Basic Immunology I Flashcards
What does immunology have to do with oral biology and dentistry?
The body’s natural immune response is the primary mechanism for fighting bacterial, viral, fungal, and parasitic infections, and for protecting us from cancer.
____ can aid the body by reducing or eliminating some types of infection, and they can let the immune response function more ____.
Knowing how these work is essential to providing effective health care.
In some situations, a ____ immune response may cause ___ ____(_____) or may be directed to the ___ ____ themselves (____). This is an undesirable situation that needs to be remedied if possible.
We live in a time when treatments of medical issues are complex, many of which directly affect the immune response.
Examples:
Patients undergoing ___ treatment
Tissue or organ ____
Treatment of ____ disorders (e.g., Crohn’s disease, rheumatoid arthritis, SLE).
It is important that dentists understand how those disorders are treated, and how dental care might impact that.
What does immunology have to do with oral biology and dentistry?
The body’s natural immune response is the primary mechanism for fighting bacterial, viral, fungal, and parasitic infections, and for protecting us from cancer.
Antibiotics can aid the body by reducing or eliminating some types of infection, and they can let the immune response function more efficiently.
Knowing how these work is essential to providing effective health care.
In some situations, a hyperactive immune response may cause tissue damage (immunopathology) or may be directed to the body’s tissues themselves (autoimmunity). This is an undesirable situation that needs to be remedied if possible.
We live in a time when treatments of medical issues are complex, many of which directly affect the immune response.
Examples:
Patients undergoing cancer treatment
Tissue or organ transplantation
Treatment of autoimmune disorders (e.g., Crohn’s disease, rheumatoid arthritis, SLE).
It is important that dentists understand how those disorders are treated, and how dental care might impact that.
The Immune System
What?
It is a____ system composed of multiple ___, ___, and ___ that interact to protect the body from ___ and ___.
Where?
In nearly __ ___of the body, with the exception only of the ____ and the ___ ___ ___
- Brain has its own protection
Localized in ____ _____ _____- the ___ tissues.
The Immune System
What?
It is a physiological system composed of multiple cells, tissues, and organs that interact to protect the body from infection and disease.
Where?
In nearly all tissues of the body, with the exception only of the brain and the central nervous system.
Brain has its own protection
Localized in specialized immunological compartments - the lymphoid tissues.
Immunity requires a balance in the immune response in ____ and ____
Health: Immune system ___ you from disease and infection
Disease: Immune system is __ ___
Allergy, immunodeficiency, transplant rejection, autoimmune disease
Immunity requires a balance in the immune response in health and disease
Health: Immune system protects you from disease and infection
Disease: Immune system is hurting you
Allergy, immunodeficiency, transplant rejection, autoimmune disease
CD (___ of ____) markers
- Molecules on cells that ___ ____ ____ ____of the immune system.
- More than ___ different CD markers now identified (the number is still growing).
- _____ expressed on cells of the immune system.
- A few expressed on ___ cells
- Most are___ expressed, e.g., CD4 (_____), CD8 (____), CD19 (___), CD14 (____).
- Extremely useful to immunologists and clinicians for ____ lymphoid cell populations.
- To know which groups of cells are present
- For example, the human CD4:CD8 ratio is normally about ____
- In AIDS because of the loss of ___ cells, the ratio drops to ___than 2.0 as the number of CD4+ T cells declines (e.g., 1.0, 0.8, 0.6, 0.4, etc).
CD (Cluster of Differentiation) markers
Molecules on cells that define specific cell populations of the immune system.
More than 350 different CD markers now identified (the number is still growing).
Differentially expressed on cells of the immune system.
A few expressed on all cells
Most are selectively expressed, e.g., CD4 (T helper cell), CD8 (T cytotoxic cell), CD19 (B cells), CD14 (macrophages).
Extremely useful to immunologists and clinicians for identifying lymphoid cell populations.
To know which groups of cells are present
For example, the human CD4:CD8 ratio is normally about 2:1 (or 2.0).
In AIDS because of the loss of CD4+ cells, the ratio drops to less than 2.0 as the number of CD4+ T cells declines (e.g., 1.0, 0.8, 0.6, 0.4, etc).
Antigen vs. Immunogen
Antigen (Ag): Any substance that ___ with a cell of the immune system (can be ___ or “__” Ag).
Self Ag involved in autoimmunity
Immunogen: An ___ that induces an ___ ____; not all ___ are ____
You can have something recognized by the immune system that doesn’t induce a response
Antigen vs. Immunogen
Antigen (Ag): Any substance that reacts with a cell of the immune system (can be foreign or “self” Ag).
Self Ag involved in autoimmunity
Immunogen: An antigen that induces an immune response; not all antigens are immunogens.
You can have something recognized by the immune system that doesn’t induce a response
Primary and Secondary Lymphoid tissues
- Primary Lymphoid tissues (also called ‘___ Immune System)
- The site of immune system__ ___
- ___ ___
- _____
- Secondary Lymphoid tissues (also called ‘____ Immune System)
- ___ ____ other than ____ lymphoid tissues (s___, b___, l___ ____, a___, t___, a___, P____’s patches in intestines, etc.)
- ___ ___ of the immune system.
- This is where immune response is ___ and ____
Primary and Secondary Lymphoid tissues
Primary Lymphoid tissues (also called ‘Central Immune System)
The site of immune system cell development
Bone marrow
Thymus
This is where immune system develops
Secondary Lymphoid tissues (also called ‘Peripheral Immune System)
All tissues other than primary lymphoid tissues (spleen, blood, lymph nodes, adenoids, tonsils, appendix, Peyer’s patches in intestines, etc.)
Work place of the immune system.
This is where immune response is generated and maintained
Blood-Lymph Circulation
- Two mechanisms for movement of cells throughout the body.
- The ____ action of the ___ moves cells through the ___
- ____ ____ deposit and retrieve cells passively ____ of tissues.
- Cells in the lymphatic vessels are ____ to the _____
- They relate to each other.
- Infection in foot. Infectious material makes its way to a lymph node.
- Cells of immune system would move thru lymph node
- Those cells dumped back into circulation after tissue
- From the circulation, they come down into lymph node
- Both systems feed___ of the ___ ___ through the___ ___
Blood-Lymph Circulation
Two mechanisms for movement of cells throughout the body.
The pumping action of the heart moves cells through the circulation.
Lymphatic vessels deposit and retrieve cells passively in/out of tissues.
Cells in the lymphatic vessels are returned to the circulation.
They relate to each other.
Infection in foot. Infectious material makes its way to a lymph node.
Cells of immune system would move thru lymph node
Those cells dumped back into circulation after tissue
From the circulation, they come down into lymph node
Both systems feed cells of the immune system through the lymph nodes.
Lymph Nodes in the Jaw and Neck
More than ___ lymph nodes in the jaw/neck region alone and at least ___ in the body overall
Each one of these lymph nodes is a station where the immune response will be ____
Immune response ___ in lymph node and then cells are sent out to the ___ of ___
Regional/Draining lymph nodes: ______________
Lymph Nodes in the Jaw and Neck
More than 50 lymph nodes in the jaw/neck region alone and at least 120 in the body overall
Each one of these lymph nodes is a station where the immune response will be generated
Immune response starts in lymph node and then cells are sent out to the area of infection
Regional/Draining lymph nodes: Ones close to infection
Four ways leukocytes enter and leave a lymph node
- Enter from the ____ via the ___ ___ ___
- Return to ___ via the ___ ___ ____
- Enter from the____ via the ____ ___ ____
- Return to the ____ via the ___ ___ ___.
Four ways leukocytes enter and leave a lymph node
- Enter from the circulation via the lymph node artery
- Return to circulation via the lymph node vein.
- Enter from the lymphatics via the afferent lymphatic vessel.
- Return to the lymphatics via the efferent lymphatic vessel.
Structural Organization of a Lymph Node
- Lymph nodes are areas where ____ (T cells and B cells), ____, _____ cells, or ____ cell, and____ (Ag) come together to_____ an immune response.
- This occurs in ____ ___ within the lymph node.
- Lymph nodes are ______.
- Well cells of immune system are fed into lymph node they go and find their own compartment
- Areas for B cells, T cells, macrophages
- If Ag is brought in with these 3 cells then the immune fcn takes place
Structural Organization of a Lymph Node
Lymph nodes are areas where lymphocytes (T cells and B cells), macrophages, dendritic cells, or Langerhans cell, and antigen (Ag) come together to initiate an immune response.
This occurs in specialized regions within the lymph node.
Lymph nodes are compartmentalized.
Well cells of immune system are fed into lymph node they go and find their own compartment
Areas for B cells, T cells, macrophages
If Ag is brought in with these 3 cells then the immune fcn takes place
The Spleen
- An organ with some_____properties.
- Not _____ a lymphoid organ
- It has many more _____ than the lymph nodes.
- Acts as a ___ for the ___ to remove ___ ___
- It has numerous ____ located in the ‘___ ___’.
- Red pulp: ___
- White pulp: ___
The Spleen
An organ with some immunological properties.
Not exclusively a lymphoid organ
It has many more RBCs than the lymph nodes.
Acts as a filter for the blood to remove dying RBCs.
It has numerous leukocytes located in the ‘white pulp’.
Red pulp: RBC
White pulp: WBC
Hematopoietic vs. Leukocyte
Hematopoietic cells are ___ of the ___ ___ – the ___ (the white blood cells), the ____ and ____ (cells involved in ____), and the ____(red blood cells).
Leukocyte refers only to the ___ blood cells, the cells of the ___ ___
Hematopoietic vs. Leukocyte
Hematopoietic cells are all of the blood cells – the leukocytes (the white blood cells), the megakaryocytes and platelets (cells involved in clotting), and the erythrocytes (red blood cells).
Leukocyte refers only to the white blood cells, the cells of the immune system.
Leukocytes
- ____ (____ cells)
- ___
- ___
- ____ (___ cell)
- B
- E
- N____= G_____
- M____ (precursor of _____)
- M____
- And…
- __ ___
- ___
- ___
- We really don’t know what they doing
- ____ cells
- ____ cells
- __ ___
Leukocytes
Lymphocytes (lymphoid cells)
T cells= T lymphocyte
B cells= B lymphocyte
Myelocytes (myeloid cells)
Basophils
Eosinophils
Neutrophils= Granulocyte
Monocytes (precursor of macrophages)
Macrophages
And…Mast cells (tissue and mucosal mast cells)
We really don’t know what they doing
Dendritic cells
Langerhans cells
Hematopoiesis (aka hemopoiesis)
- Process of ___ the ____, the cells of the immune system for our purposes.
- Takes place in the ___ ____
- Bone marrow provides:
- ___ ____ (stromal cells)
- ___ ___ for development
- ____ ___ ___ cells.
- A cell that is the source of all cells of the immune system.
*
- A cell that is the source of all cells of the immune system.
Hematopoiesis (aka hemopoiesis)
Process of generating the blood cells, the cells of the immune system for our purposes.
Takes place in the bone marrow.
Bone marrow provides:
Structural support (stromal cells)
Growth factors for development
Hematopoietic pluripotent stem cells.
A cell that is the source of all cells of the immune system.
Bone marrow pluripotent stems cells give rise to all leukocytes (and erythrocytes)
Pluripotent stem cells:
- A __ ____ cell population
- Some become __ __ ___
- Some ____ into a cell of the ___ ___
- Each stem cell will become ___ (and __ ___) type of cell of the immune system.
- Thus, all cells of the immune system arise from a ___ ___ ___
Bone marrow pluripotent stems cells give rise to all leukocytes (and erythrocytes)
Pluripotent stem cells:
A self-renewing cell population
Some become new stem cells.
Some differentiate into a cell of the immune system.
Each stem cell will become one (and only one) type of cell of the immune system.
Thus, all cells of the immune system arise from a pluripotent stem cell.
____ bone marrow transplantation
- Collect patient’s ___ cells from their __ ___using a___ -activated cell ___
- ____ patient to destroy __ ___ (the source of the leukemia).
- Inject patient’s __ ___ __ back to ____the immune system.
- There is no need for _____ drugs or tissue matching to prevent failure of the bone marrow graft.
Autologous bone marrow transplantation
Collect patient’s stem cells from their bone marrow using a fluorescent-activated cell sorter.
Irradiate patient to destroy bone marrow (the source of the leukemia).
Inject patient’s healthy stem cells back to regenerate the immune system.
There is no need for immunosuppressive drugs or tissue matching to prevent failure of the bone marrow graft.
Clinical relevance: A ‘Differential Count’ is a calculation of the___ number (____) of each of the ___ major types of ___ in the circulation.
During bacterial and many fungal infections, ____ counts go up (can approach 80-90%). During viral infections,_____ counts go up (60-70%). This provides immediate insight into whether the patient has a viral vs. a non-viral infection.
Clinical relevance: A ‘Differential Count’ is a calculation of the relative number (percentage) of each of the five major types of leukocytes in the circulation.
During bacterial and many fungal infections, neutrophil counts go up (can approach 80-90%). During viral infections, lymphocyte counts go up (60-70%). This provides immediate insight into whether the patient has a viral vs. a non-viral infection.
Immunity
- Innate
- ___
- ____
- Adaptive
- ____
- ___
- Specificity: Response is ____ to a ___ ___
- Ag Memory: ____ to the same antigen leads to a ___ and more___ response.
- *
Immunity
Innate
Ag Non-Specific
No Memory
- Adaptive
- Ag Specific
- Memory
Specificity: Response is restricted to a single antigen.
Ag Memory: Re-exposure to the same antigen leads to a stronger and more rapid response.
Innate Immunity
- Cells
- ___, ___, ___, ___ cells, ___ cells
- Cells that release ____ ____(___, ____, ___cells)
- Toll-like receptors
- Key elements in the ____ of cells of ___ immunity
Adaptive Immunity
- Cells
- ____
- ____
- ____ cells (B cells that produce ___ levels of ___)
- Plasma cells are terminally differentiated B cells
- All are antigen-___
There is collaboration bw two types of immunity
Innate Immunity
Cells
Neutrophils, monocytes, macrophages, dendritic cells, Langerhans cells
Cells that release inflammatory mediators (eosinophils, basophils, mast cells)
Toll-like receptors
Key elements in the activation of cells of innate immunity
Adaptive Immunity
Cells
T lymphocytes
B lymphocytes
Plasma cells (B cells that produce high levels of Ab)
Plasma cells are terminally differentiated B cells
All are antigen-specific
There is collaboration bw two types of immunity
Four broad types of innate immunity
- _____ Barriers (e.g., ___, ___ _____ of stomach)
- ____ Barriers (e.g., ___, __ __ of intestine, __ __, ___)
- ___ Barriers (___ of ___ molecules); ____ (engulfment of ___ ___)
- ____ Barriers (___, cells of the ___ ___, ___)
Four broad types of innate immunity
Physiological Barriers (e.g., fever, low pH of stomach)
Anatomical Barriers (e.g., skin, tight junctions of intestine, mucosal membranes, saliva)
Endocytic Barriers (engulfment of small molecules); Phagocytosis (engulfment of particular antigen)
Inflammatory Barriers (edema, cells of the immune system, complement)
Cells of Innate Immune System and FCNS
Neutrophils: ___ and _______
Monocytes: ___ and ________
Macrophages: ___ and ___________
Dendritic cells and Langerhans cells: ____ and _________
Cells of Innate Immune System and FCNS
Neutrophils: phagocytosis and production of immunological mediators
Monocytes: phagocytosis and production of immunological mediators
Macrophages: phagocytosis and antigen-presentation to lymphocytes
Dendritic cells and Langerhans cells: phagocytosis and antigen-presentation to lymphocytes
What is innate immunity?
Antigen non-specific defense that is used ____or within several ____of exposure to ____.
Already___ (i.e., does not require ___ to be____). Thus, it is the ___ response of the body to eliminate infectious organisms.
Universally____ first-line-of-defense against infection.
Evolutionarily,___ the adaptive immune response.
Found in ___ ____ organisms.
Uses ____ and ___ that are ancient in their lineage.
Must provide protection against a ___ ___ of pathogens
Defects in innate immunity are very ___ but tend to be __
What is innate immunity?
Antigen non-specific defense that is used immediately or within several hours of exposure to antigen.
Already present (i.e., does not require time to be generated). Thus, it is the first response of the body to eliminate infectious organisms.
Universally conserved first-line-of-defense against infection.
Evolutionarily, predates the adaptive immune response.
Found in all multicellular organisms.
Uses receptors and cells that are ancient in their lineage.
Must provide protection against a wide variety of pathogens
Defects in innate immunity are very rare but tend to be lethal.
Misconceptions about Innate Immunity
Innate immune system is an evolutionary rudiment whose only function is to ___the infection until the ___ immune response is activated.
Adaptive immunity developed because of the____ of the innate immune response.
Innate immune system cannot cope with the __ ___ ___ and extreme ____ of pathogenic organisms.
All of these are ___ __
Misconceptions about Innate Immunity
Innate immune system is an evolutionary rudiment whose only function is to contain the infection until the “real” immune response is activated.
Adaptive immunity developed because of the inflexibility of the innate immune response.
Innate immune system cannot cope with the high mutational rate and extreme heterogeneity of pathogenic organisms.
All of these are not true.
Toll-Like Receptors (TLRs)
Until recently, the specific mechanisms involved in innate immune system activation were poorly understood.
___, a surface receptor on ____, was believed to be the primary mechanism of cell activation by ___ ___ such as lipopolysaccharide (LPS).
Our understanding of this has been greatly expanded with the discovery of toll-like receptors (TLRs).
TLRs are molecules on cells of the innate immune system that ___ ___ ___
Toll-Like Receptors (TLRs)
Until recently, the specific mechanisms involved in innate immune system activation were poorly understood.
CD14, a surface receptor on macrophages, was believed to be the primary mechanism of cell activation by bacterial products such as lipopolysaccharide (LPS).
Our understanding of this has been greatly expanded with the discovery of toll-like receptors (TLRs).
TLRs are molecules on cells of the innate immune system that recognize foreign antigens.
How do TLRs Work?
TLRs recognize ___ ___ ____ ___ shared by many different infectious agents (__ __ ___ ___).
The structures recognized by the innate immune system are referred to as ___ ___ ___ ___ (PAMPs).
The receptors for PAMPs are referred to as ___ ___ ____ (PRRs), i.e., TLRs. They are ___ on ___ of the innate immune system.
There is an immediate opportunity for the innate immune system to respond to a wide spectrum of infectious agents.
How do TLRs Work?
TLRs recognize highly conserved molecular structures shared by many different infectious agents (virus, bacteria, fungi, protozoa).
The structures recognized by the innate immune system are referred to as Pathogen-Associated Molecular Patterns (PAMPs).
The receptors for PAMPs are referred to as Pattern-Recognition Receptors (PRRs), i.e., TLRs. They are expressed on cells of the innate immune system.
There is an immediate opportunity for the innate immune system to respond to a wide spectrum of infectious agents.
Pathogen-Associated Molecular Patterns (PAMPs) Recognized by TLRs
L______ (LPS from the gram___ ___ ___)
P____ (gram-positive and gram-negative __ ___)
L____ ___ (gram___ ___ ___)
M___-rich ____ (___ but not___ glycoproteins and glycolipids)
F___ (bacterial flagella)
P___ (bacterial pili)
Bacterial __ ___(high frequency of____ ___ ___ dinucleotide sequences in ____but not ____ DNA)
N_______ (an amino acid common to ___ proteins)
___-stranded RNA (unique to many___)
G____ and z___ (___ and ___ cell walls)
P____and other ___ (microbial ___)
Pathogen-Associated Molecular Patterns (PAMPs) Recognized by TLRs
Lipopolysaccharides (LPS from the gram-negative cell wall)
Peptidoglycans (gram-positive and gram-negative cell walls)
Lipoteichoic acids (gram-positive cell wall)
Mannose-rich glycans (microbial but not human glycoproteins and glycolipids)
Flagellin (bacterial flagella)
Pilin (bacterial pili)
Bacterial nucleic acid (high frequency of unmethylated cytosine-guanine dinucleotide sequences in bacterial but not mammalian DNA)
N-formylmethionine (an amino acid common to bacterial proteins)
Double-stranded RNA (unique to many viruses)
Glycolipids and zymosan (yeast and fungal cell walls)
Phosphorylcholine and other lipids (microbial membranes)
There are about 12 TLR
TLR 1 and 2 work together as a ___
Several Different TLRs may be expressed on a Cell of the Innate Immune System
TLRs use very ___ receptors (approximately __ in all) to recognize antigens distributed across many types of infectious agents.
For example, a particular TLR that is specific for bacterial LPS will recognize LPS regardless of the type of bacteria that expresses it (E. coli, salmonella, etc.).
This, therefore, is a very efficient way for the cells of the innate immune system to operate.
There are about 12 TLR
TLR 1 and 2 work together as a dimer
Several Different TLRs may be expressed on a Cell of the Innate Immune System
TLRs use very few receptors (approximately 13 in all) to recognize antigens distributed across many types of infectious agents.
For example, a particular TLR that is specific for bacterial LPS will recognize LPS regardless of the type of bacteria that expresses it (E. coli, salmonella, etc.).
This, therefore, is a very efficient way for the cells of the innate immune system to operate.
____ Pathogen-Associated Molecular Patterns (PAMPs) can be recognized by ________ Expressed on Cells of the Innate Immune System
Note: the same PRR (TLR) may bind to products of___ microbial or viral agents provided they express the same ___
Multiple Pathogen-Associated Molecular Patterns (PAMPs) can be recognized by Pattern Recognition Receptors (PRRs) Expressed on Cells of the Innate Immune System
Note: the same PRR (TLR) may bind to products of different microbial or viral agents provided they express the same PAMP.
Once the TLR is triggered, what does it do?
TLRs transmit a ___to the innate immune cell’s ___ to activate ____ for the synthesis of immune response ____ ____ (_____)
___ , ____ and ____responses are initiated.
TLRs that recognize viral components induce the synthesis of ____, which blocks viral ____ in infected host cells.
Once the TLR is triggered, what does it do?
TLRs transmit a signal to the innate immune cell’s nucleus to activate genes for the synthesis of immune response regulatory molecules (cytokines).
Inflammation, fever, phagocytosis responses are initiated.
TLRs that recognize viral components induce the synthesis of interferon, which blocks viral replication in infected host cells.
How TLRs Drive an Inflammatory Response in Oral Tissues
Rapid (___ hrs) secretion of _____ ____ from ___, ___ cells, ____cells, and ____.
IL-1b
TNFa
IL-6
IL-12
How TLRs Drive an Inflammatory Response in Oral Tissues
Rapid (4-24 hrs) secretion of proinflammatory cytokines from macrophages, dendritic cells, Langerhans cells, and neutrophils.
IL-1b
TNFa
IL-6
IL-12
Infectious agents common to the oral cavity that are recognized by TLRs
Gram Positive Bacteria all use _____
- Strep
- Lactobacillus
- Staphylococcus
- Actinomyces
Gram Negative Bacteria Use TLR ___ or ___
- Haemophilus
- Prevotella
- Actinobacillus
- Porphyromonas
- Fusobacterium
- Spirochetes
- Other
Herpes: ___
Epstein-Barr Virus: ___
Cytomegalovirus: ___
Hep-A: ___ or ___
Candida, Aspergillus: ____ or ___
Infectious agents common to the oral cavity that are recognized by TLRs
Gram Positive Bacteria all use TLR 1/2 (dimer of 1 and 2)
Strep
Lactobacillus
Staphylococcus
Actinomyces
Gram Negative Bacteria Use TLR ½ or 4
Haemophilus
Prevotella
Actinobacillus
Porphyromonas
Fusobacterium
Spirochetes
Other
Herpes: TLR9
Epstein-Barr Virus: TLR9
Cytomegalovirus: TLR9
Hep-A: TLR7 or 8
Candida, Aspergillus: TLR 1/2 or 6
Topical applications of TLR ___ (TLR activators) and ____ (TLR blockers) may soon be used to ___ or ___ the____ response as needed.
Topical applications of TLR agonists (TLR activators) and antagonists (TLR blockers) may soon be used to enhance or block the inflammatory response as needed.
Cells of the Lymphoid Lineage
T Cell Maturation Occurs in the____
T cell= Thymus Derived Lymphocyte
B Cell Maturation Occurs in the___ and ___ ___
“B”= Bursa of Fabriciusà Birds only
Cells of the Lymphoid Lineage
T Cell Maturation Occurs in the Thymus
T cell= Thymus Derived Lymphocyte
B Cell Maturation Occurs in the Blood and Lymph nodes
“B”= Bursa of Fabriciusà Birds only
Adaptive Immunity
- Antigen receptor-mediated (specificity) and immunological memory.
- ____ immunity: antibody-mediated immunity associated with _ cells and ___cells.
- Cell-mediated immunity (CMI):__ __on tissue cells.
- This is what the _ cells perform*
- Cells of adaptive immunity:
- _ cells (___ & ___)
- _ cells and ___ cells (produce __)
Adaptive Immunity
Antigen receptor-mediated (specificity) and immunological memory.
Humoral immunity: antibody-mediated immunity associated with B cells and plasma cells.
Cell-mediated immunity (CMI): direct effect on tissue cells.
This is what the T cells perform*
Cells of adaptive immunity:
T cells (T helper cells & T cytotoxic cells)
B cells and plasma cells (produce Ab)
Antigenicity of Macromolecules
Most antigenic–> Least antigenic
______/_____
____
___
___ ___
Antigenicity of Macromolecules
Most antigenic–> Least antigenic
- Proteins/glycoproteins
- Carbohydrates
- Lipids
- Nucleic Acids
Antigenic ‘Determinants/Epitopes’
Adaptive immune system reacts with a ____ of a protein molecule, not the___ molecule.
The reactive portion is referred to as an antigenic ‘____ ‘or ‘___’. —> __aa
There may be __ or ____ determinants present on one protein molecule.
Antigenic ‘Determinants/Epitopes’
Adaptive immune system reacts with a portion of a protein molecule, not the whole molecule.
The reactive portion is referred to as an antigenic ‘determinant ‘or ‘epitope’. à 4-5 aa
There may be one or several determinants present on one protein molecule.
Types of Antigens
Foreign antigen: antigen expressed on a __ ___tissue (e.g., __ agent [virus, bacteria, etc], ____ agent [food antigen, etc].
Self antigen (____): antigen expressed on one’s ___ tissue cell.
Heterophile antigen: ____ antigens that have some ____ in ___. (e.g., streptococcal M-protein and human heart muscle).
Cross-reacting antigen: two or more antigens that are____ or ___, e.g., viral antigen and a self antigen.
Alloantigen: antigen expressed on a ____ ____ ____, e.g., a skin or organ tissue from an unrelated donor.
Allergen: antigen that induces an ___ ___, e.g., hay fever pollen.
Hapten: a molecule that is an ___ but not an ____ (e.g., dinitrophenol); it can be rendered immunogenic if it is ___ to a ____ ____ molecule.
Types of Antigens
Foreign antigen: antigen expressed on a non-self tissue (e.g., infectious agent [virus, bacteria, etc], non-infectious agent [food antigen, etc].
Self antigen (autoantigen): antigen expressed on one’s own tissue cell.
Heterophile antigen: Unrelated antigens that have some determinants in common. (e.g., streptococcal M-protein and human heart muscle).
Cross-reacting antigen: two or more antigens that are similar or identical, e.g., viral antigen and a self antigen.
Alloantigen: antigen expressed on a foreign tissue cell, e.g., a skin or organ tissue from an unrelated donor.
Allergen: antigen that induces an allergic response, e.g., hay fever pollen.
Hapten: a molecule that is an antigen but not an immunogen (e.g., dinitrophenol); it can be rendered immunogenic if it is attached to a larger immunogenic molecule.
A Hapten becomes immunogenic if coupled to a molecule that has immunogenicity
Inject with hapten (dinitrophenol [DNP]): _______
Inject a large foreign protein (BSA): ______
Inject with hapten (dinitrophenol [DNP]) coupled to BSA:___________
A Hapten becomes immunogenic if coupled to a molecule that has immunogenicity
Inject with hapten (dinitrophenol [DNP]): No antibody to DNP
Inject a large foreign protein (BSA): Antibody to BSA
Inject with hapten (dinitrophenol [DNP]) coupled to BSA: Antibody to both BSA and to DNP
Immunoglobulins (Igs) a.k.a. Antibodies (Abs)
Large _____ molecules produced by__ cells.
B cells express Abs on__ __
Activation of B cell (Ag triggers Ab) by Abs leads to _____ into a ___ ___, i.e., a B cell secreting a large amount of Ab.
Each B cell makes Ab with only ___specificity, e.g., a B cell making Ab to herpesvirus will not make Ab to influenza virus.
Immunoglobulins (Igs) a.k.a. Antibodies (Abs)
Large glycoprotein molecules produced by B cells.
B cells express Abs on cell surface.
Activation of B cell (Ag triggers Ab) by Abs leads to differentiation into a plasma cell, i.e., a B cell secreting a large amount of Ab.
Each B cell makes Ab with only one specificity, e.g., a B cell making Ab to herpesvirus will not make Ab to influenza virus.
Basic Organization of Ig Molecule
Two ___ ____ (mirror image).
Each half consists of a ‘___ chain’ (___ molecular weight) and a ‘___ chain’ (___molecular weight).
Light chains and heavy chains are further divided into ___ and ____ regions.
The two variable regions of the light and heavy chains form the ‘___ ___ ____’.
Constant heavy chain may be used to anchor the __ to the __ __ __ via the __ region.
Basic Organization of Ig Molecule
Two identical halves (mirror image).
Each half consists of a ‘light chain’ (small molecular weight) and a ‘heavy chain’ (large molecular weight).
Light chains and heavy chains are further divided into variable and constant regions.
The two variable regions of the light and heavy chains form the ‘antigen-binding sites’.
Constant heavy chain may be used to anchor the Ig to the B cell membrane via the Fc region.
The Fab binds ___ determinants on ___ antigen or to determinants on___ ___ ___
The Fab binds two determinants on same antigen or to determinants on two different antigens
Classification of Immunoglobulins
- Five classes (isotypes) of Igs defined by the ___ region of the heavy chain:
- IgM – usually exists as a ____ molecule (five IgM joined together); ___ Ig made by B cell
- IgG – predominant Ig in ___; several ___ exist
- IgA – Ig found in ___ ___; it usually exists as a ____ molecule (two igA molecules joined together)
- IgD – found in ___ in ___ concentrations; function __ ___
- IgE – Ig responsible for ___ ___
- Two classes of light chains:
- _ light chain
- _ light chain
*
Classification of Immunoglobulins
Five classes (isotypes) of Igs defined by the Fc region of the heavy chain:
IgM – usually exists as a pentameric molecule (five IgM joined together); first Ig made by B cell
IgG – predominant Ig in serum; several subclasses exist
IgA – Ig found in mucosal tissues; it usually exists as a dimeric molecule (two igA molecules joined together)
IgD – found in serum in low concentrations; function not clear
IgE – Ig responsible for allergic reactions
Two classes of light chains:
λ light chain
κ light chain
IgM is the ___ type of Ab produced during an immune response.
It is especially effective at ‘__ __’ antigen, e.g., virus or bacteria that is in the circulation.
It usually exists as a ____ molecule – five single (monomeric) IgM molecules attached together.
As the immune response develops, B cells shift to from making___ antibodies to___, __ or ___. This is called ___ ___
The ___of the antibody molecule___ ___ ___, however, because the same ___ portion is used.
IgM is the first type of Ab produced during an immune response.
It is especially effective at ‘mopping up’ antigen, e.g., virus or bacteria that is in the circulation.
It usually exists as a pentameric molecule – five single (monomeric) IgM molecules attached together.
As the immune response develops, B cells shift to from making IgM antibodies to IgG, IgA, or IgE. This is called class switching. The specificity of the antibody molecule does not change, however, because the same Fab portion is used.
IgM
Pentameric IgM molecule made from five monomeric molecules connected by a ___ ___at the base of the __ region
Covalent ___ ___ between monomeric molecules
IgM
Pentameric IgM molecule made from five monomeric molecules connected by a joining (J) chain at the base of the Fc region
Covalent disulfide bonds between monomeric molecules
IgG, IgD, and IgE
These Abs are ____ ___ but ___ ___
IgG, IgD, and IgE
These Abs are Structurally Similar but not Identical
IgA
- This Ab usually exists as a ___ of two monomeric IgA molecules connected by a __ __
- Because IgA is found mostly in mucosal surfaces, it needs a specialized way for being transported ___of ___ ___. (From behind___ ___ out it into ___region)
- __ ___ to __ ___ (lumen)
- Dimeric IgA uses a ‘__ __’ to be transported through the epithelial layer.
- Steps in IgA transport:
- Plasma cell makes IgA
- IgA binds to __ ___receptor at __of an epithelial cell.
- IgA is placed in a __ __ and moved to the ___ ___
- The dimeric IgA molecule is ___ into the lumen/oral cavity.
IgA
This Ab usually exists as a dimer of two monomeric IgA molecules connected by a J chain
Because IgA is found mostly in mucosal surfaces, it needs a specialized way for being transported outside of epithelial cells. (From behind epithelial cell out it into mucosal region)
Sub mucosa to Oral cavity (lumen)
Dimeric IgA uses a ‘secretory component’ to be transported through the epithelial layer.
Steps in IgA transport:
Plasma cell makes IgA
IgA binds to poly-Ig receptor at base of an epithelial cell.
IgA is placed in a transport vesicle and moved to the luminal surface.
The dimeric IgA molecule is released into the lumen/oral cavity.
IgE and its Function
IgE binds to ____ receptors on ___cells
____ (antigen) binds to IgE
Release (____) of ____ and ____ mediators
IgE FCN always linked to a mast cell
IgE and its Function
IgE binds to IgE-Fc receptors on mast cells
Allergen (antigen) binds to IgE
Release (degranulation) of histamine and allergic mediators
IgE FCN always linked to a mast cell
Relative Concentrations of different types of Ig in the Serum
Ig__> Ig__> Ig__> Ig__> Ig__> Ig__
IgM/IgD mostly in ___
IgG mostly in ___
IgA mostly in ___ ___ (___ in serum)
IgE mostly in ___ ___;(___ in serum)
Relative Concentrations of different types of Ig in the Serum
IgG1> IgA1> IgA2> IgM> IgD> IgE
IgM/IgD mostly in serum
IgG mostly in serum
IgA mostly in mucosal tissues (some in serum)
IgE mostly in mucosal tissues;(rarely in serum)
Three Ways Immunoglobulins Work
- Neutralization:
- Ab ___ to ___ and prevents it from ____ a cell
- ___ infectivity
- Complement-Mediated Cell Lysis:
- Ab binds to ___ ___ on cell surface
- Complement___ ___ ___
- Infected cell ___
- Opsonization: (by definition: enhanced phagocytosis)
- Ab binds to ____
- ___ portion of Ab binds to ___ on ____ cells (macrophage or neutrophil)
- Phagocytosis is ____
- ___ of pathogen
Three Ways Immunoglobulins Work
Neutralization:
Ab binds to pathogen and prevents it from entering a cell
Halts infectivity
Complement-Mediated Cell Lysis:
Ab binds to virus Ag on cell surface
Complement ruptures cell membrane
Infected cell destroyed
Opsonization: (by definition: enhanced phagocytosis)
Ab binds to pathogen
Fc portion of Ab binds to receptor on phagocytic cells (macrophage or neutrophil)
Phagocytosis is enhanced
Removal of pathogen
