Midterm Flashcards
Inflammation is a protective response, as part of the ___ immune system
Innate
What is PRISH
The signs of inflammation
Pain Redness Immobility Swelling Heat
What are some major triggers of inflammation
Pathogenic organisms
Damaged tissue
How do pathogens and damaged tissue trigger inflammation
By binding to pattern recognition receptors in complement and sentinel cells such as macrophages, dendritic macrophages and mast cells
What are the mechanisms of inflammation? What signs of inflammation are each responsible for?
Vasodilation: in response to histamine and prostaglandins by macrophages, mast cells and basophils -this increases blood flow (redness and heat)
Increased capillary permeability: also in response to histamine and prostaglandins -causes increases fluid in the area (swelling)
Increased sensitivity to pain due to mediators released by sentinel cells (immobility)
Initially the predominant inflammatory cell is the
Neutrophil -activated by mediators from activated complement and sentinel cells
Initially, blood tests will show ___ levels of neutrophils. Why is this?
Low levels
Because all the neutrophils have migrated to areas of inflammation
As the body catches up the blood neutrophil levels will increase
Describe the neutrophils role in inflammation
Activated by mediators from activated complement and sentinel cells
The neutrophils attach to endothelium of capillaries
These migrate to the tissues and are further activated when they bind to molecules from pathogens or damaged tissue at their pattern recognition receptors
These phagocytose and kill ingested material
Neutrophils have a short life, what so dead neutrophils collect as
Pus -made of dead neutrophils, cells and bacteria
Describe the activation of clotting
Proteins in the exudate include clotting factors and fibrinogen
Clotting is activated by damaged tissue
Fibrin net is formed from fibrinogen -acts as a net to trap pathogens and can form capsules around the specific site
With chronic inflammation, neutrophils decrease (neutropenia), what cell predominates in chronic inflammation tissue
Macrophages and lymphocytes
Describe healing of inflamed tissue
Initial insult/cause is removed by phagocytosis
Inflammatory mediators production stops and inflammation decreases
Damaged tissue is replaced by new tissue and/or fibrous tissue (scarring)
Moderate and severe inflammation is often accompanied by
A whole body systemic response
What are the ways the whole body responds to severe inflammation
Changes in neutrophil count
Fever
Removal of trace nutrients from the blood
Decrease in appetite
Breakdown of muscle to fuel metabolism
Acute phase proteins
What are the changes on neutrophils levels with severe inflammation
Initially neutrophils in blood will decrease (neutropenia) as they move to the site of inflammation
Bone marrow increases production in response to inflammation
Neutrophil count then increases (neutrophilia) usually in response to moderate inflammation
True or false
Mild inflammation still results in a change in neutrophil blood levels
False
There is often no to very little change
Describe a fever with the systemic response to inflammation
Actions on the hypothalamus -Prostaglandins mediated
This increases the “set point” in body temp
The body responds by shivering/huddling/raised hair coat because it is told it is cold (not at the set point)
This directly inhibits growth of some pathogens (can’t survive high temps)
Increases activity of some immune cells including neutrophils/macrophages/T cells
When a fever breaks the set point is set lower and the body is told it’s hot
Why is there a fine line in terms of temperature within the body that it should not cross
If it gets too high proteins will start to denature
Why would the body remove trace nutrients from the blood in a systemic response to severe inflammation
Mainly iron
Low iron availability and fever (alone or together) work to limit the growth of bacteria and viruses
Why would the body decrease appetite in response to severe inflammation
May allow better control of nutrient intake so that less nutrients are available for microbes
What is a decrease in appetite used as in the medical field
A clinical sign
What are acute phase reaction proteins
A part of the response to inflammation, the liver produces a group of proteins (innate system response)
Some are part of the clotting system (fibrinogen and prothrombin)
Some remove iron
Some are complement system proteins (opsonization, attract immune cells)
Some degrade inflammatory products (plasminogen breaks down blood clots) to control inflammation
Why are fibrinogen and prothrombin measured on a CBC panel?
If they are present, it is an indicator of acute inflammation
What are some ways you can control inflammation
Cold
Antihistamines
NSAIDs
Corticosteroids
Why does cold help control inflammation
Effective in early stages of some types of inflammation
Stops destructive enzymes
especially effective in laminitis
Antihistamines are especially effective in
Allergic reactions
What are NSAIDs
Non steroidal anti inflammatory drugs
Block the synthesis of some/all prostaglandins, thromboxanes,
Reduce swelling, heat, pain and fever
What are corticosteroids
Not effective on fevers
Blocks the activation of cells when a pattern recognition receptor is bound to
Acts EARLY in inflammation cycle
Can be immunosuppressive because it is a steroid
Describe what could cause inflammation characterized by swelling under the skin that “pits” on pressure with no heat, pain or redness
Leaky capillaries result in increase educate -low proteins in the blood (albumin)
Usually non inflammatory edema
Seen with congestive heart failure
Describe what could cause inflammation characterized by swelling under the skin, feels soft and fluctuant with no heat, may be painful and may be discoloured red through purple
Bleeding
Hematoma
Describe what could cause inflammation characterized by swelling under the skin, feels soft and fluctuant with no heat, no pain and no discolouration
Lipoma or Seroma
Fluid of blood is leaking out
Pitting is a sign that fluid is within the tissue (connective tissue) rather than
Free fluid (hematoma)
Describe T Lymphocytes
Mature in the thymus, reside in lymph nodes and spleen
Circulate through blood and tissues
Function: adaptive immune response (cell mediated) specific in response, when activated they clone themselves (genetically identical with the same antigen receptors)
Several different types: helper, suppressor, cytotoxic, memory
What is the difference between different types of T cells
All genetically identical with the same antigen receptor but have different effects once activated by its antigen
Describe B Lymphocytes
Found mainly in the lymph nodes and spleen and some in blood (these migrate to the lymph nodes)
Function: humoral adaptive immunity: recognize specific antigens and differentiate into plasma cells
When activated: they clone themselves and some become plasma cells which make antibodies, some become memory B cells that float around waiting for their specific antigen
Describe bone marrow
Site of formation of white and red blood cells
Maturation of red blood cells and many white blood cells
Site where lymphocytes are first formed (move to thymus to mature)
Describe the thymus
Largest in early life and decrease with age
Lymphocytes migrate from the bone marrow to the thymus and multiply in the thymus while randomly making new antigen receptors
Why do most T cell die in the thymus
They get killed off if they do not react to nonself cells or if they react to self cells
Only useful T cells are released from the thymus
Describe the lymph nodes
Contain many T and B cells, antigen presenting cells (dendritic macrophages) and plasma cells (activated B cells)
Lymph that is filtered through the lymph nodes brings immune cells and antigens with it
What is the clinical significance of lymph nodes
Lymph nodes increase in size with inflammation and when there are tumors present
We palpate to detect disease and localize the nodes
Sites: submandibular, superficial cervical, axillary, popliteal, inguinal
With dental disease, what lymph node is normally enlarged
Submandibular
If ALL lymph nodes are enlarged, what does this indicate
Lymphomas (tumors in the lymph nodes)
Or a systemic infection
Describe the spleen
Similar function to lymph nodes but it filters blood
Red pulp: removes old red blood cells and contain monocytes
White pulp: rich in T and B cells
What are the 3 main receptors of the adaptive immune system that help determine self from nonself
Pattern recognition receptors
Lymphocyte antigen receptors
Major histocompatibility receptors
What are pattern recognition receptors
Recognize components commons to groups of pathogens or damaged tissue
What are lymphocyte antigen receptors
Each lymphocyte recognizes a specific antigen found on non self pathogens
How was the major histocompatibility complex discovered
Scientist could transfer tumor tissue between closely related mice but not mice of different strains unless you killed their immune system
Discovered that tissues carry antigens unique to that individual (called MHC)
What is the MHC Type 1 molecules
Marks cells as “self” found on cell surfaces. These are all the same in a given individual. This is how NK cells recognize cells as self and do not kill them
Binds to internal proteins and displays them on the cell surface: have a binding site for lymphocytes so they can check the internal proteins of the cell. This help T cells recognize pathogens or non self cells
All nucleated cells in the body display some MHC antigens, EXCEPT what? What does this make easier to accomplish?
red blood cells
Blood transfusions
What are MHC type 2 molecules
Found on professional phagocytes
Binds to molecules released when pathogens or damaged tissue is phagocytosed and displays it on the cell surface
Similar to type 1
What are MHC type 3 molecules
These are pattern recognition receptors that help signal molecules
What are lymphocyte antigen receptors
Very diverse: millions of types
Found in T and B cells (not NK)
T cells have antibody-like receptors
On each lymphocyte the receptor only binds to one specific antigen)
Formed from a limited number of genes: each gene codes for a part of the binding site, the genetic material is randomly modified and rearranged. Results in millions of different binding sites.
In the process of differentiating, only cells with non self receptors are allowed to survive
What are the 2 types of receptors T lymphocytes have?
Lymphocytes antigen receptors
MHC receptors
Describe how the MHC receptors and lymphocytes antigen receptors work together on a T cell
These are next to each other
The T cell binds to other cells using MHC to see if the cell is “self” and then tests the antigens present using the lymphocyte antigen receptor
If it does not have MHC the T cell is activated and the cell is destroyed, if it has antigens present the T cell is activated to start multiplication of that T cell
Where are T cells found
Initially produced in the bone marrow and move to the thymus to mature
Once mature, they move to lymph nodes and other lymphoid organs
Some circulate in blood and lymph
When activated they move to areas of inflammation and draining lymph nodes
What is the T cell “education” or maturation
Occurs in the thymus
Initially T cells are selected for cells that will recognize MHC so they can communicate with other cells
Further selected for T cells with lymphocytes antigen receptors that are NOT activated by self antigens -only non self antigens
What is tolerance
The failure of the immune system to respond to an antigen
What are normal T cells tolerant to
Tolerant to normal tissue and cells
When might tolerance become an issue? Give an example?
If the body becomes tolerant to something harmful to the body
Occurs with cows infected with Bovine Viral Diarrhea (BVD) at 45-120 days of gestation. T lymphocytes that react with BVD are killed off in the thymus because the body thinks it’s normal. This results in a persistent infection (now tolerant to it)
Explain how T lymphocytes are activated
Occurs when a T cell lymphocyte antigen receptor binds to its specific antigen (typically an abnormal protein displayed in an MHC molecule)
Ex. Virus infected cell with the virus antigen on its surface
Ex. Dendritic macrophages displaying bits of material on its surface after phagocytosing something
What are dendritic cells
These reside in tissue to identify pathogens and damaged tissue using pattern recognition receptors. They degrade ingested material and display components of the ingested material on their surface with their MHC molecule
They then move to lymph nodes where they activate the specific T cell with the receptor to its antigen on its surface
What is initial activation of T cells called
Priming
Once T cells are activated they clone themselves and differentiate into different T cells, describe these, what is similar and different about each?
The different types are all genetically identical with the same antigen receptors but have different effects once activated
Regulatory or Suppressor T cells
Some stimulate inflammation
Cytotoxic T cells (destroy cells by releasing interferon or perforin)
Memory T cells (allows for a more rapid response at a subsequent infection)
What is interferon
Shuts down the virus production within a cell
What is perforin
Punches holes into the infected cell causing it to rupture and die
Describe T cell mediated immunity
Takes time to develop (days to months)
Specific for a particular antigen
Involved in memory so there is a more rapid and efficient response at the next presentation (adaptive immunity)
Differentiates between self and non self
Describe B lymphocytes
Produced and mature in bone marrow or lymphoid tissue in the gut
Then travel through the blood to populate the lymph nodes, spleen and all other lymphoid tissue
Produce immunoglobulins (antibodies) - some is bound to the cell surface to act as a receptor (lymphocyte antigen receptor)
Describe B cell activation
2 stage process
B cell binds to its antigen using its surface immunoglobulin receptor (antigen can be free or cell bound) (MHC not needed)
Needs a second signal to complete activation: can be from using the pattern recognition receptor by binding to a particle common to pathogens or activated by helper T cells (when T cells are activated by binding to its antigen it secretes cytokines and express surface molecules that activate B cells)
What happens when B cells are activated
Divide and produce clones of themselves (all respond to the same antigen) this strengthens the response
Some become memory B cells
Some become plasma cells
What are plasma cells
Antibody factories
Secrete immunoglobulin: released into circulation, bind to antigen and inactivates it
What are memory B cells
Persist for years
Responds rapidly when an antigen is seen in subsequent exposures (numbers and efficiency increase with exposures)
Benefits: rapid production of effective antibodies, used as the basis for vaccination
What is a anamnestic response
Secondary response
Antibodies are part of the ____ adaptive immune system
Humoral
Immunoglobulins are produced by ___ cells derived from B cells
Plasma cells
Immunoglobulins are useful in
Host defence (binding and neutralization)
Vaccination
Testing
How are immunoglobulins used diagnostically
To detect infections
Rising titers indicate a recent infection
How are immunoglobulins used to fight infections
Vaccines boost antibody titers (basis for judging their effectiveness) and stimulate the immune system to make more
Hyperimmune sera are given to fight off infections
What are the 4 types of immunoglobulins and how are the similar/different
IgM, IgA, IgG, IgE
Each class binds to the same antigen but their structure and effects vary
Where can you find immunoglobulins
Produced by B cells and plasma cell
B cells put immunoglobulins on their surface to act as a receptor (lymphocyte antigen receptor)
Plasma cells excrete immunoglobulins into the body fluids
What is the basic structure of immunoglobulins
Y shaped
Head: 2 binding sites per “Y”
Tail: constant within a class of antibodies, this determines the class, responsible for the different effects of the immunoglobulins when the head binds to its antigen
What is IgM
The first made in response to an antigen
It is a pentamer -has 10 binding sites (5 Ys = 2 binding sites each)
Large molecule restricted to plasma
Binds very weakly
Once activated, what does IgM do
Inactivates pathogens by
1) agglutination: creates clumps by binding antigens together (very good at this)
2) neutralization: binds to antigens making them ineffective -blocks the ability for the antigens to bind to host cells
3) complement activation: classical pathway activation that results in stimulation of inflammation, opsonization and the membrane attack complex
What is IgG
As the immune response progresses, it switches to making IgG
This is the major antibody in serum/blood and tissue
Monomer: Smaller than IgM so it can move to sites of inflammation
What does IgG do once activated
Agglutination of antigens (not as good as IgM)
Neutralization (binds much tighter than IgM, blocks adhesion sites on pathogens and binds and blocks toxins)
Complement activation
Opsonization by direct binding
Antibody dependent cell mediated cytotoxicity (too big to be phagocytosed so the antigen IgG complex binds to NK cells which can then kill the cells) (antigen-antibody complex may also bind to neutrophils and eosinophils to stimulate them to release oxidants)
What is IgA
The major antibody of the mucosal surfaces (resp and GI tract)
Gut lymphoid tissue is a major site of IgA production
Secreted as a dimer with a secretory piece -transportation for epithelial cells, gives resistance to digestive enzymes (prevents destruction from digestive enzymes)
IgA gets produced the most in a day then all others -large amounts in order to protect the entry points of the body
What does activation of IgA result in
Neutralization
Tail can activate phagocytosis (opsonization) but does not activate complement
What is IgE
Mainly produced by plasma cells just below the body surfaces
Some binds to the surface of mast cells and basophils Before it binds to its antigen (waits for the antigen to come along)
This is a sentinel antibody, when it binds to the antigen it causes degranulation
Triggers inflammation
Very important in parasite defence and allergies
Describe free IgE
Small amounts
Head of IgE binds to pathogens And the tail complex attracts and binds to eosinophils which release enzymes that digest the parasite
Example Of antibody dependent cell mediated cytotoxicity
