What is defined as pathogens?
Microorganisms causing DAMAGE to the host
What is virulence?
Measure of the ability to cause damage
What are the 5 virulence factors pathogens use?
- Adhesins (attachement to host cell surface)
- Capsule (protects [from host immune cells] & attachement)
- Enzymes (extracellular enzymes to invade tissues or to protect pathogen)
- Invasins (surface or injected proteins that trigger endocytosis of pathogen)
- Type 3 & Type 4 Secretion Systems (injects effectors that take control of the host cell)
What are the 6 extracellular enzymes pathogens might use?
H.C.L-P.C.L.
- Hyaluronidase (destroys hyaluronic acid = saccharides holding cells together)
- Collagenase (degrades collagen in connective tissues)
- Lecitinase (degrades lecithin [phosphatidylcholine] of cell membrane)
- Leucocidin (cause lysis of WBC [protects agains immune sys.])
- Protease (degrase complement proteins & antibodies of immune syst.)
- Coagulase (cloaks the pathogen with insoluble fibres)
What are the differences between T3SS & T4SS? (Secretion Systems)
Type 3: form a channel, acts as a syringe
Type 4: acts as a gun, shoots effectors
What are the two main ways pathogens damages the host?
Invasiveness (microorganism establishes itself in the host and speads into the tissues)
Toxigenicity (microorganism produces toxins damaging the host’s tissues)
What are the 5 steps of an infection?
Exposure Attachement/adherence Invasion Colonization & Growth (Toxicity/Invasiveness) Tissue damage
What are the 2 categories of disease related with toxigenicity?
Infectious disease (infected w/ bacteria producing toxins damaging the host) Intoxication (ingest [a food containing] toxins damaging the host; the bacteria do not infect the host)
What are the two types of toxins and their characteristics? (4&5)
- Exotoxins
a) secreted or released [when organism lyse]
b) usually heat-labile proteins
c) highly immunogenic (big antibody response)
d) AB toxins (B = binds to SPECIFIC receptor of host cell; A = enzymatic part modifying & damaging the host cell) - Endotoxins
a) are part of the pathogen (lipid A of LPS)
b) heat stable
c) weekly immunogenic (no antibody produced)
d) activate the complement
e) induce vasodilation->inflammation->fever->SEPTIC SHOCH
Which type of toxin can be used to make vaccines?
Exotoxins (produce antibody response and can be inactivated by heat to form… TOXOID)
Endotoxins cannot be inactivated and cannot be converted to a toxoid
What type of toxin is produced by Clostridium Botulinum & Vibrio cholerae and how do they differ?
Both are AB toxins => exotoxins
Botulinum toxin: target motor neurons, inhibits muscle contraction (stops the heart)
Cholera toxin: produce cAMP in intestinal epithelial cells; block Na intake and induces ions mvmnt to the lumen; water is attracted into the lumen (instead of into the blood with normal Na flow); massive fluid loss (diarrhea)
When it comes to host’s defenses, what are the two main types of defenses?
Innate defenses (always present in the host and are non-specific defenses) Adaptive defenses (relies on DETECTION & RESPONSE to infection; are specific to FOREIGN ANTIGENS)
What consist of the Innate First barrier defenses? (4)
Skin (thick layer of dead cell)
Mucosa (mucus + ciliated cells of airways)
Normal microbiome (occupies sites, produces bacteriocin [kills other invading bacteria])
Antimicrobial substances (lysozymes [cleavage of peptidoglycan], antimicrobial peptides [creates pores in membranes])
Of what is composed the Innate Second line of defense? (3)
Complement system (protein inducing lysis by pore formation)
Phagocytes (digests pathogens)
Inflammation (vasodilatation [inc. blood flow], inc. fluid, recruitment of immune cells [complement, macrophages])
How does the complement system works?
Set of blood proteins activated by classical pathway (antibodies) or alternative pathway (microbial cell component [LPS]) resulting in the formation of membrane attacking complex (MAC) causing lysis of bacteria.
MAC complex consist of C(5b)(6)(7)(8)(9) proteins
Which bacteria are more sensitive to the complement system (MAC)?
Gram-negative bact. (target Outer membrane)
Which cells undergo phagocytosis and how (2,4)?
Macrophage & Neutrophil
- Attachement
- Ingestion
- Killing:
a) lysozyme fuses w/ phagosome (injested bact.)-> hydrolytic enzymes-> degradation/lysis
b) oxidative by reactive oxygen species (ROS)-> oxidizes bact. - Digestion
What is the role of fever in the Innate Second line of defense?
Activated by IL-1 released by macrophages;
Increases temperature to inhibit growth of some pathogens
What are the 3 characteristics of the adaptive defenses?
- Specificity: each immune cell is specific to one antigen
- Memory: exposure of an antigen to immune cells induces their reproduction; Subsequent exposure illicit a stronger and faster response
- Tolerance: immune cells are tolerant to host’s (self) antigens (so don’t attack yourself)
What are antigens?
molecules of microorganisms that can be recognized by the immune system
What are T cells, what do they do and how do they get activated?
T-helper (T-h) cells: Big chiefs; T Cell Receptor (TCR) recognize antigen from MHC-2 (from macrophage or B cells) -> release IL-2 -> reproduction & differentiation into T-h and memory T cells; Once activated by IL-2, releases TNF-α -> activates macrophages into ANGRY KILLER CELLS
T-cytotoxic (T-c) cells: Killers; TCR recognizes antigen from MHC-1 (from any cell) -> releases IL-2 -> reproduction & differentiation into T-c and memory T cells; Once activated by IL-2 -> releases PERFORINS & GRANZYMES -> induces apoptosis (controlled death of infected cell presenting antigen on MHC-1)
What are the two ways antigen are presented to and by the immune system?
With the Major Histocompatibility Complex (MHC):
{you are 1 with the cell = comes from inside {infection}; you are 2 with the cell = different, comes from outside (phagolysosome)}
MHC-1: (expressed by all cells) Presents antigen originating from inside cell (infection); recognized by T-c cells
MHC-2: (expressed by macrophages and B cells) Presents antigen processed in the phagolysosome; recognized by T-h cells
What happens when macrophages are affected by TNF- α?
They become Angry Killer Cells -> produce lot of oxidative stress and oxidizes everything on their way (even themselves)
What are B cells, what do they do?
B cells have antibodies on their surface to recognize antigens. Once antigen recognized -> phagocytosed and then presents it on MHC-2 -> antigen recognized by T-h cells -> T-h releases IL-4 -> induces reproduction & differentiation of B cells into Plasma cells & Memory B cells; Plasma cells produces antibodies
