Immune Mechanism to Bacteria, Parasites, Fungi, And Viruses

8/18/2019 Immune Mechanism to Bacteria, Parasites, Fungi, And Viruses

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IMMUNE MECHANISM TO BACTERIA, PARASITES, FUNGI, AND VIRUSES

GENERAL FEATURES OF IMMUNE RESPONSE TO MICROBES

• Mediated by effector mechanisms of innate and adaptive immunity

o Innate Immunity _______________________________

o Adaptive Immunity _____________________________

•

_________________________________________affect microbe survival and pathogenicity• Many infections may be caused by host response to the microbe and its products rather than the microbe itself

INFECTION

• Happens when there is ________________________________________________

Pathogenic Extracellular Bacteria

Microbe Disease MOA

Staphylococcus

aureus

• Skin and soft tissue

infections

• Lung abscess

• ________________

Skin infections:

________________________________________

Systemic Enterotoxin

Induced by cytokine production by ________ causing skin

necrosis, shock, diarrhea

Streptococus

Pyogenes (Group A)

• Pharyngitis and skin

infections

• ____________________

• ____________________

• ____________________

• ____________________

• acute inflammation by various __________

___________________

• Damages cell membrane

Streptococcus

pyogenes ______________

• Pneumonia

•

Meningitis

• _________________

o induces acute inflammation by ___________________

Escherichia coli • ____________________

• ____________________

• septic shock

• _______________________

o stimulates cytokine secretion by macrophages

• Toxins that act on intestinal epithelium affects __________

and _________ secretion

Vibrio cholerae • • ________________

o ADP ribosylates G protein subunit increased cAMP-

Cl secretion and water loss

Clostridium tetani • Tetanus • Tetanus toxin binds to the _____________ of the NMJ

causing irreversible muscle contraction

Neisseria

meningitides

• Meningitis • ________________ causes acute inflammation and

systemic disease

Corynebacterium

diphtheriae

• Diphtheria • Diphtheria toxin

o ADP ribosylates _______________ and inhibits protein

synthesis

IMMUNITY TO EXTRACELLULAR BACTERIA

• Mechanisms of disease

ASMPH Batch 2020 Removal Ops: HEMATOLOGY and IMMUNOLOGY

Prepared by: Regrine B. Lagarteja, BSMT, RMT, MLS(ASCPi)CM 1 / 13


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o ____________________ - tissue destruction

o ____________________ - production of endotoxin and enterotoxin via cell wall component of bacteria

Diphtheria toxin-changes in RNA of cell

Cholera toxin- interact with potassium channels causing diarrhea

Tetanus toxin- acts on neurotransmitters

INNATE IMMUNE RESPONSE

• ________________________________

• ________________________________

• ________________________________

Complement activation

Gram (+) Gram (-) Mannose on surface

Membrane

Component

Pathway

• C3a and C5a

o ________________• C3b

o Common activation pathway of Classic, Alternative, and Lectin Pathway

o Initiate the ________ steps of complement activation

o Promotes:

______________

______________

• C9




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o Membrane attack complex

o Causes ______________________

Phagocytosis

• Microbes may be infested by different membrane receptor of phagocytes

o

Some directly bind to microbeso Others binds to opsonized microbes

o Mac-1 Integrin- binds to microbes ____________________________________

o Microbes are internalized into PHAGOSOMES which fuse with lysosomes, which kills microbes by

_______________

_______________

_______________

• Mannose and Scavenger Receptors

• Mannose Receptor

o Recognize ____________________ on the surface of microbes that facilitate their phagocytosis

_______________________

_______________________

_______________________ (PAMPS- Pathogen Associated Molecular Pattern)

• Scavenger Receptors

o Expressed on ______________ and mediate phagocytosis of microorganisms

Characteristic: Mediate uptake of Oxidized Lipoproteins

o _________________

recognition of bacteria opsonized with antibody

expressed by leukocytes

binds to the ___________ region of antibodies, promoting phagocytosis of Ig coated particles

Fc-gamma

− Most important Fc receptor for phagocytosis of opsonized particles

o ____________________

Type 1 Type 3 Type 4

Used by ________________ ________________




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________________

Function __________________________

_

__________________________

_

________________________

_

maydirectly recognize

bacteria for phagocytosis by

binding to some unknown

microbial molecules

o ________________

plasma proteins that are normally inactive but become activated once attached to microbes or Ab

Cleavage products formproteolytic enzyme complexes along the complement pathway

ADAPTIVE IMMUNE RESPONSE

• Activation of __________________

Humoral Immunity

• Major protective immunity against _____________________

• Functionso _____________________

o _____________________

o _____________________

• consist of _______________________

o neutralize and eliminate microbes

Th17 Responses

• requires ___________ and _______________




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o Recruitment of which promotelocal inflammation

• Genetic defects in Th17 will develop multiple skin abscesses

Injurious Effects of Immune response

• Inflammation

o

Usually self-limited and controlled; if unregulated, may develop intoSeptic Shocko Neutrophils, macrophages, ROS, Lysosomal enzyme

• Septic Shock

o Pathologic consequence

o Primary Cytokines: _____________, ___________, ___________

Major cytokine associated with septic shock: _____________

IL-1 causes septic shock if combined with IL-6 and TNF

• You can produce antibodies against your self tissues

o Happens in _______________ infection to clear up the infection

• Production of disease-producing bodies

o _______________________

post-streptococcal GNE

Rheumatic fever

• Variation of Surface antigen

o Pili

Gonococci

E. coli

o Changing of ____________ to evade recognition by the immune system

IMMUNITY TO INTRACELLULAR BACTERIA

• Intracellular bacteria

o Breach in the mucosa of skin• Introduced by vectors

• Survive and replicate within phagocytes

• Inaccessible to circulating Ab

• Elimination requires _________________________

Microbe Human Disease MOA

Mycobacteria • _____________________

• _____________________

• Macrophage activation resulting in

o __________________________

o __________________________

• Opportunistic

Listeria monocytogenes • Listeriosis • Listeriolysin

o Damages cell membrane

Legionella pneumophila • Legionnaire’s disease Cytotosin lyses cells causing lung

injury and inflammation




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• The innate immune response of phagocytes and NK cells, interactions among which are mediated by cytokines (lL-12

and IFNy). The typical adaptive immune response is cell- mediated immunity, in which T cells activate phagocytes to

eliminate the microbes.

• Innate Immunity

o Control bacterial growth

• Adaptive Immunity

o Elimination

INNATE IMMUNE RESPONSE

• ___________

• ___________

o major protective innate immune response

NK Cell

• Activation by

o ___________________________________________

o ___________________________________________

o ___________________________________________

• Produces _________ that activates macrophages

ADAPTIVE IMMUNE RESPONSE• T-mediated recruitment and activation of phagocytes

• ______________

o activates phagocytes through CD40 ligand

• express CD40-L and IFN-y production

Reaction of CD4+ T-Cells




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1.Effector cells are recruited from the circulation.

2.T-cells use CD40-L and cytokines to activate phagocytes and cytokines to recruit more leukocytes

3.In adaptive immunity, the intracellular bacteria is usually cell mediated where macrophage activation is due to

intracellular infection

4.CD8 T-cells execute cellular killing

Cooperation of CD4 and CD8 T cells in defense against intracellular microbes




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1.Microbes phagocytosed by macrophages may survive and escape into the cytoplasm

2.CD 4+ T-cells responds to Class II-MHC associated peptide antigens from the intravesicular bacteria

o Produce IFN-y which activates macrophages to destroy microbes in phagosomes

o CD8+ T-cells respond to Class I- associated peptides to kill the infected cells

3.Macrophage activation may produce tissue injury

Bacteria persists and evolved to resist killing chronic antigen stimulation ___________

EVASION MECHANISMS

• How bacteria evade intracellular killing

o _______________________

o _______________________

o _______________________

o _______________________ (PAMPS, PRR- Pattern Recognition Receptor)

• Major Mechanisms

Immune System Element Thwarted Bacterial Mechanism

Host PRR Production of modified PAMPs to inhibit normal signaling or

trigger abnormal signaling that inhibit APCs

Phagosomal destruction ____________________________________________

____________________________________________

____________________________________________

____________________________________________

Hyperactivated macrophages Gene expression blockade

Antibodies Spread to a new host via pseudopod invasion

T-cells ____________________________________________

____________________________________________

IMMUNITY TO FUNGI• ______________

o infection to fungi

o may be local or generalized

o usually ____________


Candida albicans Acute inflammation

____________________________

Aspergillus fumigatus Invasion and thrombosis of blood

vessels

Histoplasma capsulatum _____________________

INNATE IMMUNITY TO FUNGI

• Principal mediator: ______________ and _____________

o Liberation of fungicidal substances

o Phagocytosis

ADAPTIVE IMMUNITY TO FUNGI

• _____________________




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INTRACELLULAR FUNGI

• CD4 and CD8

o __________________________

o __________________________

EXTRACELLULAR FUNGI

• TH17 response

• Driven by ____________________

IMMUNITY TO VIRUSES


Polio Poliomyelitis

Influenza Influenza pneumonia

Rabies Rabies encephalitis

Herpes simplex Skin herpes infection

Hepatitis B Viral Hepatitis

Epstein-barr Virus Infectious mononucleosis

B cell proliferation

Lymphoma

HIV AIDS

Obligate intracellular parasite

Use components of nucleic acid and protein synthesis machinery of the host to replicate and spread

Can cause latent infections

INNATE IMMUNITY TO VIRUSES

• Principal mechanisms

o _______________- create an antiviral state

o _______________

• Main cytokine interfering with viruses: __________________, followed by peak of ____________

ADAPTIVE IMMUNITY TO VIRUSES




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EVASION MECHANISMS

• Blocking of transporter or receptor

• Inhibition of signal

Latency

• Persistence in host cell in a defective form

• __________, ____________, ___________

Antigenic variation

• most important evasion mechanism

• Antigenic Drifto small changes in the genes that happen continually over time as the virus replicates

o These small genetic changes usually produce viruses that are pretty closely related to one another

o Reason for annual release of influenza vaccine

• Antigenic Shift

o Enables a strain to jump from one species to another

o Production of new strain, usually characterized by change in Hemagglutinin and Neuraminidase in influenza virus




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Interfere with Antigen Presentation

• Usually MHC Class I

IMMUNITY TO PARASITES

• Parasites have ____________ and __________ stages

INNATE IMMUNITY TO PARASITES

• _____________

o Principal mechanism

o Secretion of microbidical substances

• Complement pathway activated: _________________

• Protozoa: ___________________

ADAPTIVE IMMUNITY TO PARASITES

• Principal mechanism: __________________

• Th1 derived cytokines activate _________________

• Th2 derived cytokines stimulate ________________ and _____________




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• Helminths

o Become coated with antibodies

o Recognized by __________________

Degranulate

EVASION MECHANISM

Antigenic Variation

• Two forms

o Stage Specific

Mature stages produces antigens different from infective stage

Continuous variation of major surface antigens

o Continuous variation

Clinical correlations

• Amoebiasis

o Amoeba has two life stages: cyst and trophozoite

One causes the disease; one is a harmless carrier

Both have very different compositions

Transitions between these life stages occurs inside the host

this is why it is a challenge for the immune system




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o Can be ingested from contaminated water enter GI tract – go to a series of morphological changes – they become

infective

• Schistosoma

o Farmers eating snails with Schistosoma eggsmatures and travels to the lungs (sometimes the brain and liver)

o One of the ways they can evade immune system – they can develop inside the body


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Immune Mechanism to Bacteria, Parasites, Fungi, And Viruses