The Immune SystemThe Immune System
An organisms’ protection from Pathogens
Video
PathogenPathogenAny infectious agent that causes diseaseAny infectious agent that causes disease
• Bacteria
•Viruses
•Fungi
•Protists/parasites
2 Divisions of Immunity in 2 Divisions of Immunity in Humans and Other MammalsHumans and Other Mammals
I.I. Innate Innate Immunity Immunity – “Non-Specific” – “Non-Specific”
This defense is not concerned with ‘what’ the pathogen is. This defense is not concerned with ‘what’ the pathogen is. This system merely prevents the pathogen from This system merely prevents the pathogen from entering the body or destroys it before identifying it.entering the body or destroys it before identifying it.
It shoots first and asks questions laterIt shoots first and asks questions later
Innate Immunity involves several layers of defense:Innate Immunity involves several layers of defense:
A.A. Barrier DefensesBarrier Defenses B. B. Inflammatory Inflammatory ResponseResponse
C. C. Cellular DefensesCellular Defenses D. D. Natural Killer CellsNatural Killer Cells
E. E. Antimicrobial DefensesAntimicrobial Defenses
A. Barrier DefensesA. Barrier Defenses
1.1. Epidermis – impenetrable barrierEpidermis – impenetrable barrier
2.2. Oil and Sweat have low pHOil and Sweat have low pH
3.3. Resident Flora – your own bacteriaResident Flora – your own bacteria
4.4. Mucous Membrane – mucus and Mucous Membrane – mucus and ciliacilia
5.5. LysozymeLysozyme
SkinSkin
EpidermisEpidermis an impenetrable barrier to an impenetrable barrier to pathogenspathogens
Oil and SweatOil and Sweat have a have a low pHlow pH that that reduces pathogen growthreduces pathogen growth
Resident FloraResident Flora your own colonies of your own colonies of bacteria that live on your skin out-- bacteria that live on your skin out-- competes with harmful bacteria for competes with harmful bacteria for spacespace
Mucous MembranesMucous Membranes Un-keritonized skin of the mocous Un-keritonized skin of the mocous
membranes have a different layer of membranes have a different layer of defensedefense
MUCUS and CILIAMUCUS and CILIA
Lysozyme
B. Cellular DefensesB. Cellular Defenses
Leukocytes – Leukocytes – phagocytic phagocytic
white blood cells have surfacewhite blood cells have surface
receptors that detect typicalreceptors that detect typical
pathogen compounds calledpathogen compounds called
antigensantigens..
Microbes/antigens
PHAGOCYTIC CELL
Vacuole
Lysosomecontaining enzymes
Groups of Groups of pathogens pathogens are are recognized recognized by by TLRTLR, , Toll-Toll-like like receptorsreceptors
EXTRACELLULARFLUID Lipopolysaccharide
FlagellinTLR4
TLR5
Helperprotein
TLR9
TLR3
WHITEBLOODCELL
VESICLE
CpG DNA
Inflammatoryresponses
A white blood cell A white blood cell engulfs a microbe, engulfs a microbe, then fuses with a then fuses with a lysosome to destroy lysosome to destroy the microbethe microbe
There are different types of There are different types of phagocytic cells:phagocytic cells:
NeutrophilsNeutrophils engulf and destroy microbes engulf and destroy microbes
Macrophages Macrophages are part of the lymphatic are part of the lymphatic system and are found throughout the bodysystem and are found throughout the body
EosinophilsEosinophils discharge destructive discharge destructive enzymesenzymes
Dendritic cellsDendritic cells stimulate development of stimulate development of acquired immunityacquired immunity
Fig. 43-7Fig. 43-7
Adenoid
Tonsil
Lymphnodes
Spleen
Peyer’s patches(small intestine)
Appendix
Lymphaticvessels Lymph
nodeMasses ofdefensive cells
Bloodcapillary
Lymphaticvessel
Tissuecells
Adenoid
Tonsil
Lymphnodes
Spleen
Lymphnode
Masses ofdefensive cells
Bloodcapillary
Lymphaticvessel
Tissuecells
Interstitial fluid
Appendix
Peyer’s patches(small intestine)
C. Antimicrobial ProteinsC. Antimicrobial Proteins
Peptides and proteinsPeptides and proteins function in innate function in innate defense by attacking microbes directly or defense by attacking microbes directly or impeding their reproductionimpeding their reproduction
Interferon Interferon proteinsproteins provide innate defense provide innate defense against viruses and help activate against viruses and help activate macrophagesmacrophages
About 30 proteins make up the About 30 proteins make up the complement systemcomplement system, which causes lysis of , which causes lysis of invading cells and helps trigger inflammationinvading cells and helps trigger inflammation
Following an injury, Following an injury, mast cells mast cells release release histaminehistamine,, which promotes changes in which promotes changes in blood vessels; this is part of the blood vessels; this is part of the inflammatory responseinflammatory response
These changes increase local blood supply These changes increase local blood supply and allow more phagocytes and and allow more phagocytes and antimicrobial proteins to enter tissuesantimicrobial proteins to enter tissues
Pus, Pus, a fluid rich in white blood cells, dead a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at microbes, and cell debris, accumulates at the site of inflammationthe site of inflammation
D. Inflammatory ResponsesD. Inflammatory Responses
Fig. 43-8-3Fig. 43-8-3
Pathogen Splinter
Macrophage
Mast cell
ChemicalSignals (Ligand)
Capillary
Phagocytic cellRed blood cells
Fluid
Phagocytosis
D. Inflammatory ResponsesD. Inflammatory Responses
Fever is a systemic inflammatory Fever is a systemic inflammatory response triggered by pyrogens response triggered by pyrogens released by macrophages, and released by macrophages, and toxins from pathogenstoxins from pathogens
Septic shockSeptic shock is a life-threatening is a life-threatening condition caused by an condition caused by an overwhelming inflammatory overwhelming inflammatory responseresponse
LymphocytesLymphocytes- are white blood cells that - are white blood cells that recognize and respond to antigens, foreign recognize and respond to antigens, foreign molecules.molecules.
Lymphocytes that mature in the Lymphocytes that mature in the thymus thymus above the heart are called above the heart are called T cellsT cells,, and and those that mature in bone marrow are those that mature in bone marrow are called called B cellsB cells
Lymphocytes have immunological memory.Lymphocytes have immunological memory.
IIII. Acquired immunity. Acquired immunitylymphocyte receptors provide pathogen-specific lymphocyte receptors provide pathogen-specific
recognitionrecognition
Fig. 43-9Fig. 43-9
Antigen-bindingsite
Antigen-binding site
Antigen-bindingsite
Plasmamembrane
T cellCytoplasm of T cell
(b) T cell receptor
Cytoplasm of B cell
(a) B cell receptor
B cell
B cells and T cells have receptor proteins that can recognize and bind to antigens
Antibody Genes
Assembled antibody molecule
VDJ
C
Gene components scattered through one chromosome
Heavy chain
Antigen-binding region
Constant region
Light chain
V
V
V
DD
JJJJ
C
Rearranged gene
components encoding a heavy chain
Markers of Self:Major Histocompatibility Complex
Antigenic peptide
Antigen-presenting cell uses MHC Class I or II
Cell membrane
MHC Class II
Antigenic peptide
Viral infection
Infected cell
MHC Class I
Antigenic peptide
MHC Class I
Body Cell with “Self-Markers called MHC
B Cells
Plasma cell
Class II MHC and processed antigen are displayed
bacteria
Antigen
Antigen-specific B cell receptor
Antibodies(Immunoglobins)
B cell
Activated helper T cell
Cytokines (Lymphokines)LIGAND
T Cells
Activated killer cellActivated helper T cell
Resting cytotoxic T cellResting helper T cell
Cytokines Released by
Helper T-Cells
Granule w/destructive
enzymes
Activated when they encounter infected cells that are presenting antigens
Killer Cells: Cytotoxic Ts
Killer cell
Target-oriented granules
Surface contact
Target cell
T cells bind to antigen fragments T cells bind to antigen fragments presented on a host cell presented on a host cell
These antigen fragments are bound to These antigen fragments are bound to cell-surface proteins called MHC moleculescell-surface proteins called MHC molecules
MHCMHC molecules are so named because molecules are so named because they are encoded by a family of genes they are encoded by a family of genes called the called the major histocompatibility major histocompatibility complexcomplex
The Role of the MHCThe Role of the MHC In infected cells, MHC molecules bind In infected cells, MHC molecules bind
and transport antigen fragments to and transport antigen fragments to the cell surface, a process called the cell surface, a process called antigen presentationantigen presentation
A nearby T cell can then detect the A nearby T cell can then detect the antigen fragment displayed on the antigen fragment displayed on the cell’s surfacecell’s surface
Depending on their source, peptide Depending on their source, peptide antigens are handled by different antigens are handled by different classes of MHC moleculesclasses of MHC molecules
Fig. 43-12Fig. 43-12
Infected cell
Antigenfragment
Class I MHCmoleculeT cellreceptor
(a)
Antigenassociateswith MHCmolecule
T cellrecognizescombination
Cytotoxic T cell (b) Helper T cell
T cellreceptor
Class II MHCmolecule
Antigenfragment
Antigen-presentingcell
Microbe
1
11
2
22
Activation of B Cells to Make Antibody
Antigen-presenting cell
Antigen
Circulating antibody
Antigen is processedClass II MHC
Antigen
Activated helper T cell
Class II MHC and processed antigen are displayed
Antibodies
Plasma cellAntigen-presenting cell
Antigen-specific B cell receptor
B cell Cytokines(LIGAND)
Fig. 43-14Fig. 43-14
B cells thatdiffer inantigen specificity
Antibodymolecules
Antigenreceptor
Antigen molecules
Clone of memory B cells Clone of plasma cells
Animation: Role of B CellsAnimation: Role of B Cells
Fig. 43-16Fig. 43-16
Humoral (antibody-mediated) immune response
B cell
Plasma cells
Cell-mediated immune response
Key
Stimulates
Gives rise to
+
+
++
+
+
+Memory B cells
Antigen (1st exposure)
Engulfed by
Antigen-presenting cell
MemoryHelper T cells
Helper T cell Cytotoxic T cell
MemoryCytotoxic T cells
ActiveCytotoxic T cells
Antigen (2nd exposure)
Secretedantibodies
Defend against extracellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.
Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.
+
+ +
AnimationAnimation: Helper T Cells: Helper T Cells
Fig. 43-17Fig. 43-17
Antigen-presentingcell
Peptide antigen
Cell-mediatedimmunity (attack on
infected cells)
Class II MHC moleculeCD4
TCR (T cell receptor)
Helper T cell
Humoralimmunity
(secretion ofantibodies byplasma cells) Cytotoxic T cell
Cytokines
B cell
Bacterium
+
+ +
+
Cytokines
Cytotoxic T Cells: A Cytotoxic T Cells: A Response to Infected CellsResponse to Infected Cells
Cytotoxic T cells are the Cytotoxic T cells are the effectoreffector cells cells in cell-mediated immune responsein cell-mediated immune response
The activated cytotoxic T cell The activated cytotoxic T cell secretes proteins that destroy the secretes proteins that destroy the infected target cellinfected target cell
Animation: Cytotoxic T CellsAnimation: Cytotoxic T Cells
Fig. 43-18-3Fig. 43-18-3
Cytotoxic T cell
Perforin
Granzymes
TCRCD8
Class I MHCmolecule
Targetcell
Peptideantigen
Pore
Released cytotoxic T cell
Dying target cellperforin
granzymes
B Cells: A Response to B Cells: A Response to Extracellular PathogensExtracellular Pathogens
The humoral response is characterized The humoral response is characterized by secretion of antibodies by B cellsby secretion of antibodies by B cells
Activation of B cells is aided by Activation of B cells is aided by cytokines and antigen binding to helper cytokines and antigen binding to helper T cellsT cells
Clonal selection of B cells generates Clonal selection of B cells generates antibody-secreting plasma cells, the antibody-secreting plasma cells, the effector cells of humoral immunityeffector cells of humoral immunity
Fig. 43-19Fig. 43-19
Antigen-presenting cell
Endoplasmicreticulum ofplasma cell
Secretedantibodymolecules
B cell
Class II MHCmolecule
TCR CD4
Helper T cellActivatedhelper T cell
Cytokines
Clone of memoryB cells
Clone of plasma cells
2 µm
+
Bacterium
Peptideantigen
The Role of Antibodies in The Role of Antibodies in ImmunityImmunity
NeutralizationNeutralization occurs when a pathogen occurs when a pathogen can no longer infect a host because it is can no longer infect a host because it is bound to an antibodybound to an antibody
OpsonizationOpsonization occurs when antibodies occurs when antibodies bound to antigens increase phagocytosisbound to antigens increase phagocytosis
Antibodies together with proteins of the Antibodies together with proteins of the complement system generate a complement system generate a membrane attack complexmembrane attack complex and cell lysis and cell lysis
Animation: AntibodiesAnimation: Antibodies
Fig. 43-21Fig. 43-21
Viral neutralization
Virus
Opsonization
Bacterium
Macrophage
Activation of complement system and pore formation
Complement proteins
Formation ofmembraneattack complex
Flow of waterand ions
Pore
Foreigncell
Antibodies bound to antigens on viruses can neutralize the virus
Binding of antibodies to bacteria Promotes phagocytosis of the Bactria by Macrophages
Binding of antibodies to antigens on the surface of a foreign cell activates a complex system.
Following activation the attack complex forms pores in the foreign cell’s membrane , allowing water and ions to rush in.
The Cell swells and eventually lyses.
Evolution and ImmunityEvolution and Immunity
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