Lecture 1 & 2 Flashcards
term for when the immune system loses the ability to discriminate b/w self and non-self
autoimmunity
‘self’
normal body constituents expressed by healthy cells
non-self
cells/molecules that the immune system doesn’t have exposure to during its maturation or doesn’t normally encounter on healthy cells
foreign cells/substances
damaged, transformed or senescent
pathogen
causes disease
evades innate immunity
opportunistic pathogens
typically don’t cause disease but under the right conditions they can
innate immunity
components of the immune system that rapidly respond to non-self invaders in a non-specific way
protects us from non-pathogens
adaptive immunity (‘third line of defense’)
= acquired immunity; can be cell-mediated or humoral
- antigen-specific responses that are highly adapted to specific pathogens
- composed of lymphocytes
- regulated by communication b/w innate and adaptive immune cells
at rest until a specific antigen interacts w/ their antigen receptor
what type of immunity develops immunological memory
adaptive
- memory causes improved immune response over time
how does innate immunity prevent microbes from establishing infection?
by blocking the entry of microbes by physical, mechanical, microbial or chemical methods = barrier defenses
barrier defenses
skin, chemicals on skin like oil, mucous membranes
skin as barrier
dry, acidic environment prevents growth of many bacteria, keratins discourages colonization, sloughing of skin cells removes bacteria that adheres to skin cell.
mucosal epithelium
tears, the stomach is acidic, mucous traps things in airway entrance, colon has resident microbiota, bladder sphincter keeps bacteria out of urethra, etc.
what prevents bacteria from accessing subcellular surfaces in mucosal epithelium
tight junctions
importance of goblet cells
make and secrete mucus
- mixture of glycoproteins
- prevents bacteria from reaching epithelial cell surfaces
mucociliary escalator
in respiratory track
- ciliated epithelial cells that line airways
- coated w/ mucus that traps pathogens
- cilia move mucus up and out of lungs
what are the cells of innate immunity
WBCs (phagocytic and natural killer cells)
Complement (serum proteins that trigger inflammatory response and initiate phagocytosis of bacterial cells)
Cytokines (proteins made by immune cells to coordinate attack on invading pathogens)
how do microorganisms gain access to cells or tissues
by colonizing or breaching the epithelial barrier
colonization of the surface can lead to…
infection of epithelial cells, epithelial damage allowing microbe to cross into underlying tissue
PAMP (pathogen-associated molecular pattern)
repeating patterns of molecular structures on surface of pathogens
cells express ________ that recognize common microbial structures (PAMPs)
pattern recognition receptors (PRR)
what are examples of PAMPs
LPS (lipopolysaccharides)
peptidoglycan
LTA (Lipotechoic acid)
Flagellin (major component of bacterial flagella)
viral RNA (dsRNA)
unmethylated CpG DNA
what is CpG DNA?
CpG = cytosine phosphate guanine
what is an example of pattern recognition receptors?
Toll-like receptors (TLRs)
**TLR4 binds to LPS
- LPS is released during bacterial cell lysis
Imiquimoid (Aldara TM) does what
enhances immune response against equine sarcoids and aural plaques by binding TLR 7/8
what does lysozyme break down
peptidoglycan
NADPH oxidase generates what
superoxide
what complement proteins induce pro-inflammatory cytokines
C3a and C5a
activated macrophages and dendritic cells
TNF, Interleukin 1 & 6 and others
what is the main function of cytokines
recruit immune cells and increase lymph flow
- lymph returns antigens and microbes to lymphoid tissues to generate adaptive immune response
physical signs of the inflammatory response are caused by ….
increased blood flow and leakage of fluid and blood proteins into tissues
what causes septic shock
bacterial infections
Septicemia = bacteria in blood stream, causes inflammatory response throughout the body
how does septic shock lead to death
septicemia leads to drop in BP, lower blood flow to vital organs and organs begin to fail
function of natural killer cells
induce apoptosis in infected host cells
- they store toxic granules
a collection of soluble proteins present in blood and other body fluids, activated in response to pathogens or antibodies bound to pathogens
complement
- made in liver
- ‘complement’ to antibody activity
what is an antigen
Antibody Generator
* foreign substances that bind B cell receptors, T cell receptors or antibodies
when are antibodies raised for attack
only when specific molecules are found
what is an epitope
4-16 amino acids that are recognized by the antigen binding site of an antibody
why are adaptive immune responses specific?
b/c each B and T cell expresses a unique receptor on the cell surface
- every B and T cell has surface receptors (BCR and TCR) that have an antigen-binding site specific for one epitope
how do BCR and TCR differ
BCR - binds antigens of varying shapes and sizes
TCR - binds linear peptides displayed by MHC (HLA) molecules
what T cells are responsible for expressing different versions of TCR
CD8 and CD4 T cells
antibody-based immunity produced by effector B cells (plasma cells)
Humoral immunity
- important in defense against extracellular pathogens
Cell-mediated immunity is mediated by ______ cells that produce their effect by _______ contact w/ target cells
effector T cells
direct contact
what cells are involved in cell-mediated immunity
Helper T cells
Cytotoxic T cells
what causes the activation of B and T cells
upon antigen recognition
how do effector cells participate in the elimination of antigens ?
secretion of antibodies or through cell-mediated killing
adaptive immunity includes what two types of immunity and what cells make them up
cell-mediated - T cell defense
humoral - antibody defense (B cells)
Proteins made by immune cells to co-ordinate attack on invading pathogens
cytokines
Serum proteins that trigger inflammatory response and initiate phagocytosis of bacterial cells
complement
what are the 2 types of WBCs involved in the innate immune response
Phagocytes (neutrophils, macrophages, dendritic)
Natural Killers
- Frequent sites of methylation in Mammals
- Unmethylated in bacteria
- Aberrant DNA methylation involved in many cancers
CpG
when are lipopolysaccharides released
during bacterial cell lysis
LPS binding protein (LBP) binds what
CD14 and ultimately TLR4
3 pathways of complement
classical
alternative
lectin
**all converge at the generation of C3b from C3
C3 convertase does what
it is a protease that cleaves C3 –> C3a and C3b
C3b directly binds to pathogens leading to what
opsonization = tag foreign pathogens for elimination by phagocytes
what are antibodies made by?
B cells
* they bind epitopes on antigens
has to do with epitopes
types of antigens
- monovalent: antigen w/ one epitope
- multivalent: antigen w/ multiple of the SAME epitope
- polyvalent: antigen w/ several different epitopes
what are haptens
antigens that bind to antigen receptor but can’t initiate an immune response alone
* can become immunogenic if conjugated to a carrier
conjugated vaccines!
membrane bound antibody on B cell surface
binds antigens of various shapes and sizes
BCR
B cell receptor
what type of cells are effector B cells
plasma cells
The first exposure to an antigen leads to development of a ________
primary immune response
* Results in clonal proliferation and differentiation of activated B and/or T cells into populations of effector and memory B and/or T cells
* Activation of these memory cells by the original antigen results in generation of a secondary immune response
has to do w/ repeated exposure…
why do we vaccinate?
Repeated exposure to the same antigen induces a heightened
state of reactivity higher antibody titers)
MHC Class 1 (major histocompatability complex)
- made by all nucleated cells
- presents antigens to CD8 or cytotoxic T cells
- displays antigens from INTRACELLULAR bacteria
- results in apoptosis of antigen presenting cells
MHC Class II
- made by APCs (antigen presenting cells) only
- presents antigens to CD4 or helper T cells
- displays antigens from EXTRACELLULAR sources
- Leads to activation of macrophages, stimulation of B cells to produce antibodies
APCs use _____ to display antigens
MHC molecules
CD8 T cells AKA…
Cytotoxic T cells
* similar to NK cells but w/ specificity
What do CD8 T cells do
- Deliver toxic granules to infected cells
- Can target all cells with MHC Class I molecules (All nucleated cells)
Helper T cells AKA…
CD4 T cells
* help other cells activate
function of Th1
activates macrophges
function of Th2
- responds to extracellular bacteria and fungi generating
inflammatory response
function of Th17
stimulate neutrophil response to extracellular bacteria and fungi
function of Tfh
stimulate antibody production from B cells;
including class switching and affinity maturation
function of Treg
regulates immune response
cytokines
- intercellular regulatory proteins produced by a variety of cells in response to microbes and other antigens.
- Primarily act as autocrines or paracrines, but
some have endocrine action.
which class of MHC results in the apoptosis of the presenting cell
Class I
