EX2 Immunology 1 Flashcards
What are the 3 key properties of the immune system?
- A diverse repertoire of antigen receptors (allowing for recognition of plethora of pathogens)
- Immune memory - rapid recall of immune responses
- Immunological tolerance - prevent immune damage to normal self-tissues
what is the immune system known as, it is one of the greatest _____
first and last lines of defense
one of greatest communication systems of the body
what does the immune system require
coordination between innumerable cells and molecules joining to defend against disease/ invading microorganisms
each component reacts w other components (cell to cell or via chemical mediators)
each cell/process must be understood as it relates to the maintanance of homeostasis
what is a pathogen, give examples
any organism that has potential to cause disease
bacteria, viruses, fungi, parasites ( also unicellular protozoa and multicellular worms)
What are the 3 roles of the Immune System?
- Defense against invasion (bacteria, viruses, foreign substances)
- Distinguish between self and invader
- Defense against abnormal cells/molecule formation in the body.
What is the most important function of the immune system?
Defending against infection by preventing infection and/or eliminating established infections.
what is the def of immune system
the collection of cells, tissues, and molecules that mediate the resistance efforts
what is immunity
the bodys ability to defend against pathogens/ foreign substances that cause disease
what is the immune response
coordinated reactions of those cells and molecules against infectious microorganisms
What are the two types of immunity and their differences?
Innate/Natural immunity is the first type of immunity and includes the skin and epithelial layers (physical sep from envmt), and our innate immunity.
Adaptive/Acquired immunity is the 2nd line of defense and is found only in vertebrates. It includes adaptive immunity and antigen specific immunity
what is adaptive/aquired immunity dependent on
influences from the innate immune system
when is the immune response initiated- what are the two players timing
immune response activated once the epithelial barriers are breached and pathogens enter the body
innate immunity gives initial protection
adaptive immunity gives a slower, more specialized response
what is the time of response, diversity, microbe recognition, principle immune cells involved, and memory of INNATE immunity
-time- immediate (minutes to hours)
-diversity- limited number of antigens recognized/groups microbes identified
- microbe recog- general patterns on microbes, NONSPECIFIC
- principle immune cells involved- granulocytes, monocytes/macrophages, natural killer cells, dendritic cells
-memory- NONE- responds same way to repeat encounters with the same pathogen
what is the time of response, diversity, microbe recognition, principle immune cells involved, and memory of ADAPTIVE (acquired) immunity
- time- delayed (days-weeks)
- diversity- large number of highly SELECTIVE antigens recognized
- microbe recog- SPECIFIC to individual microbes and antigens
- principle immune cells involved- B lymphocytes, T lymphocytes, dendritic cells, natural killer cells
- memory- YES- responds more effectively after each encounter with the same pathogen
what is hematopoesis
another term for hemopoiesis- formation of blood cellular components
all starts from hematopoietic stem cell
What is progenitor of the granulocytes and the lymphocytes?
Stem cells differentiate into lymphoid stem cells and myeloid orogenitors.
Myeloid progenitors differentiate into granulocytes(neut, eos, bas, mast, mono) while lymphoid stem cells differentiate into lymphocytes.
What cell types do lymphocytes differentiate into?
B cells, T cells, and NK cells.
what do B cells differentiate into
plasma cells and memory cells
what do T cells differentiate into
Th (T helper) and Tc (T cytotoxic killer cells)
what does innate immunity consist of
physical, chemical, cellular and molecular defenses that are ready for activation and mediate rapid, initial protection against infection
What are dendritic cells derived from?
Monocytes
What are the epithelial barriers of the body? what are the three categories and examples?
All portals of entry into our body (skin, GI, resp, urogenitla).
Includes:
- Mechanical/Physical: flow of fluids, mucus, saliva, urine, tears
- Chemical: sebum, enzymes, and lysozymes, acids, antimicrobial peptides
- Microbiological/Cellular: normal flora of skin, GI tract, resp tract, GU tract, and eyes.
What are the cells involved in our innate immune response?
Monocytes, macrophages, dendritic cells, NK cells, neutrophils, basophils, eosinophils, and mast cells.
what differentiation of a stem cell is innate immunity from (plus one exceoption)
myeloid progenitor - plus natural killer cells from lymphoid stem cells
What is % of WBCs is a monocyte?
It is 3-7%.
what are monocytes size and what are they a precursor to
they are the largest of all WBC
precursor to macrophages- when monocyte enters tissues they are called macrophages (sometimes given special names depending on location)
may also mature into dendritic cells
what is the first phagocyte microbes encounter when entering the host
monocyte-macrophages
What cells are not granulocytes in our innate immunity?
Monocytes,macrophages, dendritic cells and NK cells.
What are the immune functions of macrophages?
Clearing out bacteria that get past the epithelial barrier
Phagocytosis
Produce cytokines that help initiate inflammation and recruit other cells
Present antigens to T cells
Non-immune function: garbage disposal
What is the function of dendritic cells?
- Resides in the body’s tissues
- serves as cellular messengers that initiate adaptive immune response.
- present antigens to T lymphocytes (APC)
what type of cell initiates the adaptive immune response and how is it done?
dendritic cells
degrading pathogens from infected tissues and transport them to organs that specialize in synthesizing adaptive immune responses
what are NK cells
lymphocytic cells that functions in innate immunity
circulates in blood until needed in tissues
how do NK cells work?
doesn’t directly recognize pathogens via antigen receptors but has membrane receptors that recognize damaged cells (virus infected cells, tumor cells)
NK cells release contents of their granules that cause lysis or apoptosis to destroy target cells (can immediately kill cells without previous exposure)
Why are NK cells important?
They help limit the spread of infection via cytokine production.
why are NK cells called “natural”
because they are active without having been exposed to a virus previously
what are the amplifiers and effectors of the innate immune response
granulocytes of innate immunity (eosinophils, basophil, neutrophils)
What can the unchecked accumulation and activation of granulocytes lead to?
Host tissue damage, such as in systemic necrotizing vasculitis.
What is the most abundant WBC? Approx what percentage of WBC? Length of life?
Neutrophils, which consist of 55% of all WBCs.
They will degrade after a few days if not sent to site of bacteria infection
What kind of infection are neutrophils usually present in?
Bacterial infections.
how do neutrophils kill via phagocytosis
contain cytoplasmic granules with toxic substances that kill/inhibit bacteria and fungi +activate respiratory burst causing ROS to attack pathogens
What are the two ways neutrophils kill pathogens?
Phagocytosis with ROS.
NETs
What is ROS?
Reactive oxidative species, which uses free radicals to destroy all cells.
Neutrophils activate a respiratory burst that produces ROS to attack pathogens
What is a NET?
Neutrophil Extracellular Trap, which immobilize pathogens, facilitate phagocytosis, and directly kill pathogens.
What is the second most abundant granulocyte?
Eosinophils, which account for 1-4% of all WBCs.
What are the immune functions of Eosinophils?
Release granules containing toxic proteins, peroxidase, and hydrolases.
Display surface membrane receptors for IgE antibodies.
when are eosinophils recruited
recruited into tissues in response to large parasitic worm infections (helminths)
can also be associated with allergic responses
What is the rarest granulocyte in circulation and what percent is that? what do they respond to?
Basophils, which account for <1% of all WBCs.
respond to parasitic infections (go from blood into tissue)
what other granulocyte are basophils similar to and how?
mast cells except basophils circulate in blood until they are needed
What mediators can basophils and mast cells release?
Histamine and heparin
What additional mediator can a mast cell release that a basophil does not?
Lipid mediators to affect blood vessels and smooth muscle.
what are mast cells
- granulocyte found in tissues surrounding blood vessels
- granules contain bioactive amines (histamine) and lipid mediators
- important role in initiating inflammatory reactions
- display surface membrane receptors for IgE antibodies
what cell is responsible for sx related to immediate hypersensitivity (allergy)
mast cells
how do immune system players recognize self from non self
via use of and recognition of specific and molecular patterns and recognition receptors specific to different pathogens
DAMPs, PAMPs, PRRs, TLRs
What are PAMPs
Pathogen associated molecular pattern
-molecules shared by a number of pathogens that are not present on normal human cells (host cells)
- recognized by host cell PRRs of innate immune system
what are DAMPs
Damage associated molecular patterns
molecules released by damaged/dying cells recognized by some innate immune system cells
what are PRRs
pattern recognition receptors
innate immune cell receptors that recognize the PAMPs or DAMPs
what are TLRs
toll like receptors
PRRs that help regulate wound healing, tissue repair and regeneration
How do NK cell receptors work?
They have activating and inhibitory receptors. Healthy cells engage with the inhibitory receptors (via ligands), while damaged cells express stress molecules that trigger the NK activating receptors to overpower the NK inhibitory receptors
Describe a receptor-ligand interaction
Two cells in close contact with each other must interact via one having a ligand and one having a receptor specific to the ligand. Once activated, the receptor can carry out its function.
*requires very close contact
What are the soluble factors and mediators of innate immunity?
Opsonins, Inflammatory cytokines, Acute phase proteins, and the complement system
Where do opsonins bind to?
PRRs on pathogens.
What are opsonins?
Opsonins are proteins that can coat a cell to enhance phagocytosis of that cell.
It commonly includes acute phase proteins, lectins, and complements.
What are the inflammatory cytokines (with examples) involved in innate immunity?
TNFs, IFNs, and chemokines
small proteins that act as intracellular signals
What are the acute-phase proteins involved in innate immunity?
C-reactive protein and mannose-binding lectin
activate complement, act as opsonins
What are the goals of the complement system in innate immunity?
To increase inflammation, opsonization, and to form the membrane attack complex.
what are cytokines
soluble proteins that are principal mediators of communication between innate and adaptive immunity
What are the functions of cytokines on immune cells?
- Regulating the growth, development, and activation of immune system cells.
- mediate inflammatory response
What are two distinct characteristics of cytokines?
Redundant (Overlapping functions) and Pleiotropic (multiple pathways create them)
What is the difference between autocrine, paracrine, and endocrine?
autocrine is self-signaling
paracrine is nearby signaling (nearby cell or between gap junctions)
endocrine is far off signaling
What is the function of a chemokine in innate immunity?
they are cytokines that direct migration of leukocytes to areas of injury and to locations where the immune response has been activated.
cytokines and chemokines can _____ with cells ______ from source of ________
cytokines and chemokines can communicate with cells at a distance from the source of the cytokine or chemokine
what happens when chemokines work in conjunction with one another
they antagonize or activate chemokine receptors
What are the major sources of cytokines in immunity?
Macrophages and T-cells
cells responding to cytokines or chemokines must have..
receptors that are SPECIFIC for the cytokine or chemokine
What does the response of a cell depend on in regards to cytokines?
The sum of the signals received.
What is the function of IL in immunity?
It enhances our acquired immune response or it can enhance/inhibit the inflammatory response.
when are ILs produced
produced by macrophages and lymphocytes when microbe invades or inflammation is initiated
What is the function of IFNs in immunity? who produces each IFN
Protection from viral infections and to modulate the inflammatory response.
specific cells of immune response produce each IFN ( T lymphocytes produce IFN-gamma 1)
What is the function of TNFs in immunity and what triggers its release?
one of most important mediators of inflammation.
Acts as an endogenous pyrogen to stimulate the liver to make proinflammatory substances.
It is produced by macrophages when a PAMP is detected by a TLR.
what do chemokines serve to do
serve to control deployment of leukocytes to their primary destination in the immune response
What are the classes of chemokines in the immune response?
C, CC, CXC, and CX3C
Which chemokine class is responsible for chronic inflammation and what does it attract?
CC is responsible for chronic inflammation and it attracts monocytes, lymphocytes, and eosinophils.
Which chemokine class is responsible for acute inflammation and what does it attract?
CXC is responsible for acute inflammation and it attracts neutrophils.
What communicates with G-protein coupled receptors in target cells? what does it allow for?
Chemokines
allows for further activation of leukocytes based on host needs
what is the complement system
a system of soluble proteins (C1-C9) that play a role in innate immunity ( can work with adaptive immunity)
activation of this system is highly regulated
helps body localize infection and destroy invaders
What triggers the complement system? what does it result in?
Infection
results in cascade of plasma enzyme, regulatory proteins, and protein formation, leading to cell lysis
Where are complement proteins synthesized and primarily found?
They are synthesized in the liver and primarily found in the plasma inactivated.
What regulates the complement system?
Host cell proteins inhibit it to prevent self-damage ( so that normal host cells are untouched)
What are the 3 pathways of the complement system?
Alternative (innate immunity)
Classic (humoral immunity)
Lectin/MBL (microbes with mannose groups)
differ in how they are activated but the by products are the same
what is alternative complement pathway triggered by? what type of immunity is this
triggered by molecules on microbes without surface antibodies (innate immunity)
what is classic complement pathway triggered by? what type of immunity if this
triggered by IgM or IgG antibodies attached to microbes (humoral immmunity) *triggered by antibodies
what is the lectin/ MBL complement pathway activated by
activated by microbes with terminal mannose groups
What are the starter complement proteins?
C1, C2, and C4
What is the central complement protein formed by all pathways and what does activation of this protein lead to?
C3b
C3b initiates late stage complement which results in formation of membrane attack complex (MAC)
what are the two other important byproducts of complement
C3a, C5a
all have components that have different “effector” functions
What are the 3 functions of C3b?
Opsonization, phagocytosis, and precursor to the MAC.
(coats microbes and tells phagocytes- macrophage and neutrophils- who to target)
**all pathways lead to this step
What are the functions of C3a and C5a?
chemoattractants for neutrophils and monocytes which promote inflammatory reactions
What complements make up the MAC? and what does MAC do?
C5b, C6, C7, C8, and C9.
inserts itself into microbial cell membranes causing lysis
what complement proteins initiate complement cascade
C1, C2, C4
what complement protein activates C5 ( and result sin opsonization)
C3b
what complement proteins stimulate inflammation
C3a, C5a
what is adaptive immunity
complex series of interactions between components of the immune system and antigens of foreign invaders
What are antigens? what do they interact with to be recognized?
Molecules on a cell’s surface that are recognized and responded to by cells in the adaptive immune system.
an antigen has to interact with a receptor in the immune cells membrane in order to be recognized
two characteristic subtypes of antigens and examples
-soluble and particulate molecules
- proteins, polysacharides, glycoproteins, nucleoproteins
- molecules of whole cells
- bacteria, protozoa, tumor cells, virus infected cells
how much of WBC do lymphocytes make up
~36% of WBC
Where do B and T cells mature?
B-cells in the bone marrow
T-cells in the Thymus
What does CD stand for and how does it occur?
CD stands for cluster of differentiation and is a receptor protein for a specific antigen that B and T lymphocytes get during maturation.
CD followed by a number indicates that cells specific surface protein on the lymphocyte
what happens to lymphocyte once matured in lymphoid organ
Lymphocytes leave their lymphoid organ to circulate in the blood and lymph
What produces antibodies?
B lymphocytes , specifically plasma cells, which are activated B lymphocytes.
(Memory B cells cannot produce antibodies unless they differentiate back into plasma cells.)
what are B lymphocytes responsible for
humoral immunity
(immunity mediated by macromolecules in the ECF– involves sub. found in humor or fluid)
what are plasma cells and what do they do
activated B cells
plasma cells secrete antibodies that neutralize and eliminate antigens
what are T lymphocytes responsible for and what do they contain
responsible for cell mediated immunity (immune response not involving antibodies)
T lymphocytes have antigen receptors that recognize peptide fragments bound to specialized peptide display molecules presented by antigen presenting cells (APCs)
What are the subclasses of T cells?
T helper cells (CD4)
Cytotoxic T cells (CD8)
Regulatory T cells
what do T helper (CD4) cells do
help B lymphocytes produce antibodies and help macrophages destroy ingested microbes
what do cytotoxic (CD8) T cells do
kill cells that contain intracellular microbes
what do regulatory T cells do
prevent or limit immune responses
What cells do T helper cells assist?
Help B lymphocytes produce antibodies
Help macrophages destroy ingested microbes
how does adaptive immunity do pathogen reocgnition
recognize specific microbial molecules so they can distinguish one pathogen from another
What is the difference between an antibody/BCR and a TCR?
An antibody/BCR is the receptor for an antigen on a B cell, while a TCR is the receptor for an antigen on a T cell.
Antibodies can be secreted, whereas TCRs must stay on the cell surface.
what is one way B and T cells are similar and different
similar in their antigen receptor structure but different in how they recognize antigens
What is the difference between B cell and T cells when it comes to antigen recognition?
B cells recognize all organic molecules while T cells recognize protein antigens.
*B cells can recognize an antigen in its native state (by itself) , while a T cell must be presented with it by another cell or it wont recognize
What is the variable region of a lymphocyte’s receptor?
antigen binding site
Describe the makeup of B cell and T cell receptors (an antibody).
- have multiple chains
- Variable region
- constant region
- heavy chain (Fc)
what is the variable region of a b/t cell receptor ( or an antibody)
where they will interact with antigen
(antigen binding site)
light chain
what is the constant region of b/t cell receptor (or an antibody)
the heavy chain constant region of secreted antibody defines the function of that class of antibody
(Fc portion of antibody molecule)
T cell receptor constant region does NOT define a specific effector function
what cells can export their receptors and which remain tightly attatched
B cells can export (secrete) its receptors as antibody but
T cells receptors remains tightly attatched to its surface membrane
(in picture B cell tilt to side and T are straight vertical line)
What is MHC and what is its function?
It is a display molecule known as a major histocompatibility complex protein. Its goal is to help lymphocytes ignore self-antigens.
What are the MHC classes and their purpose?
Class I and II are genes that encode human leukocyte antigens (HLA) in humans
Class III is for genes that encode complement components.
how do MHC proteins work with T lymphocytes
T cells use their receptors to “view” the antigen presented by the MHC proteins
MHC proteins display____ but not _____
MHC proteins display peptides but not intact microbial protein antigens
what is antigen processing
conversion of proteins into peptides able to bind to MHC
Where do I find MHC class I molecules and what recognizes them?
MHC Class I molecules are found on host cells (all nucleated cells) and are recognized by CD8 cytotoxic lymphocytes.
Where are MHC class I molecules derived from?
MHC Class I molecules present peptides derived from protein antigens found within the processing cells cytoplasm and present them to CD8 cytotoxic T lymphocytes
Where do I find MHC class II molecules and what recognizes them?
MHC Class II molecules present peptides derived from extracellular protein antigens and are presented to CD4 T helper cells (can do alone).
expressed ONLY on selected cells called “professional” antigen presenting cells
What are the APCs (antigen presenting cells)?
Dendritic cells, Macrophages, and B lymphocytes.
What are the central/primary lymphoid organs?
The bone marrow and the Thymus
What are the peripheral lymphoid organs?
Lymph nodes, spleen, and mucosal associated tissues such as the adenoids, tonsils, appendix, and peyer’s patches in the small intestine.
Why are lymph nodes essential for the immune system? how are they arranged
They provide areas for lymphocytes from tissue to live and enter/exit the bloodstream via afferent(enter) and efferent(leave) lymphatic vessels.
important for responding to pathogens in the blood
in chains along lymphatic vessels throughout body
what are the only circulating immune cells that can enter the lymph node via blood
B and T lymphocytes
how are antigens and dendritic cells able to get into lymph nodes
lymph from tissues entering the lymph node via afferent lymphatic vessel
what is lymph and what is its pathway
lymph is fluid that leaks out of blood into tissue
it is collected from tissues by lymphatic vessels, passes through lymph nodes, and returns to the blood
What is the function of the spleen?
It is a filter for blood and responds to pathogens in the blood.
B, and T Lymphocytes, antigens, and dendritic cells all enter it via blood.
What is MALT and where is it found?
Mucosal associated lymphoid tissue
It is lymphoid tissue that is around mucosal epithelia, such as the GI/respiratory tracts, tonsils, adenoids, lymph nodes and peyer’s patches.
what contains the most diverse and largest population of microbes? what is a result of this?
GI and respiratory tracts
makes areas susceptible to infection thus they contain large amounts of lymphoid tissue (MALT)
what does MALT contain
T and B lymphocytes, plasma cells, dendritic cells, macrophages
responds to pathogens on mucosal surfaces
