Transcript Chapter 6

Chapter 6
Adaptive Immunity
“third line of defense”

Develops more slowly
 Specific
 Memory
Adaptive Immunity
 Antigens – “foreign or non self” (Ag=
foreign proteins)
◦ Viruses, bacteria, cancer, fungi or parasites
◦ Noninfectious – pollens, foods, bee venoms
◦ Drugs, vaccines, transfusions and transplants
Adaptive Immunity
 Principal cells: Lymphocytes
◦ Accessory cells: APC & dendritic cells
◦ Effector cells
 B cells → antibodies to blood → Ag
 T cells → attack Ag directly
 Functionally
◦ Regulatory
◦ Effector
 Specific
◦ Each cell recognizes only
ONE specific Ag
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25-35% of blood leukocytes
99% reside in the lymph glands
60-70% of blood lymphocytes are T-cells and
10-20% are B-cells
Foreign protein recognition:”surface
receptor proteins-unique”
◦ B-cells: membrane bound immunoglobulin
◦ T-cells: self-recognition protein(major
histocompatibility complex)
 “self
from non self”
Chromosome # 6
 Two Classes

Class I *: endogenous pathogens -viruses & cancer
 Cytotoxic T cells… “must destroy me”
◦ Class II
: extracellular pathogens - bacteria & toxins
 Phagocytic cells: macrophages, dendritic cells, B
lymphocytes
: Ag binds with MHC II
Helper T
cell (CD4+)
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Human Leukocyte Antigens:WBCs
◦ Multiple allelles: A (120 genes) & B (250 genes)
◦ Halotype: inherited unit
 * all nucleated cells… not on RBCs

Class I… “all nucleated cells” (endogenous
antigens)*
Function:present processed antigen to
cytotoxic CD8+ T cells or
NK cells
“constant
screening”
* Seen as abnormal…autoimmune disease
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Class II …APC (dendritic, B cells, macrophage)
(exogenous antigens)
Function: presents processed antigen
fragment to CD4+ T cells
effective interaction
among immune cells*
*Figure:6-1
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“Additional membrane bound proteins”
Uses
◦ Aid the function of the immune cells
◦ Define the functionally distinct subset of cells
 CD4+ helper T cells – binding receptor: from APCs
 CD8+ cytotoxic T cells- binding receptor: from all
nucleated cells
Adaptive Immunity
 Clonal
diversity
– 1st phase – fetus
◦ Recognition of millions* of foreign Ag
◦ Large population of T & B cells
◦ Develop in primary lymphoid organ (thymus, bone
marrow)
◦ Migrate to secondary lymphoid organs
*108 or 100 million foreign
antigens(proteins)
Generation of Clonal Diversity
“primary lymphoid organ – fetus”
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Lymphoid stem cell
B and T cells recognize more than 108
antigens
B lymphocytes – bone marrow “hormones” –
to secondary lymphoid organs*
T lymphocytes – thymus “hormones” to
second lymphoid organs*
*lymph nodes & spleen
Secretory (Mucosal) Immune System
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Lymphoid tissue that protects the external
surface of the body
Ab present in tears, sweat, saliva, mucus and
breast milk.
IgA dominant immunoglobulin
◦ Prevent attachment and invasion of pathogens
Adaptive Immunity
“two arms”
 Humoral –
◦ Antibodies –
 Cell
B cells
bacteria, viruses, and toxins
mediated – T cells
◦ Subpopulations
 React directly with Ag on cell surfaces –
NK(see next slide)
 Stimulate other leukocytes (cell to cell or
cytokines) T
 Cytotoxic cells – viruses infected cells
and cancer

“lymphocytes” :functionally & phenotypically
distinct from T cells, B cells,
and monocyte-macrophages
◦ Automatically kill foreign cells: programmed
◦ No activation as with cytotoxic T cells
◦ Inhibition with contact of normal host MHC
molecules
Antigens
“molecule that reacts with antibodies or
receptors on B and T cells”
 Immunogens-antibodies
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Epitope – antigenic determinant (recognized)
Paratope – Ag binding site (antibody or
lymphocyte)
Antigens
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Self-antigen – every cell*, genetically
determined (MHC), HLAs+
*glycoproteins – not RBC
+ human leukocyte antigens
 Tolerance
Humoral* Immune Response
 Antibodies
◦ Immunoglobulins
◦Plasma cells
◦ Classes
 IgG, IgA, IgM, IgE and IgD
*fluid
Classes of Immunoglobulins
 IgG
◦ Most abundant (80 to 85%)
◦ Transported across the placenta
◦ Four classes
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IgA
◦ Two classes
 IgA1 – blood
 IgA2 – body secretions
Classes of Immunoglobulins
• IgM
– Largest
– First Ab produced during 1° response to an Ag
– Synthesized during fetal life
•
IgD
– Low concentration
– Ag receptor on surface of early B cells
•
IgE
– Allergic responses
– Parasite infections
Functions of Antibodies
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Direct effects
◦ Neutralization
◦ Agglutination
◦ Precipitation
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Indirect effects
◦ Opsonization
◦ Complement
B Cell Antigen Receptor
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Surface of B cell
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Consists
◦ Antigen – recognition molecule :
monomer
◦ Intracellular signaling molecules
IgM,IgG
Cell Mediated Immune Response
•
Mature T cells
–1.Cytotoxic (Tc) – attack and destroy directly
–2.Regulatory helper T (Th) – controls
• Cell mediated
• Humoral mediate
• Suppressors (Ts)
–3.Memory cells
“viruses, tumors, pathogens resistant to neutrophils
and macrophages”
T Cell Recognition of a Target Cell
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T cell receptor complex
◦ Antibody-like transmembrane protein
◦ Accessory proteins for intracellular signaling
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Antigen presentation molecules
◦ By antigen presenting cells
◦ Major histocompatibility complex (dendritic cells*,
macrophages, B-lymphocytes)
◦ *Nobel Prize Medicine & Physiology 2011: Beutler,
Hoffman & Steinman
Functions of T-lymphocyte

“Killing abnormal cell”
◦ Cytotoxic T lymphocytes (viruses, tumors)
 Attach to target cell : MHC-I molecules
 Appropriate CD molecules
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Activate macrophages
◦ Cytokines – chronic inflammation
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Regulate immune response
◦ T-helper (Th) cell
– humoral & cellular
◦ T-suppressor cells – affects immune response
Primary and Secondary Immune Responses
 Primary
◦ Initial exposure
◦ Latent period (B cell differentiation)
◦ After 5 - 7 days – IgM antibodies detected
◦ An IgG response follows
Primary and Secondary Immune Responses
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Secondary
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More rapid
Large amounts of Ab are produced
Rapid response - 2° to memory cells
IgM – similar to 1° response, IgG – greater number
Figure 6-15 Page 161
◦ “MEMORY”
Active vs. Passive Immunity
 Active
Immunity
◦ Antibodies or T cells produced after either a natural
exposure to an antigen or after immunization
 Passive
Immunity
◦ Preformed Ab or T lymphocytes are transferred
from a donor to a recipient.
◦ Example: IgG for hepatitis A exposure
: tetanus toxoid