PC 2 mod 2.1 lec 1

innate immunity includes

--> physical barriers (skin)

--> ______ removal (urination, mucous membranes, cough)

--> chemical microbicides such as ______

--> biological microbicides such as _____

--> _______ microbiota

- mechanical

- stomach acid

- lysozymes

- commensal/mutual existence

innate immunity includes ______ and ______ system

- macrophages/neutrophils

- complement system

macrophages/neutrophils are part of INNATE/ADAPTIVE immunity and use _____ to recognize _____ of microbes to phagocytose and kill bacteria

- innate

- PRRs (pattern recognition receptors)

- PAMPS (pathogen associated molecular patterns)

complement system is part of INNATE/ADAPTIVE immunity and recognizes and forms ______ to lyse bacteria

- innate

- membrane pores

______ and ______ recognize, phagocytose, and process bacteria through endocytic pathway to generate antigens to present to CD4+ helps cells

- dendritic cells (MHC-II)

- antigen presenting cells (APCs)

dendritic cells, which are ____ and APCs process bacteria through _____ pathway to present antigens to ______

- specialized macrophages

- endocytic pathway

- present to CD4+ helper T cells

CD4+ helper T cells interact with _____ to form a linked recognition of the same antigen, resulting in conversion of these cells to ______ and _______

- B-cells

- antibody producing plasma cells

- B memory cells

Ig___ is most abundant, long half life, crosses placenta and provides immunity to fetus

IgG

Ig___ is for mucosal integrity

IgA

Ig___ is first antibody produced (BCR)

--> ______ on naive B cell surface

--> ______ in blood as free molecule

- IgM

- monomer

- pentamer

Ig___ is a BCR on more mature B cell

IgD

Ig___ is for hypersensitivity

IgE

antibodies function to ______ pathogens, tag bacteria for ______, activate ______ and prevent ______ of bacteria

- neutralize

- phagocytosis

- complement

- attachment

antibodies generated can

--> inactivate ______ factors

--> inactivate ______

--> increase _____ and removal

--> provide antigen-specific ____ for mucosal defense

- virulence factors

- toxins

- phagocytosis

- IgA

acute (LOCAL) inflammation results in...

--> local ______ response to limit injury/infection

--> _____ infiltration to kill bacteria

- vasculature

- neutrophil

SYSTEMIC inflammatory response results in...

--> _______ production to tag or kill bacteria such as ____

--> release of _____ to further activate immune cells

--> stimulation of ____ production

--> ____ generation to reduce bacterial activity

--> increased serum _____ to bind _____

--> increased _____ storage

- acute phase protein --> C reactive protein

- cytokines

- WBC

- fever

- transferrin --> iron

- iron

extracellular bacteria is inside _____ but outside ______

body

host cell

_______ can have rapid growth if uncontrolled and toxins can cause local tissue damage, inflammation and sepsis

extracellular bacteria

INNATE/ADAPTIVe immunity plays a big role in prevention of extracellular bacteria both at the surface and inside the body

innate immunity

intact skin is relatively impermeable do to thick layer of ______ and glands secreting _____, toxic lipids called ______, and ______

- keratin

- lysozymes

- sebum

- hydrogen ions

with few exceptions, bacterial infection is caused only when skin is...

damaged

mucosal epithelium IS/IS NOT keratinized and is moist and rich in nutrients which favors _____

- is not

- bacteria

mucosal defense works MECHANICALLY to prevent bacterial proliferation by mechanical ______ and lack of available ______

- cleaning

- free iron

______ defense prevents bacterial proliferation by mechanical cleaning and lack of available free iron

mucosal mechanical defense

cigarette smoking disturbed _____ defense due to reduced mucociliary movement in lower respiratory

mucosal mechanical

_______, ______, and ______ reduce ______ movement in elderly so compromise immune defense and promote opportunistic infections

- cigarette smoke

- bacterial infection

- viral infection

- mucocilliary defense

mucosal defense has both ____ and _____ mechanism

- mechanical

- bactericidal

mucosal defense has bactericidal agents in mucosal fluid, such as... (4)

- lactoferrin

- defensin

- lysozyme

- IgA

_____ is part of mucosal bactericidal defense that binds free iron

lactoferrin

lactoferrin is found in ______ defense and works by binding _____

- mucosal bactericidal

- free iron

______ is part of mucosal bactericidal defense that forms pores in bacterial membrane to allow efflux of iron and nutrients

defensin

______ is part of mucosal bactericidal defense and breaks down peptidoglycan

lysoszyme

____ is part of mucosal bactericidal defense and works by interfering with bacterial adhesion, inactivating toxins, promoting bacterial aggregation for removal by mucus

IgA

IgA is part of _____ defense and works by interfering with ______, inactivating _____, promoting ______ for removal by mucus

- mucosal bactericidal

- adhesion

- toxins

- bacterial aggregation

mucosal bacteria can invade deeper into tissues through mechanisms like producing _______ to destroy host tissue

enzymes

H. pylori produces _____ to generate _____ to neutralize stomach acid

- urease

- ammonia

inflammation caused by initial bacterial infection could lead to _____ allowing additional entry

tissue damage

innate immunity parts in BLOODSTREAM is done by _______ and ______

- complement system (MAC water lyse)

- neutrophils

innate immunity parts in TISSUE is done by phagocytosis through _______ and release of _______ by these

- macrophages/mast cells

- inflammatory factors

bacteria can evade by using _______ to establish strong adhesion to surface of host epithelial and compete with host cells for _______

- surface molecular ligands

- iron

N. meningitis uses complex surface transport system to steal ______ from _____

- iron

- host transferrin

E.coli secretes high affinity ______ to steal _____ in local environment

- high affinity iron chelators

- soluble iron

bacteria can use ______ to reduce immune cell recognition

capsule

bacteria capsule can use _____ to make components more eukaryotic and it cause use a MASK to cover up ______

- mimicry

- surface antigenic epitope

4 parts of bacteria capsule

- mimicry

- mask

- inaccessibility

- phase variation

phase variation of bacteria cycle stages...

--> high (on): when needed for _______

--> low (off): when needed to ______ to host cell

--> high (on): after gaining access to ______ with abundance of complements and phagocytes

- evading host immune response

- adhere

- deeper tissue

bacteria have means to reduce tagging and phagocytosis, and this is done by 3 ways...

--> proteins in outer layer to inhibit ______

--> proteins in outer layer that prevent ______

--> bacterial ______

- complement deposition

- antibody binding

- IgA protease

2 bacterial proteins that inhibit complement deposition

PsPA/C (pneumococcal suface protein)

C3 binding protein

example of protein in outer layer that prevents antibody binding is ______ of ______ that prevents binding to ___ region of Ig and prevent opsonization and phagocytosis

- protein A

- staph aureus

- Fc

PspA/C and C3 are proteins to inhibit...

complement deposition

protein A of staph aureus is a protein to...

prevent antibody binding

bacterial IgA proteins works by removing _____ of bound antibody to cripple opsonization and cover up its ______

- Fc fragment

- antigen

bacteria can use _____ to deplete complement proteins

pneumolysin

bacteria can use pneumolysin to deplete _____

complement proteins

bacteria can use C5a peptidase to inactivate _____ and reduce _____

- C5a

- neutrophil infiltration

bacteria can produce ______ to inactivate neutrophil free radical

antioxidants

bacteria can use _____ to convert neutrophil H2O2 to water

catalase

bacteria can use catalase to convert neutrophil ____ to ____

H2O2

water

intracellular bacteria invades _______ and survives and replicates insides, causing spread to other cells/tissue and causes ______ infection

- host cell

- systemic

target host cells include...

first encounter BARRIER cells: (1)

first encounter IMMUNE cells: (2)

BARRIER/LINING cells: (1)

other: (3)

- epithelial

- macrophages and neutrophils

- endothelial cells

- hepatocytes, erythrocytes, schwann cells

immune cells (macrophages and neutrophils) are designed to recognize extracellular _____ via PRR as well as ____ or _____ tagged bacteria via _____ or ______ receptors, causing phagocytosis

- PAMPs

- Ig

- complement

- Fc receptor

- complement-receptors

intracellular bacteria are able to remain and replicate inside a host cell, staying in _____ to avoid being killed

vacuoles

endocytic pathway (normal)

--> microbe is phagocytosed by immune cell and becomes ______

--> this fuses with _______

--> forms _____ which chops up bacteria

--> presented to _____ which produces antibodies

- phagosome

- lysosome

- phagolysosome

- MHCII

bacteria (mycobacterium tb) can evade endocytic pathway by prevention of ______ formation by impairing _______ which is requires for this process

- phagolysosome

- lysosomal acidification

bacteria (anaplasma phagocytophylum) can evade endocytic pathway by prevention of _____ killing in neutrophil due to prevention of production of ______ and _____

- free radical mediated

- NADPH oxidase cytosolic

- membrane subunits

evasion of endocytic pathway can be done by escape from _____ and entering _____

phagosome

cytosol

evasion of endocytic pathway by escape from phagosome and entering cytosol is done by _____, which ruptures the ______

--> advantage is it can rapidly replicate due to _____ and it facilitates ______

- listeriolysin o (LLO)

- phagosome

- ingredients in cytosol

- repeated infection

listeriolysin o (LLO) evades ______ by escape from ______

- endocytic pathway

- phagosome --> cytosol

disadvantage of LLO is bacterial proteins in cytosol of host cell can be processed and presented to ______, resulting in recognition and killing by ______

- MHC1

- CD8+

success of controlling LLO depends on rate of ______ and abundance of ______

- bacterial proliferation

- CD8+

non-immune cells CAN/CANNOT recognize and phagocytose bacteria, so bacteria enter these by inducing their own ________ and this causes evasion

- cannot

- phagocytosis

steps of salmonella enterica crossing GI epithelial cell (NON IMMUNE)...

--> bacterium encounters GI epithelial cell

--> assembles multiprotein needle complex called ______ , crossing bacteria inner and outer membrane and epithelial plasma membrane to form channel between ______ and ______

--> injects ______ into epithelial cell to induce ______ that results in engulfment of bacterium

--> remains in original ______ formed by host cell

- T3SS

- bacteria cytosol and epithelial cytosol

- effector protein

- cytoskeleton rearrangement

- vacuole

immune response against intracellular bacteria is MORE/LESS effect than to extracellular, and is primarily by ______

- less

- cell mediated immunity

neutrophils and macrophages are effective in intracellular infection that cause...

death of host cells

infections of epithelial cells by L. monocytogenes causes that ______ of infected epithelial cells and the release of _____ to recruit _______ and also _______

--> if phagocytosed bacteria is not killed, ______ form to contain it

- apoptosis

- chemoattractants

- neutrophils

- macrophages

- granulomas

______ immune response plays major role in defense against intracellular bacteria

t cells

when intracellular bacteria replicates inside a host cells, some of its components will be processed as ______ and presented to ____ which will be killed by _____

- antigens

- MHC-1

- CD8

formation of _____ serve to contain intracellular bacteria if they cannot be eliminated completely, and the structure of this is a core of pathogen containing ______ and scattered _____ surrounded by a layer _______ which causes core to eventually die

- granulomas

- pathogen-containing macrophages

- CD4+

- CD8+

2 types of bacteria that are killed by CD4+ and granuloma

- L. monocytogenes

- M. TB

steps of granuloma formation

--> macrophages fail to kill phagocytosed bacteria and release _____

--> this activated ______ to release _______ that hyperactivate macrophages to release _____ and _____ to enhance killing

--> ______ fuse to form core

--> remanent _____ and _____ cells form the shell

- IL-12

- t-helper cells

- IFN-y

- ROS and RNS

- hyperactivated macrophages

- CD4+ and CD8+

antibody has _____ effect against intracellular bacteria

limited

example of antibody against intracellular bacteria

anti-LLO

antibody works against intracellular bacteria by...

--> blocking bacteria and host receptor for entry into______

--> ______ of extracellular bacteria

--> antibodies taking into the ______ together with bacteria act _____

- host cell

- opsonization

- phagosome --> in situ

immunogenicity of LPS from different gram negative bacteria is effected by multiple structural features in _____ and ____

- O antigen

- lipid A

lipid A can vary in...

--> number of _____

--> ______ of acyl chains

--> ______ of acyl chains

- phosphate groups

- length

- number

LPS-induced inflammatory response steps... (pt 1)

--> LPS binds to _____

--> binds to _____ which binds to _____ which is transmembrane through _____

--> this transduces signal to ______

- LPS binding protein

- CD14 --> TLR4 --> MD-2

- transcription factors

LPS-induced inflammatory response steps... (pt 2)

--> causes gene transcription of inflammatory response by release _____ from iNOS and ____ from NADPH oxidase complex to form _____

--> turns on transcription for cytokines, including _______, _____ and _____

--> produces ______ to become mature then secreted products

- NO + O2= PEROXYNITRITE

- TNFa, interleukins, IFNs

- propeptides

mechanical mucosal defense is by ______ and ______

- mechanical cleansing

- lack of free iron

which of the following are sterile?

a. GI

b. lower resp

c. urinary

b. lower resp

c. urinary

innate immunity against intracellular bacteria is by ______ or ________

- neutrophil

- macrophages