Chapter 21 The Lymphatic and Immune Systems

Functions of the lymphatic system

Drains excess interstitial fluid
Transports dietary lipids and lipid- soluble vitamins
Carries out immune responses

lymphatic system structure

-Lymph
-Lymph vessels
structures/organs with lymphatic tissue
-Red bone marrow
--Lymphocytes
-Most components of blood plasma filter through capillary walls to form interstitial fluid
-When this interstitial fluid passes into lymphatic vessels, it's called lymph
-Lymphatic capillary → lymphatic vessel → lymph node

formation and flow of lymph

More fluid filters out of blood capillaries than returns to them by reabsorption
--Excess filtered fluid drains into lymphatic vessels and become lymph
--Important function of lymphatic vessels to return lost plasma proteins to bloodstream
Contain valves

primary lymphatic organs

Sites of formation and maturation of lymphocytes
Red bone marrow and thymus

secondary lymphatic organs

Sites where most immune response occurs, houses lymphocytes
Lymph nodes, spleen, lymphatic nodules, tonsils, MALT

Mucosa-associated lymphatic tissue (MALT)

Not surrounded by capsule
Scattered throughout lamina propria of mucous membranes lining GI, urinary, reproductive tract
Most small and solitary
Some larger- tonsils, Peyer's patches, appendix

lymphatic vessels

-Do not form circuit (one way only)
-Vessels begin as lymphatic capillaries
-Unite to form large lymphatic vessels
-Like veins but
--Thinner walls
--More valves
--Endothelial cells just overlap, no tight junctions
-Tied closely with cardiovascular system
-Found everywhere except avascular tissues, CNS, parts of spleen, bone marrow, cornea

blood vessels

form circuit

which parts of the body the thoracic duct and right lymphatic ducts each drain

The right duct drains most of the right upper quadrant whereas the thoracic duct drains the lower body including the extremities and abdomen

macrophages

very large, avidly phagocytic cells of the connective tissues
-antigen -presenting cells (APCs): macrophages and other cells that alter the immune system to the presence of an enemy

dendritic cells

branched, mobile APCs found in the epidermis, mucous membranes, and lymphatic organs
-Alert immune system to pathogens that have breached the body surfaces

reticular cells

branched, stationary APCs that contribute to the connective tissue framework (stroma) of the lymphatic organs

red bone marrow

Soft, loosely organized, highly vascular material, separated from osseous tissue by the endosteum of the bone
Red color comes from abundance of erythrocytes

thymus (cortex)

T cells, dendritic cells, epithelial cells, macrophages
Only 2% of developing T cells survive → medulla

thymus (medulla)

More mature T cells, epithelial cells, dendritic cells, macrophages
T cells migrate to lymph nodes and other lymphatic tissue

When does the thymus atrophy?

puberty

lymph nodes

Located along lymphatic vessels through body
Lots of pathways into the lymph nodes but only one pathway out of the lymph node (efferent pathway)
Functions as a filter: 99% of foreign substances are trapped and destroyed in each node

regions of lymph nodes

-Outer cortex: aggregates of B cells called lymphatic nodules (follicles)- site of plasma cell and memory B cell formation
-Inner cortex- mainly T cells and dendritic cells
-Medulla- B cells, antibody producing plasma cells from cortex, macrophages

spleen

Organ near the stomach that produces, stores, and eliminates blood cells

spleen white and red pulp

White pulp: lymphatic tissue
Red pulp: blood filled venous sinuses
Functions of red pulp:
--Removal of ruptured/worn out/defective blood cells and platelets by macrophages
--Phagocytosis of bacteria
--Platelet storage
--Hematopoiesis (during fetal period only)

tonsils

Tonsils are a type of Mucosa-associated lymphatic tissue (MALT)
Help protect against foreign substances that are inhaled or ingested

appendix

Small tube located at the first part of the large intestine
Contains a high concentration of lymphoid follicles
Helps destroy bacteria in GI tract

metastasis

Spread of disease from one part of the body to another
Can occur via lymphatic vessels (you can predict secondary tumor sites by direction of lymph flow)
Cancer spreads this way

pahtogen

disease-producing microbe

immune system

a system of diverse defenses against disease

first line of defense

Defenses present at birth
Epithelial barriers (skin and mucous membranes)
Nonspecific- impenetrable to most of the pathogens we face daily
Include
--Cells (neutrophils, macrophages, NK cells)
--Chemicals (IFN, complement)
--Processes (inflammation, fever)

second line of defense

-Protections against pathogens that break through external barriers
-Leukocytes and macrophages, antimicrobial proteins, natural killer cells, fever, and inflammation

third line of defense

-Adaptive immunity
-Group of mechanisms that defeat the pathogen and leave the body with a memory of it, enabling one to defeat it quicker in future encounters so that the pathogen causes no illness

innate vs adaptive immunity

Innate immunity: An individual's genetically predetermined resistance to certain diseases.

Adaptive immunity: Ability of the body to react to specific microbial infection. ANTIGEN SPECIFIC

neutrophils

aggressively antibacterial leukocytes
-Respond most quickly too tissue damaged by bacteria
--Use lysozymes, strong oxidants, defensins

basophils

secrete chemicals that aid mobility and action of other leukocytes
-Leave capillaries and release granules containing heparin, histamine and serotonin, at sites of inflammation
(Intensify inflammation reaction)

Eosinophils

Found especially in mucous membranes
Stand guard against parasites, allergens, and other foes

Lymphocytes

-T lymphocytes (T cells): lymphocytes that mature in the thymus
--T \= thymus dependent
-B lymphocytes (B cells): lymphocytes that differentiate into plasma cells- connective tissues cells that secrete antibodies
--B \= think bone marrow

monocytes

Leukocytes that emigrate from the blood into the connective tissues and transform into macrophages

natural killer cells (NK cells)

large lymphocytes that attack and destroy bacteria, transplanted tissues, and host cells that have become infected with viruses or turned cancerous

immune roles of interferons

-Induce synthesis of antiviral proteins
-Interfere with virus replication inside body cells
-Stimulate macrophages and NK cells to destroy infected cells
-Binds to neighboring cells, preventing infection
-Effective against any type of virus

complement end result

-Composed of ~30 normally inactive proteins
-Enhances other innate and adaptive immune reactions
-Mechanisms of action
--Opsonization
--Inflammation
--Cytolysis (membrane attack complex)
--Elimination of immune complexes

opsonization

'butters up' the foreign cells to make them more appetizing to phagocytes (makes bacteria more tasty)

membrane attack complex (cytolysis)

the complex of terminal complement components that forms a pore in the membrane of the target cell, damaging the membrane and leading to cell lysis.

leukocytosis

Increase number of neutrophils in 4-5x in a few hours

Margination

Inflamed endothelium sprout selectins (CAMs, 'velcro' for WBCs)
CAMs on WBCs stick to the CAMs on endothelium

Diapedesis

Neutrophils squeeze through endothelial cells into interstitial fluid

chemotaxis

Neutrophils arrive at infected site by following chemicals

phagocytosis

1. Phagocyte adheres to pathogens or debris
2. Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome
3. Lysosome fuses with the phagocytic vesicles, forming a phagolysosome
4. Lysosomal enzymes digest the particles, leaving a residual body
5. Exocytosis of the vesicle removes indigestible and residual material

Describe the mechanism of fever and the role of pyrogens

Hypothalamic 'thermostat' is reset by pyrogens
Pyrogens released by activated WBCs
Bacterial toxins also sometimes elevate temperature

why fever can be beneficial

Intensifies effect of interferons
Inhibits some microbe growth/reproduction
Speeds up repair

process of inflammation

Immediate, local, nonspecific defense to tissue damage
-itis ending
Stages
--Inflammatory chemical release
--Vasodilation, increased vascular permeability
--Phagocyte mobilization
--Tissue repair

4 cardinal signs of inflammation

redness, heat, swelling, pain

histamine

major contributor to inflammation (basophils)

Kinins (bradykinin)

extremely painful, kickstarts inflammation

Eicosanoids

-Prostaglandins: cause a person to feel pain
-Leukotrienes: bring WBCs which can help clean up the area

complement (inflammation)

stimulate basophils and mast cells to secrete inflammatory chemicals

inflammatory chemical release

-Macrophages have special toll-like receptors (TLRs) that allow them to 'sound an alarm' when they bind an antigen
--11 types of TLR
--Each different type of TLR recognizes a different type of pathogen
--TLRs signal the release of cytokines

why can inflammation be beneficial

The area you injured will become red and swell as an army of beneficial white blood cells flow in to fight infection and help you heal.

Interleukins (ILs)

regulate immune cells

Interferons (IFNs)

antiviral agents

Tumor necrosis factor (TNF)

destroys tumor cells, may have other functions

Define adaptive immunity (third line of defense)

Generates a specific response to a specific pathogen
Has memory from previously encountered antigens

Cellular (cell-mediated) immunity

-employs lymphocytes that directly attack foreign cells or diseased host cells
--Rid the body of intracellular viruses, bacteria, yeasts, and protozoans
--Also acts against parasitic worms, cancer cells, and cells of transplanted tissues and organs

Humoral (antibody-mediated) immunity

employs antibodies, which don't directly destroy pathogens but tag them for destruction
--Effective against extracellular viruses, bacteria, yeasts, protozoans, and molecular (noncellular) disease agents

active immunity

the body makes its own antibodies or T cells against a pathogen

passive immunity

the body acquires antibodies or T cells from another person or animal that is immune to the pathogen

natural immunity

Immunity that is partly inherited and partly developed through healthy living.

artifical immunity

Immunity gained either by vaccination or receiving ready made anti bodies.

How are vaccines made?

Attenuated or dead microorganism
Designed to not cause disease, but make your body produce antibodies

antigen

a substance that generates an immune response
-Antibody generating
-Can be foreign or self (autoimmune disorders)
-Can be part of cell or a whole cell
-Epitope (aka antigenic determinant): specific site on antigen that is recognized by immune system

antigen receptor

a surface protein, located on B cells and T cells, that binds to antigens, initiating adaptive immune responses. The antigen receptors on B cells are called B cell receptors, and the antigen receptors on T cells are called T cell receptors.

T cell development

The thymus is the central lymphoid organ of T cell development
Development of antigen-specific T cell receptors (TCRs)
Leave thymus, travel to and reside in lymphoid tissue as mature immunocompetent cells

B cell devlopment

-B cells mature in the red bone marrow.
-About 10% of the total produced per a day enter circulation, while the others are destroyed during positive and negative selection.
-Similar to T cells, the self tolerant B cells form many clones, which disperse throughout the organs and lymphatic tissues of the body.

antigen-presenting cells (APCs)

-any immune cell that functions to tell other immune cells about an antigen presence
Types of APCs
--Dendritic cells
--Macrophages
--B lymphocytes (B cells)

role in immune response (antigens, lymphocytes, and interleukins)

-Lymphocytes act both as antigen presenting cells and as cells which recognize antigens and APCs. They can attack foreign cells.
-APCs have surface proteins which bind antigens and internalize them via endocytosis, where it is then digested. The cell "tags" itself with epitopes and presents to T cells.
-Interleukins are a class of chemical signals with which lymphocytes and APCs talk to one another.

Describe the structure of antibodies

-Heavy chains: about 400 amino acids long (identical to each other)
-Light chains: about 200 amino acids long (identical to each other)
-Constant region
--Determines the mechanism of an antibody's action (whether it can bond complement proteins)
--Nearly the same in all antibodies
-Variable region
--Tips of heavy and light chains; form an antigen binding site on each arm
-Antigen binding site
--Where the antibody attaches to the epitopes of antigen molecules

IgG

immunoglobulin G
Main ab type in circulation
Binds to pathogens
Activates complement
Enhances phagocytosis
Only ab that can cross placenta

IgA

immunoglobulin A
Main ab in secretions (saliva, sweat, milk)
Prevents pathogens from attaching in digestive and respiratory tract

IgM

immunoglobulin M
Largest ab
Pentamer, or monomer on B cell surface
Activates complement
Causes agglutination (clumping and lysis)

IgE

immunoglobulin E
Ab found on basophils and mast cells
Immediate allergic response
Hypersensitivity reactions

IgD

immunoglobulin D
Found on immature B cells
Involved in B cell activation

helper (CD4) T cells

promote action of TC cells as well as play key roles in humoral and innate immunity (all other T cells are involved in cellular immunity only)

cytotoxic (CD8) T cells

are the 'effectors' of cellular immunity that carry out the attack on foreign cells

memory cells

descended from TC cells and are responsible for memory in cellular immunity

MHC

major histocompatibility complex antigens

MHC class I are found in

all body cells except RBCs

MHC class II are found in

antigen-presenting cells

MHC I and MHC II function

Both classes of proteins share the task of presenting peptides on the cell surface for recognition by T cells

why do T cells mature

-T cells mature in the thymus and undergo the positive and negative selection to become limited to recognizing a specific class of MHC protein
--Positive selection: TCRs must recognize and bind MHC (self-recognition)
--Negative selection: TCRs must not bind to self-antigens (self-tolerance)

What class do T cells recognize

Helper (CD4) T cells: MHC II
Cytotoxic (CD8) T cells: MHC I

T cell activation

1. Antigen recognition: T cell binds to an APC displaying an antigen fragment (epitope)
2. Costimulation: T cell binds to a second protein on the APC
3. Clonal selection: T cell undergoes repeated mitosis and produces a large number of effector cells and memory T cells
4. Attack: effector TC cells attack and destroy abdominal cells with a lethal hit; TH cells secrete interleukins that stimulate multiple forms of attack

colonal selection

the development of clones of B and T cells against a specific antigen

1st encounter with antigen

Only a few lymphocytes will recognize it
Lymphocytes need time to replicate
You start feeling better when antigen-specific lymphocytes start to outnumber antigens
Even after the pathogen is eradicated, some specific "memory" lymphocytes hang around

2nd encounter with antigen

Memory lymphocytes quickly replicate and eradicate pathogen
You may not even know you had an infection
Memory lymphocytes can live for decades

helper T cells (CD4 cells)

-When a helper cell recognizes an Ag-MHC protein it secretes interleukins that exert three effects
--Attract neutrophils and natural killer cells
--Attract macrophages, stimulate their phagocytic activity and inhibit them from leaving the area
--Stimulate T and B cell mitosis and maturation

cytotoxic T cells (CD8 cells)

-When cytotoxic cell recognizes a complex of antigen and MHC-I protein on a diseased foreign cell it 'docks' on the cel, delivers a lethal hit of chemicals that will destroy it, and goes off in search of other enemy cells while the chemicals do their work
-Chemicals:
--Perforin and granzymes: kill target cell in same manner as \---NK cells
--Interferons: inhibit viral replication and recruit and activate macrophages
--Tumor necrosis factor (TNF): aids in macrophage activation and kills cancer cells

Explain the role of memory cells in cellular immunity.

-Thousands of memory cells exist after initial encounter with an antigen
-Next time antigen appears can proliferate and differentiate within hours
-Antibody titer measure of immunological memory
--Amount of Ab in serum

roles of a B cell

-B cells are also antigen presenting cells
-Begins with B cell activation
--B cell receptor can bind an antigen
--B cells can also be activated by Helper T cells
--Helper T's secrete IL-4 to stimulate B cells
-B cells → plasma cells after activation
-BCRs look like the antibodies they will produce
-Clonal selection
--Some cells become plasma cells
--Others become memory cells

antigen presentation

antigen-MHC complex is inserted into plasma membrane of a body cell
B cells can recognize and bind to antigens in lymph, interstitial fluid, or blood plasma
T cells must have antigens processed and presented to them

endogenous antigen processing

-body cell
-MHC I
-cytotoxic CD8 T cells
-cell death (apoptosis)

exogenous antigen processing

-APC
-MHC II
-Helper CD4 T cells
-release cytokines and stimulate APC

plasma cells vs memory B cells

Following an immune response two types of differentiated B cells persist in the memory pool:
plasma cells: confer immediate protection by the secretion of specific antibodies
memory B cells: confer rapid and enhanced response to secondary challenge

Neutralization

the masking of critical regions of an antigen molecule by the antibodies
--Antibodies can neutralize an antigen by masking active regions (pathogenic regions)

complement fixation

antibodies complement proteins to an enemy cell, leading to its destruction
--Primary mechanism of defense against foreign cells such as bacteria and mismatched erythrocytes