capillary walls (diapedesis). Phagocytose 5-20 bacteria
Die after engulfing bacteria and dead tissue
Monocytes
Circulate in blood until they move into tissues by diapedesis
In the tissues, monocytes mature to become macrophages
Macrophages
Phagocytotic giants that are usually present locally and respond first to injury or infection by engulfing pathogens
Can engulf as many as 100 bacteria
Can also be produced by maturing from monocytes
Die after engulfing bacteria and dead tissue
Pus
Tissue fluid, dead tissue, and dead leukocytes (neutrophils, macrophages) form this substance
Eosinophils
Innate immune cell related to neutrophil
Responds mostly to parasitic infections and control mechanisms associated with allergy and asthma
Granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood
Basophils
Least common, but largest granulocytes
Responsible for inflammatory reactions during immune response, formation of acute and chronic allergic diseases
Produce histamine, serotonin that induce inflammation, heparin that prevents blood clotting
What are the two types of acquired immunity?
B-cell / humoral / antibody-mediated immunity
T-cell / cell-mediated immunity
B-cell Immunity
Effective against bacteria, fungi, parasitic protozoans, viruses, and blood toxins
Cannot act against invading substances that have already made their way into cells
Promoted by B-lymphocytes (each make specific antibody which can bind to antigen on pathogen)
B-lymphocytes
Differentiate and mature in adult bone marrow and fetal liver
Each makes a single type of antibody / immunoglobulin, which recognizes and binds to foreign particle / antigen
B-lymphocyte displays antibody on membrane (B cell receptor or BCR)
Recognizes antigen by binding and triggers primary response (20 days)
Antigen-antibody recognition
When B cell receptor (BCR) binds to specific foreign antigen
Portion of antibody is highly specific to antigen and is known as antigenic determinant
What is the primary response of B-cell mediated adaptive immunity?
BCR of B-lymphocyte binds to foreign antigen
Assisted by helper T-cell, B-lymphocyte then differentiates into plasma cells and memory B-cells which can produce many antibodies to respond to foreign invaders
Takes 20 days to reach full potential
What is the secondary B-cell mediated response?
When memory B-cells and Plasma cells have already been made be previous recognition, the B-cells and plasma cells will act to produce many antibodies to bind to foreign invader quickly
Takes ~5 days to reach full potential
How do antibodies promote destruction of harmful invading substances?
- Antibodies may mark antigen for phagocytosis by macrophages and natural killer cells
- Antibodies can bind and start cascade of complement protein response to perforate foreign cell
- Agglutination or precipitation of antigenic substances, or block chemically active portion
- Free antibodies attach bases to mast cells, which release histamines and other chemicals once antibody binds to antigen
How do vaccines use the adaptive immune system?
Expose body to inactivated portion of pathogen to build memory B-cells and plasma cells, which can then mount a powerful and specific attack against pathogen once exposed
Protects against future infection
Antibody Structure
Made up of two heavy chains and two lights chains
Has variable region which is the antigen-specific region, constant region which is just below this, and then transmembrane domain which attaches antibody to cell in some cases
Connected via disulfide bonds
Variable region: composed of 110-130 amino acids from both heavy and light chains
T-cell Immunity
Effective against free-floating substances and involves T-lymphocytes, which have T cell receptors (TCRs) that recognize antigens
TCR recognizes appropriate antigen and differentiates into helper T-cells, memory T-cells, suppressor T-cells, and killer T-cells (cytotoxic T-cells)
Helper T-cells
Assist in activating B-lymphocytes
Activate other types of T-lymphocytes, including killer and suppressor T-cells
Memory T-cells
Long-lived memory cells which have similar function to memory B-cells in secondary immune response
Suppressor T-cells
Play negative feedback and regulatory role in immune system
Killer T-cells
Bind to antigen-carrying cell and release perforin (protein that punctures the antigen-carrying cell)
Can attack many cells because they do not phagocytize their victims (unlike macrophages, or neutrophils)
Not destroyed when they kill pathogens
Responsible for fighting some forms of cancer and for attacking transplanted tissue
Major histocompatibility complex (MHC)
All human cells express these molecules on their cell surface (except cells without nuclei) Display antigens for recognition Two classes: MHC class I, MHC class II
MHC Class I
Display antigens derived fro intracellular pathogens, such as viruses and some bacteria All nucleated cells have MHC class I Endogenous pathway: process by which intracellular antigens are processed and displayed on cell surface
MHC Class II
Display antigens derived from extracellular pathogens
Antigens must be phagocytosed, so displayed on phagocytotic cells termed professional antigen presenting cells (APCs)
- include macrophages, dendritic cells, some B-cells
Exogenous pathway: Process by which antigens are processed and displayed by MHC class II moelcules
What purpose does the requirement of two signals to active B and T cells have?
First signal: BCR or TCR recognizes appropriate antigen
Second signal: ‘danger’ signal received with active infection
Protects against autoimmune response
What are the four general steps of the exogenous and endogenous pathway for MHC molecules?
- Antigen uptake: antigen either already present or phagocytosed into cell
- Antigen processing: pathogen or molecule processed into smaller peptides (antigens). Cytosol in endogenous pathway, vesicles in exogenous
- Peptide-MHC association: antigens associate with MHC molecules, which are folded in ER. Endogenous, fuses with ER, exogenous vesicle with MHC molecules fuses with vesicle with antigens
- Cell surface expression: antigen-MHC complex expressed on cell surface to interact with immune cells
Where do T-cells receive signals 1 and 2 for activation?
Signal 1 is from professional APCs through binding to MHC complex II with antigen
Signal 2 provided via different cell surface receptors- components of innate immune system in response to infectious insults (cytokines or other membrane surface proteins)
Causes proliferation and differentiation
Where do B cells receive signals 1 and 2 for activation?
Signal 1: free floating antigen cross-links multiple BCRs on same cell
Signal 2: usually by helper T cells
Both required for proliferation and differentiation
Where does lymphocyte activation usually occur?
Infection often occurs in connective tissues
B-cell and T-cell activation often take place in nearest lymph node
Spleen, gut, and other locations with lymphatic tissues in body
Why do lymph nodes swell during infection?
B and or T-lymphocytes are rapidly proliferating in response to pathogen
Why is proper regulation important for immune system function?
Too much regulation renders the immune system deficient and unable to properly protect against foreign invaders
Too little regulation can result in autoimmune diseases, where a hyperactive immune system attacks the body’s own tissues
Clonal selection
A process in which after the random generation of BCRs or TCRs, only certain types are permitted to mature and proliferate
- Cells must show that they are capable of recognizing antigens in context of host MHC molecules. If cannot recognize MHC molecule, undergoes apoptosis (positive selection)
- Cells must show that they are not inappropriately activated by host cells in absence of infection. B and T cells that respond too strongly to MHC molecules with self-antigens undergo apoptosis (negative selection)
Where do B and T cells undergo clonal selection?
T cells undergo clonal selection in thymus
B cells undergo clonal selection in bone marrow
Cells that survive selection process are released to lodge in lymphoid tissue or to circulate between blood and lymph fluid
What are some causes of autoimmune diseases?
One major cause could be a failure of clonal selection
For example, a failure in negative selection can result in the production of B or T cells that respond to self-antigens
There are many other immunoregulatory mechanisms can result in autoimmunity as well
What types of cells will react to an antigen bound to an MHC class I molecule?
Cytotoxic T cells which then are stimulated by helper T cells as well to differentiate into memory cytotoxic T-cells and active cytotoxic T cells
Active cytotoxic T cells will cause lysis of infected cells
Memory cytotoxic T-cells will respond quicker in secondary infection
In secondary infection, what does an antigen stimulate?
Stimulates memory B-cells, Memory helper T-cells, and Memory cytotoxic T-cells
How are blood types identified?
A and B surface antigens
In type A blood, RBCs have A antigens and not B antigens
Immune system will make B antibodies and not A antibodies
In type O blood, immune system makes both A and B antibodies
Rh factors
Surface proteins on RBCs, first identified in Rhesus monkeys
Individuals that encode for nonfunctional products of Rh gene are Rh-negative, while others are Rh positive
In second Rh positive pregnancy, mother has produced Rh positive antibodies which could pass through placental barrier and attack the fetus
