Immunology Flashcards
What are the 3 defining characteristics of the innate immune system?
- response is antigen independent
- immediate maximal response
- no memory is formed
What are the 3 defining characteristics of the adaptive immune system?
- response is antigen dependent (or antigen specific)
- lag time between exposure and maximal response
- immunologic memory is formed
The three tenants of adaptive immunity are:
- Specificity
- Self recognition
- Memory
Which immune cells differentiate from the lymphoid stem cell?
Lymphocytes:
- T cell
- Natural Killer cell
- B cell:
- plasma cell
- memory B cell
Which 6 immune cells differentiate from the myeloid progenitor cell?
Granulocytes
- neutrophil
- eosinophil
- basophil
- mast cell
- monocyte
- dendrittic cell
- machrophage
What are the two major categories of immune cells?
Lymphocytes and granulocytes
What activates neutrophils?
Tumor necrosis factor (a cytokine)
Which immune cell makes up 60-65% of WBCs?
Neutrophils
Which cells are polymorphonuclear and phagocytic?
Neutrophils
How common are basophils? What do they release, and what part of the immune system triggers that release?
These cells make up 0.1-0.3% of WBCs. They release histamines and are triggered by IgE antibodies.
What cells are triggered to release histamine by IgE?
Basinophils and Mast cells (mast cells are found in the tissue only)
Which immune cells are involved in the destruction of parasites?
Eosinophils
What two cells differentiate from monocytes when they migrate into the tissue and become activated?
Macrophages and dendritic cells
Which cells have a multilobed nucleus?
Macrophages (bi-lobed) neutrophils (more lobes the older they get)
In what kind of tissue will you find macrophages?
Reticuloendothelial (liver, spleen, bone marrow, CNS, GI)
What are the two primary functions of macrophages?
Phagocytosis and antigen presentation
What are characteristics of dendritic cells?
- mobile, branched
- highly phagocytic
- part of adaptive immune response
- antigen presenting cells
Where do T lymphocytes mature?
Thymus
What are the two main subtypes of T cells and what do they do?
T-helper cells: coordinate immune response
and
T cytotoxic cells: destroy infected cells
Where do B lymphocytes mature?
Bone marrow and fetal liver
What are the subtypes of B lymphocytes and what do they do?
Plasma cells: create antibodies
And
Memory B cells: retain blueprints for antibodies to specific antigens to allow for faster immune response
How do natural killer cells kill their prey?
Creating holes in the cell membrane
What kind of cells do natural killer cells attack?
Infected human (self) cells , but not the microbe that has infected the cell
Which immune system contains natural killer cells?
Innate - they do not require presentation of an antigen to attack
Which parts of the immune system use cytokines to stimulate cells?
Both innate and adaptive
Cytokines are chemical messengers that induce ? In immune cells
Chemotaxis (follow a chemical gradient to a destination)
Diapedesis (movement into tissue from circulation)
What are common types of cytokines? What is the major function of each type?
- Interleukins: WBC communication
- tumor necrosis factor: tumor suppression
- interferons: disrupt viral replication (interfere!) AND activate immune cells
What are the peripheral lymphoid organs?
- Lymph nodes
- spleen
- tonsils
- adenoids
- appendix
What are the primary lymphoid organs?
- Bone marrow
- thymus
What kind of cells are in germinal centers of lymph nodes?
Dividing lymphocytes - both T and B cells.
Lymphocytes are mitotic, which is why lymph nodes swell when you are sick
What about T cells contributes to reduced immunocompetence as we age?
T cells mature in the thymus, which involutes during puberty. After puberty no new lines of T cells are created, so when a T cell line reaches it mitotic limit, we have fewer of them!
What is the main function of the spleen?
To filter and destroy old RBCs
To host lymph tissue
The tonsils and peyers patches (in the GI tract) are what kind of ALT?
MALT: mucosal associated lymphoid tissue
What is the function of MALT?
- phagocytosis
- secretion of immunoglobulin (IgA)
What makes an immune cell immunocompetent?
Maturation within primary lymph organ —> it means they are capable of mounting an immune response
The thymus is responsible for what two things, in addition to producing what immune processing hormone?
- immunogenesis (children)
- T cell maturation
- production of thymosin, which functions in processing T cells and developing B —> plasma cells
What is DiGeorge syndrome, and what are some characteristics?
A condition of thymic deficiency resulting from a deletion on chromosome 22
Depending on the length of the deleted segment:
- t cell deficiency
- congenital heart disease, and other cardiac anomalies
What are immature T cells in the thymus?
Thymocytes
Thymocytes develop into two types of cells, what are their markers, and subpopulations?
CD4 = HELPER T cells
- TH-1: cell mediated immune response
- TH-2: activate B cells (stimulate antibody production)
CD8 = CYTOTOXIC cells
Destroy virus infected cells and tumor cells
What is negative selection?
When a failing T cell enters apoptosis
What is the first layer of the innate immune system, and what are some of it’s feature functions?
Skin
- mechanical barrier
- shedding
Skin resistance increases with age, improving it’s efficacy as a barrier to disease due to what compositional change?
Increased fatty acids
What is the second layer of the innate immune system, and what are some of it’s features?
Mucosal membranes:
- cilia remove microbes
- GI tract has enzymes and acids
What antimicrobial substances does the body produce to prevent infection?
- sweat
- lysozyme (skin, tears, mucous)
- saliva
- stomach acid
How do the body’s normal flora help protect against infection?
Competitive exclusion of pathogens
What is the difference between microbiota and microbiome?
Microbiota = population of microbes living on and in humans
Microbiome = the genomes of the microbial population living on humans
What is the primary sensory for the immune system by which it becomes aware of the presence of a pathogen?
The toll-like receptor, which recognizes compounds unique to microbes (like bacteria DNA, which is different than ours)
What is an immune complement?
A series of proteins always present in the blood that participate in microbe destruction when activated - often they trigger protein cascades
What are the three functional strategies of complement proteins?
O - Opsonization
I - Inflammation
L - Lysis
What is opsonization?
The process of coating a pathogen with proteins that correspond to binding sites on phagocytic cells, making it easier for the pathogen to be consumed.
What role does inflammation play in immune response?
- dilation of blood vessels - induction of fever
What is lysis (related to immune response)?
Lysis is the loss of cellular contents following a membrane attack complex (MAC) that makes holes in the membrane of the pathogen
What is the purpose of blood vessel dilation in immune response?
Dilation increases vessel permeability, allowing for more migration of cells into damaged or infected tissue. (Swelling, redness, pain may result)
Inflammation also promotes the chemotactic attraction of macrophages, neutrophils, and natural killer cells to an area of infection.
What is the purpose of fever in immune response?
Fever (induced by interleukin-1, or IL-1) is an attempt to weaken pathogens by shifting body temperature away from ideal replication temp (at least bacteria replicate at physiologic normal for humans)
What is the most antigenic substance or class of molecule?
Proteins
Lipids and polysaccharides can also be antigenic
What is a hapten? What is an example?
A hapten is an antigen that is too small to be recognized on its own, but that will be recognized as a pathogen when bound to a larger molecule.
Poison oak is an example
What is the difference between humoral and cell-mediated immunity?
Humoral = EXTRAcellular, antigens are outside self cells. Ex: bacteria in blood.
Cell-mediated = INTRAcellular, antigens are inside self cells. Ex: a virus inside a T cell, as in HIV.
What is an epitope?
An antigenic determinant - the part of an antigen that is displayed on MCH-II proteins and presented to T and B cells, for which a corresponding antibody is made.
What is the difference between endogenous and exogenous antigens?
Exogenous = originating from outside the cell, entering the body through inhalation, injection, or ingestion.
Endogenous = generated within a cell as a result of normal metabolism or infection
What is cross reactivity of antigens?
Antigens are considered cross reactive if more than one antigen will bind to, or elicit production of, the same antibody.
What is self-tolerance and how is it related to autoantigens?
Self tolerance is the ability to recognize one’s own tissues as being the self, and therefore sparing them from immune response.
Autoantigens are normal self tissues that fail to be recognized as such, and therefore are attacked by antibodies.
What is special about a superantigen?
Superantigens do not bind to the normal MHC groove of an antigen presenting cell, they bind to the side of the receptor.
What is the consequence of superantigen binding?
The atypical binding pattern of a superantigen causes an explosion of unregulated T cell activity, which ultimately destroys surrounding tissue due to toxic levels of molecules like interferons.
What is an MHC?
What does it do?
Major Histocompatibility Complex - 3 classes of proteins - 2 of which are membrane associated molecules that are part of self identification.
What is HLA?
Human Leukocyte Antigen - a section of genes on chromosome 6 that code for the MHCs.
What kind of cells present MHC Class 1?
All nucleated cells
What kind of antigens do MHC 1 present?
Endogenous proteins
What is the death mechanism for cells presenting abnormal MHC 1 proteins?
Cytotoxic T cells
What kind of cells present MHC II receptors?
Antigen presenting cells - cells of the immune system:
- activated dendritic cells
- activated macrophages
- activated B-cells
All of these cells ALSO have MHC I receptors so they aren’t destroyed.
What kind of antigens do MHC II present?
Exogenous antigens - from outside the cell
Where are activated dendritic cells found?
In tissues that contact the environment - skin, mucosal linings of airway and GI tract.
In which stage of infection are macrophages most active?
The early stages - they are part of the innate immune system.
What are 2 major kinds of chemicals produced by macrophages?
- lysosomal enzymes for digesting
- cytokines, including IL-1 which induces fever and activates other cells
5 types of cytokines
- lymphokines
- interleukins
- tumor necrosis factor
- interferons
- transforming growth factor
What are lymphokines?
produced by lymphocytes to manage macrophage activity —>
- Macrophage activation factor
- Macrophage migration inhibitory factor
What are interferons?
Interfere with viral reproduction
What is the relationship of T cells to antigens and antibodies?
T cells do not produce antibodies - they activate B cells to do that.
T cells do not interact with free antigen, they respond to MHC-I and II presentation of antigens.
What two signals are required for T cells to migrate into tissues?
- Antigen presentation on MHC
- stimulation by other molecules —> CD28/B7, CD40 is the most common
What is TGF and what does it do?
Transforming Growth Factor -
TGF-beta is the most potent growth inhibitor
Inhibits the proliferation of T-cells
An activated T cell divides and differentiates into what types of cells?
- Helper T cells: CD4
- TH1
- TH2 - Cytotoxic T cells: CD8
- Memory T cells
Why does HIV kill you?
HIV targets the CD4 receptor - which means it destroys T helper cells, preventing specific immune responses to infections (including itself).
What do TH1 cells do upon recognition of antigen?
Release cytokines to stimulate the development of other T cells, and summon macrophages / natural killer cells.
ENDOgenous antigen
What do TH2 cells do upon recognition of the antigen?
Activates B cells to produce antibody.
EXOgenous antigens
What kind of markers do T regulatory cells have?
CD4
What do T regulatory cells do?
Turn off the adaptive immune system —> block induction and activity of T and B cells.
What kind of T cells have CD8 markers?
- T cytotoxic cells
- T memory cells
How do T cytotoxic cells recognize dysfunctional cells and what do they do about it?
They recognize the MHC I proteins and induce apoptosis in cells that are infected
How do T cytotoxic cells kill their victims?
They inject degradative enzymes into the cell —> perforin makes holes in things
What are T memory cells?
Long lived cells with a heightened reactivity to a specific antigen that will stimulate a faster immune response
Primary antigen stimulates which kind of antibody production?
IgM
What is the difference between agglutination and precipitation?
Agglutination refers to the binding of an antigen and antibody when the antibody is a cell (or component of a cell).
Precipitation is the binding of any other pathogenic molecule to an antibody.
What is an antitoxin?
An antibody with the ability to neutralize a specific toxin
What is the Fab on an antibody?
The fragment binding portion - where the antigen binds
What is the Fc porting of an antibody?
The crystallizable fragment of an Ig: part of phagocytosis, inflammation, and tissue targeting
What is the variable region of the antibody?
The end of the Fab region - where the antigen actually binds
What is the constant region of the antibody?
The entire Fc region, and part of both heavy and light chains.
What are characteristics IgG?
- Gamma globulin
- most abundant
- triggers compliment cascade when multiple IgG bind together
- only class of antibody to cross the placenta
- heavily present in breast milk
- monomer (valance 2)
Which class of immunoglobulin is passed from mother to fetus / baby through the placenta and breast milk?
IgG
What are some characteristics of IgM?
- first class of Ig produced during antigen response
- largest immunoglobulin
- cannot escape vasculature to enter tissue
- first Ig class a baby can produce (~3mos)
- pentamer (valance = 5)
Which class of antibody is most abundant?
IgG
Which class of antibody is the largest?
IgM
Which class of antibody is first produced in response to a pathogen?
IgM
Which class of antibody is the first a baby can produce?
IgM
What are some characteristics of IgA?
- found in mucosal tissue and body secretions: saliva, mucous, tears, milk
- dimer (valance 4) in secretions, but monomer (valance 2) in blood
What is the valence of an immunoglobin?
The number of antigen binding sites
What are some characteristics of IgE?
- normally bound to mast cells and basinophils, and therefore undetectable in blood
- involved in allergy —> triggers histamine release
- can cause anaphylactic shock
- monomer (valance = 2)
What are some characteristics of IgD?
- generally found on surface of B cells, as an antigen receptor
- does not bind complement
- role uncertain
- monomer (valance = 2)
What is the trigger for the the classical complement pathway?
Antigen binding to antibody - either IgM or IgG
What is the alternative complement pathway?
Properdin is triggered by the presence of macromolecules from various pathogens like fungi or bacteria
What is the newest complement activation pathway?
The Mannan-Binding Lectin pathway in which MBL binds to microbial surfaces
What can complement proteins do?
- act as opsonins
- adhere to mast cells to trigger histamine release
- increase vessel permeability
- form a membrane attack complex (MAC) to induce lysis
What is a dangerous aspect of the complement response?
- complement is a self-amplifying system, which can lead to dangers:
- a systemic activation can lead to anaphylaxis due to mast cell activation
- intense activation of complement results in complex interactions with coagulation processes, which can ultimately result in hemorrhage.
How do some viruses escape the MAC?
Some viruses have managed to implant MAC inhibitors (necessary to control the complement system) into their membranes, and thus are safe from MAC.
What are characteristics of the secondary response (the response to the second presentation of a familiar antigen)?
- shorter lag time
- higher levels of IgG immediately
- less antigen required to stimulate response
What is the difference between vaccination and immunization?
Immunization = purposeful exposure to an antigen to induce active or passive immunity
Vaccination = purposeful exposure to an antigen to induce active immunity
What is passive versus active immunity?
Passive = Transfer of antibodies produced by another
Active = Production of antibodies following exposure to antigen
Most vaccines create what kind of immunity?
Active, artificial: the patient is deliberately exposed to an antigen in a controlled setting to stimulate the production of antibodies
What is a live attenuated vaccine?
A vaccine containing the weakened form of a disease causing microbe that has been rendered unable to cause disease
What kind of vaccines are the most effective?
Live, attenuated vaccine
What are some risks of live attenuated vaccines?
Mutation of the attenuated microbe allowing a return to virulence
What is an inactivated vaccine?
The virus in the vaccine is dead and therefore cannot replicate, but retains its identifying properties for antibody production.
What is a subunit vaccine?
A vaccine composed of key protein antigens or antigen fragments, rather than whole cells or viruses.
What is passive immunization?
Antibodies produced by one living thing is transferred to another - either from mother to baby through placenta and breast milk, or through injections
Who / when / what is the first widely know vaccine experiment?
Edward Jenner experimented with cowpox / smallpox in 1796
What is antiserum?
Blood serum containing antibodies that is used to create passive immunity to a toxin. This immunity is often temporary.
What is tolerance and when is it developed?
Self-recognition.
Tolerance is developed to self antigens during fetal development
What are autoreactive cells and what happens to them?
Auto reactive cells respond to self antigens and therefore injure self tissue.
They are destroyed through apoptosis or receptor editing to change their reactivity.
What is peripheral tolerance?
Ways to protect self tissue whose antigens are not present in the thymus or bone marrow during lymphocyte education
What are the 3 mechanisms of peripheral tolerance?
- deletion: killing auto reactive cells through apoptosis
- anergy: disable the offensive cell entirely
- suppression: modify the cell to prevent self aggression
- we don’t know why all autoreactive cells can’t undergo suppression
What is acquired tolerance and what are 2 naturally occurring examples?
Tolerance to non-self antigens, which takes place during pregnancy (the fetus is non-self) and oral tolerance (food is non-self)
What are some causes of autoimmune disorders?
- infection
- response to drugs
- cross reactivity with bacteria
- hormones
- immune response breakdown
What is serology?
Using serum antigens to detect antibodies, or vice versa.
What is a serotype?
A strain of microorganism that is similar enough to other strains to be considered the same organism, but different enough to require different antibodies.
Example: strains of the flu or common cold
What is a titer, and what does it tell you about an immune system?
A method of identifying the amount of antibody present following a disease state - gives important information about current immunity to disease.
In serology, what is agglutination?
The interaction between antibody and antigen that cross links cells
In serology, what is precipitation?
The interaction between antibody and soluble antigen that results in visible precipitate
In serology, what is immunodiffusion?
Placing suspected antigen with it’s corresponding antibody in agar and seeing if they migrate toward each other.
In serology, what is complement fixation?
An indicator system using sheep blood cells - the cells will lyse unless the antibody/antigen complex is present in solution.
What is a Schick test?
Intracutaneous test to distinguish between individuals based on susceptibility to disease.
(Developed by Schick in 1913)
What does a non-reaction to a Schick test indicate?
Antibodies to diphtheria - no antibodies will result in a visible skin response
What does the tuberculin skin test look for?
A type IV hypersensitivity to TB - which means the person has been exposed to TB before
What is immunodiagnosis?
Testing blood serum to detect the presence of a specific microorganism
