PSL NOTES

IMMUNITY SYSTEM

OVERVIEW

FUNCTIONS OF IMMUNE SYSTEM

• Destroy pathogens
• Detect and kill abnormal cells (ex. cancerous)
• Remove dead cells and other debris from body.

PATHOGEN CLASSIFICATION
Can be classified by size and where they live in the body. Other than parasitic worms, everything
else is microorganisms. Worms, fungi, protozoa, bacteria, viruses

VIRUSES
• Must reproduce inside cells.
• Take over host mechanisms.

BACTERIA, PROTOZOA, FUNGI

• Some hide inside cells, but most are extracellular

PARASITIC WORMS

• Always extracellular

LINE OF DEFENCE
1. Surface Barriers (Innate External Defenses)
2. Innate Internal Defenses - check identification and always ready to attack foe
3. Active Defenses (adaptive), consists of 2 Lymphocytes, T and B

INNATE DEFENSES
• Recognize markers on pathogen
• When overwhelmed, secrete chemical messenger to mobilize lymphocyte

ADAPTIVE IMMUNITY
• Specificity
• Involves the two group of clones, B and T lymphocyte
• Have memory
• Systemic, act anywhere on body
• They recognize specific markers for pathogen (antigenic determinant), usually proteins, but
can be carbohydrate and nucleic acids.
 • Antibody can also bind antigen, and is secreted by cells known as plasma cells (descendent
of B cells)
• Humoral immunity target extracellular pathogen, can be transferred through body fluid,
carries antibody and B Cells. . Require helper T Cells.
• Cellular immunity target intracellular pathogen, it involves T Cells and attack our own cell.
Cannot be transferred through body fluid.

CHARACTERISTICS OF B AND T LYMPHOCYTES

• Specificity of receptors
• Diversity of receptors (for different antigens)
• Regulations of activation. Activation lead to clonal expansion.
• Memory
• Normal body cells can produce its own antigens, but lymphocyte must not recognize it or
it's autoimmune disease. Specificity stops this from developing, and this is developed in a
process called education.
• Each B and T cell surface have lymphocyte antigen receptor, which bind to antigenic
determinants, and determine specificity.
• all the antigen receptor on an given cell is identical
• Cells with different specificity have different antigen specificity, and bind optimally only to
one antigenic determinant.
• B and T cell antigen receptor have differences in their shape and ways of interactions.
• Immune system have to recognize millions of antigens.
• Variety of receptors are made in advance, antigen select for the correct receptor, and the cell
attached gets signaled and make clones, thus called clonal selection.
• Clonal selection theories assume body makes 100 millions of different receptors.
• Small number of genes create many receptors.
• The bone marrow and thymus is referred to as primary lymphoid organs because
lymphocyte is produced there.
• Lymphocyte circulate the system to hunt for antigens.
• They go through secondary lymphoid organs (spleen, and lymph node) to find antigen, then
search in circulation. Repeat.
• Activation occurs when naive cell bind to antigen.
• Clonal expansion create effector cells and memory cells (can be reactivated).

RECEPTOR PRODUCTION
• Constant region - always the same, the gene code for it never changes
• Variable region- Mixes and matches bits of DNA in the small set of genes to create the final
protein
• Both T and B cell receptor work under the same concept
• Random selection of DNA create cases where the protein is non-functional, during which
case the cell that made them dies

MATURATION
• Must create a successful receptor through DNA segment matchin
 • Survive education, or apoptosis.
• Education for T cell occur in the thymus.
• Some lymphocyte that can weakly recognize self-antigens are allowed to mature, which can
cause autoimmune diseases. Ex. Type 1 diabetes mellitus, Grave's disease, multiple
sclerosis, and hemolytic anemia.
• Activation of lymphocytes, and regulatory T Cells can suppress self-reactive lymphocyte.
Failure to do so can be caused by pathogen that resemble self-antigens, changes in structure
of self-antigens by attachment of foreign particles, or trauma that release self-antigens that
are normally hidden, for ex. behind the BBB
• Those that pass education are immunocompetent.
• They are naïve because they haven't encountered antigens.

B CELLS
• Receptor is an anti-body, similar to the ones excreted except it is buried in the membrane.
• When bacteria bind, receptor signal binding to cell.
• Start and mature in bone marrow.
• When activated, forms effector cells called plasma cells, which produce antibodies.
• Measure immune response magnitude by measuring antibody concentration
• First antibody response appears in about 7 days, then peak, then decline.
•

T CELLS
• Receptor is not an antibody, or Y-shaped.
• Bind to major histocompatibility complex (MHC) proteins which express the antigen on the
surface of cells.
• Start in bone marrow then migrate to thymus to mature.
• Go to thymus, divide, reshuffle DNA, create new antigen receptor.
• Education occur from thymus, and migrate to medulla.
• Test 1 - positive selection, the receptor can recognize self MHC by binding to it on antigen-
presenting cells, for example, dendritic cells. Failure to recognize Apoptosis
• Test 2 - test to see if it recognize any self-antigens presented by antigen presenting cells. If
recognized  Apoptosis, if not, then it's self-tolerant and continues to mature.

PRIMARY IMMUNE RESPONSE

• First time encounter
• Secondary lymphoid organs are site of activation
• Generate first memory cell
• Make use of this when introducing artificial antigen to cause a primary response

SECONDARY IMMUNE RESPONSE

• Infected again by previously infected antigen
• Memory cell from first response allow for faster and greater response
• Can normally get rid of pathogen without showing symptoms
ANATOMY OF IMMUNE SYSTEM

• Immune system is positioned where pathogen is most likely to enter

• respiratory, digestive tract
• Consists of leukocyte and lymphoid organs (bone barrow, lymph nodes, spleen, thymus-
where lymphocyte are and come into contact to pathogens)

CELLS OF IMMUNE SYSTEM

• Originate in bone marrow
• can migrate to target tissue and stay or circulate in blood
• traveling immune cells are leukocytes.
• From least to most: Neutrophil > Lymphocytes > Monocytes > Eosinophil > Basophil
• Leukocyte normally found in blood

NEUTROPHIL PHYGOCYTE
• multi-lobed nucleus • Engulf and destroy
• most common pathogen, dead cells
• in blood and debris
• normally not found • essential in both
in health tissues innate and adaptive
• first to leave blood immune response
and enter tissue at • destroy pathogen
site of infection or using lysosomal
trauma enzymes
• attracted to tissue • use mannose
by chemicals receptor and Toll-
released from cell like receptors
• shor t lived, only (TLRs) on their
phagocyte a few membrane to
pathogen before recognize molecules
dying on pathogens
MONOCYTE MACROPHAGE • at least 10 TLRs ANTIGEN-
bind to different PRESENTING CELLS
• U shaped • came from (APC)
pathogen
nucleus monocyte
• when bind, it ingest • present antigen on
• no granules • less in number
pathogen and send surface to t cells
• develop into • in tissue chemical signal to
macrophages • normally present in mobilize other
• follow influx of tissue, either free innate and adaptive
neutrophil to that circulate immunity
tissue, and system, or fixed • it wraps its
transform into such as Kupffer cytoplasm around
macrophage cells in liver or pathogen to form
microglia in brain phagosome, and
• can consume many engulf it
pathogen • H+ are pumped into
• if pathogen is too phagosome to make
large, macrophage it acidic
 can release • enzyme in
enzymes phagosome convert
oxygen gas to
reactive oxygen
intermediate called
respiratory burst.
For ex. super oxide,
or hydrogen
peroxide, other
enzyme create boxi
nitric oxide
• phagosome combine
with lysosome to
form
phagolysosome
where hydrolytic
enzyme digest
pathogen, defensins
poke holes in
bacteria, and
enzymes convert
reactive oxygen
intermediate to
chemicals similar to
bleach
• have receptor for
opsonins
DENDRITIC CELL
• capture antigen in
periphery, then
migrate to lymph
node, to present it
• on skin surface
LYMPHOCYTES B CELLS EFFECTOR CELLS
• rounded nucleus • specialized • adaptive immunity
• small lymphocyte
• B cells and T cells • antibody on
• originate from stem membrane
cell in bone marrow • in blood
T CELLS
• specialized
lymphocyte
• MHC on membrane
• in blood
MAST CELLS
• other function in
host defenses
 • found in tissue

EOSINOPHIL

• bi-lobed nucleus
• Red staining granules
• defend against parasites
• contribute to allergies

BASOPHIL
• blue staining
• least in quantity
• granule chemical mediate inflammation, include histamine

PRIMARY LYMPHOID ORGANS

• Thymus
• Bone Marrow
• Where lymphocyte matures

SECONDARY LYMPHOID ORGANS

• Tonsils (guard the mouth and nose), spleen, lymph nodes, Peyer's patches (guard digestive
track), appendix
• where lymphocytes are activated, and come into contact with pathogen
• strategically located
• house macrophages and other immune system cells

LYMPHATIC SYSTEM
• one way vessel, with fluid called lymph
• overlap with immune system
• have lymph node
• 3L of interstitial fluid escapes the circulatory system and goes from the capillary to lymph
capillaries
• interstitial fluid is filtered through lymph node and remove antigens and return to
circulation
• if lymphatic do not function properly, fluid build up in tissue (lymphedema), antigen is not
delivered to lymph node, and lymphocyte will not activate, thus have increased risk of
infection.
• Lymph capillaries are full of overlapping endothelial cells that anchored to surrounding cell
by collagen filament.
• It allow build up fluid to push through and enter but create a one-way valve.
• Plasma proteins, pathogen, antigens, and dendritic cells enter lymphatics this way.
• Larger lymph vessel have valves
• Lymph drains into circulatory system at the neck vein
• Lacteal (special lymph cappilaries) transport fat into blood.
• Lymph node occur where cluster of lymphatic vessel occur (axillary-armpit, cervical-neck,
and inguinal)
 • Lymph node filter fluid, and collect antigen to activate B and T cells.
• Afferent vessel (into node) carry antigen, go into cervical side of lymph node
• Efferent vessel, fewer than afferent, slow flow speed to filtering, lined with dendritic,
lymphocyte and macrophages.

LYMPH NODE
• Covered by connective tissue capsule
• Separated into sections by trabecula (capsule extended into center)
• Beneath capsule is subcapsular sinus (interconnected dilated channels)
• Lymph from afferent first enter subcapsular sinus, then outer cortex
• Outer cortex is below subcapsular sinus
• Lymphoid follicles (contain B cells) is in outer cortex
• Lighter regions in side lymphoid is germinal centers, where B cell proliferate in response to
antigen
• Deep cortex is after outer cortex, lymphocyte exit blood and enter here
• T cell located in deep cortex
• The central region (medulla) is medullary cord
• Medullary cord contain macrophage, plasma cells, and both type of lymphocyte
• Hilium is where the efferent vessel is attached

SPLEEN
• blood rich
• cleansing function, spleen is to blood, as lymph node is to lymph
• remove pathogen, aged erythrocyte and platelet from blood
• Store platelets, break down products of erythrocytes
• Provide interaction between lymphocyte to antigens in blood
• Highly vascular, veins and artery go through hilium
• Also contain capsule and trabeculae
• Most spleen is red pulp, where filtering occurs, contain reticular fibers (fibroblasts anc
macrophages  splenic cords)
• White pulp surround artery  collection of lymphocyte
• artery go into the spleen, and divide, and become central artery, which divide and go into
red pulp, and squeeze to the venous sinusoids
• Macrophage in splenic cord gobble up aged erythrocytes and platlets
• aged erythrocytes are stiff so they fragment when going through sinusoids, thus engulfed by
macrophage
• White pulp consists of B and T cells (light staining germinal centers), removes antigen

MUCOSA-ASSOCIATED LYMPHOID (MALT)

• include tonsil, appendix, Peyer's patches
• include some cells from respiratory and other mucosae
• have unencapsulated or partially encapsulated lymphocytes
• contain both B (MALT) and T cells
• pathogen that escapes MALT is detected in spleen or lymph node

PALATIN TONSIL
 • Posterior end of oral cavity

PHARYNGEAL TONSIL
• in nasopharynx
• pathogen go into crypts, and stimulate immune, form germinal centers
• when overflow bacteria, it will harbor instead of kill bacteria

LINGUAL TONSIL
• collection of lymphoid nodules at base of tongue

APPENDIX
• stems from large intestine
• large concentration of lymphoid follicles
• can be overflow with bacteria as well appendicitis (blocked entrance, swelling due to
bacterial growth)
• Ruptured appendix spills pathogen to peritoneal cavity (usually steril)

PEYER'S PATCH
• distal small intestine
• also have lymphoid follicles

THYMUS
• site for maturing of T cells
• release thymic hormones and other factor to develop immature T cells
• bi lobed
• in mediastinum
• Thymus tissue slowly replaced by fat as we age  thymic atrophy
• thymic lobe divide into lobules
• lobules consists of outer cortex, and inner medulla
• thymic epithelial cell surround immature T cells and secrete thymic hormones
• within medulla is Hassall's corpuscle

HASSALL'S CORPUSCLE

• scattered in medulla
• keratinized epithelia cells
• might be responsible for development of regulatory T cells

HUMORAL IMMUNITY

• involves B cells
• secreted antibody from B cells are also known as gamma globin
• can be acquired passively or actively
• Active is when body make antibodies when encountering antigen
• Active can be naturally or artificially acquired
• Active immunity generate memory cells
 • Passive immunity occurs when you receive antibodies from another person
• It can also be naturally or artificially acquired
• Naturally acquired can be from mother to fetus in placenta or through breast milk
• Artificially have gamma globulins, Given when our body can't mount enough of immune
response, like hepatitis A or rabies. Antivenom is also included.

Humoral Immunity
Active
Passive
Body encounter pathogen and generate
its own antibodies Acquired immunity from another
individual
Generate memory cells

Naturally Artificially
Artificially From mother to fetus Given when body can't
Naturally
Vaccination through placenta, or mount enough
breastr milk immune response

ANTIBODIES
• antibody has 4 subunit, 2 heavy, 2 light, symmetrical, connected by disulfide bond
• variable region is the antigen binding pocket
• constant regions never change
• contain two antigen binding site, both heavy and light chain contribute to it
• arm interact with antigen, the stem determine its fate, whether it's on B cells, or
complement, or opsonin for phagocyte, whether it dimerizes and etc, and whether it's
secreted into blood, or in lumen, or across placenta, of in secretion like saliva.
• Five classes determined by the stem: IgM, IgA, IgD, IgG, IGE (aka MADGE)
• do not by themselves destroy pathogens

IGG
• most referred class of antigen
• largest group, promotes inactivation or destruction of toxins
• natural passive immunity, by crossing from mother to baby through plencata
• formed late in primary response, always present in second response
• used clinically to artificially transfer immunity

IGM
• secreted as a pentamer, 10 binding site
• good at forming aggregates
• good at activating complement
 • first antibody secreted to face new antigen in primary response
• is a monomer on surface of B cells, act as receptors

IGA

• secreted into mucosa of: GI system, respiratory, and genitourinary system

• into fluid like: saliva, sweat and tears, and mother's breast milk (passive immunity to baby)
• Plasma cell secrete IGA, located beneath the epithelial cells
• secreted as dimers, bind to epithelial receptor, and transported across cell in endocytosis,
and wait in mucus on the other side
• covers mucous membrane to protect against pathogen from external environment
• monomers can be found in the plasma
• most produced

IGE
• when parasite interact with parasite warm, Helper T cells and Interleukin-4 (a cytokine) aid
to produce IgE, which coat parasite to mark it for attack
• eosinophil bind to IgE and release toxins from granules to kill parasite
• responsible for allergies, bind to allergens
• sensitization: allergen bind to IgE on mast cell or basophils
• binding to mast cell release granules (include histamine and inflammatory agents. Cause
blood vessel dilation and capillary become more leaky (runny age)
• histamine activate itch receptor  bronchiconstriction, difficulty breathing
• allergy reaction can be cured by anti-histamine
• extensive leaking cause circulatory system collapse  anaphylaxis

IGD
• locate on naïve B cells (along with IgM)
• a B cell receptor, and involved in activating B cells

ANTIBODY MECHANISM
• They work in 4 general way: PLAN
• P: act as opsonin for phagocytosis
• L: initiate complement pathway, which lyses bacteria via membrane attack complex (MAC)
• A: clump pathogens together, agglutination, help phagocytosis, IgM is good at this.
• N: bind to virus's receptor to stop them from binding to cell, also neutralize toxins.

B CELL ACTIVATION
• concentrated in lymph node
• can circulate in blood, then collect in lymph node to find antigen or T or B cells.
• enter lymph node from blood vessel
• move from deep to outer cortex, where they dominant
• go to antigen and encounter follicles
• bound antigen brought into cell
• if it's protein, it is degraded and displayed on surface in MHC
• full activation require T helper cells (located in deeper cortex)
 • B cell migrate to deeper cortex
• Helper T cell recognize and bind to MHC + antigen on B cell
• Other receptor on both cell surface then bind
• cytokine then release from T cell to fully activate B cell
• This process is called co-stimulation, prevent in appropriate activation of B
• antigen formed of repeated subunit like polysaccharide do not need helper T cell, they are
called T cell-independent immune response. IgM is usually responsible for this.
• Activated cell then form plasma effectors and memory.
• Plasma go deeper into lymph node and secrete IgM
• Other form germinal centers in follicles
• B cell in germinal center divide and mutate, then is selected once more for their affinity to
bind to the antigen
• only the best binding B cell survive, this is affinity maturation.
• Depending on cytokine produced by helper T cells, B cell may switch from IgM to IgE, IgA,
IdG
• Plasma release antibody, memory recirculate system to find antigen again

INNATE HOST DEFENSES

• First line of defense: Intact skin, and mucous membrane of GI, Gastrointestinal, and
genitouranary tract

SKIN
• Keratin on surface, tough water resistant layer
• intracellular junctions that hold cells together, like desmosomes and tight junctions
• Acidic skin secretion, such as lysozymes

MUCOUS MEMBRANE
• acidic secretion, including lysozymes (normally included in all secretion)
• Stomach have digestive enzymes, and low pH
• sticky mucous lines digestive and respiratory to trap pathogen
• pathogen traps in mucous get's moved by cilia
• moved back in nasal, up in trachea, toward throat, so they are swallowed
• stomach enzymes kill them

INNATE DEFENSE
• prevent spread of pathogen
• fast acting
• non-specific
• crude protection against pathogen
• Innate defense can pass information to adaptive defenses through chemical messages
• shapes adaptive defenses

PHAGOCYTES
• neutrophils and macrophages
 • essential for both innate and adaptive defenses

NETURAL KILLER
• kill traitorous cells (virus or cancerous)
• a type of lymphocyte, but is part of innate immune system
• Attack infected cells like T cells, also attack transplanted tissue
• larger than other lymphocyte, and have granules
• does not express receptors for antigens
• identify virus and pathogen which lowers expression of membrane protein that define them
as "self" cells.
• both NK and T scan the system, immune surveillance
• NK look for absence of normal protein, T look for presence of abnormal protein
• induce apoptosis in cell
• important in early response, and continue to be present after B and T cell activation
• more effective after cytokine release from certain T cells and coating cells with antibodies

ANTIMICROBIAL PROTEIN
• complements and interferons
• interferons are part of cytokines
• Interferons stop viral replication
• interferon activate immune cells, and modulate inflamation
• they have: alpha, beta, and gamma.
• Gamma signal immune and non-immune cells.
• Interferons produced when viruses replicate in it
• Interferon bind to nearby cell receptor to warn of viral infection
• nearby cell respond by producing protein that degrade viral RNA and prevent synthesis of
viral proteins
• the mechanism is not specific, so a response from one virus can work on any virus in the
area
• complement system enhances other innate and adaptive defenses
• They are a cascade that each enzyme activate to activate the next until product is formed
• they mark cell for phagocytosis, promote inflammation, and can kill bacteria themselves
• The cascade is complex to provide regulation
• both innate and adaptive defense can activate it
• complement identify pathogen by finding abnormal membrane protein, or not finding
normal proteins
• Complement activation involves many pathway, which all end into common pathway

COMMON PATHWAY
• All pathway activate C3
• C3 is split into C3a (inflammation) and C3b (opsonization)
• Enhance inflammation alerts and attract both adaptive immune and innate immune
• C3b cleaves C5 C5a (inflammation) and C5b
• C5b combine with C6+C7+C8+C9 on bacteria membrane to form membrane attack complex
(MAC)
 CLASSICAL PATHWAY
• antibody involved

LECTIN PATHWAY
• involves lectin, which bound to abnormal polysaccharide on bacteria

ALTERNATIVE PATHWAY
• when normal inhibitory proteins on surface membrane is not found

INFLAMMATION
• formed during cuts or lesion
• named with "-itises"
• are usually short lived
• four cardinal signs for inflammation: Pain, Heat, Redness, Swelling
• Goal: bring white blood cell and plasma proteins to area
• this prevent spread of agents, disposes of pathogen and dead cell, and prepare for repair
• chemical messenger called inflammatory mediators cause two effect: vasodilation, vascular
permeability
• vasodilation increase blood flow, cause redness and heat
• gap between capillary cells and postcapillary venules increase, makes it leaky, allow for
plasma protein and phagocyte to enter tissue
• inflammatory mediator activate endothelial cell of capillaries and sprout cell adhesion
molecules which neutrophil and monocyte bind, this is margination.
• upon magination, neutrophil is activated and come out of the cell in a process called
diapedesis
• neutrophil go to the tissue and follow the inflammatory mediator to high concentration,
process called chemotaxis
• when capillary becomes leaky, more fluid leak into injured area, causing edema (increase in
interstitial fluid), this contribute to swelling and pain.
• 3 protein that leaks are antobodies, complements, and clotting factors
• injuries that introduce bacteria will have antibody acting on them as opsonins
• Complements C5a and C3a increase vascular permeability and act as chemotaxins, which
attract more macrophages
• clotting factor create a mesh in tissue, and create a scaffold for repair, and hold pathogen in
place, some bacteria have enzymes that break down this net
• basophils and mast cells can release histamine, a inflammatory mediator
• mast cell is in tissue, so they can react immediately to injury
• Prostaglandin and kinins are inflammatory mediator released from cell when injured. They
also activate pain receptor.
• Cytokins are also a inflammatory mediator.

FEVER
• overall temperature increase
• bacterial and cytokines act as pyrogens (fire creators), increase body temperature by goin
to hypothalamus, the body's thermostat
• fever is useful
 • most pathogen do not grow well in high temperature
• essential elements, iron and zinc are sequestered by liver and spleen, making it less
available to bacteria
• high temperature enhances phagocytosis and other enzymatic processes

PATHOGEN EVASION TACTICS

• capsulated bacteria makes it difficult for phagocyte to engulf it
• opsonization deals with this
• two opsonins are: antibody and complement
• opsonin allow phagocyte to engulf bacteria
• Other strategy pathogen developed are: resistance to lysosome enzymes and reactive
oxygen intermediate, release chemical to stop fusion of lysosome with phagosome, and
escape from phagosome and develop inside cytoplasm of phagocyte
• Counter measures are to enhance killing of bacteria inside phagocyte, certain T cells can
help this enhancement
• enhancement only happen when macrophage present part of the antigen to T cells

VIRUSES
• takes over host system to make more copies of itself

CELLULAR IMMUNITY

CYTOKINE
• sent messages
• defend against viruses (alpha and beta interferons)
• control differentiation and proliferation of immune cells
• promote inflammation
• promote activation of immune cells
• trigger apoptosis
• act usually on the secretion cell or nearby cell, rarely go into blood stream to other cells
• Macrophage secrete interleukin-1, it act as chemical alarm for pathogen

INTERLEUKIN-1
• promote activation of lymphocyte
• at higher concentration, it act as pyrogen at hypothalamus, via blood stream
• stimulate helper T cell to release interleukin-2

INTERLEUKIN-2
• cause proliferation in activated T cells
• act on the helper T cell, as well as nearby lymphocyte

T CELLS
• can be divided based on a cell receptor on their surface called CD proteins
 • they are CD4 (2/3 of T cells) and CD8 (1/3 of T cells)
• CD8 will become cytotoxic T cells, kill cancerous cells
• CD4 becomes usually helper T cells, which orchestrate immune response, or sometimes
regulatory T cells.
• CDs are co-receptors that bind to different MHC
• CD8 bind to MHC I, CD4 bind to MHC II
• HIV bind to CD4, go to go Helper T cell

CYTOTOXIC T CELL
• activated CD8 cells
• examine cell surface with MHC I
• MHC I continuously bring endogenous pieces of protein to surface for examination
• triggering apoptosis in infected cell
• no co-stimulation required, because it's already activated
• perforin (pore forming) or granzymes (hydrolytic enzymes) are released
• perforin have a pore with size similar to MAC, it allow movement of molecules
• the pore allow granzymes to enter
• granzyme activate apoptosis
• second mechanism involves binding to apoptosis inducing receptor on cell membrane,
triggering apoptosis
• both T cells and NK cells share these mechanisms

HELPER T CELL

• required for activation of B cells and cytotoxic T cells

• CD4 cells are easily activated
• matured dendritic cells normally have enough co-stimulatory molecules to activate CD4 but
not CD8
• Helper T cell that recognize antigen on MHC II can help activate cytotoxic T cells
• It can stimulate dendritic cell to express more co-stimulatory molecules
• helper T cells can secrete interleuken-2, which help activate CD8
• there are 2 types of helper T cells, TH1, and TH2
• TH1:triggered by bacteria in macrophage (intracellular pathogen), promoted by IL-12,
secrete Gamma interferon and others (promote macrophage to kill bacteria, and immunity
by cytotoxic T cells)
• TH2: triggered by extracellular pathogen, promoted by IL-4 and others, secrete IL-4 and 5,
which produce B cell activation, and release of certain class of antibodies

REGULATORY T CELLS
• suppress self-reactive cells
• supress other T cells
• derived from CD4, three major kind of T cells
• can inhibit via cell to cell contact, or release of cytokine (IL-10, TGF-beta)

MHC PROTEINS
• self-antigens
• histocompatiblity means tissue compatibility
 • during transplant, a donor's MHC is matched closely to the recipient's
• unlikely to find a perfect match except in identical twin
• closer the match, less chance of rejection
• MHC I and MCH2 are distinct in structure

MHC I
• Exist in all nucleated cells
• proteins are degraded continously
• transport protein bring them to ER to load into I MHC
• it then present itself to surface
• so if viral protein is brought to surface, it is recognized

MHC II
• displayed in only APC: dendritic cells, macrophages, and B cells.
• They present exogenous antigens, which originate outside of the cell
• pathogen such as bacteria is phagocytosed
• phagosome then fuse with lysosome, which then break it down into fragments
• MHC produced in rough ER, and exported to surface
• on the way they fuse with phagolysosome and loaded with exogenous antigens
• the antigen is presented to helper T cell to activate them
• already activated T cells become further activated, and enhance effectiveness

DENDRITIC CELLS
• T cells is almost always activated by this
• can get extracellular antigen by phgocytosis
• can get intracellular antigen by phogocytizing dead cells debris, or receive antigenic peptide
from abnormal cells through gap junction
• it express both MHC I and MHC II
• can activate both CD4 and CD8
• Upon encountering antigen, it is signaled by innate system to migrate to secondary
lymphoid organs
• it will express antigen to T cell there
• as it goes, it will mature and express large number of MHC I and MHC II protein and co-
stimulatory molecules that activate T cells
• Dendritic cell can express exogenous molecule on both MHC I and MHC II
• when CD8 protein encounter MHC I with foreign antigen, instead of killing it, it will only be
activated
• once in lymph node, they migrate to deep cortex (where T cells are) to activate the
appropriate T cell
• T cell need both binding to MHC and co-stimulatory molecule to become activated
• Once activated, clonal expansion occurs in presence of cytokine including interleukin-2
• co-stimulatory factor is only expressed when innate defense mechanism signals infection is
present, otherwise, it's a self antigen
• when T cell bind to dendritic cell MHC without co-stimulatory molecule, they are
permanently deactivated, process called anergy
•