Immune Mechanism To Bacteria, Parasites, Fungi, and Viruses

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
Staphylococcus
Skin and soft tissue
aureus
infections
Lung abscess
________________
Streptococus
Pyogenes (Group A)
Streptococcus
pyogenes
______________
Escherichia coli
Pharyngitis and skin

infections
____________________
____________________
____________________
____________________
Pneumonia
Meningitis
____________________
____________________
septic shock
Vibrio cholerae
Clostridium tetani
Tetanus
Neisseria
meningitides
Meningitis
Corynebacterium
diphtheriae
Diphtheria
MOA
Skin infections:
________________________________________
Systemic Enterotoxin
Induced by cytokine production by ________ causing skin
necrosis, shock, diarrhea
acute inflammation by various __________
___________________
Damages cell membrane
_________________
o induces acute inflammation by ___________________
_______________________
o stimulates cytokine secretion by macrophages
Toxins that act on intestinal epithelium affects __________
and _________ secretion
________________
o ADP ribosylates G protein subunit increased cAMP-
Cl secretion and water loss
Tetanus toxin binds to the _____________ of the NMJ
causing irreversible muscle contraction
________________ causes acute inflammation and
systemic disease
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
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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 microbes
o 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
__________________________
_
__________________________
_
________________
________________________
_
may directly 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 form proteolytic enzyme complexes along the complement pathway
ADAPTIVE IMMUNE RESPONSE
Activation of __________________
Humoral Immunity
Major protective immunity against _____________________
Functions
o _____________________
o _____________________
o _____________________
consist of _______________________
o neutralize and eliminate microbes
Th17 Responses
requires ___________ and _______________
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o Recruitment of which promote local 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 into Septic Shock
o 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
Mycobacteria
_____________________
_____________________
Listeria monocytogenes
Listeriosis
Legionella pneumophila
Legionnaires disease

MOA
Macrophage activation resulting in
o __________________________
o __________________________
Opportunistic
Listeriolysin
o Damages cell membrane
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 ____________
Microbe
Candida albicans
Human Disease
Aspergillus fumigatus
Histoplasma capsulatum
MOA
Acute inflammation
____________________________
Invasion and thrombosis of blood
vessels
_____________________
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
Microbe
Polio
Influenza
Rabies
Herpes simplex
Hepatitis B
Epstein-barr Virus
Human Disease
MOA
Poliomyelitis
Influenza pneumonia
Rabies encephalitis
Skin herpes infection
Viral Hepatitis
Infectious mononucleosis
B cell proliferation
Lymphoma
AIDS
HIV
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 Drift
o 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

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IMMUNE MECHANISM TO BACTERIA, PARASITES, FUNGI, AND VIRUSES

GENERAL FEATURES OF IMMUNE RESPONSE TO MICROBES

Pharyngitis and skin

IMMUNITY TO EXTRACELLULAR BACTERIA