streamlinedimmuno.ppt
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Introduction to the immune system
Innate immunitythe “front line” of defensenon specific
Acquired immunitymechanisms- antigen specificityimmunological memoryprinciples of vaccination
Important features of the immune system
Must be able to distinguish foreign antigens fromself antigens (what is an antigen?)
Must have memory (responds slowly to firstexposure, but more rapidly to subsequentexposures TO THE SAME ANTIGEN)
What does the immune system actually do?
Phagocytes- kill and remove foreign ordamaged cells
Antibodies- “tag” invading cells or viruses for destruction
Cytotoxic cells- killed altered cells
Regulate the immune response
What/where is the immune system?
Barriers
Circulating blood cells
Tissue-fixed cells
Lymphatic system
p. 375, physical barriers to infection
p. 377, origin of lymphoid cells
Cells with immune function (p. 378)GranulocytesNeutrophils
most common leukocyte (50-70%)most potent phagocyte
Eosinophils (2-4%)probably phagocyticinvolved in allergic responses, parasitic infections
Basophils (0-1%)mostly found in tissues (mast cells)release inflammatory molecules
Agranulocytes
Monocytes (5-10%)more common in tissues
In tissues:macrophages- phagocytes; help regulateimmune response (“antigen presenting cells”)
dendritic cells- present antigen to lymphocytes
Lymphocytes (20-40%)B cells- make antibodiesT cells- some are cytotoxic, some are regulatory
Where are the lymphoid cells?
In the blood
In the tissues
In the lymphoid system
Can be recruited to site of injury or infection
p. 396, the lymphoid system
The lymphoid system parallels the circulatorysystem
Primary lymphoid organs- where lymphoid cellsdevelopbone marrow (ALL blood cells)
thymus- T cells mature there (become cytotoxic or helper T cells) and thencirculate
Secondary lymphoid organsPurpose: to trap antigen and present it to lymphocytesMost lymphocytes actually reside in these tissues
Lymph nodes- “filter” antigen from lymph
Spleen- “filters” antigen from blood
Lymphoid tissue in mucosa, gut and skin
Innate defenses
If they are “non-specific” how are they actually activated-appropriately??
Barriersskinantimicrobial chemicals
lysozyme (in tears and salivastomach acidoxygen metabolites
normal flora (“healthy competition”)
If barrier is breached- then what?
Pattern recognition- something is perceived asabnormal
Damaged tissue
Structures associated with bacteria (peptidoglycan,LPS, etc.)toll-like receptors on phagocytes, endothelialcells- some recognizes viruses, tooCell is then activated in response
Toll-like receptors, p. 381
Complement proteins- circulate in blood
Are normally inactive, but become active when binding to antigen, or antigen-antibody complexes
What happens next?
A series of reactions, resulting in:destruction of antigeninflammationenhanced phagocytosis of antigen
Complement system, p. 382
Phagocytosis; how do the cells know whence toengulf?
detectors of microbes and/or damaged cells(pattern recognition)
response to cytokines (produced by damagedcells and other immune cells
complement receptors
What happens in phagocytosis?
Process of phagocytosis, p. 384
Neutrophils are more potent killers, but die quickly
Macrophages can present antigen; amplifyimmune responsecan prolong activity by regenerating lysosomes
Both contribute to inflammatory response toinfection and/or damage
What is the inflammatory process?
What triggers the inflammatory process?
What are the outcomes of inflammation?
What is apoptosis, and how does it preventinflammation?
Inflammatory process, p. 387
Inflammation is triggered by infection or injuryPurpose: to contain damage (and response)
repair damage
“Cardinal signs of inflammation”:swelling, redness, heat, pain
Why swelling?
Chemical signals are released by damaged tissue
Neutrophils, monocytes recruited to the site andenter tissuesfluid enters tissues, too
Why redness?
Chemicals promote vasodilation Blood vessel walls relax; more blood (and
therefore more blood cells) can bebrought to the region
Why heat?Chemicals raise temperature at the spot(pyrogens)Increased temperature kills microbes
phagocytes are more activemore cells are formed
Effect can be systemic (fever)
Why pain?
Chemicals effect free nerve endings (painreceptors)Pain inhibits mobility; can help localizedamage
Inflammation can cause a lot of “bystanderdamage”
Ideally, damaged is confined to the site of injury
Some sites are more sensitive to damage thanothers
Damage can be systemic (septic shock, dueto blood infections: loss of blood volume,tissue damage, excess clot formation
Not all cell death causes inflammation
Apoptosis: programmed cell death
Under genetic control
(In immune response a large number of cells areformed to fight the infection- what happens tothem after the infection is cleared?)
Summary
Innate defense consists of barriers, phagocytesurveillance, and mechanisms to detectinfection or damage
Inflammation is the first line response to infection
Lymphocytes may be activated during this processwhich will respond more rapidly and inten-sively to subsequent infections
Adaptive immunity
SpecificityMemoryDistinguishes self from non-self
Components of adaptive immunity:Humoral
Cell-mediated
Principles of vaccinationImmune deficiency and its consequences
Adaptive immunity takes several days todevelop (to first exposure to antigen)
Cells proliferateAntibodies are producedCytokines (signaling molecules) are produced
Meanwhile, innate mechanisms act
Adaptive mechanisms respond if infection hasnot been eliminated
What are the adaptive mechanisms?
Humoral immunity against “extracellular”antigens (bacteria, free viruses,toxins, etc.)antibodies and other molecules
Cell-mediated against “intracellular” antigens(virus-infected cells; tumor cells)
Responses are orchestrated by helperT cells
p. 395 (be sure to come back to this slide)
How does humoral immunity work?
B cells proliferate (in lymphatic tissues) andmake antibodies
Antibodies circulate and bind to antigen
Neutralization; immobilizationImmune complexesFacilitates phagocytosisFacilitates complement-mediated lysis
B cells are activated clonally
p. 401How antibodies work
Applies to T cells, too (p. 403)
In bone marrow
In the system
Clonal selection theory
Antibodies have certain features in commonbut different classes (isotypes) havedifferent properties.
p. 398
Variable region is unique, because each bindsto a different antigen
Constant regions fall into five classes
(table 16.1, p. 399)
What happens in the primary response thatleads to antibody production?
T cells respond to antigen; produce cytokines
These cause B cells to proliferate and becomeplasma cells (antibody-producing cells)
They become more able to react with antigenClass-switching (for appropriate response)
from IgM to IgA, IgG, IgE (unclear about IgD)Memory cells- more of them; they respond faster
in subsequent responses
p. 405
What about the memory cells?
• There are more of them in the circulation• Antigen specificity does not change• They have already gone through
development so can become active right away (note the secondary response on previous slide)
• Both T and B memory cells have been identified
• Memory cells can live for years
T cells also have an antigen-specific receptor
Receptor is NOT released
T cell must come in direct contact with antigen-presenting cell
Major antigen-presenting cells:macrophagedendritic cellB cell
How do these cells present antigen (and where)?
What are the different types of T cells
CD4(helper) and CD8 (cytotoxic)
Both have antigen-specific receptorsCD4 and CD8 molecules help with antigen
presentation
CD4 cells “see” antigen + MHC Class II(helper T cells)
CD8 cells “see” antigen + MHC Class I (cytotoxic T cells)
What is MHC? (major histocompatibilitycomplex)
Groups of cell- surface proteins, inherited
When cells process antigen they return fragments(peptides) to the surface, bound to eitherMHC Class I or Class II
MHC Class I is found on most cells
MHC Class II on antigen-presenting cells (andlevels can vary)
How do cells present antigen?
Class II-bearing cells take up and “process” antigen, then antigen is expressed on cell surface bound to MHC Class IIRemember, only certain cell types express MHCClass II- so not all cells can do thisLots of antigen-presenting cells in lymphoid tissues!
Class I-bearing cells (remember, virtually all cells),if infected or transformed, will express antigen boundto MHC Class I
When T cells are activated they proliferateand produce cytokines
Dozens of cytokines have been identified(and other cells can produce them, too)
Cytokines bind to neighboring cells and activate them
Recall that immune response is characterizedby rapid proliferation and activation ofcells!
(And: you don’t want cells activated all the time)
What do T cells actually do?
T helper cells- cytokine production(Some are engaged in “delayed-type hypersen-
sitivity)
Cytotoxic T cells- cause apoptosis in targets
What about natural killer cells?similar targets as CTLsno antigen-specific receptorno memory responsehave antibody receptorsprobably immune surveillance
Natural killer cells vs cytotoxic T cells
• Natural killer cells part of innate immune system
• Early protection against transformed cells or virus-infected cells (Same targets as cytotoxic T cells)
• Cytotoxic T cells become activated if natural killer cells cannot eliminate these cells
How DO immune cells avoid reacting withself antigens?
Remember that T cells regulate the immuneresponse
Most self-reactive cells are eliminated in thethymus
Antigen-presenting cells seem to be key
Model of antigen presentationNotice the APC has MHC ClassII and other molecules requiredto present antigen
APC: antigen presenting cell
Summary, p. 412
Immune system responds to antigens thatenter body in course of infection
Vaccination: antigens are DELIBERATELYintroduced to body to generate a specificimmune response (and memory)
Immune system normally distinguishes “harmful”antigens from self antigens or harmlesssubstances
What happens if it does not?
What happens if immune system is deficient?
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