Abnormal Immune Response Flashcards
What are the 3 major types of abnormal immune responses?
1) Immunodeficiency
2) Autoimmunity
3) Hypersensitivity
Immuno-?
Immune Response
Deficiency?
Something is missing/absent/incomplete
Immunodeficiency?
The IR occurring partially or is absent. The immune response is compromised.
What are individuals who are immunodeficient at risk for?
It predisposes immunodeficient individuals to disease
Primary?
Something that happens first/ early (eg. primary stage)
Secondary?
Something that happens after primary (eg. secondary phase)
A person has the flu and develops pneumonia. What would pneumonia be considered in this situation?
It would be secondary to the flue because it developed due to the flu
Primary immunodeficiency?
Genetic or congenital (development failure)
Secondary immunodeficiency?
Acquired (post-natal)
What kind of immunodeficiency is occurring in the following example?:
An individual treated with drugs that suppress the IR.
Secondary Immunodeficiency
What kind of immunodeficiency is occurring in the following example?:
Incomplete thymus development
Primary immunodeficiency
What kind of immunodeficiency is occurring in the following example?:
Chemotherapy for cancer
Secondary immunodeficiency
What kind of immunodeficiency is occurring in the following example?:
AIDs- HIV virus
Secondary immunodeficiency because it damages the T helper cells causing it to be a secondary condition to infection
Which cells are considered most important in the IR?
T cells
Humoral immunity?
involves B cells and production of antibodies
Cell-mediated immunity?
Involves T cells
Pyogenic?
Production of pus
What are the types of immunodeficiency?
- B cell disorders
- T cell disorders
- B & T cell disorders
- disorders of phagocytosis
- disorders of complement
- combination of all of these
B cell disorder?
Impaired antibody production [humoral immunodeficiency]
T cell disorder?
Impaired T cell function [& cell-mediated response]
CD4?
Helper cells
CD8?
Cytotoxic cells
What are some of the functions of T cells?
- T cells protect against fungal, protozoan, viral, and intracellular bacterial infections
- T cells control malignant cell proliferation
- T cells are responsible for coordinating the overall IR
T & B disorders?
- impaired immune function [defects in humoral and cell-mediated immunity]
What kind of immunodeficiency is occurring in the following example?:
Disruption of the normal communication between B and T lymphocytes.
T&B disorders
What kind of immunodeficiency does the following occur in?:
This increases the risk of pyogenic infections
B cell disorders
What are the types of treatments used for immunodeficiency?
- Replacement therapy
- Stem Cell Transplant
What does replacement therapy do?
It enhances the immune function
What is the following an example of?:
Giving your pt antibodies (ex. gamma globulins) intravenously in the hospital.
Replacement therapy
What is the following an example of?:
Repopulating the bone marrow and reestablishing hematopoiesis.
Stem Cell Transplant
Self-tolerance (in terms of IR)?
The immune system can normally differentiate self from non self
Autoimmunity?
Loss of self-tolerance [Loses the ability to identify that own cells are not foreign]
What occurs in autoimmunity?
Cells target own cells (considers them as foreign) which causes tissue damage and inflammation resulting in necrosis.
Which cells are attacking its own antigens in autoimmunity?
Either T cells, Ab or BOTH are targeting own cells. (It is t-cell mediated or Ab-mediated)
How is self-tolerance lost?
1) Molecular Mimicry
2) Abnormal T cell Function
3) Disease exposes masked Antigens
Epitope?
Specific chemical structure on one part of the protein of an antigen in which an antibody binds
What occurs when an antibody recognizes a foreign epitope?
Antibody detects the specific chemical structure on one part of the protein (epitope). Antibody opsonize, neutralize, cause agglutination and activate complement to destroy the antigens that bear this epitope.
What occurs in Molecular Mimicry?
If our own cells happen to have an epitope with a similar chemical structure, then our own antibodies bind to our own cell and cause an immune response, damaging our own cell.
What occurs in abnormal T cell function?
T cells activated and normal immune response continues. Once foreign antigens are attacked, the IR NORMALLY is suppressed. Self-tolerance in this case is lost when there is an issue suppressing the IR and T cells are continuously produced. T cells continue to attack own cells even once foreign cells have already been destroyed.
What occurs when self-tolerance is lost by diseases exposing masked antigens?
During development of the immune system in utero, some parts of the body are closed off. But if later injury occurs here then blood and lymph are exposed to it for the first time. [think Ags are foreign and attack]
Which self-tolerance is lost in the following example?:
ocular disease
Disease exposes masked antigens
Which self-tolerance is lost in the following example?:
no suppression
Abnormal T cell function
Which self-tolerance is lost in the following example?
Similar epitope -> antigen mis-indentified
Molecular mimicry
What is an example of Autoimmunity?
Systemic Lupus Erythematosus (SLE) also known as Lupus
What is Lupus?
A condition that produces antibodies that target nuclear components of cells. Any cell with a nuclear is affected [which is 99.99% of cells] excluding erythrocytes. It targets genetic information and is a multi-system target causing destruction.
What do IgE immunoglobulins do?
They attach to receptors on mast cells which triggers histamine release.
Hypersensitivity?
Immune Response is inappropriate or exaggerated resulting in inflammation and tissue damage.
What are the 4 types of Hypersensitivity?
Type 1/ Allergy/ IgE-mediated Hypersensitivity
Type 2/Cytotoxic Hypersensitivity
Type 3/Immune-Complex Hypersensitivity
Type 4/Delayed/T-cell Mediated Hypersensitivity
Which hypersensitivities are mediated by antibodies and which are mediated by T-cells?
Type 1/2/3= mediated by antibodies
type 4= mediated by T cells
Which cells do antibody-mediated involve?
B cells
What are the main points of Type 1/Allergy/ IgE-mediated Hypersensitivity?
- common type
- allergy triggered by allergens (eg. drugs, food)
- IgE mediated
- Rapid response
- genetic predisposition
- requires initial mast cell sensitization
What do B cells differentiate into?
Plasma cells
Degranulation?
cells releasing mediators
Bronchospasm?
muscles constricting and locking in the constricted state.
What occurs in initial mast cell sensitization?
1 contact with the allergen. Allergen triggers T helper cells. T- helper cells release TH2 cytokines (mediators). TH2 activates B cells. Activated B cells differentiate into plasma cells. Plasma cells produce IgE (which attaches to the surface of mast cells). When IgE antibody bind to the mast cells, the mast cells become sensitized.
(NOTE: YOU DO NOT REACT UPON THE FIRST EXPOSURE OF AN ALLERGEN)
What occurs during any re-exposure to the allergen/antigen?
Allergen binds to the IgE antibody directly on the mast cell forming an immune complex. Mast cell degranulates (releases inflammatory mediators @ the site of exposure eg. histamine). Depending on where the inflammatory mediators are released, they will bind to different receptors and cause a different effect in that area of the body. This results in inflammation so pt will have erythema, pruritus, exudate, swelling, rash, pain.
Pruritus?
Itching
What are some sites of exposure in an allergic reaction?
Digestive tract, respiratory tract, skin etc
Depending on where the inflammatory mediators are released, they will bind to different receptors and cause a different effect in that area of the body. Name some effects that occur.
Binding to smooth muscle receptors causes dilation
Binding to the respiratory tract causes constriction of the airway (bronchospasm)
What are some conditions that develop from Type 1 Hypersensitivity?
- Allergy (mild-severe)
- Asthma (complex, chronic disease, only one component is type 1 hypersensitivity
- Anaphylaxis (life-threatening d/t difficulty with perfusion)
What does shock result in?
Results in hypoperfusion and hypotension (acute onset)
What does shock generally indicate?
A problem with the cardiovascular system such as CV failure leading to hypoxia.
Is hypoxia a manifestation of shock?
No, but it can lead to it.
Circulatory shock?
Acute failure of the circulatory system to supply the tissues and organs of the body with adequate blood supply, resulting in cellular hypoxia.
What are the 4 types of circulatory shock?
- Cardiogenic
- Hypovolemic
- Obstructive
- Distributive
Cardiogenic shock?
An alteration in cardiac function
Hypovolemic shock?
loss of whole blood, loss of plasma or loss of ECF
decrease in blood volume d/t injury or hemorrhage
Obstructive shock?
Obstruction of blood flow through the circulatory system.
eg. embolism
Distributive shock?
Alteration of blood flow and maldistribution of blood due to increase and inappropriate vasodilation.
eg. anaphylactic/septic shock
What are the manifestations of shock?
- Impaired perfusion of body tissue = cyanosis, low O2 sat, low BP
- Body’s attempt to maintain perfusion = kidneys retain water (fluid from ECF goes into ICF which activates the sympathetic NS to increase HR and resps)
What is Anaphylactic shock a problem of?
Distributive and hypovolemic shock
What is Anaphylactic shock?
Systemic hypersensitivity due to severe allergic reaction
What occurs in anaphylactic shock?
Mediators cause dilation of blood vessels and increase the capillary permeability. @ the same time, fluid leaks into the interstitial space out of the vessels, resulting in decreased blood volume. [now we have less blood to pump around and more difficulty pumping it] resulting in circulatory shock.
What occurs with excessive dilation in anaphylactic shock?
decrease in total peripheral resistance so blood cannot be distributed around the body effectively.
What does anaphylactic shock result in?
Edema due to increased fluid in the interstitial spaces
Bronchospasm
* POTENTIALLY FATAL*
What is septic shock?
due to severe infection/multiple infections [injury & inflammation are no longer localized]
What is occurring in septic shock?
Septic shock has vasodilatory mediators that dilate blood vessels causing hypoperfusion and hypotension.
[It is a systemic response meaning there will be systemic inflammation]
What does septic shock lead to?
Multi-organ failure [potentially fatal]
Which antibodies mediate type 2/ cytotoxic shock?
IgG or IgM
Cytotoxic?
Toxic to cells
Endogenous antigens?
Self antigens (present on cell membrane)
Exogenous antigens?
Antigens that enter the host from the outside through inhalation, ingestion or injection
What occurs in Type 2 / Cytotoxic Hypersensitivity?
Faulty self-reactive B cells produce IgG or IgM antibodies that attack exogenous and endogenous antigens. Antibodies bind to the antigen and form an immune complex. Any cell bearing this complex is destroyed (including the endogenous Ag). IC activates complement proteins which causes phagocytosis leading to inflammation.
What is an Incompatible Transfusion an example of?
Type 2/ Cytotoxic Hypersensitivity
How does Type 2 / Cytotoxic hypersensitivity remove the damaged cells?
Natural killer cells recognize the Immune Complex and release performs resulting in apoptosis.
What else can occur in Type 2 Hypersensitivity (that is not cytotoxic)?
Antibody mediated cellular dysfunction
What occurs in antibody mediated cellular dysfunction?
Changes in cell function. When antibody binds it can either block or activate the receptors.
List an example of when receptors are blocked in cellular dysfunction.
Myasthehnia Gravis -> antibody binds to ach receptors on the neuromuscular cells and block the action of ach = decreased neuromuscular function
List an example of when receptors are activated in cellular dysfunction.
Graves disease-> hyperthyroidism due to overactive thyroid receptors.
What occurs in type 3/ Immune Complex Hypersensitivity?
Antibodies bind to free-floating antigens and form an immune complex that is deposited in the tissue. Immune complex circulates in the blood until it is deposited on the basement membrane of the blood vessel. Binding activates the complement system. Enzymes cause inflammation and tissue damage.
Why is the immune complex not destroyed in type 3 hypersensitivity?
- It is too small (escapes detection by enzymes and phagocytes)
- It is insoluble (it doesn’t dissolve in the blood)
Why does. the immune complex prefer the basement membrane when depositing? [type 3 H}
Basement membrane is negatively charged and the immune complex is positively charged so they become ionically charged.
What is responsible for vessel and tissue injury in type 3 hypersensitivity?
The activation of the complement system leads to the attraction of leukocytes [which are responsible for tissue damage and injury]
What are 2 examples of type 3 Hypersensitivity?
Glomerulonephritis [exclusively type 3]
Rheumatoid Arthritis [complex disease, only 1 component is type 3]
Which immune disorder is glomerulonephritis an example of and what is occurring?
Type 3 / Immune complex hypersensitivity.
IC is deposited in capillaries in the kidneys
Why does tissue damage occur in type 3 hypersensitivity?
Because you damage the endothelium lining
In type 3 hypersensitivity, what makes the endothelium pores larger during inflammation?
Macrophages
What is different about type 4 hypersensitivity in comparison with type 1/2/3?
It is T cell mediated (T cell response)
What occurs in type 4/ Delayed hypersensitivity?
Bacteria enters the cell and is engulfed by dendritic cells which present it to T cells in the lymph node. T cells become sensitized and form clones specific for that antigen [normal]. Cytotoxic T cells attack macrophages holding the foreign antigen and kill its own cells [abnormal]. Destruction of normal cells = injury. Inflammation occurs due to injury and whenever there is inflammation there is some degree of tissue damage.
What are the 2 types of type 4 hypersensitivity?
- Direct
2. Delayed
Direct Hypersensitivity?
Immediate reaction
- T cells attack any cell with that antigen
Delayed Hypersensitivity?
takes 48-72 hrs via lymphokine production.
Pre-sensitized t helper cells release cell damaging lymphokines
What are lymphokines?
Mediators specifically produced by lymphocytes [more specific type of cytokine]
Why is delayed hypersensitivity delayed?
It takes 2-3 days to produce lymphokines so the reaction is delayed until the mediators form.
In direct hypersensitivity what shouldn’t be happening?
The macrophage is being destroyed which shouldn’t be happening
What are 2 examples of type 4 hypersensitivity?
- contact dermatitis
2. tuberculin test
What is contact dermatitis? Why is considered a type 4 hypersensitivity?
Lesion in skin, it takes a few days to develop
What is CD4 & CD8?
CD4 is a protein found on the surface of T helper cells. CD8 is a protein found on the surface of Cytotoxic T cells.
What is ANA?
Anti nuclear antibodies is a serum marker for autoimmunity.
Where are antibodies secreted from?
Plasma cells
