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The branch of biomedicine concerned with the structure and function of the immune system, innate and acquired immunity, the bodily distinction with specific Ab
immunology
Constitutive immunity (innate immunity) 3 defenses against opportuniatic agents
1. primary defense - physical barriers
2. secondary defense - innate immunity
3. Tertiary defense - acquired immunity
3 examples of the primary defense (physical barriers) of the constitutive immuninity.
1. skin
2. flushing action
3. normal flora
3 examples of the secondary defense (innate immunity) of constitutive immuninity.
1. soluble factors (serum and secreations)
2. cellular component (neutrophil, NK cells, and macrophage)
3. inflammation
2 examples of the tertiary defense (aquired immunity) of the constitutive immuninity.
1. Antibody
2. Cell-mediated-immunity (CMI) [T-lymphocyte]
How does they body react when it recognizes a focal nonself (foreign body) induced into a local site? i.e., opportunistic agent or pathogen
a. danger signal initation
b. measured response (whatever is necessary to remove foreign body)
What is the body's reaction to systemic responses to invading agents (pathogens) or cancer (viral infections, septicemia, toxins)?
a. danger signals
b. aggressive immune response
What is the composition of the immune system? (2 parts) Name some examples
1. mulitple cell/multiple organs
ex: lymphocytes, macrophages, dendritic cells, mast cels, NK cells, granuloctyes, thymus, LN, spleen, BM, etc
2. Soluble factors in serum and other body fluids
ex: Ab, cytokines, complement, acute phase proteins, HSP, etc
T/F
The immune response can distinguish between self and non-self.
True
T/F
The immune response often damages itself (normally).
False, does not damage itself normally
2 ways the immune response communicates with the body. name an example of each
1. cell-to-cell contact -adhesion molecules
2. secreated factors - cytokines
The immune system is distributed throughout the body. Where does it has a particularly heavy concentration?
Surfaces - skin and mucosa
Besides the skin and mucosa, where can the immune response be found throughout the body? (3)
1. Free = blood
2. Lymphoid organs = spleen, thymus, lymph nodes, bone marrow
3. Associated with other organs and tissues = intestine, lung, liver, skin, urinary tract, blood
3 characteristics of the immune response structure.
1. orderly process
2. regulated
3. hierarchy
3 ways the immune response can lead to immune-mediated pathology (chronic immune stimulation).
1. chronic inflammation
2. autoimmune disease
3. cancer
The range of immune function is from:
undesirable <-- normal --> undesirable
What diseases and conditions are associated with ranges outside of normal?
undesirable <-- normal --> undesirable

immune deficiency (opportunistic infections) <-- normal --> autoimmune disease or hypersensitivity (pathology)
What does the immune system do for us?
Provides defense against infectious agents and carries out biologic house keeping functions ie, clearance of non-infectious substances, clearance of senescent red blood cells.
Explain the steps of immune response to immune initation.
1. Primary Event (insult)
2. DANGER SIGNAL (takes minutes)
3. INNATE IMMUNITY = Amplification (hours)
-Cytokines, Complement chemokines
4.INFLAMMATION
5. Adaptive Immunity(days)
-T-cell Responses, Antibodies
A substance to which the immune system can react. Usually foreign (nonself).
Antigen = Ag
Differentiation of self substances (proteins, carbohydrates, etc) from foreign substances. Clonal deletion mechanism.
Self-Recognition
iso =
equal
graft between genetically identical subjects
isograft or autograft
xeno =
strange or foreign
graft between subjects from different species
xenograft
allo =
other
graft between subjects from different species
allograft
tissue from same individual
autochthonous tissue
An individual organism whose body contains cell populations derived from different zygotes, of the same or different species, occurring spontaneously, as in twins or produced artifically, as an organism which develops from combined portions of different embryos, or one in which tissues or cells of another organism have been introduced.
chimera
T-cells and B-cells have a predisposed specificity to respond to a particular epitope or antigenic receptor. Each individual cell can respond to only __ epitope, but as a population either T- or B-cells have the capability to recognize approximately ___ different epitopes.
1, 1 billion
What is the immune repretoire (immune contingency)?
immune system has the potential to respond to perhaps 1 billion antigentic determinants.
Ab and cell mediated reactions to Ag. Involving B-lymphocytes, T-lymphocytes, and antigen presenting cells (APC).
Immune Response
Examples of Ag
•Examples: bacteria, viruses,
parasites, cancer cells, organ
transplants, pollen, drugs??, self??
Two strategies of the immune repertoire
1. unique gene for each Ag (like chinese alphabet)
2. gene modulation (phoenician alphabet)
8 physical and biochemical primary barriers of the immune system
1.skin and mucous membrane
2. acid in stomach
3. sebaceous gland secreations
4. lysozyme in most secretions
5. commensal organisms in gut and vagina
6. spermine in semen
7. flushing action of urine slow, tears, saliva, and bowel movement
8. mucous
Two strategies of the immune repertoire
1. unique gene for each Ag (like chinese alphabet)
2. gene modulation (phoenician alphabet)
8 physical and biochemical primary barriers of the immune system
1.skin and mucous membrane
2. acid in stomach
3. sebaceous gland secreations
4. lysozyme in most secretions
5. commensal organisms in gut and vagina
6. spermine in semen
7. flushing action of urine slow, tears, saliva, and bowel movement
8. mucous
Based on the genetics
constitution of the individual. These are nonspecific
means of clearing or removing most
undesirable substances
NON-SPECIFIC or INNATE IMMUNITY: (native
or inherent immunity)
(acquired
immunity) Specific immunity attributable to the
presence of antibody or reactive lymphocytes
following prior exposure to an infectious agent or
antigen.
SPECIFIC or ADAPTIVE IMMUNITY: (acquired
immunity)
PAMPs often initiate the non-specific immune response. What does PAMP stand for?
Pathogen-associated molecular patterns (PAMP)
What are some characterisics of PAMP? (4)
Characteristics:
• Produced only by microbial pathogens -- NOT HOST
• Usually essential for the survival or pathogenicity
of microorganism
• Usually invariant structures shared by entire
class of pathogens
Some examples of PAMPs are?
Examples:
• Lipopolysaccharide (LPS, endotoxin)
• Peptidoglycan
• Mannans
• Bacterial DNA (CpG)
• Double-stranded RNA
• Glucans
What is PRR? Who makes it?
Pattern-recognition receptors, host
What are some characterisics of PRR? (3)
• Expressed on “effector” cells of innate immune
system (macrophage, dendritic cells, B-cells)
• Non-clonal – all of a particular class of PRR are
identical
• PAMP interaction with PRR induces an immediate
response (no proliferation required)
What are 3 functional types of PRRs? Name some examples of each.
Secreted – opsonins, C-reactive
protein, mannon binding lectins
• Endocytic – mannose receptor
• Signaling – Toll family of receptors =
Toll- like-receptors (TLR)
Dendritic cells (and other APCs) respond to specific PAMPs by producing cytokines and cell-to-cell signals that determines the type of immune response. What are the 4 possible immune responses?
Th 1, Th 2, Th 3, anergic (Tr)
T/F Cytokines are soluble proteins.
True
Describe the general function of cytokines.
mediate and regulate immune and inflammatory response
T/F Cytokines are only produces in few cells types.
False. multiple cell types
Cytokines are pleiotropic. What does that mean?
same cytokine many actions
Cytokines exhibit redundancy. What does that mean?
mulitple cytokines act the same
T/F All cytokines are synergistic.
False. can be synergistic or antagonistic
T/F Cytokines bind to specific high-affinity receptors.
True
T/F Cytokine receptors are continously expressed.
False. expression is regulated
T/F Cytokine associated reaction are rapid, require tRNA, and protein synthesis.
False, slow, require mRNA and protein synthesis
T/F Cytokine action is usually endocine or autocrine rarely paracrine.
False, usually autocrine or paracrine rarely endocrine
2 major groups of danger signals
1. endogenous - "damaged cell" signal
2. exogenous - PAMP
3 reasons that cells release endogenous danger signals
tissues undergoing: stress, damage, abnormal death
What are some endogenous danger signals that have recently been discovered?
heat-shock proteins
nucleotides
reactive oxygen intermdiates
extracellular-matrix breakdown products
neuromediators
cytokines e.g. IFN
What do the danger signals do?
They induce the activation of dendritic cells, necessary for the initiation of primary and secondary immune responses.
APC orchestrates the nature of the immune response by the type of signal given to _______. What is the result if pathogens corrupt this process?
T-helper cells.
Misdirected immune response
Reticuloendothelial system (mononuclear phagocytic system), granulocytes, natural killer cells, eosinophils, basophils, and mast cells are all part of what immune cells? What do they do?
Innate immune cells.
Immediately available to reaction to infectious agent
Soluble factors of innate immune system (5)
• Acute phase proteins
• Interferons
• Tumor necrosis factor (TNF)
• Interleukin 1
• Complement
What is the origin of acute phase proteins?
plasma proteins of hepatic origin
When does the concentration of acute phase proteins increaes?
result of injury
Define acute phase protein
protein's who's concentration increases >25% after induction
2 examples of proteins that increase up to 50%
1. complement (C3, C4, FB)
2. Ferritin
2 examples of proteins that increase up to 4X
1. C1 esterase inhibitor
2. Fibrinogen
2 examples of proteins that increase up to 100 to 300X
1. C-REACTIVE PROTEIN (CRP)
2. Serum Amyloid A Protein
What is the name derived from inflammatory response to C polysaccharid of pneumococcus?
C-REACTIVE PROTEIN (CRP)
What is the general function of C-REACTIVE PROTEIN (CRP)?
protective scavenger
Specifically what 5 things does C-REACTIVE PROTEIN (CRP) do?
1. binds to bacterial cell wall material
2. opsonin (increases phagocytosis)
3. activates complement by classic pathway
4. Induction of IL-1 production
5. Causes platelet aggregation
Where is C-REACTIVE PROTEIN (CRP) produced? What is it released in response to?
The liver.
Released response to cytokines (IL-6) from macrophage endothelial cells, T-cells, and adipocytes
How is C-REACTIVE PROTEIN (CRP) diagnosically helpful?
marker of inflammation
What acute phase protein is associated with chronic inflammatory disease?
Serum Amyloid A Protein
T/F Acute phase proteins vary with species.
True
What is a cytokine?
immunomodulating agents of signaling molecules used between for cellular communication
There are hundreds of specific cytokines. What are 4 large groups seperated by function?
interferons, tumor necrosis factor, interleukin 1, complement
3 types of interferons (IFN)
alpha, beta, gamma
Describe the class, induced by, and function of each type of interferon.
Alpha = Type I, leukocytes, antiviral
Beta = Type I, fibroblasts, antiviral
Gamma = Type II, t-lymphocytes and NK cells, immune activation
IFN are produced in response to what type of pathogen?
virus
What are the activites of IFNs? (11)
-block virus transcription
-block virus synthesis
-block virus budding or budding virus may not be infectious
-induce tumor necrosis factor(TNF) production
-modulate immune response
-inhibit tumor growth
-B-cell maturation factor (gamma)
-Enhances Class I & II protein expression
-Increases Fc receptor expression
-Causes maturation and proliferation of NK-cells
-Inhibits cell growth
Tumor necrosis factor (TNF alpha, beta) aka Cachectin are produced primarily in what cell? In addtition they are produced in four other cells, what are they?
Macrophages.
Lymphocytes, NK cells, astrocytes, and mast cells
TNF is induced by an __; causes many of the effects formally attributed to endotoxin poisoning. Can also be induced by 7 other causes.
-Endotoxin
-viruses, tumor cells, bacterial toxins, C5a, parasite toxins, INF gamma, and IL-2
6 immunologic functions of TNF
-tumor cell toxicity
-up regulated Class-I and Class-II proteins
-stimulated endothelial cells to express adhesion protein for lymphocytes and PMNs
-stimulated IL-1 production
-stimulateds synthesis of prostaglandins and production of oxygen free radicals
-major contributor to inflammation
Interleukin 1 works similarly to __ another cytokine.
TNF
Where is interleukin 1 produced primarily? Where else?
Macrophage.
-Dendritic cells, lymphocytes, endothelial cells, fibroblasts, and keratinocytes
What are the two forms of Interleukin 1? What's the main difference?
IL1 alpha = cell bound, IL1 beta = secreated
What clinical signs does IL1 cause the patient?
fever, lethargy, malaise, loss of apetite
Where do IL1 act upon? What is the outcome of their action at this source?
Liver, acute phase protein production
What effect does IL1 have lympocytes and T-helper 2 cells?
activates lymphocytes and induces T-helper 2 cells to secrete IL-4, IL-5, IL-10
Complement proteins are a family of __ proteins; many having __ activity.
21, enzymatic
Complements can be activated via 2 pathways. What are they called?
Classical Pathway, Alternative Pathway
What activates complements via the classical pathway? (2)
Activated by Ab: IgM, IgG
What activates complements via the alternative pathway? (6)
-polysaccarides
-parasites
-erythrocytes
-bacteria
-virus infected cells
-tumor cells
5 functions of complements
-opsonin
-chemotaxis
-mast cell degranulation (anaphylatoxin)
-cell lysis
-prevent large immune complex formation
What is opsonin?
Enhances phagocytosis, CRP complement
What process is a tissue based startle reaction to trauma?
inflammatory process
The go/no go decision of the inflammatory process is based on __ __ for tissue penetration by microbes.
molecular clues
4 steps of the inflammatory process
1. beckoning, instruction, and dispatch of cells
2. kiling of microbes and infected host cells
3. liquefaction of surrounding tissue
4. healing
For each of the complements, describe their function:
C3a, C3b, C5a, Membrane Attack Complex (MAC)
C3a = Mast cell degranulation (anaphylatoxin)
C3b = Opsonin, Prevent large immune complexes
C5a = Chemotaxis, Mast cell degranulation (anaphylatoxin )
Membrane Attack
Complex (MAC) = Cell lysis
The innate immune response to tissue damage and inflammation induces a system response. What is the purpose of this?
To protect the body as a whole
What are some of the clinical signs of innate immune response to tissue damage and inflammation?
fever, neutrophilia, lethargy, muscle wasting
Innate immune response is mediated by what cytokines?
TNF-alpha, IL-1 & IL-6
The cytokines involved with the innate immune response to ts. damage and inflamation have what effect on the brain? (3)
1. raise body temperature
2. induce sleep
3. suppress appetite
The cytokines involved with the innate immune response to ts. damage and inflamation have what effect on the nervous and immune system? (3)
1. enhance protein catabolism of muscle (increase pool of AA)
2. IL-1 acts on bone marrow to increase PMN output
3. Stimulate liver to release acute phase proteins: complement components, C-reactive protein (CRP) or serum amyloid P (SAP)
Summary of mechanisms of action for barrier and innate immune system (6).
1. barriers
2. flushing
3. microstatic and microcidal factors
4. phagocytosis
5. inflammation
6. target cell killing
2 components of adaptive immunity and their cells.
1. Humeral Immuity (Ig or Ab produced by B-cells)
2. Cell Mediated Immunity (CMI) T-cell Function
7 functions of humeral immunity.
1. opsonin
2. neutralization of toxins and viruses
3. immune complex formation
4. interference with bacterial colonization
5. activation of complement
6. passive immunity to neonates
7. antibody dependent cell cytotoxicity (ADCC)
4 functions of Cell Mediated Immunity (CMI): T cell function
1. kills cells carrying intracellular parasites (viruses, bacteria, rickettsia, etc)
2. kills tumor cells
3. allograft rejection
4. limited passive transfer
Innate or Adaptive Immunity:

Requires prior exposure to Ag
Adaptive
Innate or Adaptive Immunity:

Resistance improves by repeated exposure to Ag
Adaptive
Innate or Adaptive Immunity:

Ag specific
Adaptive
What are the effector soluble factors of Innate Immunity?
complement, lysozyme, C-reactive protein (CRP)
What are the effector soluble factors of Adaptive Immunity?
Ab
What are the effector cells of Innate Immunity?
NK & Phagocytes (PMNs, macrophage, other RE cells)
What are the effector cells of Adaptive Immunity?
T & B cells
A substance that can combine with Ab or be the target of cell-mediated immunity
Ag
___ is the property of a substance that allows it to react with products of specific immune response (Ab or specifically sensitized T-lymphocytes)
Antigenicity
A substance that when introduced into the body stimulates humoral or cell-mediated immunity
Immunogen
Defined as the property of a substance that endows it with the capacity to provoke a specific immune response
Immunogenicity
(A special class of Ag) A substance that can combine with Ab but can initiate an immune response only if it is bound to a carrier molecule. They often have low molecular weights (<1000) and only 1 or 2 antigenic determinants.
Hapten
T/F Substances that are antigenic are always immunogenic, but antigens are not necessary immunogenic.
False... substances that are immunogenic are always antigenic
Haptens can function as ___ but not ___.
Ag but not immunogens
Example of a hapten
PCN = penicillin
Determinants or region of antigenic substance which is recognized by Ab or cytotoxic T-cells
Epitope
T/F Ag may have many determinants or epitopes.
True
T/F Hapten is similiar to an Ab.
False, similiar to epitope
Group of antigens from apparently unrelated animals or microorganisms which are so closely related immunologically that they cross-react extensively with Ab against any one member of a particular heterophile group.
Heterophile Ag
Example of heterophile Ag
Forssman Ag is present on RBCs of many species as well as in some bacteria (pneumococcus and others)
Why is strep throat such a danger?
Rheumatic fever... Group A streptococcus cell wall cross reacts with glycoprotein of the heart valve and other myocardial tissue of humans = Autoimmune disease, i.e., rheumatic heart disease
What is the usual size of immunogens?
>10,000 Daltons (molecular weight)
B-cells two functions
Ag processing
Ab production
5 parts of Ag structure
1. Heavy chain
2. Light chain
3. Joining factor
4. Secretory piece
5. Constant & variable regions
Describe the variable region antigen binding areas of Abs seperately and together (3)
1. three hyper-variable regions on each heavy chain.
2. three hyper-variable regions on each light chain.
3. Together one light an dhone heavy chain for Ag recognition/binding groove
Heavy chain constant region genes:
a. IgD =
b. IgM =
c. IgG =
d. IgA =
e. IgE =
a. delta
b. mu
c. gamma
d. alpha
e. epsilon
2 Light chain constant regions.
kappa
lambda
What is the J chain of Ig?
the joining chain
Which Ig exhibits this function: Expression on immature B-cells
IgD
Which Ig exhibits this function: B-cell receptor
IgM-R
Which Ig exhibits this function: First antibody to appear: fixes
complement, binds to Fc receptor; opsonin
IgM
Which Ig exhibits this function: Later production; some fix complement;
some bind to Fc receptors; opsonin
IgG
Which Ig exhibits this function: Secretory antibody; associated with
mucosal immunity; does not fix complement
IgA
Which Ig exhibits this function: Cytophilic via IgE Fc receptor (FcR-E);
activates degranulation by mast cells or
basophils; Type 1 hypersensitivity
IgE
What is secretory IgA and what is its function?
-Secretory component (piece) is also called pIgR (polymeric immunoglobulin receptor).
-pIgR is a cell membrane receptor that binds to free dimeric IgA or pentameric IgM and transports them through endothelial cells before release at teh mucosal surface
B cells have what 4 types of receptors?
1. Ag receptor (BCR)
2. Complement receptors
3. Cytokine receptors
4. Ig receptors
IgM and IgD have transmembrane extension on heavy chains. This allows them to be ___ ___ ___.
B-cell receptor (BCR)
Ig composition:
-heavy chain constant regions=
-gene composition=

-light chain constant region =
-gene composition=
heavy chain constant region = mu, alpha, delta, gamma, epsilon
gene compositin = v, d, j

light chain constant region = lambda, kappa
gene composition = v, j
T/F Somatic mutations of BCR leads to decreased Ab affinity.
False, increased
4 types of Ab response
1. T-cell dependent response
2. T-cell independent response
3. Primary and secondary antibody
response
4. Anamnestic response
7 Antibody-mediated reactions
• Immune complex disease
• Agglutination
• Precipitation
• Enhanced phagocytosis (opsonin)
• Initiate complement cascade
• Antibody-dependent cell-cytotoxicity
• Neutralization of viruses & toxins
What is a neoplastic plasma plasma cell?
myeloma
Myeloma cell fused with Ag-specific B cell from immunized animal to produce immortilized B cell for specific Ab production
Hybridoma
Hybridomas and Myelomas are both ___ Abs.
Monoclonal
What does MHC stand for?
Major Histocompatibilty Complex
What is a cluster of genes some of which code for proteins expressed on the surface of cytoplasmic membrane of somatic cells.
Major Histocompatibilty Complex (MHC)
What is the function of MHCs?
unique self markers which participate in cell to cell recognition and communication.
What happens if the MHC's self markers become mismatched?
This may lead to graft rejection
Who act as shuttle molecules that pass antigenic peptides to the cell surface for presentation (interaction) with T lymphocytes.
Class I and II MHC proteins
T/F Class I MHC polymorphic proteins are expressed on all body cells.
False, almost all! except sperm, trophoblastic cells, neurons
Class I MHC protein is associated with ___ microglobulin (12,000MW)
beta-2
Class I MHC proteins are associated with ___ ___ (and suppressor cell) activation and cytotoxicity.
T-cell
These are polymorphic protein expressed on antigen presenting cells only (e.g., macrophage, B-lymphocyte, epithelial cells, dendritic, and activated T-lymphocytes)
Class II MHC
Describe how the Class II MHC are linked chemically.
2 non-covalently linked chains (heterodimer) alpha an dbeta (34K and 29K MW)
In humans there are at least __ genes found on Class II MHC.
3 - DR, DQ, DP
What does Class II MHC proteins do?
present antigenic peptide to helper T-cell
Class I and Class II molecules act as shuttle molecules which pass __ __ to the cell surface for presentation to T-lymphocytes.
antigenic peptides
Th MHC is highly __. There are a large number of genetic variats (alleles) at each genetic locus.
polymorphic
T/F Many of the MHC alleles are represented at a significant frequency (>1%) in the population.
True
Besides high representation of alleles, addition the alleles are generally __ from one another by many AA substitutions.
different
What upregulates class I, in preparation for cytotoxic T-cells?
cytokines
T/F Most cells have MHC class I.
True
3 functions of T-cells
1. helper
2. cytotoxic
3. suppressor/regulator
8 T-cell surface markers
1. CD4
2. CD8
3. CD3
4. TCR (T-cell Receptor)
5. Class I MHC
6. Clss II MHC (sometimes after activation
7. CD25 (IL-2 receptor) - associated with T-regulator cells
8. FcR
The thymus is composed of two compartments.
1. thymic epithelial space (TES)
2. thymic parivascular space (TPS)
What happens to the thymus with age?
TES is replaced with TPS
Describe step 1 of the T-Cell Maturation: Thymus processing of T-cells
1. Pre T-cells enter through blood.
Describe step 2 of the T-Cell Maturation: Thymus processing of T-cells
2. In the thymus, T-cells undergo multiple gene rearrangement to form either the alpha/beta or gamma/delta that will eventually code for the heterodimer T-cell Receptor (TCR).
Describe step 3 of the T-Cell Maturation: Thymus processing of T-cells
3. At the time of TCR expression, the pre-T-cells begin to express both CD4 and CD8 surface proteins.
Describe step 4 of the T-Cell Maturation: Thymus processing of T-cells
4. One TCR is expressed, T-cells begin a process of interacting with various Class I or Class II MHC molecules expressed on thymic stromal cells
During step 5 of the T-Cell Maturation: Thymus processing of T-cells, describe the outcome and function of each interaction.
1. TCR does not bind to MHC molecule
2. TCR binds to both MHC molecule and peptide
3. TCR binds to MHC molecule but not peptide
The following outcomes are possible:
1. Function = useless
Outcome = death in the thymus
2. Function = dangerous, possible autoimmune
Outcome = death in the thymus
3. function = potentially useful
outcome = remains alive
During step 6 of the T-cell Maturation: Thymus processing of T-cells, the T-cell differentiation into CD4 ro CD8 T-cells. What is the outcome of this step?
-T-cells recognizing Class I MHC become CD8+T-cells (cytotoxic T-cells)
-T-cells recognizing Class II MHC become CD4+ T-cells (helper T-cells)
T/F TCR recognizes the combination of the peptide and MHC molecule thus a particular T-cell will "work" both bussets of MHC molecule expressed by the individual.
False, will "work" with only one subset of individual.
Class I is expressed on virtually all __ cells and Class II is expressed on select __ __ cells.
-somatic
-Ag preseneting
T/F Some T-cells with auto-reactivity (recognize self peptides) will escape the thymus and must be made responsive by other means.
True
• Accelerated thymic involution is a hallmark of FIV infection of young cats and also pediatric AIDS. Why?
• The thymus is an early and major target
for FIV infection
Where do pre-T-cells originate from before reaching the thymus.
Bone marrow
T-cell will can express either __/__ or __/__ Ag receptors. If the T-cell has alpha/beta Ag receptors, it can then recognize the accessory molecules, __ or __. What will the varying functions be based up the accessory molecule.
-alpha/beta
-gamma/delta
-CD4+ or CD8+
-CD4+ = helper1, helper2, regulatory
-CD8+ = cytotoxic, regulator
Th1 lymphocytes produce ___ and ___ which promotes the cytotoxic T-cells response
IFN-gamma, IL-2
Th2 lymphocytes produce __, __, __, and __ which promotes B-cell responses
IL-4, IL-5, IL-6 and IL-10
T/F Th1 and Th2 pathways cross interfere
True
How do the Th1 and Th2 pathways cross interfere?
• IFN-gamma down regulates Th2 cells
• IL-10 down regulates Th1 cells
• The type of immune response to a given antigen
will depend on the balance between ___ and ___
cell influences
Th1 and Th2
T/F TCR-CDR-CD3 complex recognizes peptide in combination with Class-II proteins, but not whole parental protein.
True
What happens during Th recognition after TCR-CD4-CD3 complex recognizes peptide in combination with Class-II protein?
Second signal is sent (cell-to-cell) between T-cell and APC
After the second signal of Th recognition CD3 transmits a signal across cell membrane. What does this stimulate?
Th cell to release soluble factors and to proliferate. These soluble factors are growth factos that stimulate the B-cells to proliferate and differentiate and other Th and T-cytotoxic cells.
That do regulatory T-cells do?
-Suppress T-cells in response to Ag
-Prevent autoimmune dz
-Prevent inappropriate T-cell activation
-Tr function is overridden by IL-6 from DC in response to Danger Signal
Oral administration of Ag induces which Tcell?
Regulatory T-cells
Three types of regulatory t-cells
Tr, Tr1, Tr3
Which type of T-regulatory cell is being described:
– CD4+, CD25+
– Secrete IL10 and TGF-beta (suppresses Th1 and Th2)
– Many Tr recognize self-peptides (suppression of autoimmune
response)
– Removal of Tr leads to autoimmune disease
Tr
Which type of T-regulatory cell is being described:
– Similar to Tr except low CD25 expression
– Require IL10 for development and produce IL10
– Abundant in intestine (food tolerance??)
Tr1
Which type of T-regulatory cell is being described:
– Also found in intestine but produce primarily TGF-beta
– Suppress immune responses to food stuff
Tr3
After the TCR-CD8-CD# recognizes peptide in combination with Class I. What does CD3 do?
• CD3 transmits signal across cell membrane stimulating
cytotoxic T-cell to become activated, to proliferate and
to destroy target cells
How do cytotoxic t-cells kill the infected cell?
Cell killing through lymphotoxin, and/or perforin
release, and Fas/FasL
Cells expressing FasL can be kill cells expressing ___.
Fas
When do T-cells express FasL or Fas?
When activated
What sites in the body express FasL?
sites that do not have a lot of immune action. i.e, eyes, brain
List 9 cell surface markers.
-Class I (MHC)
-Class II (MHC)
-T-cell receptor (TCR)
-CD4
-CD8
-CD3
-Fc receptor
-C3b receptor
-B-cell receptor (IgM-R)
Where is CD3 present? What kind of marker is it?
present on all mature T-cells; Pan T-cell marker
What does C3b bind?
binds third component of complement
3 characteristics of Ag presenting cells (APC).
1. process Ag
2. express Class II protein
3. Present Ag to T-helper cells
List ells which express Class II constitutively (professional APC). (6)
1. Follicular dendritic cells
2. dendritic cells
3. Langerhans cells
4. macrophage and other RE cells
5. B-cells
6. Epithelial cells
5 cells which express Class II after induction of IFN/TNF.
1. activated T-cells
2. astrocytes
3. microglial cells
4. thyroid epithelial cells
5. keratinocytes
General 4 steps to Ag presentation and for helper t-cell stimulation
1. Ag uptake
2. Proteolytic cleavage
3. Association with Class-II protein
4. Travel to cell surface for presentation