Immunology Flashcards
What is immunity?
Resistance to a disease, specifically infectious disease
What is the immune system?
The collection of cells, tissues, and molecules that mediate resistance to infections
What is an immune response?
The coordinated reaction of the cells and molecules to infectious microbes
What is the physiologic function of the immune system?
To prevent infections and eradicate established infections
How many lines of defense fir the immune system are there ?
3 lines of defense
Differentiate the first 2 lines of defense of the immune system from the 3 rd line of defense
First 2 lines of defense are nonspecific or innate
3rd line of defense, the immune response, is very specific or adaptive
-In the 3rd line of defense, special proteins called antibodies are produced in response to foreign substances called antigens
What line(s) of defense are innate/intrinsic ?
First and second line
What lines of defense use acquired/adaptive immunity?
3rd line of defense
Describe an innate response
First and second response is immediate to “new” and “repeat” invaders (non-specific)
Describe an adaptive response
Third response is delayed and highly specific in response to “new” invaders. Memory cells can respond to “repeat offender” rapidly
Describe the first line of defense?
-Skin and Mucous membranes as MAJOR physical barriers
- Cellular and Chemical factors
- pH, temperature, perspiration, cilia, and secreted enzymes
- Microbial Antagonism
- When indigenous microflora prevent colonization of “new arrivals” as a result of competition for sites and nutrients and production of lethal substances
What 8s microbial antagonism?
-When indigenous microflora prevent colonization of “new arrivals” as a result of competition for sites and nutrients and production of lethal substances
Part of the first line of defense
What is the second line of defense?
The compliment system
A group of about 30 different proteins found in normal blood plasma including C3-“complementary” to the immune system
Complement components interact with each other in a stepwise manner known as the complement cascade, including cleavage of C3 to C3b (bound version)
-Opsonization is a process by which phagocytosis is facilitated by the deposition of antibodies or C3b onto microbes
What is opsonization ?
-When indigenous microflora prevent colonization of “new arrivals” as a result of competition for sites and nutrients and production of lethal substances
What is the second line of defense ?
Complement system(comeback to 9/65)
Cytokines
What are cytokines?
Chemical mediators released from manu different types of cells in the body; enable cells to communicate with each other- within the immune system and other systems of the body
-second line of defense
What are interferons?
Type of cytokines
-small, antiviral proteins produced by virus-infected cells; they prevent viruses from multiplying
Interferons are virus specific, but they are species specific
-interferons can cause nonspecific “flu-like” symptoms
What are the types of interferons?
- Alpha
- beta
- Gamma
Produced by 3 different types of cells
What are phagocytes?
Phagocytic white blood cells and use a process by which they surround and engulf (ingest) foreign material is called phagocytosis
What are the types of white blood cells (leukocytes)?
The 3 major categories of leukocytes (white blood cells) found in blood are monocytes, lymphocytes and granulocytes
The 3 types of granulocytes are: eosinophils, basophils and neutrophils
The most important groups of phagocytes in the human body are macrophages, neutrophils and dendritic cells
What are the functions of Macrophages?
They are resident in the tissues and are the first responders to infection
- recognize pathogens via Toll-like receptors
- Phagocytosis
- Cytokine production
- Antigen presentation of intracellular bacteria to CD4+ T cells
- Tissue repair
What are the functions of Neutrophils?
- Recognize pathogens via receptors
- Phagocytose microbes and destroy them with the toxic contents of the neutrophil granules, especially extracellular bacteria and fungi
- Kill microbes with enzyme-rich granules and Reactive Oxygen Species (ROS)
- Die within hours, responsible for pus formation (pyogenic infection)
What are the Natural Killer cells (NK)?
- NK cells are in a sub population of lymphocytes
- They resemble lymphocytes, but lack typical T or B cell surface markers
- Do not proliferate in response to antigen and appear not to be involved in antigen-specific recognition
What are the functions of NK cells?
NK cells kill target cells, including foreign cells, host cells infected with viruses or bacteria, and tumor cells
What are the 3 types of granulocytes?
Mast cells, Basophils and eosinophils
What are granulocytes?
Contain intracellular compartments with pre-firmed effector molecules (ex. Histidine)
What are the functions of mast cells?
- Granulocytes that resident in tissues
- Play a role in inflammation and allergies
What are basophils and eosinophils?
- Granulocytes
- Recruited to site of inflammation
- Play a role in chronic allergies
- Important fire infections with parasites (worms, etc.)
What are Dendritic cells?
A specialized type of leukocyte called Dendritic cells (DC) are important for Antigen Presentation, also called APC(antigen presenting cell)
What are the functions of dendritic cells?
- DC cells capture antigens in tissue via phagocytosis
- DC process antigens and load onto a surface receptor
- DC migrate to regional lymph node
- DC present antigen to T cells
How do dendritic cells take up antigen ?
Via 2 ways and present peptide on Major Histocompatibility Complex
- Extracellular antigens
- Intracellular antigens
How do dendritic cells take up extracellular antigens?
Extracellular antigens are phagocytosed and presented on MHC Class II to CD4+ Helper T cells
How do dendritic cells take up intracellular antigens?
Intracellular antigens, like viruses, are translated in the cytosol and presented on MHC Class I to CD 8+ Cytotoxic T cells
What is inflammation?
The body responds to any local injury, irritation, microbial invasion, or bacterial toxin by a complex series of events referred to as inflammation
What are the 3 major events of inflammation?
the 3 major events in acute influenza are:
- An increase in the diameter of capillaries (vasodilation) which increases blood flow to the site
- Increased permeability of the capillaries, allowing the escape of plasma and plasma proteins
- Exit of leukocytes from the capillaries and their accumulation at the site of injury.
What are the purposes of inflammation?
- To localize infection
- To prevent spread of pathogens
- To destroy and detoxify pathogens
- To aid in repair and healing
- To remove harmful stimuli(damaged cells, pathogens, irritants etc.)
- To initiate the healing process
What are the classical signs of inflammation?
P.R.I.S.H. (I=inflammation)
- Pain
- Heat
- redness
- Swelling
What line of defense are dendritic cells classified as?
Second to third line of defense
What is inflammatory exudate?
The accumulation of fluid, cells and cellular debris at the inflammation site
What is purulent exudate/pus?
If inflammatory exudate is thick and greenish-yellow, containing many live and dead leukocytes, it is known as a purulent exudate/pus
What are pyogenic microorganisms? How are they consequential to pus formation?
Pyogenic microorganisms (pus-producing microorganisms) like Staph aureus or Strep pyogenes result in additional pus formation
Do all inflammatory responses form pus or exudate?
In many inflammatory responses (e.g., arthritis) there is no exudate and no invading microorganisms
Distinguish the lines of defense in detail
First-anatomical and physiological barriers -intact skin, ciliary clearance, low stomach pHlysozyje in tears and saliva
Second - innate- cellular=NK and T cells,neutrophils, dendritic cells, macrophages, eosinophils, mast cells
Humoral- complement, antimicrobial proteins, mannose binding Lectin, LPS binding proteins, C-reactive protein
Third line- cellular- T cells, B cells
Humorous- antibodies
What are the primary functions 9f adaptive immune system?
- differentiate between “self” and “non-self”
- destroy “non-self “
Where do adaptive immune system cells originate?
Cells involved in these immune responses originate in bone marrow and activated in lymph nodes
What are the 3 lines of lymphocytes derived from lymphoid stem cells?
3 lines of lymphocytes are derived from lymphoid stem cells of bone marrow: B lymphocytes(or B cells), T lymphocytes (or T cells) and natural killer cells (NK) cells
What are the functions of primary lymphoid tissues?
Education- T cells develop in Bone marrow
—> thymus B cells develop in bone marrow
What are the functions of secondary lymphoid tissue?
Dispersed throughout body and connected via lymphatics; site of T cell and B cell activation
What are the encapsulated secondary lymphoid organs? What are there functions?
Encapsulated- lymph node and spleen
Lymph node- immune response to antigens in tissues
Spleen- to antigens in blood
What is the unencapsulated secondary lymphatic organ? What is its function?
MALT (Mucousal associated lymphoid tissue)
Function- to antigens at mucousal surfaces
How does a lymph undertake immune function?
In context of infection, Dendritic cells (APC) and soluble antigens enter lymph node
B and T cells:
- recognize antigen
- T cells recognize peptides on APC
- B cells recognize soluble antigens with surface immunoglobin
- antigen
- clonally expand
- differentiate
- Activated T cells travel to infection site
- B cells remain in LN(lymph node) and secrete antibodies
What are the two major arms of the adaptive immune system?
Humoral
Cellular
What comprises the cellular arm of the two major arms of the adaptive immune system?
Effector CD4+ Helper T cells activate macrophages and CD8+ Cytotoxic lymphocytes (CTL) destroy host cells infected with intracellular pathogens
What comprises the humoral arm of the two major arms of the adaptive immune system?
B cells secrete soluble antigen-specific antibodies to neutralize extracellular pathogens
How fast does the adaptive immune system respond to the first encounter of antigens?
First encounter: Naive to activated lymphocytes respond in about 1 week
How fast do memory cells respond to the second encounter ?
Second encounter: Memory lymphocytes respond in about 1 day
What are antibodies?
- Proteins produced by activated B cells in response to the presence of an antigen
- In a class of proteins called immunoglobins Ig-globular glycoproteins that participate in immune reactions
Briefly contrast how humoral immunity and cell mediated
Humoral immunity- secretes antibodies to block infections and eliminate extracellular microbes
Cell mediated-elimination of phagocytosed microbes(helper T cells)
Or
Kill infected cells and eliminate reservoirs of infection (cytotoxic T lymphocytes)
What are the number of and types of antibodies produced depend on?
The amount and type of antibodies produced by a given antigenic stimulation depend on the nature of the antigen, the site of antigenic stimulus, the amount of antigen and the number of times the person is exposed to the antigen
Why do B cells process antigens and cytokines?
The processing of antigens and cytokine activation results in B cells developing into plasma cells, which are capable of secreting antibodies. B cells can develop memory from activating signals of helper CD4+ T cells
What is the primary response?
The initial immune response to an antigen (it takes 7-14 days for antibodies to be produced)
What is the secondary response?
The increased production of antibodies following the second exposure to a particular antigen
What is the function of IgM?
1st to circulate, indicates primary infection; activates complement
What s the function of IgG?
Most abundant and indicated immunity to past infection; crosses walls of blood vessels and placenta; protects against bacteria, viruses and toxins; activates complement
What is the function of IgA?
Produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration
What is the function of IgD?
Found in surfaces of B cells; involved in maturation and differentiation of B cells into plasma and memory cells
What is the function of IgE?
Very large; small in quantity; defense against parasites and histamines-allergic reaction
Where is IgM located?
Blood
Where is IgG located?
Everywhere
Where is a IgA located?
Mucousal
Where is IgE located?
Connective/skin/mucousal
How does the mother pass on IgA and IgG?
IgG is passed to fetus
IgA is passed to neonate via milk
What are the ways in which antibodies to antigens inactivates antigens by?
- Neutralization (blocks viral binding sites; coats bacteria and/or opsonization)
- Agglutination of antigen-bearing particles, such as microbes
- Precipitation of soluble antigens
1-3 enhances phagocytosis
- Complement fixation (activation of complement)and leads to cell lysis
What are the functions of helper CD4+ T cells?
Helper CD4+ T cells will recognize antigen presented on macrophages or B cells and “help” with activating cytokines
- Macrophages can kill intracellular microbes more efficiently
- B cells are activated to secrete cytokines and to induce memory
What is the function of cytotoxic CD8+ T cells?
-Protein antigens of microbes that live in the cytoplasm of infected cells (esp. viruses) are recognized by CD8+ cytotoxic T lymphocytes, whose function is to kill infected cells
What is adaptive/acquired immunity?
Immunity that results from the active production or receipt of antibodies during one’s lifetime
What is Active acquired immunity?
- Antibodies are produced within the person by B cells(plasma cells)
- Provides long lasting protection (memory cells)
- Can be artificial induced with vaccine
What is passive acquired immunity?
- Antibodies are received that were produced by another person or persons or by an animal
- Usually provides only temporary protection
What are vaccine introduction?
Vaccines create long-lasting immunity without infection
Give an example of natural passive
Moms pass IgG (placenta) and IgA(breast milk) to infant (maternal)
Give an example of Natural active
Memory immune cells are established after infection(infection)
What is artificial passive immunity?
Administer IgG to high risk patient (antibody transfer)
What is Artificial passive immunity?
Introduction of harmless agent related to infectious leads to establishment of memory immune cells(immunization)
What are the types of vaccines?
- Live, attenuated
- Killed, inactivated
- Passive IgG
- Subunit
- DNA vaccines
What are DNA vaccines?
engineered gene fragment encoding antigen is delivered to host via viral package
What is Passive IgG vaccine?
Purified immunoglobin administered for high risk of exposure immune-protection is very transient
Used for rabies
What are killed/inactivated vaccines?
Previously virulent micro-organisms killed by chemicals or heat incomplete or short-lived immune response may occur
Used for influenza shot, rabies
What are live, attenuated vaccines?
Live microbe cultivated under conditions that disable their virulence preferred type of healthy patients, not with compromised immune systems
Used for measles/mumps/ rubella (MMR)
What are subunit viruses?
An extracellular fragment of the microbe can create an immune response require adjuvant for second signal and boosters
Toxoids= tetanus (DPT)
Conjugate to sugar capsule= hib
What is hypersensitivity?
Refers to an overly sensitive immune system
What are the different types of hypersensitivity?
Immediate type: occurs from within a few minutes to 24 hours after contact with a particular antigen.
-Type I, II, and III hypersensitivity reactions
Delayed type: usually takes more than 24 hours to manifest
-Also known as type IV hypersensitivity reactions
What is the most frequent disorder of the immune system?
Allergies-the most frequent disorders of the immune system, estimated to affect about 20% of the popular
What is an allergy?
A rapid, IgE antibody and mast cell-mediated vascular and smooth muscle reaction, often followed by inflammation
What are the common types of type 1 hypersensitivity ?
Common types of type 1 hypersensitivity include asthma, food allergies, local wheal and flare, and anaphylactic shock
Explain the process of type 1 hypersensitivity: allergy
- First exposure to allergen
- Antigen activation of T helper cells and stimulation of IgE class and switching in B cells
- Production of IgE
- Binding of IgE to FceRI on mast cells
- Repeat exposure to allergen
- Activation of mast cells: release of mediators
What are anaphylactic reactions?
Anaphylactic reactions are serious systemic allergic reactions can be prevented avoiding known allergens, like peanuts
What are skin tests used for?
Skin tests (scratch tests) are used to identify offending allergens in patients
-A positive test is indicated if cutaneous reaction occurs at the site of the scratch
How can allergies be treated?
Immunotherapy (i.el allergen shots-IM doses of the allergen ) May be used to treat the patient)
IgG blocking antibodies are produced in response to allergy shots
What is a type 2 hypersensitivity reaction?
Type 2 hypersensitivity reactions are cyto-lytic reactions, meaning cells are destroyed if antibody is bound
Rhesus disease in newborn is a classic example
What is the sequence of examples in a type 2 hypersensitivity reaction ?
- An Rh(-) mom produces antibodies to Rh(+) blood cells
- The Anti-Rh IgG antibody passes the placenta
- The Anti-Rh antibody from mom binds to the surface of a fetus Rh(+) blood cell
- Complement activation on the cell surface is initiated
- The complement cascade leads to lysis of the cell
- Fetus develops severe anemia
What happens when a Rh-negative woman carries a Rh-positive fetus?
She will produce Rh-antibodies if fetal cells leak into the maternal curculation(normally during labor of first child or miscarriages)
Subsequent pregnancies are more susceptible to developing HDN
The IgG antibodies cross the placenta and bind fetal red cells
What is type III hypersensitivity reactions?
Immune complex reactions- such as those that occur in serum sickness and certain autoimmune diseases (e.g., systemic lupus, erythematosus SLE and rheumatoid arthritis )
-Involve IgG and IgM antibodies, complement and neutrophils
Untreated/ inadequately treated of street throat and other Streptococcus pyogenes infections result in…
Type III hypersensitivity reactions (e.g., rheumatic fever and glomerulonephritis
What is a type IV hypersensitivity reactions?
- delayed-type hypersensitivity (DTH) or cell-mediated immune reactions, and are part of cell-mediated immunity
- Reactions are usually observed 24-48 hours or longer after exposure or contact.
A classic example of DTH is a positive TB skin test (also called PPD test) to test for memory T cells for Mycibacterium tuberculosis
What is the prime mode of defense against intracellular bacteria and fungi?
DTH
Involved a variety of cel, types, including macrophages, helper T cells, cytotoxic T cells, and NK cells
How does delayed hypersensitivity IV respond to infections?
Delayed-type hypersensitivity reactions, CD4+( and sometimes CD8+ cells) respond to tissue antigens by secreting cytokines that stimulate inflammation and activate phagocytes, leading to tissue injury
-In some diseases, CD8+ CTLs directly kill tissue cells
What are autoimmune diseases?
Result when a person’s immune system no longer recognizes certain body tissues as “self” and attempts to destroy those tissues as if they were “non-self “ or foreign
-May occur I with certain tissues that are not exposed to the immune system during fetal development and, thus, are not recognized as “self”
How many autoimmune diseases are there? How can they be classified?
There are more than 80 recognized autoimmune diseases
Can be classified as organ-specific and non-organ specific
Examples: diabetes, multiple sclerosis, rheumatoid arthritis
Outline the complement cascade
Classical pathway(antibody complexes), MB lectin pathway (lectin binding pathogen surfaces) and Alternative pathway lead to complement activation
Complement activation leads to recruitment of inflammatory cells, opsonization of pathogens abs killing of pathogens
How does opsonization of pathogens help the complement system?
Opsonization and phagocytosis- Binding if C3b or cb4 to microbe leads to phagocyte receptor recognizing C3b receptor and phagocytosis of microbe
Recruitment of Binding of C3b to microbe, release of c3a leads to destruction destruction of microbes by leukocytes via activation of leukocytes by c3a, c5a
Killing of pathogens-binding of C3b to pathogens, activation of late components of complement leading to osmotic lysis of bacteria via formation of membrane attack complex
