8. Host defenses Flashcards
DEFINE:
- innate defenses
- adaptive defenses
- first barriers (2)
- physical barriers (3)
- are innate and adaptive defenses separate of each other?
INNATE defenses:
- properties of the normal host, non-specific defenses –> target whatever
ADAPTIVE defenses:
- induced/turned on by the infection, specific to the pathogen (based on antigens).
FIRST barriers:
- physical barriers and innate defenses that block pathogens
invasions.
PHYSICAL barriers:
– Skin: thick layer of dead cells.
– Mucous membrane: mucus.
– Junction between cells.
- no! they interact together! not separate at all
INNATE DEFENSES:
1) what are the innate defenses of the airways? (ie lungs)
2) describe innate defenses of skin + mucous membrane (4)
- what are AMPs?
1) mucous membrane! mucus in trachea/lungs trap bacteria + ciliated cells removed mucus/trapped bacteria up the trachea, into the pharynx + stomach –> acid kills bacteria
*same thing in GI tract
a) Shedding of skin cells takes microbes away.
b) Movement of mucus takes microbes away.
c) Antimicrobial substances in any secretion! (ie tears, urine, sweat…): fatty acids, lysozymes (destroy peptidoglycan), antimicrobial peptides (AMPs), antibodies (if the host is immune).
d) Normal microbiome: competes (vs pathogens) for attachment sites and nutrients, secretes bacteriocin (antimicrobial compounds)
AMPs = antimicrobial peptides –> short peptides that inset into lipid membranes = make pores in the bacterial membrane
INNATE DEFENSES
- describe how flushing action of (2) consists of innate defenses (3 ish)
IF a pathogen manages to overcome first line of defenses, it will encounter WHAT? (3) + briefly describe
flushing action of tears and urine!!
- Tears contain lysozymes, AMPs,
and other antimicrobial
substances.
- Tears flush microbes away from
the eyeball; this is facilitated by
the eyelid.
- Urine washes microbes away
from the urethra.
encounter SECOND LINE OF DEFENSES:
COMPLEMENT SYSTEM:
- set of proteins that creates pore in the pathogen membrane
and induces lysis.
PHAGOCYTES:
- cells that take up and digest pathogens.
INFLAMMATION:
- general nonspecific response of the innate system to toxins, pathogens and tissue damage.
- helps complement system and phagocytosis happen
COMPLEMENT system:
- what is it? why are they called complement?
- can be activated by which 2 pathways? explain
- activation results in WHAT
- causes ________ of gram-neg or gram-pos bacteria?
- serum sensitivity tests for what?
- Set of blood proteins (produced by liver –> goes to blood/lymph –> can also go into tissues) –> known as complement because they complement the action of antibodies.
Proteins: C1, C2, C3, C4, C5, C6, C7, C8, C9.
1) classical pathway: antibodies.
2) alternative pathway: microbial cell wall components (polysaccharides, lipopolysaccharide, LPS)
- results in the formation of a membrane attack complex (MAC, made of proteins C5b6789) –> 5 proteins are activated + polymerize C9 on cell membrane –> makes pore/really big hole –> bye bye cell
*highly regulated bc you don’t want that to happen to your own cells - causes LYSIS of some Gram-negatives (bc have outer-membrane) + no effect on Gram-positives (peptidoglycan is too thick that proteins can’t diffuse to membrane)
- Serum sensitivity: test sensitivity to complement by exposing pathogens to serum (blood without RBC).
CELLS OF THE IMMUNE SYSTEM
- all cells originate from which cell produced by what?
- what are the 3 types of white blood cells + sub (+ explain/describe)
- from multipotent hematopoietic stem cell (hemocytoblast) –> from bone marrow
1) MONOCYTES:
- circulate in the blood stream –> patrol: when they see infection, exit bloodstream and goes into tissues
- attracted to inflamed tissues,
DIFFERENTIATE into macrophages (can move around) in tissues, phagocytic
- Fixed macrophages in
tissues.
2) GRANULOCYTES:
- their cytoplasm contains granules
- ie: Eosinophils, basophils, neutrophils, mast cells
- Neutrophils are phagocytic, also called polymorphonuclear leucocytes (PMNs)
3) LYMPHOCYTES:
- B cells: produce antibodies –> plasma cell = activated B-cell
- T cells: T helper cells (regulators), cytotoxic T cells. (kills infected cells)
PHAGOCYTOSIS
- carried primarily by which 2 cells? main difference btw the 2?
- 4 steps ish
- by neutrophils (soldiers) and macrophages (lieutenants: also activate immune system)
- Attachment of the organism/bacteria to the
membrane of the phagocyte. - Ingestion: the bacteria/pathogen become enclosed in a phagosome.
- A) Granules (endosomes,
lysosomes) containing hydrolytic
enzymes (ie phospholipase, hyaluronidase…) fuse with the phagosome, formation of the phagolysosomes.
B) Oxidative burst: macrophage produces reactive oxygen species (ROS) = toxic
*phagolysosome releases lysozyme proteins, production of peroxide, superoxide, hypohlorous acid (bleach), nitric oxide –> kill bacteria - Killing and digestion of the
microorganism –> macrophage can us bacteria as source of nutrient and/or release of bacterial fragments
INFLAMMATION
- resident ________ sens presence of ________ (ie WHAT) and produce ___A_____
- _____A_____ –> 2 functions
- resident macrophages sense presence of endotoxins (ie LPS) and produce cytokine IL-1 (interleukin-1 = pro-inflammatory cytokine
1) Increase movement of fluid and immune cells to the infection sites
*opening of blood vessels ish
*mvt from blood to infection site –> brings complement protein to infection sites
*macrophages and neutrophils follow concentration gradient/chemotaxis
2) activate cells of the immune system (e.g. increase phagocytosis)
*hopefully neutrophils + macrophages resolve infection
INFLAMMATION
- what are characteristic signs? (4) + due to WHAT?
- functions? (2)
- redness
- heat
*Redness and heat are due to
vasodilatation – enlargement of the blood vessels. - swelling: due to the passage of
fluid (plasma contains antimicrobial proteins) from blood vessels to the tissues – increased vascular permeability (vasodilatation). - pain
1) allows the recruitment of immune cells to the site of infection (vascular permeability)
2) allows an increase concentration of molecules (complement subunits and antibodies)
FEVER:
- how is fever triggered?
- why does the body want to trigger fever?
- max temp?
- Il-1 acts on the thermoregulatory center of the brain, which in turn causes the body temperature to increase = fever
- Temp higher than 37°C (37-41°C ish) reduce the growth of some pathogens (ie bc some die at 39°C) + also help fight infection
- Death if temperature reaches 44°C –> bc some of your organs don’t function anymore
name the 4 innate defenses (excluding primary physical barriers)
- Complement –> MAC complex
- Antimicrobial proteins (lysozymes, AMPs, etc.)
- Phagocytes (neutrophils, macrophages).
- Inflammation (and fever) –> only fever if widespread infection
ADAPTIVE DEFENSES:
- when are the adaptive defenses being primed vs called upon?
- rely on WHAT
- what are the cells of the adaptive immune system?
- During infection, the adaptive defenses are being primed. If the infection is prolonged (and innate defenses are not able to control infection), adaptive immunity will be called upon to help in the fight against the invading microorganisms.
- Adaptive defenses rely on the detection and response to FOREIGN ANTIGENS (ie stuff from outside you: toxins, proteins), molecules of the microorganisms that can be recognized by the immune system.
- B cells, T cells and antigen presenting cells (APCs: macrophages, dendritic cells; important for activation of the adaptive defenses).
APCs sample the environment + show T-cell what is good/bad –> T-cell will be activated if recognize bad stuff
IMMUNE CELLS:
explain:
- specificity (4 infos ish)
- memory
- tolerance
SPECIFICITY
- immune cells recognize and react with individual molecules (antigens) via direct molecular interaction
- specific response to a unique/specific antigen!
- each cell has a unique receptor: only binds to 1 specific antigen
- at population level, T cells and B cells recognize billions of antigens
*antigen specificity is randomly generated during development of T and B cells
MEMORY
- immune response to a specific antigen is faster and stronger upon subsequent exposure bc initial antigen exposure induced growth and division of antigen-reactive cells resulting in multiple copies of antigen-reactive cells (memory cells!)
- ie after exposure: next time you encounter same antigen, instead of having 1 t-cell responsive, you’ll have 10, 100 or 1000 = stronger response!
TOLERANCE
- immune cells are not able to react with self antigen!
- self-reactive cells (ie cells that recognize your own antigens) are destroyed during development of immune response
what happens when a T cell or B cell is activated by the antigen they recognize?
- If the T cell is specific for this antigen, T-cell will become activated and produce interleukin 2 (Il-2). This induces multiplication and differentiation into effector T cells and memory T cells.
- they grow and produce copies of themselves
- a cell that is specific to antigen X will produce more cells specific for antigen X
- some cells will differentiate into memory cells –> which role is to remember the antigen X (and not participate in controlling the invading pathogens)
- what are the 2 types of T-cells?
- how are T-cells specific?
- what presents antigens to T cells?
- what are the parts of the T-cell?
1) T helper cells (TH): activate B cells
and macrophages. –> ie big chief
2) Cytotoxic T cells (TC): kill host cells that display foreign antigen on their surfaces –> cytotoxic for cells: kills cells infected by virus/bacteria
*both can secrete IL-2 and multiply!
- each T cell is specific for one antigen. They use the T cell receptor to bind to the antigen. Each T cell have a unique T cell receptor that recognize a unique antigen.
- Antigen presenting cells (APCs) present antigen to T cells.
- Variable region = antigen-binding site –> different in each cell!
- constant region (has extracellular, transmembrane and intracellular domain) –> all cells make the same thing + has disulfide bond
how do cells present antigens?
- what are the 2 classes + describe:
*expressed by which cells?
*present antigens from what?
*recognized by which cells?
- cells use the major histocompatibility complex (MHC)! –> antigen-presenting molecular complex.
1) MHC I: - expressed by all nucleated cells (ie not RBC)
- present antigen that comes from inside the cell (important during infection by viruses/intracellular pathogens)
*ie virus inside cell - Recognized by TC (cytotoxic T-cells)
2) MHC II:
- expressed by APCs (antigen presenting cells) and B cells
- present antigens processed in the phagolysosomes (from microorganisms that were phagocytosed)
*antigens that come from outside! ie after phagocytosis, from macrophages, dendritic B-cells…
- Recognized by TH (T helper cells)
ie cell infected by pathogen –> presents antigen from that pathogen to a cytotoxic T-cell
- antigen presented through which MHC?
- what double checks if it’s the right MHC?
- what does the cytotoxic T-cell do after it binds? (3 ish)
- this whole process: very useful against what?
- MHC1!
- CD8
*Cells that display foreign antigens on MHC 1 are killed by TC that are specific for this antigen
activated TC:
- produces IL2
- releases perforins and granzymes that kill the cell.
- Some of the activated TC will be memory cells.
- Very useful against infection by viruses/intracellular pathogens.
*highly regulated!
HELPER T-Cells
- recognize antigen on which MHC?
- what checks if right MHC?
- once activated, what does helper T-cell do? (4 ish)
- if there’s a match between ie a dendritic cell/macrophage and a helper T-cell –> what does T cell say to the macrophage?
- activation of macrophage is important for what?
- MHC 2!
- CD4
Once activated, TH cell - produces IL-2
- can activate macrophages (by releasing TNF-α) that are presenting antigens for which the T cell is specific. (TH1 cell does that)
- activate B-cells (TH2 cell does that)
- proliferation and differentiation into memory helper T-cell
- T cell will activate macrophages + tell them to produce TNFa + have increased phagocytic activity and produce much higher levels of hydrolytic enzymes + ROS. Often referred to as “angry killer cells” –> very good at killing bacterial cells
- Activation of macrophage is important against bacterial pathogens (especially against intracellular pathogens of macrophages)
B cells = WHAT
- types of WHAT (4)
- describe structure of B-cells
*what shape?
antibodies!
- IgA, IgG, IgM, IgE
- Fab region = variable region = antigen binding sites –> highly variable –> each B cells produce a unique Fab that is specific for a unique antigen
- Fc region = constant region –> binds to receptor on macrophages and activates complement (classical pathway)
*heavy chain! (purple) (both Fc and Fab region) + light chain (green) (only Fab region)
*like a “Y”
describe activation of B-cells: 4 steps!
1) B cell displays its antibody (B-cell receptor) on its surface. Acts as a receptor to pick up the foreign antigen it recognizes.
2) recognizes antigen –> needs to put that antigen on an MHC so it can activate a T-cell –> This antigen will be processed and displayed on surface of B cell by MHC II.
*a macrophage/APC will have pre-activated the T-cell
3) A pre-activated T cell specific for the antigen recognizes this complex (MHC II-antigen) (CD4 makes sure its MHC2) and activates the B cell
4) T-cell produces IL-4 –> triggers replication and differentiation of B cell: B cell multiplies (clonal expension) and differentiates into PLASMA cells (produce the antibody –> free floating!) and MEMORY cells (waiting for the next exposure to the antigen).
what are the functions of antibodies?
*antibodies: against which substances? ish
- Antibodies function as opsonins (ie antibody binds to bacterium: acts as a flag to ell macrophage to come and kill it), which increase phagocytosis efficiency.
- Bind to toxins, which prevents binding of toxin to host cells –> ie binds to the cell-binding part of a toxin
- Bind to adhesins or virus “spike” protein, which prevents adhesion of microorganism to host cells.
*basically can bind to fimbriae, flagella –> any tool used by virus pathogen –> once bound, decrease virulence factor of virus yay!
- against proteins! not sugar or lipids (so doesn’t work against LPS)
what is the role of memory cells?
Memory cells ensure that the immune response, following a second exposure to the same antigen, is faster and stronger
*graph!
- so strong that you don’t suffer any symptoms at the second exposure
what is acquired immunity?
a) ________ immunity: WHAT + 2 types
b) ________ immunity: what + 2 types + give examples!
a) ACTIVE immunity: involves the production of memory cells in response to antigenic stimulus.
- Natural: following infection
- Artificial: vaccination (live, attenuated, dead agents or subunit: adhesins, capsular polysaccharide, toxoids)
b) PASSIVE immunity: involves the acquisition of preformed antibodies
- No exposure to the antigens.
- No long term memory
- Natural: placental transfer or colostrum (1st milk –> basically just preformed antibodies –> baby gets antibodies from mother)
- Artificial: serum from an immune animal
ie: use plasma from someone who got COVID –> transfer it to ppl at risk (or Trump lol)
Vaccines against toxins:
- which toxins are highly antigenic? vaccines work against them?
- vs which type of toxins do vaccines not work against?
EXOTOXINS: are highly antigenic: stimulates the host defense systems to produce antibodies that can neutralize the toxin.
VACCINES against exotoxins:
- A toxin is toxic, it cannot be used as it is –> produced in lab: then
- Toxins are first inactivated by heat or formaldehyde (so they lose function)–> forms toxoids
- Toxoids are no longer toxic, but still antigenic (induce antibody response).
– Ex.: vaccines against the diphteria toxin (DTaP)
- ENDOTOXINS cannot be inactivated by heat or formaldehyde and cannot be converted to a toxoid: no vaccine against endotoxins.
ie no antibody against LPS
NATURAL IMMUNITY:
- what?
- examples
- can be explained by what?
Natural immunity (species resistance): humans are naturally resistant to many infectious diseases of lower animals and vice versa:
ie:A ctinobacillus pleuropneumoniae causes pleuropneumonia in pigs but does not cause disease in humans.
- Salmonella typhi causes typhoid only in humans (not in pigs)
- Natural immunity may be explained in part by the incompatibility of the virulence factor with the genetics of a species. Ex: absence of the appropriate receptors in the animal for the adhesins expressed by the pathogen (same rationale for toxins and other virulence factors).
INTEGRATION:
you cut your hand (part 1)
1. which primary barriers are breached if bacteria manage to get into your hand? (4)
2. bacteria 1 (B1, normal gram-neg bacteria) gets in: what is the body’s first reaction?
3. how does body kill B1? (3 ish)
- dead skin cells, lysozymes, AMPs and bacteriocins are secreted, tight junction btw cells
- monocyte from blood stream gets into tissue –> becomes macrophage and phagocytoses B1
3.
a) phagosome merges with lysozyme to form phagolysozome: hydrolytic enzymes kill bacteria
b) reactive oxygen species are produced –> oxidative burst
c) macrophage produces interleukin-1 = alarm!
- produces inflammation: vasodilation of blood vessels
- increase fluid in tissues –> brings complement! produces MAC complex (to which gram-neg bacteria are sensitive vs gram-neg with capsule and gram-pos are resistant)
- increase cells to tissue = help join the fight!
INTEGRATION:
you cut your hand (part 2)
4) bacteria 2 (B2, has a capsule): is it killed the same way as B1 (normal gram-neg)
5) explain the steps by which B2 will be killed (6 steps)
6) what are the functions of antibodies?
4) no! not killed by innate system bc capsule can resist phagocytosis: B2 can hide in macrophage + capsule makes it more resistant to hydrolytic enzymes and ROS
5)
a) macrophage takes in B2 –> present piece of B2/antigen on MHC2 to set up adaptive immune system!
b) Helper T-cell recognizes the antigen through its TCR –> T-cell is activated and produces IL-2
c) IL-2 induces replication of helper T-cell + differentiation into memory TH
d) TH also produces TNF-a –> turns macrophage into an angry killer cell –> able to kill bacteria even with capsule
e) ALSO, B-cell can phagocytose B2 –> presents an antigen on MHC2 –> TH recognizes it: oh yeah macrophage showed it to me and had trouble dealing with it –> now activates B-cell by producing IL-4!
f) IL-4 activates B-cell –> B-cell now produces memory and plasma cells (produce antibodies!)
6)
- acts as opsonins (tags cells for destruction)
- neutralize toxins (inhibit Hyaluronidase, etc.)
- block flagella/virulence factors
- neutralize adhesins
INTEGRATION:
you cut your hand (part 3)
7) bacteria 3 has T3SS: what can it do?
8) how is B3 killed?
7) it can take control of macrophage! so B3 grows inside macrophage (macrophage doesn’t mature into phagolysosome)
8)
a) B3 grow inside macrophage –> macrophage now has an intracellular infection –> antigen is presented on both MHC1 and MHC2
b) MHC2 will trigger same response as B2 (helper T-cell + B-cell –> secretion of TNF-a –> but not enough to kill T3SS bacteria)
c) MHC1 is detected by cytotoxic T-cell (TC) –> interleukin-2 is produced –> induces replication + differentiation into memory TC
d) TC will produce perforins and granzymes –> kill the cell.
*now any macrophage that gets infected by B3 and present MHC1 will be detected and killed as well = limit infection
