Basic Immunology I

Question 1

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.

Answer 1

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.

Question 2

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.

Answer 2

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.

Question 3

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

Answer 3

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

Question 4

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).

Answer 4

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).

Question 5

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

Answer 5

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

Question 6

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 ____

Answer 6

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

Question 7

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___ ___

Answer 7

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.

Question 8

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: ______________

Answer 8

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

Question 9

Four ways leukocytes enter and leave a lymph node

1. Enter from the ____ via the ___ ___ ___
2. Return to ___ via the ___ ___ ____
3. Enter from the____ via the ____ ___ ____
4. Return to the ____ via the ___ ___ ___.

Answer 9

Four ways leukocytes enter and leave a lymph node

1. Enter from the circulation via the lymph node artery
2. Return to circulation via the lymph node vein.
3. Enter from the lymphatics via the afferent lymphatic vessel.
4. Return to the lymphatics via the efferent lymphatic vessel.

Question 10

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

Answer 10

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

Question 11

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: ___

Answer 11

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

Question 12

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 ___ ___

Answer 12

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.

Question 13

Leukocytes

• ____ (____ cells)
  
  • ___
  • ___
• ____ (___ cell)
  
  • B
  • E
  • N____= G_____
  • M____ (precursor of _____)
  • M____
• And…
  
  • __ ___
    
    • ___
    • ___
      
      • We really don’t know what they doing
  • ____ cells
  • ____ cells

Answer 13

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

Question 14

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.
      *

Answer 14

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.

Question 15

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 ___ ___ ___

Answer 15

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.

Question 16

____ bone marrow transplantation

1. Collect patient’s ___ cells from their __ ___using a___ -activated cell ___
2. ____ patient to destroy __ ___ (the source of the leukemia).
3. Inject patient’s __ ___ __ back to ____the immune system.
4. There is no need for _____ drugs or tissue matching to prevent failure of the bone marrow graft.

Answer 16

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.

Question 17

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.

Answer 17

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.

Question 18

Immunity

• Innate
  
  • ___
  • ____
• Adaptive
  • ____
  • ___
• Specificity: Response is ____ to a ___ ___
• Ag Memory: ____ to the same antigen leads to a ___ and more___ response.
• *

Answer 18

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.

Question 19

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

Answer 19

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

Question 20

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 ___ ___, ___)

Answer 20

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)

Question 21

Cells of Innate Immune System and FCNS

Neutrophils: ___ and _______

Monocytes: ___ and ________

Macrophages: ___ and ___________

Dendritic cells and Langerhans cells: ____ and _________

Answer 21

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

Question 22

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 __

Answer 22

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.

Question 23

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 ___ __

Answer 23

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.

Question 24

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 ___ ___ ___

Answer 24

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.

Question 25

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.

Answer 25

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.

Question 26

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 ___)

Answer 26

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)

Question 27

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.

Answer 27

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.

Question 28

____ 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 ___

Answer 28

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.

Question 29

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.

Answer 29

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.

Question 30

How TLRs Drive an Inflammatory Response in Oral Tissues

Rapid (___ hrs) secretion of _____ ____ from ___, ___ cells, ____cells, and ____.

IL-1b

TNFa

IL-6

IL-12

Answer 30

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

Question 31

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 ___

Answer 31

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

Question 32

Topical applications of TLR ___ (TLR activators) and ____ (TLR blockers) may soon be used to ___ or ___ the____ response as needed.

Answer 32

Topical applications of TLR agonists (TLR activators) and antagonists (TLR blockers) may soon be used to enhance or block the inflammatory response as needed.

Question 33

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

Answer 33

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

Question 34

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 __)

Answer 34

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)

Question 35

Antigenicity of Macromolecules

Most antigenic–> Least antigenic

______/_____

____

___

___ ___

Answer 35

Antigenicity of Macromolecules

Most antigenic–> Least antigenic

• Proteins/glycoproteins
• Carbohydrates
• Lipids
• Nucleic Acids

Question 36

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.

Answer 36

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.

Question 37

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.

Answer 37

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.

Question 38

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:___________

Answer 38

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

Question 39

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.

Answer 39

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.

Question 40

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.

Answer 40

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.

Question 41

The Fab binds ___ determinants on ___ antigen or to determinants on___ ___ ___

Answer 41

The Fab binds two determinants on same antigen or to determinants on two different antigens

Question 42

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
    *

Answer 42

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

Question 43

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.

Answer 43

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.

Question 44

IgM

Pentameric IgM molecule made from five monomeric molecules connected by a ___ ___at the base of the __ region

Covalent ___ ___ between monomeric molecules

Answer 44

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

Question 45

IgG, IgD, and IgE

These Abs are ____ ___ but ___ ___

Answer 45

IgG, IgD, and IgE

These Abs are Structurally Similar but not Identical

Question 46

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.

Answer 46

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.

Question 47

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

Answer 47

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

Question 48

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)

Answer 48

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)

Question 49

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

Answer 49

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