micr 201 microbiology for health related sciences
DESCRIPTION
Lecture 10: Adaptive Immunity Edith Porter, M.D. MICR 201 Microbiology for Health Related Sciences. Lecture outline. Concept of immunity Innate immunity Adaptive immunity Humoral and cellular adaptive immunity Antigens and antibodies B cells and humoral immunity - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/1.jpg)
1
MICR 201 Microbiology for Health Related Sciences
Lecture 10: Adaptive ImmunityEdith Porter, M.D.
![Page 2: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/2.jpg)
2
Lecture outline Concept of immunity▪ Innate immunity ▪ Adaptive immunity
Humoral and cellular adaptive immunity Antigens and antibodies B cells and humoral immunity Effects of antigen-antibody binding T cells and cellular immunity Antigen presenting cells Cytokines Immunological memory
![Page 3: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/3.jpg)
3
Overview of host defenses
First Line of Defense Second Line of Defense
• NK cells
![Page 4: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/4.jpg)
4
Concept of immunity
INNATE IMMUNITY Functional at birth Rapid responses:
preformed or available within hours after infection
Limited specificity: pattern recognition via toll like receptors
Widely present in nature including in plants, invertebrates and vertebrates
ADAPTIVE IMMUNITY Acquired, available
within days High specificity Memory In higher
vertebrates
![Page 5: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/5.jpg)
5
Humoral and cellular immunity
Humoral immunity Transferable with serum Highly specific Mediated by antibodies and
lymphocytes who produce these antibodies
These types of lymphocyte mature in the bone marrow and are called B lymphocytes (B cells)
Cellular immunity Mediated by lymphocytes that
mature in the thymus and are called T lymphocytes (T cells)
T cells orchestrate the immune response
The thymus is located in mediastinum
![Page 6: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/6.jpg)
6
Lymphocytes
http://www.aamdsglossary.co.uk/i/c/1_2_lymphocytes.jpg
![Page 7: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/7.jpg)
7
Differentiation of B and T cells
B for Bone marrow
T for Thymus
![Page 8: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/8.jpg)
8
The lymphatic systemPRIMARY LYMPHATIC TISSUE Lymphocyte
formation and maturation
Bone marrow Thymus
SECONDARY LYMPHATIC TISSUE Antigen contact Spleen Lymph nodes Peyer’s patches Mucosa associated
lymphatic tissue (MALT)
![Page 9: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/9.jpg)
9
Main tasks of lymphocytes Recognize foreign agents (antigen)
Lymphocytes carry specific antigen receptors on their surface
B-cell receptor, T-cell receptor Block and eliminate foreign agents
Through antibodies By activating host defense cells via cytokines By destroying infected host cells that have
been taken over by infectious agents
![Page 10: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/10.jpg)
10
Antigen Substances that causes the body to
produce specific antibodies Any molecule that can be recognized
by and bound to an antibody (“antibody generating”) or a T cell
Typically proteins and carbohydratesEpitop (or antigenic determinant) is
part of the antigen and is the specific region with which an antibody interacts
![Page 11: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/11.jpg)
11
Antigenic Determinants
![Page 12: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/12.jpg)
12
Example: Penicillin
Haptens A molecule too small to stimulate antibody formation
by itself When combined with a larger carrier molecule it can
initiate antibody production Once antibodies are generated, hapten can be
recognized by itself
![Page 13: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/13.jpg)
13
Antibodies
Globulin proteins (immunoglobulins or Ig)
Made in response to an antigen A bacterium or virus has many
antigenic determinants against which antibodies can be made
Bi-functional One portion binds specifically to
particular structures called antigen The other part interacts with host cells
![Page 14: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/14.jpg)
14
Antibody structure 2 heavy chains 2 light chains Connected with
disulfide bridges Variable regions in
heavy and light chains: bivalent antigen binding sites, mediate specificity
Constant regions on heavy chain mediate effector function
![Page 15: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/15.jpg)
15
Antibody classes Each class shares the constant region of the
antibody molecule but has many different variable regions
Each class interacts with different types of host cells
Differ in their effector function 5 classes:
IgG IgM IgA IgD IgE
![Page 16: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/16.jpg)
16
![Page 17: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/17.jpg)
17
Monomer 80% of serum antibodies Fix and activate complement (classical
pathway) In blood, lymph, intestine Cross placenta Opsonin (enhance phagocytosis);
neutralize toxins & viruses; protect fetus & newborn
IgG antibodies
![Page 18: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/18.jpg)
18
Pentamer 5-10% of serum antibodies First Ig of an immune response Fix and activate complement (classical
pathway) In blood, lymph, on B cells Agglutinates microbes
IgM antibodies
![Page 19: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/19.jpg)
19
Dimer10-15% of serum antibodies In secretions (milk!!)Protection of mucosa
Mucosal pathogens like Haemophilus or Neisseria secrete IgA proteases
IgA antibodies
![Page 20: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/20.jpg)
20
Monomer0.2% of serum antibodiesMainly on B cells Maturation sign
IgD antibodies
![Page 21: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/21.jpg)
21
Monomer~0.002% of serum antibodiesMainly on mast cells, basophils,
and activated eosinophilsAllergic reactions; defense
against parasitic worms
IgE antibodies
![Page 22: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/22.jpg)
22
Bone marrow gives rise to B cells (B-lymphocytes)
Naïve but mature B cells migrate to secondary lymphatic tissue and become exposed to antigen
B cells recognizes epitopes with antigen specific B cell receptor
Each B-cell expresses a unique B cell receptor on its surface
B-cell receptor is actually the antibody produced by a particular B cell
B cells
![Page 23: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/23.jpg)
23
Clonal selection and expansionIncreased antibody productionPlasma cell or memory cell
development
Consequences of antigen recognition by B cells
![Page 24: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/24.jpg)
24
Clonal selection and differentiation of B cells
A clone originates
from a single cell
![Page 25: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/25.jpg)
25
Effector function of antibodies
Begin after antigen-antibody complex has been formed
Aggluntination Opsonization
Enhanced phagocytosis Complement activation
Opsonization and enhanced opsonophagocytosis via c3b
Microbial lysis through C5b-C9n Inflammation through C5a, C3a, C4a
Neutralization Toxins Viruses
Antibody dependent cytotoxicity Eosinophils: secrete toxic granules onto helminths NK cells: induce apoptosis of virus infected cells
![Page 26: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/26.jpg)
26
Effector functions of antibodies
![Page 27: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/27.jpg)
27
Anti-helminthic cytotoxicity of eosinophils
![Page 28: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/28.jpg)
28
Natural killer cells Large granular lymphocyte-like cells Part of first line of defense (innate immunity) Activated by interferons (produced by virus infected
cells) and other cytokines Target altered host cells
Virus infected Infected with intracellular organism Tumor cells
Induce cell suicide (apoptosis) Cells covered with antibodies (antibody dependent
cytotoxicity) Direct sensing of altered cells
![Page 29: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/29.jpg)
29
The kiss of death
After NK cell have recognized their target they release their large granules containing Pore-forming
toxins Enzymes that
induce suicide of target cell
Tumor Cell
NK-Cell
t0
t60’
![Page 30: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/30.jpg)
30
After differentiating in the thymus, T cells migrate to lymphoid tissue
T cells become activated effector T cells when stimulated by an antigen
T cells respond to digested antigens via T-cell receptor
T cells recognize antigen only when presented by other cells on special molecules Major histocompatibility complex (MHC)
Some effector T cells become memory cells
T-cell mediated immunity
![Page 31: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/31.jpg)
31
T-cell antigens
Short contiguous amino acid (aa) sequence
Processed antigens Antigen must have
been unfolded and degraded
Primary aa structure Only when bound to
a specialized antigen presenting molecule (MHC)
APC
MHC
T-Ly
![Page 32: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/32.jpg)
32
MHC molecules Major Histocompatibility Complex Same as HLA (human leukocyte antigen) Determine compatibility of donor and recipient in
transplantation Every individual as a unique set of MHC molecules Within an individual all cells are equipped with the same set Have a peptide binding groove onto which antigen can be
loaded MHC I: peptides newly synthesized and degraded in cytoplasma
(endogenous) MHC II: peptide fragments generated in phagolysosome
(exogenous)
![Page 33: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/33.jpg)
33
Classification of T cells
Depends on surface molecules on T cells that determine the interaction with MHC molecules and their type of response Cytokine release Sending trigger to target cell to commit
cell suicideT helper cellsCytotoxic T cells (“T killer cells”)Regulatory T cells
![Page 34: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/34.jpg)
34
T-helper cells
Express the surface molecule CD4 Recognizes exogenous digested antigen
presented on MHC type II molecule Interact with antigen presenting cells
Macrophages Dendritic cells B-cells
Respond with secretion of cytokines and activate immune cells
![Page 35: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/35.jpg)
35
Antigen presenting cells
Express MHC II Highly specialized in uptake of
foreign antigen, degradation and presentation to T helper cells via MHC II
Macrophages and dendritic cells Take up antigen via phagocytosis
B cells Bind antigen with surface
antibody and internalize the complex
![Page 36: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/36.jpg)
36
The CD4 : MHC II Interaction
Ag Presenting Cell
MHC IIDigested Ag
Microbe
CD4TCR
TH Cell
Cytokines
![Page 37: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/37.jpg)
37
T helper cells in action
![Page 38: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/38.jpg)
38
T helper cell subclasses
TH1 Secrete the cytokine IFNg▪ Activates macrophages▪ Promotes IgG antibody production in B cells
TH2 Secrete the cytokine IL4▪ Promotes IgE production in B cells▪ Pro-allergic
![Page 39: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/39.jpg)
39
Cytotoxic T cells
Express the surface molecule CD8Recognizes endogenous antigen
presented on MHC type I molecule Can interact with any nucleated cell
Respond with secretion of perforin and granzyme Kill target cells via apoptosis in a
highly specific manner
![Page 40: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/40.jpg)
40
The CD8 : MHC I Interaction
Any Nucleated Cell
MHC IEndogenous Ag
EndogenousAg
CD8TCR
CTL
![Page 41: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/41.jpg)
41
CTL mediated cytotoxicity
![Page 42: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/42.jpg)
42
Treg and TH3Differentiate from T helper cellsTurn off immune response when Ag no
longer presentUse inhibitory cytokines (IL10)
Regulatory T cells
![Page 43: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/43.jpg)
43
Summary for cell mediated immunity
![Page 44: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/44.jpg)
44
Principals cells in the adaptive immune response
![Page 45: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/45.jpg)
45
Summary for cytokinesCytokine Source Effect
Interleukin-1 Macrophages Activates TH cells, induces fever
Interleukin-2 Activated lymphocytes Activates lymphocytes, NK cellsInterleukin 4 TH2 cells IgE productionInterleukin 6 Monocytes, macrophages Acts on liver, acute phase
responseInterleukin-8
(CXCL8)Epithelial cells, macrophages,
neutrophilsActivates and attracts
neutrophilsInterleukin 10 TH3 cells InhibitoryInterleukin-12 Activated macrophages, TH1 Activates NK cells
Interferon a and b Any virus infected cell Induce antiviral activityInterferon g TH1 cells Activates macrophages
Tumor necrosis factor a
Monocytes, macrophages Activates phagocytes, NK cellsCytotoxic for tumor cells
![Page 46: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/46.jpg)
46
Superantigens Activate simultaneously
up to 20% of all TH cells Cause an intense immune
response due to release of cytokines from host cells (“cytokine storm”)
Fever, nausea, vomiting, diarrhea, sunburn-like rash, shock, death
Examples : Toxic Shock Syndrome Toxin
![Page 47: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/47.jpg)
47
Immunological memory Once lymphocytes have encountered their
specific antigen they undergo clonal expansion Some of these cells develop further into
memory cells Can circulate for many years
Upon re-contact with the same antigen they quickly proliferate and resume effector function▪ B cells: antibody production▪ T cells: cytokine production (TH, Treg) and cytotoxicity
(CTL)
![Page 48: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/48.jpg)
48
Example: Primary and secondary immune responses to an antigen
IgM is always the first antibody
IgG follows IgM IgG level does not go back
to baseline Re-exposure to the same
antigen will lead to an augmented and accelerated immune response with higher residual antibody levels
![Page 49: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/49.jpg)
49
Types of adaptive immunity
![Page 50: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/50.jpg)
50
Important to remember Key players in adaptive immunity
Antibodies B-cells T-cells
Lock- key principle: Ag-Ab B cells make antibodies 5 Types of antibodies : IgM (first), IgG (placenta), IgD (maturation), IgA
(mucosa), IgE (allergies) Antibodies can agglutinate, activate complement, promote phagocytosis,
neutralize and initiate cell lysis by NK cells T cells recognize digested antigen when presented to them on MHC molecules Main effector T-cells
Helper T-cells: strengthen defense cells Cytotoxic T-cells: kill infected cells Regulatory T cells: down regulate immune response
Cytokines serve cell-to-cell communication
![Page 51: MICR 201 Microbiology for Health Related Sciences](https://reader035.vdocuments.site/reader035/viewer/2022081513/56816584550346895dd82da2/html5/thumbnails/51.jpg)
51
Check your understanding 1) What type of immunity results from
vaccination? A) Innate immunity B) Naturally acquired active immunity C) Naturally acquired passive
immunity D) Artificially acquired active immunity E) Artificially acquired passive
immunity
3) What type of immunity results from recovery from mumps?
A) Innate immunity B) Naturally acquired active immunity C) Naturally acquired passive
immunity D) Artificially acquired active immunity E) Artificially acquired passive
immunity
15) The antibodies found in mucus, saliva, and tears are
A) IgG. B) IgM. C) IgA. D) IgD. E) IgE.
26) The best definition antibody is A) A serum protein. B) A protein that inactivates or kills an
antigen. C) A protein made in response to an
antigen that can combine with that antigen.
D) An immunoglobulin. E) A protein that combines with a
protein or carbohydrate.