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Introduction to Infectious Diseases

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mariam kavtaria

on 28 March 2017

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Transcript of Introduction to Infectious Diseases

Introduction to Infectious Diseases
Mariam Kavtaria
Infectious Agents
1. bacteria
2. Viruses
3. Fungi
4. Parasites
Immune System
Innate/ Natural Immunity
protects without prior exposure to inf. agent
immediate defense
activates adaptive immunity
is non-specific
does not confer long lasting immunity
Adaptive/ acquired Immunity
Highly specific
Develops over time
Has
Memory cells
– stronger, quicker response to previously encountered antigen.
B cells
– produce antibodies
T cells:
Cytotoxic CD8+ T cells
: directly attack and lyse cells that express foreign antigens.
Helper CD4+ T cells
: stimulate B cells and the production of immunoglobulins


2nd line:
Phagocytic Cells - Neutrophils, macrophages, monocytes, NK cells,
Complement

MHC I:
Is expressed on
all nucleated cells
Presents endogenous antigens to CD8 T cells

T lymphocytes are activated by antigens on major histocompatibility complex (MHC)
Reticuloendothelial system
Phagocytic (Kupffer cells) and Ito cells in the liver,
Alveolar macrophages in the lungs,
Macrophages and dendritic cells in the spleen and lymph nodes
Mesangial cells in the kidneys,
Microglia in the brain

clears circulating microorganisms
these cells function much more efficiently when pathogens are
opsonized

by components of the complement system such as C3b and/or by antibodies
Extracellular pathogens, are attacked by the humoral immune system.


Humoral Immune System
antibodies,
the complement cascade,
phagocytic cells.
Antibodies are produced by mature B lymphocytes:
ANTIBODIES:
directly block the invading organism
neutralize secreted toxins and enzymes
facilitate the removal of the antigen by phagocytic cells.
promote the deposition of complement components on the surface of the invader.

IgG predominates in the circulation and persists for many years after exposure;
IgM is the earliest antibody to appear in response to infection;
IgA is important in immunity at mucosal surfaces,
IgE is important in allergic and parasitic diseases.

circulate in body fluids
secreted on mucosal surfaces
specifically recognize and bind to foreign antigens.
COMPLEMENT SYSTEM
Some of these proteins (
e.g., C3b
) acts as
opsonins
for destruction of microbes by phagocytes.
The "terminal" components (
C7, C8, and C9
) can directly kill invaders by forming a
membrane attack complex
(neisseriae)
Other complement components, such as C5a, act as
chemoattractants
for PMNs.
Complement activation occurs by:
the
classic pathway
is activated primarily by immune complexes (i.e., antibody bound to antigen),

Alternative pathway
is activated by microbial components, frequently in the absence of antibody.

Consists of proteins functioning as a cascade of enzymes
disrupts the surface of invading organisms.
short-lived white blood cells that engulf and kill invading microbes
are attracted to inflammatory sites by
chemoattractants
such as C5a.
Localize the site of infection by adhering to
selectins
- molecules expressed by endothelial cells
Expression of
on endothelial cells then take place, and this receptor binds to integrins on PMNs - facilitating diapedesis

PMN CELLS
Microbial Entry
The most common sites of entry are:
mucosal surfaces
(the respiratory, alimentary, and urogenital tracts)
skin
Routes of microbial entry:
Ingestion
inhalation
sexual contact



Most microbes must anchor themselves to a tissue or tissue factor


Adhesins
- located on host surface
anchors the microbe to a tissue
promotes cellular entry


Viral Adhesins
All viral pathogens must
bind to host cells
, enter them, and replicate within them




Epstein-Barr virus:
microbial ligand: Envelope protein
host:CD21 (CR2)
HIV
Microbial ligand: Surface glycoprotein gp 120
Host: CD4 and chemokine receptors (CCR5 and CXCR4)
used by gram-negative bacteria for
attachment to host cells

shorter, straighter, thinner than flagella





Escherichia coli:
ligand-  Pili
host: Ceramides/mannose and digalactosyl residues
long appendages attached to either
one or both ends of the bacterial cell
distributed over the entire cell surface
composed basic protein
plasmodium vivax binds to the Duffy antigen Fy on erythrocyte
loss of host receptors may confer resistance to a population
70% of individuals in West Africa lack Fy antigens and are resistant to P. vivax infection
Pili or fimbriae
t. vaginallis
Flagella
RBC
P. Vivax
duffy antigen
duffy binding protein



The production of cytokines such as
IL-1, IL-18, TNF- alfa
, leads to fever, muscle proteolysis.

The
lipid A portion
of gram-negative LPS cause clinical manifestations of gram-negative bacterial sepsis

An inability to kill or contain the microbe usually results in damage that can degrade the host tissues


Tissue Tropism
- The propensity of certain microbes to cause disease by infecting specific tissues
Bacterial toxins - The staphylococcal enterotoxins, toxic shock syndrome toxin 1, and the streptococcal pyogenic exotoxins behave as
Superantigens,
directly stimulate T cells leading to massive release of cytokines
Laboratory Diagnosis
To culture bacterial, fungal, or viral pathogens, an appropriate sample must be placed into the proper medium for growth
Culture
- most accurate test
Gram's stain :
differentiates organisms with
thick peptidoglycan cell walls

(gram-positive) and those with
thin peptidoglycan cell walls
(gram - negative)
Staining:
The acid-fast stain identifies organisms
that retain dye
after acid/organic solvent disruption
Direct Immunofluorescent Antibody
technique - fluorescent antibody is directed at a specific antigen to visualize organisms or subcellular structures
Both direct and indirect methods detect viral antigens well as many difficult-to-grow bacterial agents


Indirect technique
- two-antibody system is used: Each unlabeled antibody is attached to the second antibody and the visual signal is amplified.
Nucleic Acid Tests -
Techniques for the
detection of specific DNA and RNA

sequences
are used to detect specific pathogens in clinical specimens.
used for organisms that are difficult to identify
determines whether two or more isolates are closely related
used to predict the sensitivity of organisms to chemotherapeutic agent

Target nucleic acid sequence can be amplified to detectable levels
PCR
, most common NAAT, requires
repeated heating of the DNA

separates two complementary strands of the double helix
Extends complimentary strand using PCR amplification
Detects signal via a labeled probes
Approach:
1. Physical examination
2. Diagnostic Tests
3. Treatment
4. Prevention

Treatment

Life-threatening
infections such as bacterial meningitis or sepsis, must be treated
immediately
, often before a specific causative organism is identified.


Treatment
should cover
the causing organism
Treatment should be as
specific

as possible


Risk factors
for exposure to certain types of pathogens may give important clues to diagnosis (travel history)
The physical examination must be thorough
Laboratory studies must be directed toward establishing an etiologic diagnosis in the
shortest possible
time
,
at the lowest possible
cost
with the least possible
discomfort
to the patient.
The risk of contamination should be minimized while maximizing the yield of pathogens

Approach
PREVENTION
Active
Vaccines -
Live, inactivated
Toxoids -
Bacterial toxin modified to be non-toxic

Passive
Antibodies –
immune globulins
antitoxins

Immunization
https://thinkprogress.org/vaccines-have-almost-totally-eliminated-these-13-infectious-diseases-in-the-u-s-653d4a8f930e#.2q39czn0z
1st line:
Skin
Mucous membranes/ secretions
Normal flora
MHC II:
Presents antigen to CD 4 T cells
Is Expressed only on antigen presenting cells
:
Dendritic cells,
Macrophages
B lymphocytes

intercellular adhesion molecule 1 (ICAM-1)
Vaccine Types
Live attenuated
Measles
Mumps
Rubella
Varicella
Ifluenza (intranasal)
Yellow Fever
Cholera
Hepatitis A
Influenza (injectable)
Rabies
safer than live vaccines
induces weaker immune response
booster shots usually required
Induces strong/lifelong immunity
may cause disease in immunocompromised host
Killed Vaccine
Wash your Hands!!!!
THANK YOU FOR YOUR ATTENTION!
references:
1.Harrison's Principles of internal medicine - 18TH edition
2. the merck manual of diagnosis and therapy - 18Th edition
3. First aid for the usmle step 1 - year 2014 Edition
Most pathogens exit via the same route by which they entered
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