The Lymphatic System and Immunity

3 m
The Lymphatic System and Immunity

Dian Adiningsih, SKp., M.Kes., AIFO
Overview
Introduction Organization of the Lymphatic System
Functions of the lymphatic system Lymphatic vessels Lymphocytes Lymphoid nodules Lymphoid organs Lymphatic system and body defenses Physical barriers Phagocytes Immunological surveillance Interferons Complement Inflammation Fever
Specific Defenses: The Immune Response

Forms of immunity Properties of immunity Overview of immune response T cells and cell-mediated immunity B cells and antibody-mediated immunity
Nonspecific Defenses

d_adiningsih@yahoo.com
Introduction
Pathogens: microorganisms responsible for human diseases
Bacteria Viruses Fungi Parasites
Lymphatic system
Keeps us alive and healthy
d_adiningsih@yahoo.com 3
Organization of Lymphatic System

3 components
Lymphatic vessels Fluid (lymph) Lymphoid organs
Lymphatic System
Lymph Lymphatic vessels Lymphatic tissue Lymphatic nodules Lymph nodes Tonsils Spleen Thymus
Functions of Lymphatic System

Production, maintenance, distribution of lymphocytes
Respond to presence of:
Invading pathogens Abnormal body cells (virus-infected cells, cancer cells) Foreign proteins (toxins released by bacteria)
Return of fluid and solutes from peripheral tissues to blood Distribution of hormones, nutrients, and waste products from tissues of origin to general circulation
Lymphatic Vessels
Lymphatic Vessels
Carry lymph away from tissues Lymphatic capillaries

More permeable than blood capillaries Epithelium functions as series of one-way valves
Types of Lymphocytes
T cells (Thymus dependent)
80% of circulating lymphocytes Cytotoxic T cells
Directly attack foreign cells or body cells infected by viruses (cell-mediated immunity)
Helper T cells
Stimulate activities of both B and T cells
Suppressor T cells
Inhibit both T and B cells
Types of Lymphocytes
B cells (Bone-marrow derived)
10-15% circulating lymphocytes Plasma cells
Responsible for production and secretion of antibodies (immunoglobulins)
Responsible for antibody-mediated immunity
NK cells (Natural Killer)

5-10% Attack foreign cells, normal cells infected with viruses, and cancer cells Immunological surveillance
Lymphocyte Development
Lymphocytes arise from stem cells in the bone marrow Newly formed lymphocytes are all alike But they later develop into B cells or T cells, depending on where they continue their maturation
Bone marrow
Lymphoid stem cell
Thymus
B cell
T cell
Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) d_adiningsih@yahoo.com
12
13
Lymphoid Nodules
Masses of lymphoid tissue w/o a capsule
Increase and decrease size depending on # lymphocytes present
Found beneath epithelial lining of organs in:

Respiratory system Digestive system
Tonsils Peyers patches
Urinary system
14
Lymphoid Organs: Lymph Nodes
15
Lymphatic Tissue and Nodules

Lymphatic tissue
Consists mainly of lymphocytes Encapsulated or not
Lymphatic nodules
Numerous in loose connective tissue of digestive (Peyers patches), respiratory, urinary, reproductive systems
Lymph Nodes
Organized in cortex and medulla Substances removed by phagocytosis or stimulate lymphocytes or both Only structures to filter lymph
Afferent and efferent vessels
Tonsils
Large groups of lymphatic nodules in nasopharynx and oral cavity Provide protection against bacteria and other harmful material Groups
Palatine Pharyngeal Lingual
Lymphoid Organs: Thymus
19
Thymus
Located in superior mediastinum Divisions: Cortex and medulla Site of maturation of T cells
Lymphoid Organs: Spleen
21
Spleen
Located in left superior side of abdomen
Can be ruptured in traumatic abdominal injuries resulting in bleeding, shock, death
Blood flows through at 3 different rates

Fast (most), slow, intermediate
Functions
Destroys defective RBCs Detects and responds to foreign substances Limited reservoir for blood
Spleen
Body Defenses
The Lymphatic System and Body Defenses

Nonspecific Defenses
Do not distinguish one threat from another Physical barriers Phagocytic cells Immunological surveillance Interferons Complement Inflammation Fever
Specific Defenses
Protect against particular threats Develop after birth Dependent on activity of lymphocytes B cells T cells
25
26
27
The Complement System
28
29
Macrophage
30
Specific Defense: The Immune Response

Respond to specific antigens T cells
Cell-mediated immunity (cellular immunity) Provide defense against abnormal cells and pathogens in living cells
B cells
Antibody-mediated immunity (humoral immunity) Provide a defense against antigens and pathogens in body fluids
31
Immune System
32
Properties of Immunity
Specificity Versatility Memory Tolerance
33
Overview of Immune Response
34
35
PERTAHANAN TUBUH MELAWAN BAKTERI DANVIRUS PATOGEN
PERTAHANAN TUBUH MELAWAN BAKTERI DAN VIRUS PATOGEN
PERTAHANAN TUBUH MELAWAN BAKTERI DANVIRUS PATOGEN
Forms of Immunity
Either innate or acquired Innate
Genetically determined
Acquired
Active or Passive
Active Immunity
Naturally acquired immunity Induced active immunity
Passive Immunity
Induced passive immunity Natural passive immunity
41
Innate vs. acquired immunity
INNATE IMMUNITY Rapid responses to a broad range of microbes
ACQUIRED IMMUNITY Slower responses to specific microbes
External defenses Skin Mucous membranes Invading microbes (pathogens) Secretions
Internal defenses Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Cell-mediated response (cytotoxic lymphocytes) Humoral response (antibodies)
42
Innate I: External Defenses

Physical barriers against the entry of microorganisms and viruses
Intact skin and mucous membranes
Mucus: a viscous fluid that traps microbes

and other particles
43

In the trachea, ciliated epithelial cells
Sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs
10 m
44

Secretions from the skin Give the skin a pH between 3 and 5, which is
acidic enough to prevent colonization of many microbes
Also include proteins such as lysozyme, an enzyme that digests the cell walls of many bacteria
45
Innate II: Internal Defenses

Phagocytosis by phagocytes (cells) Phagocytes: Types of white blood cells
Ingest invading microorganisms Initiate the inflammatory response
Fever, Pain .
Phagocytic Cells
Microbes 1 Pseudopodia surround microbes. 2 Microbes are engulfed into cell. MACROPHAGE
3 Vacuole containing microbes forms. Vacuole
Lysosome containing enzymes
4 Vacuole and lysosome fuse.
5 Toxic compounds and lysosomal enzymes destroy microbes. 6 Microbial debris is released by exocytosis.
3 m
e.g. Macrophages, a specific type of phagocytic cells
47

Natural Killer Cells Do not eat the pathogen itself but Attack virus-infected body cells and cancer cells Trigger apoptosis in the cells they attack
48
The lymphatic system

1 Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries. Adenoid Tonsil Interstitial fluid Lymphatic capillary 2 Fluid inside the lymphatic capillaries, called lymph, flows through lymphatic vessels throughout the body.
Lymphatic vessels return lymph to the blood via two large ducts that drain into veins near the shoulders.
Lymph nodes
Blood capillary Tissue cells Lymphatic vessel
Spleen
Peyers patches (small intestine) Appendix
Lymphatic vessels
Lymph node
Masses of lymphocytes and macrophages
3 Within lymph nodes, microbes and foreign particles present in the circulating lymph encounter macrophages, dendritic cells, and lymphocytes, which carry out various defensive actions.
49
Inflammation (set fire in Greek)

Injured hand
First response to damage or infection: Redness, Fever, Pain

INFLAMATION Response Redness, Fever, Pain

Pin Blood clot
Pathogen
Macrophage Chemical signals Phagocytic cells Capillary
Blood clotting elements
Phagocytosis
Red blood cell

1 Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable. 2 Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Clotting begins. 3 Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site. 4 Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals.
Septic shock: systemic inflammation

Acquired Immunity
Is the bodys second major kind of defense Involves the activity of lymphocytes
52
Self vs. Nonself
How immune system consider pathogens as non-self?

There are receptor for pathogens
53
Antigen Recognition by Lymphocytes

Two main types of lymphocytes
1) B lymphocytes (B cells) 2) T lymphocytes (T cells) Have about 100,000 antigen receptor that all recognize the same epitope
54
Antigen and Epitopes
Antigenbinding sites Antibody A
Epitopes (antigenic determinants)
Antigen
Antibody B Antibody C
55
Figure 43.8 Antigen receptors on lymphocytes

Antigenbinding site Light chain
C
C
Disulfide bridge
Antigenbinding site
Variable regions Constant regions Transmembrane region Plasma membrane
Antigenbinding site
V C
Heavy chains B cell
Cytoplasm of B cell
b chain a chain Disulfide bridge Cytoplasm of T cell
T cell
(a) A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges.
(b) A T cell receptor consists of one a chain and one b chain linked by a disulfide bridge.
56
B Cell Receptors for Antigens

B cell receptors
Consist of four peptides Bind to specific, intact antigens
Are often called membrane antibodies or membrane immunoglobulins

Antigenbinding site Light chain Antigenbinding site Disulfide bridge Variable regions
Constant regions Transmembrane region
Heavy chains B cell
Plasma membrane
Cytoplasm of B cell (a) A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges.
57
T Cell Receptors for Antigens

T cell receptor
Consists of two different polypeptide chains Detect
antigen + MHC
Variable regions V V Constant C C regions Transmembrane region
AntigenBinding site
Plasma membrane
a chain
b chain
Disulfide bridge Cytoplasm of T cell (b) A T cell receptor consists of one a chain and one b chain linked by a disulfide bridge. d_adiningsih@yahoo.com
T cell
58
43.8 T Cell Receptors
59
MHC molecules (produced by infected cells) Present antigens in the infected cells T cells recognize the MHC+ antigen complex
60
T Cells and Cell-Mediated Immunity

T cells recognize antigens when bound to membranes of other cells
Membrane receptors called major histocompatibility complex (MHC) proteins
Depending on their source

Peptide antigens are handled by different classes of MHC molecules Class I and Class II Present to different lyphocytes
Class I MHC Proteins

Found on the surfaces of all of our cells MHC proteins bind small peptide molecules normally present on cell membrane
Normal peptides: T cell ignores Abnormal, virus, or bacteria (nonself): T cell activated
Destroys abnormal/infected cell
62
Class I MHC on almost all nucleated cells of the body

Display peptide antigens to cytotoxic T cells
Infected cell
Produced by the cell
Antigen fragment
1 Class I MHC molecule T cell receptor 2
1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface.
2 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection.
Cytotoxic T cell
63
Class II MHC Proteins

Found only on membranes of lymphocytes and phagocytic antigen-presenting cells (APCs)
Such as monocyte-macrophage group, free and fixed macrophages Specialized for activating T cells against foreign cells and proteins
Phagocytic APCs engulf and break down foreign antigens or pathogens

Fragments of foreign antigens displayed on phagocytic cells membrane
Bind to Class II MHC proteins T cells come in contact and become activated, starting the immune response
Class II MHC on dendritic cells, macrophages, and B cells

Display antigens to helper T cells
Microbe 1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface.
Antigenpresenting cell Antigen fragment
Phagocytic Ag
1 Class II MHC molecule 2
T cell receptor
Figure 43.9b (b)
Helper T cell
Acquired immunity
65
MHC I
MHCII
Killing
Helping
Cytotoxic T cell
Helper T cell
66
67
T Cells
T cell activation for both occur when MHC protein contains specific antigen T cell programmed to detect
Once activated, T cells divide and differentiate in to cells with specific function in immune response
Cytotoxic T cells Helper T cells Memory T cells Suppressor T cells
68
Cytotoxic T Cells
Responsible for cell-mediated immunity Activated by exposure to antigens bound to Class I MHC proteins
Activated cells under cell division that produce active cytotoxic T cells and memory cells
Track down and attack bacteria, fungi, protozoa, or foreign transplanted tissue
69
Cytotoxic T Cells
Destruction occurs by:
Releasing perforin (destructive protein)
Ruptures antigenic cell membrane
Secreting lymphotoxin (poison)

Kills target cell
Apoptosis
Genetically programmed cell death T cells activate the genes within the target cell
Also called Killer T cells

Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells

Cytotoxic T cells make CD8
A surface protein that greatly enhances the interaction between a target cell and a cytotoxic T cell
Cytotoxic T cells
Bind to infected cells, cancer cells, and transplanted tissues
Binding to a class I MHC complex on an infected body cell

Activates a cytotoxic T cell and differentiates it into an active killer
71
The activated cytotoxic T cell

1 A specific cytotoxic T cell binds to a class I MHCantigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. 2 The activated T cell releases perforin 3 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the molecules, which form pores in the nucleus, release of small apoptotic bodies, target cell membrane, and proteolytic and eventual cell death. The released enzymes (granzymes), which enter the cytotoxic T cell can attack other target cells. target cell by endocytosis. Released cytotoxic T cell Cancer cell
Cytotoxic T cell
Perforin Granzymes
TCR Class I MHC molecule 1 CD8 2 Pore 3
Apoptotic target cell
Target cell
Peptide antigen
Figure 43.16
Cytotoxic T cell
72
73
74
Apoptosis and Macrophages
75
Helper T Cells
Activated by exposure to antigens bound to Class II MHC proteins Activated divide to produce
Active Helper T cells and memory cells
Release variety of cytokines that:

Coordinate specific and nonspecific defenses Stimulate cell mediated and antibody-mediated immunity
76
Helper T Cells: A Response to Nearly All Antigens

Helper T cells produce CD4, a surface protein
Bind to class II MHC moleculeantigen

complexes on antigen-presenting cells
Activation of the helper T cell then occurs
77
T helper cell (TH) activation

1
TCR + CD4 binding to MHC+Ag

Cytotoxic T cell Peptide antigen Class II MHC molecule TCR 2 1 CD4 3 Helper T cell
MHC I +Ag
Dendritic cell Bacterium
Cell-mediated immunity (attack on infected cells) Humoral immunity (secretion of antibodies by plasma cells)
Dendritic cell
Cytokines 2 Proliferation of the T cell, stimulated by cytokines from both the dendritic cell and the T cell itself, gives rise to a clone of activated helper T cells (not shown), all with receptors for the same MHCantigen complex.
B cell
3 The cells in this clone secrete other cytokines that help activate B cells and cytotoxic T cells.
78
Memory T Cells
During cell division for both cytotoxic and helper T cells, some develop into memory cells Remain in reserve If same antigen attacks 2nd time, memory T cells immediately differentiate into cytotoxic T cells and helper T cells
Allows for more rapid and effective immune response
Clonal selection of B cells

Generates a clone of short-lived activated effector cells and a clone of long-lived memory cells
Antigen molecules Antigen molecules bind to the antigen receptors of only one of the three B cells shown.
B cells that differ in antigen specificity
Antigen receptor
The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen.
Memory cells
Plasma cells (effector cells)
80
In the secondary immune response
Memory cells facilitate a faster, more efficient

response
1 Day 1: First exposure to antigen A 2 Primary response to antigen A produces antibodies to A 3 Day 28: Second exposure to antigen A; first exposure to antigen B 4 Secondary response to antigen A produces antibodies to A; primary response to antigen B produces antibodies to B
104 Antibody concentration (arbitrary units) 103
102 101 100 0 7
Antibodies to A
Antibodies to B
14
21
28
35
42
49
56 81
Time (days)
Suppressor T Cells
When activated, depress responses of other T and B cells Does not occur immediately
Takes much longer for these cells to become activated Act after initial immune response
82
Humoral and cell-mediated immunity against different types of threats

Acquired immunity The humoral immune response
the activation and clonal selection of B cells, resulting in the production of secreted antibodies
The cell-mediated immune response

involves the activation and clonal selection of cytotoxic T cells
83
Humoral immune response
Cell-mediated immune response
First exposure to antigen
Intact antigens
Antigens engulfed and displayed by dendritic cells
Antigens displayed by infected cells
Activate
Activate (by MHCII)
Activate (MHC I)
B cell
Helper T cell
Gives rise to
Secreted cytokines activate
Cytotoxic T cell
Gives rise to
Gives rise to
Plasma cells
Memory B cells
Active and memory helper T cells
Memory cytotoxic T cells
Active cytotoxic T cells
Secrete antibodies that defend against pathogens and toxins in extracellular fluid
Defend against infected cells, cancer cells, and transplanted tissues
84
B Cells and Antibody-Mediated Immunity: B Cell Activation

Each B cell carries its antibody molecules in its cell membrane
If ISF contains antigens that can bind to antibodies, B cells become sensitized
Antigens enter B cell and become displayed on Class II MHC proteins on surface of B cell
Helper T cell activated by same antigen attaches to MHC protein-antigen complex and secretes cytokines that: Promote B cell activation Stimulate B cell division Accelerate plasma cell production Enhance antibody production
B Cell Activation
Activated B cells divide several times
Produce daughter cells that differentiate into:
Plasma cells
Synthesize and secrete large numbers of antibodies on surface of sensitized B cells
Memory cells
Similar to memory T cells If exposed to same antigen, will differentiate into plasma cells
86
87
88
89
Antibody Structure
Consist of short and heavy chains of polypeptides
Each chain has constant and variable segments
Constant heavy chains form base of antibody molecule
B cells produce only 5 types of constant segments
Specificity depends on variable segments of light and heavy chains

Free tips contain antigen binding sites (very specific for each type of antigen)
Antigen-antibody complex
Forms when antibody binds to proper antigen Binds to sites and leads to B cell sensitization and an immune response
90
Antibody Classes
From lymphocytes : Ig M, Complement Ig G, Major in blood Ig E, allergic Ig D, Clonal selection
IgM (pentamer)
First Ig class produced after initial exposure to antigen; then its concentration in the blood declines J chain
Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19)
IgG (monomer)
Most abundant Ig class in blood; also present in

tissue fluids Only Ig class that crosses placenta, thus conferring passive immunity on fetus Promotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation Than IgM (see Figure 43.19)
IgA (dimer)
Present in secretions such as tears, saliva, mucus,
and breast milk

J chain
Secretory component
Provides localized defense of mucous membranes by agglutination and neutralization of antigens (see Figure 43.19)
Presence in breast milk confers passive immunity on nursing infant
IgE (monomer)
Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic reactions (see Figure 43.20)
IgD (monomer) Present primarily on surface of naive B cells that have not been exposed to antigens
Transmembrane region
Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)
91
Antibody-Mediated Disposal of Antigens

The binding of antibodies to antigens
Is also the basis of several antigen disposal mechanisms Leads to elimination of microbes by phagocytosis and complement-mediated lysis 1) Neutralization 2) Agglutination 3) Precipitation 4) Complement reaction
Antibody-mediated mechanisms of antigen disposal

Binding of antibodies to antigens inactivates antigens by
Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis) Virus
Agglutination of antigen-bearing particles, such as microbes

Bacteria
Precipitation of soluble antigens
Activation of complement system and pore formation Complement proteins
MAC
Pore Bacterium Soluble antigens Foreign cell
Enhances Phagocytosis
Leads to Cell lysis
Figure 43.19
Macrophage
93
94
95
Classes of Antibodies (Immunoglobins Igs)

IgG
Largest and most diverse Resist many viruses, bacteria, bacterial toxins Can cross placenta
What type of immunity is that?
IgM
Circulate; attack bacteria
IgA
Found in exocrine secretions
Ex?
Attack pathogens before they enter the body
IgE
When bound to antigen, stimulates basophils and mast cells to release chemicals to stimulate inflammation
IgD
Attached to B cell and involved in their activation
Antibody Function
Neutralization Agglutination and Precipitation Activation of a complement Attraction of phagocytes Enhancement of phagocytosis Stimulation of inflammation
97
Primary and Secondary Responses to Antigen Exposure
98
Pathogens (Epitopes) are manyHow to detect all of them?

Antibody for a specific antigen is newly made or already exist?
Custom-tailored
Ready-made
100
Complexity
Antigen diversity : 1015 Human gene number: ~35000
How can make a lot of 15 antibodies up to 10 ?

Light chain diversity

40 V
V4V39 DNA of undifferentiated B cell V1 V2 V3 V40 J1 J2 J3 J4 J5 Intron C
X 5J
1 Deletion of DNA between a V segment

and J segment and joining of the segments DNA of differentiated B cell V1 V2 V3 J5 Intron
2 Transcription of resulting permanently rearranged, functional gene pre-mRNA V 3 J5 Intron C
3 RNA processing (removal of intron; addition of cap and poly (A) tail) mRNA Cap V 3 J5 C Poly (A) 4 Translation Light-chain polypeptide V C B cell 102 B cell receptor
Variable Constant region region d_adiningsih@yahoo.com
Heady chain diversity

50 V X 20 D x 6 J x 9C
103
B cell receptor diversity

200 X 3600 = 720,000
Light chain
Heavy chain
Do you think
The complexity of antigen receptor is enough to detect all of pathogen in the world??
105
Somatic mutations
Some mutants binds to Ag better
106
Diversity of immune receptors
By Gene rearrangement
MHC diversity depend on the number of alleles
By Gene rearrangement
How to resolve this problem? Some antibody binds to self proteins.
108
Testing and Removal of Self-Reactive Lymphocytes

B and T cells are maturing in the bone and thymus Their antigen receptors are tested for possible selfreactivity
Self-reacting lymphocytes bearing receptors

for antigens already present in the body are destroyed
by
apoptosis or rendered nonfunctional

Active and Passive Immunization

Active immunity
Develops naturally in response to an infection Can also develop following immunization, also called
vaccination
In immunization
A nonpathogenic
form of a microbe or part of a microbe elicits an immune response to

an immunological memory for that microbe
Active and Passive Immunization

Passive immunity:
Is conferred naturally when IgG crosses the
placenta from Mother to Fetus

or when IgA passes from mother to
infant in breast milk

Can be conferred artificially by injecting
antibodies into a nonimmune person

The immune systems to distinguish self from nonself limits tissue transplantation
Detected as enemies -Pathogens -Transplanted tissues
112
Blood Groups and Transfusions

Certain antigens on red blood cells
Determine whether a person has type A, B, AB, or O blood
113
Another red blood cell antigen, the Rh factor
During pregnant
During delivery
Babys blood exposed to maternal immune system
114
Tissue and Organ Transplants
Skin graft
MHC (Major Histocompatibility complex)

Tissue
Major Role: activating T-cells via interaction with peptide antigen and T-cell Receptor.
MHC major role in tissue rejection
What is the role of MHC normally?

MHC for
Antigen presentation
antigen complex
T cells recognize the MHC+
118
Class I MHC on almost all nucleated cells of the body

Display peptide antigens to cytotoxic T cells
Infected cell
Produced by the cell
Antigen fragment
1 Class I MHC molecule T cell receptor 2
1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface.
(a) Cytotoxic T cell
119
Class II MHC on dendritic cells, macrophages, and B cells

Display antigens to helper T cells
Microbe 1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface.
Antigenpresenting cell Antigen fragment
Phagocytic Ag
1 Class II MHC molecule 2
T cell receptor
Figure 43.9b (b)
Helper T cell
120
MHC (Major Histocompatibility complex)
Each has many types of alleles

MHC alleles are polymorphic
122
MHC is polymorphic and
codominant
expression is
303 known HLAA alleles in humans (previous slide) but a maximum of 2 per person
123
The chances of successful transplantation are increased

If the donor and recipient MHC tissue types are well matched (higher between relatives) If the recipient is given immunosuppressive drugs
Why
xenograft difficult?
Pig without some antigens

Lymphocytes in bone marrow transplants

May cause a graft versus host reaction in recipients
GVHR
Donor blood cells attack host tissues

Immune-Related Diseases
Immune-related diseases
Autoimmune diseases : reaction to self tissues Immunodeficiency : no reaction to others
127
Allergies
Allergies are exaggerated (hypersensitive) responses
To certain antigens called allergens
128
In localized allergies such as hay fever

IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells The next time the allergen binds to IgE and the mast cell secretes histamines
Histamines
The allergic response

IgE Allergen 1 3 2 Histamine
Granule Mast cell 1 IgE antibodies produced in response to initial exposure to an allergen bind to receptors or mast cells. 2 On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recognize and bind the allergen. 3 Degranulation of the cell, triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergy symptoms.
130
An acute allergic response sometimes leads to anaphylactic shock

A whole-body, life-threatening reaction that can occur within seconds of exposure to an allergen
131
MEKANISME RESPON ANAFILAKSIS
Autoimmune diseases - Why?

The immune system loses tolerance for self and turns against certain molecules of the body
Rheumatoid arthritis
an autoimmune disease that leads to damage and painful inflammation of the cartilage and bone of joints
133
Other examples of autoimmune diseases include

Systemic lupus erythematosus Multiple sclerosis Insulin-dependent diabetes
134
Immunodeficiency Diseases
An inborn or primary immunodeficiency
Results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses
An acquired or secondary immunodeficiency

Results from exposure to various chemical and biological agents
135
Inborn (Primary) Immunodeficiencies

Severe combined immunodeficiency (SCID)
Both the humoral and cell-mediated branches of acquired immunity fail to function
A gene mutation results in absence or nonfunctional blood cell
How to cure him?
136
How to cure SCID?

1) Bone marrow transplantation
2) Gene-therapy
Ashanti De Silva, the first
human to receive gene therapy (1990)
137
Acquired (Secondary) Immunodeficiencies

Acquired immunodeficiencies
Range from temporary states to chronic diseases AIDS kills the helper T-cells
1m
138
T helper cell (TH) activation

1 Cytotoxic T cell
Dendritic cell Bacterium Helper T cell Cell-mediated immunity (attack on infected cells) 3 Humoral immunity (secretion of antibodies by plasma cells)
2 1 Dendritic cell 2
CD4
Cytokines 3
B cell
AIDS attack TH cells

Stress and the Immune System

Growing evidence shows
That physical and emotional stress can harm immunity
Stress test: If you see two identical dolphins, you are stress-free
140

The Lymphatic System and Immunity

Загружено:

Сведения о документе

Исходное описание:

Оригинальное название

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

The Lymphatic System and Immunity

Загружено:

Авторское право:

Доступные форматы

3 m

The Lymphatic System and Immunity

Specific Defenses: The Immune Response

Organization of Lymphatic System

Functions of Lymphatic System

Carry lymph away from tissues Lymphatic capillaries

Responsible for antibody-mediated immunity

NK cells (Natural Killer)

Found beneath epithelial lining of organs in:

Lymphoid Organs: Lymph Nodes

Lymphatic Tissue and Nodules

Lymphoid Organs: Thymus

Lymphoid Organs: Spleen

Blood flows through at 3 different rates

The Lymphatic System and Body Defenses

The Complement System

Specific Defense: The Immune Response

Overview of Immune Response

PERTAHANAN TUBUH MELAWAN BAKTERI DANVIRUS PATOGEN

PERTAHANAN TUBUH MELAWAN BAKTERI DAN VIRUS PATOGEN

PERTAHANAN TUBUH MELAWAN BAKTERI DANVIRUS PATOGEN

Innate vs. acquired immunity

INNATE IMMUNITY Rapid responses to a broad range of microbes

ACQUIRED IMMUNITY Slower responses to specific microbes

External defenses Skin Mucous membranes Invading microbes (pathogens) Secretions

Innate I: External Defenses

Intact skin and mucous membranes

Mucus: a viscous fluid that traps microbes

Innate I: External Defenses

Innate I: External Defenses

Innate II: Internal Defenses

Ingest invading microorganisms Initiate the inflammatory response

Innate II: Internal Defenses

3 Vacuole containing microbes forms. Vacuole

Lysosome containing enzymes

4 Vacuole and lysosome fuse.

e.g. Macrophages, a specific type of phagocytic cells

Innate II: Internal Defenses

The lymphatic system

Innate II: Internal Defenses

Blood capillary Tissue cells Lymphatic vessel

Masses of lymphocytes and macrophages

Inflammation (set fire in Greek)

First response to damage or infection: Redness, Fever, Pain

INFLAMATION Response Redness, Fever, Pain

Macrophage Chemical signals Phagocytic cells Capillary

Blood clotting elements

Red blood cell

Septic shock: systemic inflammation

Self vs. Nonself

How immune system consider pathogens as non-self?

Antigen Recognition by Lymphocytes

Antigen and Epitopes

Antigenbinding sites Antibody A

Epitopes (antigenic determinants)

Figure 43.8 Antigen receptors on lymphocytes

Heavy chains B cell

b chain a chain Disulfide bridge Cytoplasm of T cell

B Cell Receptors for Antigens

Are often called membrane antibodies or membrane immunoglobulins

Constant regions Transmembrane region

Heavy chains B cell