Post on 10-Apr-2018
8/8/2019 y1 Lecture 1717 Julai 2007
1/35
8/8/2019 y1 Lecture 1717 Julai 2007
2/35
8/8/2019 y1 Lecture 1717 Julai 2007
3/35
8/8/2019 y1 Lecture 1717 Julai 2007
4/35
8/8/2019 y1 Lecture 1717 Julai 2007
5/35
8/8/2019 y1 Lecture 1717 Julai 2007
6/35
8/8/2019 y1 Lecture 1717 Julai 2007
7/35
8/8/2019 y1 Lecture 1717 Julai 2007
8/35
Account for 0.5% of WB Cs an d: Have U- or S-sha ped nuclei with tw o or three
cons picuous c onstricti ons Are f uncti onally si milar t o mast cells Have large, pur plish-black (bas ophilic)
granules that c ontain hista mineHistamine in f lamm atory che mical that acts as avas odilator an d attracts other WB Cs (antihista minescounter this e ff ect)
Bas ophils
8/8/2019 y1 Lecture 1717 Julai 2007
9/35
Agranulocytes ly mphocytes an d monocytes: L ack visible cyt op lasmic granules Are si milar structurally, but are f uncti onally
distinct an d unrelate d cell ty pes
Have s pherical (ly mp hocytes) or kidney-sha ped (mo nocytes) nuclei
Agranul ocytes
8/8/2019 y1 Lecture 1717 Julai 2007
10/35
Account for 25% or mo re of WB Cs an d: Have large, dark- pur ple, circular nuclei with a
thin ri m of blue cyt op lasm Are found mo stly en meshe d in ly mphoid tissue
(some circulate in the bl ood )There are tw o ty pes of lymphocytes: T cellsand B cells T cells f uncti on in the i mm une res ponse B cells give rise t o plasma cells, which pr oduce
antib od ies
L ymphocytes
8/8/2019 y1 Lecture 1717 Julai 2007
11/35
Monocytes acc ount for 48% of leuk ocytes They are the largest leuk ocytes They have abun dant pale-blue cyt op lasms They have pur ple-staining, U- or kidney-sha ped
nuclei
They leave the circulati on, enter tissue, an d diff erentiate int o macr ophages
Monocytes
8/8/2019 y1 Lecture 1717 Julai 2007
12/35
Macr ophages: Are highly mo bile an d actively phag ocytic Activate ly mp hocytes t o mo unt an i mm une
res ponse
Monocytes
8/8/2019 y1 Lecture 1717 Julai 2007
13/35
Summ ary of For med Ele ments
Table 17.2
8/8/2019 y1 Lecture 1717 Julai 2007
14/35
Summ ary of For med Ele ments
Table 17.2
8/8/2019 y1 Lecture 1717 Julai 2007
15/35
L euk opo iesis is h or monally sti mulate d bytwo f amilies of cytokines (he matopo ieticf actors) interleukins an d colony-stimulating f actors ( CSFs) Interleukins are nu m bere d (e.g., I L -1, I L -2),
whereas CSFs are na med for the WB Cs theystimulate (e.g., granul ocyte- CSF sti mulatesgranul ocytes)
Macr ophages an d T cells are the mostimpo rtant s ources of cytokinesMan hemato oietic h or mones are use d
Pr oducti on of L euk ocytes
8/8/2019 y1 Lecture 1717 Julai 2007
16/35
For mation of L
euk ocytes
Figure 17.11
8/8/2019 y1 Lecture 1717 Julai 2007
17/35
The Immune SystemDefends body against pathogens
Can distinguish between self and non-self
General Defence System (innate)Non-specific = acts against all pathogensRapid
1. First line of general defenceSkin = barrier. Sweat (acidic pH)Clotting = also helps protect skinLysozyme = enzyme in saliva, sweat, tears. Attacks bacterial cell walls
Mucous (respiratory, digestive, urinary & reproductive tracts) = traps pathogensCilia= little hairs that help clear mucous (and pathogens) from respiratory tractAlimentary canal = lysozyme in saliva, stomach HCl kills many pathogens, specialisedimmune areas in the GI tract, very high turnover of epithelial cells, antibodies
Specific Defence System (adaptive)
8/8/2019 y1 Lecture 1717 Julai 2007
18/35
2 . Second line of general defencePhagocytic white blood cells (leukocytes) = destroy pathogens that enterComplementInflammation
Phagocytes ( Phago= eat; cyte=cell)attracted to a site of infection ( chemotaxis ) by chemicals released by injured cellsThree types neutrophils (short lived),
monocytes (short-lived..in blood) and macrophages (long-lived..in tissue)
8/8/2019 y1 Lecture 1717 Julai 2007
19/35
Macrophages very large white cells that can move
around body, or remain in certain tissues. Long lived,act as scavengers
Immune organs
8/8/2019 y1 Lecture 1717 Julai 2007
20/35
Complementset of 30 proteins found in plasma that are activated by
infectioncomplicated chain reaction that leads to the bursting ofviruses and bacteria
made in the liver
Interferonsset of proteins produced by virally infected cells cells to limit the spread of viral
infections, by inducing a state of resistance in healthy cells.induced by viruses, bacteria and other signals from the immune system
Inflammationinfected cells ( mast cells ) release histamine , which is a vasodilator . This causeslocalised swelling, redness, heat, pain. Can also cause high temperature.
brings white cells to the area of infectionAnti-histamines
2 . Second line of general defence cont.
8/8/2019 y1 Lecture 1717 Julai 2007
21/35
Comp lement Pathways
Figure 21.5
8/8/2019 y1 Lecture 1717 Julai 2007
22/35
Inter f er on (IFN)
Figure 21.4
8/8/2019 y1 Lecture 1717 Julai 2007
23/35
N eutrophilsenter blood
from bonemarrow
1
2
3
4
Margination
Diapedesis
Positive
chemotaxis
Capillary wallEndotheliumBasal lamina
Inflammatorychemicalsdiffusing fromthe inflamedsite act aschemotacticagents
n amm a ory es ponse: ag ocy cMo bilizati on
Figure 21.3
8/8/2019 y1 Lecture 1717 Julai 2007
24/35
Red bone marrow
1
2
3
Immunocompetent,but still naive,lymphocytemigrates via blood
Mature (antigen-activated)immunocompetent lymphocytescirculate continuously in thebloodstream and lymph andthroughout the lymphoid organs of the body.
Key: = Site of lymphocyte origin
= Site of development of immunocompetence
as B or T cells; primary lymphoid organs= Site of antigen challenge and final
differentiation to activated B and T cellsImmaturelymphocytesCirculation in
blood 11 Lymphocytes destined to become T
cells migrate to the thymus and developimmunocompetence there. B cellsdevelop immunocompetence in redbone marrow.
ThymusBone
marrow
Lymph nodes,spleen, and other lymphoid tissues
2 2 After leaving the thymus or bonemarrow as naive immunocompetentcells, lymphocytes seed the lymphnodes, spleen, and other lymphoidtissues where the antigen challengeoccurs.
3 3
ActivatedimmunocompetentB and T cellsrecirculate in bloodand lymph
Imm unocomp etent B or T cells
Figure 21.8
8/8/2019 y1 Lecture 1717 Julai 2007
25/35
Major r olls in i mmunity are: To engul f foreign particles
To present f rag ments of antigens on their ownsur f aces, t o be rec ognize d by T cells
Major AP Cs are dendritic cells (D Cs),macr ophages, an d activate d B cellsThe major initiat ors of ada ptive i mm unityare D Cs, which actively migrate t o thelymph nodes an d secondary ly mphoid
organs an d present antigens t o T an d B cells
Antigen-Presenting Cells (AP Cs)
8/8/2019 y1 Lecture 1717 Julai 2007
26/35
Secrete soluble pr oteins that activate T cellsActivated T cells in turn release che micalsthat: Rev u p the maturati on an d mo bilizati on of DCs Pr od macr ophages t o bec om e activate d
macr ophages, which are insatiable phag ocytesthat secrete bacterici dal che micals
Macr ophages an d Den dritic Cells
8/8/2019 y1 Lecture 1717 Julai 2007
27/35
Specific Defence System (Adaptive Immune System)
Antigens foreign molecules thatgenerate anti body production
Antibodies (immunoglogulins) proteinsproduced by lymphocytes in responseto antigens
Monocytes develop into macrophages which phagocytose foreign particles ( antigens )Lymphocytes -
8/8/2019 y1 Lecture 1717 Julai 2007
28/35
IgD mo nomer attache d to the sur f ace of B cells,impo rtant in B cell activati onIgM penta mer release d by plasma cells duringthe primary i mm une res ponse
IgG
mo nomer that is the mo st abun dant an d diverse antib ody in primary an d sec ondaryres ponse; cr osses the placenta an d conf ers passiveimm unityIgA dimer that hel ps prevent attach ment of
pathogens t o e pithelial cell sur f acesIgE monom er that bin ds to mast cells an d
bas ophils, causing hista mine release whenactivate d
Classes of Antib od ies
8/8/2019 y1 Lecture 1717 Julai 2007
29/35
Mechanis ms of Antib ody Acti on
Figure 21.13
8/8/2019 y1 Lecture 1717 Julai 2007
30/35
Maj or Ty pes of T Cells
Figure 21.14
8/8/2019 y1 Lecture 1717 Julai 2007
31/35
T-lymphocytes
Helper T-CellsRecognise antigens on
surface of leukocytes,especially macrophages
Enlagre and form aclone of T-helper cells
Secrete interferon andcytokines whichstimulate B-cells andstimulate killer -cells
Can be infected by HIV
Killer T-CellsAlso called cytotoxic
Destroy abnormal bodycells, e.g. virus infectedor cancer cells
Stimulated by cytokines(THcells)
Release perforin , whichforms pores in targetcells. This allows waterand ions in = lysis
Suppressor T-CellsControl the
immune systemwhen the antigen/pathogen hasbeen destroyed
Only recentlydiscovered solittle is knownabout them
Memory T-CellsCan survive a long tim
and give lifelongimmunity frominfection
Can stimulate memoryB-cells to produceantibodies
Can trigger productionof killer T cells
Mature in Thymus, which is most active just before and after birth.The thymus starts to shrink during puberty.
8/8/2019 y1 Lecture 1717 Julai 2007
32/35
Abnormal cell e.gcancer cell, infected cell
Normal cell
Antigen
Killer T-cellrecognises antigen
Clones of killer T-cellattach to antigen
Helper T-cell stimulatescorrect killer T-cell to
multiply
Killer T-cells releaseperforin pores
Abnormal cell gainswater, swells andbursts
Helper T-cell alsostimulates B-cellsto make antibodies
Memory T-cells stay incirculationSuppressor T-cellsturn off immune
response
X X
X
How T-cells work
8/8/2019 y1 Lecture 1717 Julai 2007
33/35
Duration of immunityMemory B-cells circulate for a long time. If the same pathogen infects thebody again, these B-cells can produce large amounts of specific antibodyvery quickly. This is why you usually dont suffer from the same infectiontwice.Memory T-cells survive a long time and trigger an immune response
Tumours in most cases the body recognises tumours as being bad, because theyexpress abnormal molecules on the cell surface. However sometimes the body doesntnotice and cancers can develop
Immune disordersSometimes the body produces antibodies against its own tissues e.g. autoimmunediseases e.g. rhumatoid arthritis, Crohns disease, SCID (bubble boy disease),
asthma
Allergies occur when the body reacts to materials which should notbe antigenic e.g. peanuts
8/8/2019 y1 Lecture 1717 Julai 2007
34/35
Induced Immunity
Active immunityProduction of a persons ownantibodies. Long lasting
Passive immunityAn individual is given antibodies by anotherShort-term resistance (weeks- 6months)
Natural ActiveWhen pathogen
enters body in the
normal way, wemake antibodies
Natural PassiveBaby in utero
(placenta)
Breast-fed babies
Artificial PassiveGamma globulin
injection
Extremely fast, butshort lived (e.g. snakevenom)
Edward Jenner
Artificial ActiveVaccination usually
contains a safe antigen
from the pathogen.Person makesantibodies without
becoming ill
yumm y
8/8/2019 y1 Lecture 1717 Julai 2007
35/35
Overview of the Immune Response