Overview of Immune Responses Flashcards
Immunity
a set of cooperative defense mechanisms which provide protection from various diseases
extracellular microbes
able to survive in animals by growing extracellularly being simply immersed in nutrients
can live in blood, lymph and interstitial tissue
ex. e. coli
intracellular microbes
invade and live and replicate intracellularly within animal cells where they utilize host-cell energy sources
ex. salmonella and viruses
multicellular
…… worms…… helminthes
all microbes can
grow, reproduce, and infect humans
types of parasites
worms, protozoans, fungi, bacteria, viruses
why are fungi difficult to treat
because they are eukaryotes which increases likelihood that treatment will effect self
immune system
comprised of immune cells and molecules (that are dissolved in plasma, interstitial tissue, and lymph) which collectively mediate an immune response
immunopathology
tissue injury caused by an immune response against microbes (because immune response creates inflammation which causes harsh environment, killing pathogens as well as healthy tissue)
aka collateral damage
antigens (Ags)
noninfectious foreign substances that can elicit an immune response
autoimmune response
pathological condition in which self antigens (Ags) in the body can elicit an autoimmune response
Antigens (Ags) include:
proteins, carbohydrates, lipids, and nucleic acids
- any polymers can invoke immune response
- size is very important
in regards to protein Ags - 5 or 6 amino acids in length are big enough to generate immune response, anything smaller and there isn’t enough structural information for immune system to recognize as non-self
each microbe has many
microbial Ags which can be recognized by the immune system
an antibody (Ab) is
a protein produced by the immune system when it detects antigens
an epitope (antigenic determinant) is
a portion of an Ag molecule to which an antibody binds
antigens can have multiple epitopes
antibody binds to epitope through
Van der Waal interactions
antibodies bind to what kind of epitopes
conformation and linear epitopes
T-cell receptors recognize
linear amino acid sequences on antigens
immunogens
antigens that can stimulate an immune response
haptens
very small antigens that can bind to antibodies but don’t initiate an immune response
the immune system comprises 2 elements:
fixed and mobile elements
fixed elements of immune system consists of
the lymphoid organs
primary (generative) fixed elements
bone marrow (all immune cells except T-cells are generated here)
thymus (T-cells are generated here)
*generate centrally and then migrate and circulate in periphery
secondary fixed elements
spleen and lymph nodes
mucosal immune tissues
mobile elements
immune cells
soluble (humoral) components: antibodies, complement, acute phase proteins
innate immunity (natural immunity)
first line of defense against infection
exists even before infection and are poised to respond rapidly to infections
reacts to products of microbes and injured cells of the body
responds in same way to repeated exposures to antigen
recognizes common antigens belonging to groups of related microbes (gram-positive vs gram-negative) - does not distinguish fine differences between microbes
- works rapidly
- gives rise to an acute inflammation
- has some specificity for antigens (doesn’t attack self)
- has no memory
adaptive immunity
- takes longer to develop
- is highly specific
- shows memory (remembers antigen it has encountered previously
most encounters with pathogens are resolved at the level of
innate immunity
components of innate immunity
cellular and chemical barriers: skin, mucosal epithelia, antimicrobial peptides
blood proteins: complement, acute phase proteins, cytokines, chemokines (humoral innate immunity)
cells: phagocytes (macrophages, neutrophils), dendritic cells, natural kills cells, innate lymphoid cells
humoral/soluble components of innate immunity
antimicrobial peptides complement acute phase proteins (APPs) cytokines chemokines phagocytes
antimicrobial peptides
small peptides which target pathogenic microorganisms ranging from viruses to parasites
complement
is a system of plasma proteins that enhances (complements) the ability of antibodies and phagocytic cells to clear pathogens from an organism
acts in cascade manner
acute phase proteins (APPs)
are a large group of blood proteins whose plasma concentrations change in response to tissue injury, acute infections, burns, or inflammation
cytokines
large group of small secreted and membrane-bound proteins with diverse structures and functions which regulate and coordinate many activities of the cells of innate and adaptive immunity
are cell signaling molecules that aid cell to cell communication in immune responses
chemokines
represent a subfamily of cytokines secreted by immune cells to induce chemotaxis (movement) in nearby cells
large subset of structurally related cytokines that regulate cell migration and movement
phagocytes (macrophages and neutrophils)
are immune cells that have the ability to ingest and digest microbes
components of adaptive immunity
cellular and chemical barriers: lymphocytes in epithelia; antibodies secreted at epithelial surfaces
blood proteins: antibodies and cytokines/chemokines (produced by B and T cells)
cells: B and T Lymphocytes
specificity for Innate vs Adaptive Immunity
Innate: can recognize common antigens on self; microbes and molecules produced by damaged host cells
Adaptive: for specific (unique) microbial and nonmicrobial antigens
diversity for Innate vs Adaptive Immunity
Innate: limited; germline encoded
Adaptive: very large; receptors are produced by somatic recombination of gene segments
memory for Innate vs Adaptive Immunity
Innate: none
Adaptive: yes
reactivity to self Antigens for Innate vs Adaptive Immunity
Innate: none
Adaptive: none
primary infection
patient has never seen the pathogen; never was vaccinated against this type of pathogen;
sick 7-10 days
many cells and molecules of the innate immune system are also
used by the adaptive immune system and vice versa
in addition to inflammation, the innate immune system is a
decision-making phase of an immune response
the innate immune system evaluates the invader in the context of ____ and then provide the instructions to adaptive immunity
intracellular vs extracellular microbes
if the immune system discovers extracellular infection (blood, interstitial tissue), what complements the innate immune system
HUMORAL-MEDIATED
antibodies
polymorphonuclear cells
phagocytes
if the immune system discovers intracellular infection (pathogens are hiding), how are pathogens eliminated?
what complements innate immune system?
CELL-MEDIATED
need to kill cells, releasing pathogens, then track down and eliminate pathogens
cytotoxic T cells
natural killer cells
phagocytes
functions of cytokines
- regulate growth and differentiation of all immune cells (growth factors)
- activate the effector functions of lymphocytes and phagocytes
each cytokine acts via a
specific signaling receptor expressed on target cells
cells of innate immunity
neutrophil, eosinophil, basophil, mast cells, monocyte, macrophage, dendritic cell, natural killer
most of innate immune cells are stationed
in the blood and delivered into tissues on demand as a part of inflammatory response
primary function of phagocytes (neutrophils and macrophages)
to ingest and destroy microbes and get rid of damaged tissues by process called phagocytosis
steps in functional responses of phagocytes
- chemokine-mediated recruitment of the cells from the blood and surrounding tissues to the sites of infection/inflammation
- receptor-dependent recognition of microbes and activation of phagocytes
- formation of phagosome and ingestion of the microbes
- intracellular destruction of ingested microbes in lysosomes
activated phagocytes also secrete cytoines/chemokines to
promote and/or regulate immune responses
most abundant white blood cells in blood
neutrophils
neutrophils are polymorphonuclear leukocytes because
their nucleus is segmented into three to five connected lobules
neutrophils mediate the
earliest phases of inflammatory reactions
properties of neutrophils
produced in the bone marrow and arise from a common precursor that also gives rise to monocytes
production of neutrophils is stimulated by cytokine called granulocyte colony-stimulating factor (G-CSF)
adult produces more than 1x10^11 neutrophils per day
are short-lived blood cells which circulates in the blood for hours or a few days
after entering tissues, they function only for 1-2 days and then die
mononuclear phagocytes
blood monocytes and residents tissue macrophages
cells of the mononuclear lineage arise from committed precursor cells in the bone marrow which is controlled by
monocyte/macrophage colony-stimulating factor (M-CSF)
mature monocytes enter blood circulation and then
migrate into tissues where they further mature into macrophages, especially during inflammation
mononuclear cells (blood monocytes and resident tissue macrophages) play a central role in both
innate and adaptive immunity
many tissues are populated with long-lived resident macrophages which assume
specialized phenotypes depending on the organ
resident macrophages are . a heterogeneous population of immune cells that fulfill tissue-specific functions including:
- maintenance of tissue homeostasis via phagocytic clearance of cellular debris and iron processing
- tissue immune surveillance
- control of an innate immune response to infection
- antigen-presentation to T cells
- contraction of the immune response and resolution of inflammation
dendritic cells are of ____ immunity
innate
like tissue macrophages, dendritic cells are ____
professional antigen-presenting cells (APCs)
dendritic cells are potent stimulators of ____
T cells to induce the adaptive immunity
most dendritic cells are differentiated in tissue from
blood monocytes
other dendritic cell subpopulations are slowly self-renewing cells including:
- langerhans cells residing in the epidermis of the skin
- kupffer cells of the liver
- microglia of the CNS
myeloid dendritic cells are derived from ____ and differentiated from peripheral blood mononuclear cells (PBMCs)
monocytes
dendritic cells can be broadly divided to ____ and ____
myeloid dendritic cells
plasmacytoid dendritic cells
mast cells, basophils, eosinophils play roles in what time of immunity
innate and adaptive immune responses
mast cells, basophils, and eosinophils help protect against ____ and mediate reactions that cause ____
helminthes
allergic diseases
mast cells, basophils, and eosinophils all contain
cytoplasmic granules filled with various inflammatory and antimicrobial mediators
mast cells are common at sites in the body that are exposed to
the external environment, such as the skin where they can regulate vascular permeability and effector-cell recruitment
mast cells do not have direct cell-cell contact with local cell populations, however they can still modulate the responses of other neighboring immune cells through the release of
mediators
two branches of adaptive immunity
humoral and cell-mediated
two major types of lymphocytes
B cells and T cells
interactions between T cells and B cells, as well as T cells and antigen-presenting cells, are critical to the development of
specific immunity
development and maturation of T cells occurs in
the thymus
development and maturation of B cells mature mainly in the ____
bone marrow
humoral immunity
immunity that involves production of soluble molecules- immunoglobulins
t-cell
intracellular
b-cell
extracellular
humoral immunity is mediated by antibodies in the ___ and ____, which are produced by B lymphocytes (also called B cells)
blood and mucosal secretions
functions of antibodies
- recognize microbial antigens
- neutralize the infectivity of the microbes
- target microbes for elimination by various effector mechanisms
humoral adaptive immunity is the principal defense mechanism against ____ because ____
extracellular microbes and their toxins
secreted antibodies can bind to these microbes and toxins and assist in their elimination
cell-mediated immunity is controlled by responses of
T lymphocytes (also called T cells) which often function in concert with antigen-presenting cells and phagocytes to eliminate microbes
CMI mediates host defense against
intracellular microbes, such as viruses and some bacteria, where they are inaccessible to circulating antibodies
function of CMI
killing infected host cells (by apoptosis) to eliminate reservoirs of infection
some T lymphocytes (called T helper lymphocytes) also help B cells to make
effective antibodies thereby contributing to eradication of extracellular microbes
in humoral immunity, B lymphocytes secrete antibodies that prevent infections and eliminate
extracellular microbes
functions of T helper cells
- activate macrophages to kill phagocytized microbes
- become cytotoxic T lymphocytes (CTLs) to directly destroy infected host cells, leaving pathogens unprotected, allowing pathogens to be recognized as extracellular in which humoral immunity can eliminate
father of humoral immunity
paul ehrlich, postulated that immune cells can secrete receptors (he called side chains) which recognize microbial toxins (we now call them antigens) and combat invading microbes
father of cell-mediated immunity
elie metchnikoff, discovered phagocytes which he believed are the principal effector mechanism of immunity
he was unable to prove that specific immunity to microbes could be mediated by cells
cellular theory of immunity became firmly re-established in the 1950s when it was shown that resistance to an intracellular bacterium listeria monocytogenes could be tranferred with cells but not with serum
properties of adaptive immunity:
- specificity
- diversity
- memory
- clonal expansion
- specialization
- contraction and homeostasis
- non reactivity to self
- specificity: ensures that the immune response to a microbe (or nonmicrobial antigens) is selective to that microbe or antigens
- diversity: enables the immune system to respond to a large variety of antigens
- memory: increases the ability to combat repeat infections by the same microbes
- clonal expansion: increases the number of antigen-specific lymphocytes to keep pace with microbes
- specialization: generates responses that are optimal for defense against different types of microbes
- contraction and homeostasis: allows the immune system to recover from one response so that it can effectively respond to newly encountered antigens
- non reactivity to self: prevents injury to the host during responses to foreign antigens
clonal selection hypothesis
suggested by Dr. Jerne and furthered by Dr. Burnet
states that antigen-specific clones of lymphocytes develop before and independent of exposure to antigen
a clone refers to
a lymphocytes of one specificity and its progeny
immune system generates large number of clones which
maximize the defense potential for recognizing diverse microbes
hypothesis of clonal selection stepss
- lymphocyte clones mature in generative (primary) lymphoid organs (bone marrow and thymus), in the absence of antigens (HEALTH)
- clones of mature lymphocytes specific for diverse antigens enter lymphoid tissues (DISEASE)
- antigen-specific clones are activated (“selected”) by antigens (CLONAL EXPANSION/DIFFERENTIATION)
- antigen-specific immune responses occur
hypothesis of clonal selection
each antigen selects a preexisting clone of specific B cells and stimulates proliferation and activation of that clone
same principle applies to T lymphocytes
when antigen is introduced into an individual, lymphocytes with receptors for this antigen seek out and bind antigens and are triggered to
proliferate and differentiate giving rise to clones of cells specific for the antigen
cells from clones (or their products) specifically react with the antigen to
neutralize or eliminate antigen
some antigen-specific cells late in the immune response is responsible for
the memory involved in adaptive immunity
phases of adaptive immune responses
- antigen recognition: naive T lymphocyte requires antigen presenting cell to recognize; Naive B lymphocyte recognizes on its own
- lymphocyte activation : clonal expansion and differentiation
- antigen elimination: antibodies and effector T cells
- contraction (homeostasis): apoptosis
- memory: surviving memory cells
expanded lymphocyte clones die in
contraction phase and homeostasis is restored
a few activated lymphocytes become antigen-specific
memory cells which may survive for years after the infection
memory cells are ____ numerous than naive cells specific for the antigen and respond ____ and ____ effectively than do naive cells
more
faster
more
generation of memory responses is important goal of
vaccination
