Mucosal and Dermal immunity Flashcards
Systemic Immune Response
no-local
What types of tissue are involved in Mucosal and Cutaneous Immunty
Mucosa and skin associated Lymphoid tissue
What makes up the Mucosa-associated Lymphoid tissue
GALT, BALT, NAlt
Relatively thin layers of Epithelial cells that line body passages
Mucosa
Surface area of Mucosa
400 square meters
Single Later of columnar Epithelial cells
Type I mucosa
Many layers, with top being squamous epithelial cells
Type II mucosa
Viscous solution of polysaccharides mixed with water
Mucus
What does Mucus cover
Apical membrane of epithelial cell
Mucus contains
Antimicrobial peptides, enzymes, antibodies…
Main Ab of Type I mucus
SIgA
Main Ab of Type II mucus
IgG
Non-inducible Defenses of GI
Acidity, Motility, Mucous Layer with under glycocalyx, Tight Junction
Where commensal bacteria for the gut hang out
in the lumen
What is found in the emithelial layer of the Gut
Intra-epithelial lymphocytes(gamma delta T cells), Goblet cells(mucus) and Paneth cells (for antimicrobial peptides)
M Cell roll in Gut
Antigen sensing
Where Imune cells are found in the gut
In the Lamina Proprea
Firs cells to touch Pathogen
Intestinal Epithelial cells
Area under the epithelial cells
Lamina Propria
Lamina Propria contain
Macrophages, neutrophils, mast cells, immature DCs, Memory T and B cells, effector Th17 cells
Cell involved with Pyer’s patches in the gut for an immune response
M cell
Ag Sampling in the gut
M cells internalize to give to Dendritic cells
CD103 DC’s-elongate through epithelial layer to sample lumen
NALT and BALT provide defense against
Inhaled AG
NALT involves
Nasal submucosal glands, Tonsils, Epithelial Cells(type II), Follicles and Diffuse Lymphocytes
Balt involves
Bronchial submucosal glands, Epithelial cells(type I), Follicles and diffuse lymphocytes
Non-inducable mechanisms for NALT and BALT
Nose Hairs(NALT only) Mucus Cilia Coughing Tonsils
why is it easy to sample Antigens in the NALT and the BALT
Environemnt is less caustic
What does the BALT have to sample Ag
M cells and follicle asssociated epithelia
DC’s in the NALT can process Ag and move where
Tonsils or diffuse lymphoid
How do macrophages recognize microbes
Via pattern recognition receptors
Macrophages recognizing microbes leads to
Activation of the macrophage and the ability to kill microbes
Activation of Pattern recognition receptors on macrophages initiates
Inflammatory response
The adaptive response in the gut is biased toward
SigA, to protect antigen from being degraded
If inflammatory response is needed in the gut what will be activated
Robust Th1/Th17 response
INductive site in the gut
Where an antigen is presented
Activation of the Inductive site leads to
Activation of the B cell and class swtiching and ends up in the effector site
Effector site role
Secretory portion of cells allow shit antibodies to go into the lumen
Where is SIgA found
Constitutively in mucus
Is SIgA Ag specific
yes, but can bind to adhesion molecules found on many pathogens
What kind of reactivity is 50% of SIgA in the gut
Cross-reactive
Does SigA activate its complement well
No, so it doesn’t trigger unnecessary inflammation
Do host and microbial protesases affect SIgA
No
When an Antibody reacts with something it normally is not made to react with
Cross-reaction
Why not initiate inflammatory response in mucosal surfaces
Cytokines, such as TNF-alpha can disrupt tight junctions between epithelial cells
What does Cutaneous Immunity
Skin-Associated Lymphoid Tissue: epidermis and dermis
Cells involved in Cutaneous Immunity
DCs, mast cells, macrophages T cells, little/no b Cells(no mucus)
Immune response of Cutaneous immunity
Activation of nearby memory T cells, or induction of systemic immunity (Th1/Th17-inflammatory)
Ability of any bacterial speicies to cause disease in a susceptible human host
Pathogenicity
Presumes pathogenicity, but allows expression of degrees from low to high
Virulence
Why does Clinical disease result
When a pathogen is able to enter a host, colonize, survive immune system defense, and cause damage
What is neccessary for primary pathogens
Breach human cellular and anatomic barriers
Avoid host defenses
And transmit to a new host
Vector Borne transmission
Like a tick biting you
Do all pathogens need the same amount of the pathogen to get you sick
No
3 stages to establish an infection
Adherence, Coloniziation/invation
Damage
How would a pathogen breach host innate defenses to colonize
Attach to unique host molecules
IgA Protease
Inherent resistance to lysozymes
Mechanisms to sequester iron
How pathogens bind to host cells
Though Pili and protein adhesins
Pili can bind to what cells
bind to cell-specific receptors present in material covering the host cell
Roll of Pili for pathogens
Allow inital attachment, bringing organism closter to cell so second Adhesin can bind
Attachment mech of bacterial pathogens
Pili or Fimbriae, Biofilms
Cleaves SIgA in the hinge region to release the Fc portion from the Fab fragment
SIgA protease
How some cells avoid lysozymes
Outer membrane of Gram negative bacteria prevent penetration of lysozymes
How bacteria fight the low levels of iron needed to grow
Produce Siderophores to compete with human proteins for iron
Sequesters iron
Lactoferrin
ways a pathogen avoids immune system
Invade and survive in host cells
avoid contact with phagocytes
Inhibit phagocytic engulfment
PAthogen that cannot invade host cells
Extracellular
Pathogen that can invade host cells, but can survive extracellular
Facultative intracellular bacteria
Require host cells for surival
Obligate intracellular bacteria
Facultative intracellular bacteria prefer to enter
Macrophages
OBligate intracellular bacteria prefer to not enter
Macrophage
Any protein produce by bacteria that allows the bacteria to invade non-phagocytic host cells/tissue
Invasins
Examples of Invasins
Effector Proteins injected by type III secretion
Secreted enzymes that interupt tight juntion
Proteins that bind integrins on host cell and facilitate uptake
Action of Effector Proteins
Promote invation of host cell
suppress host cell defenses
Endosomes normal action
Fuse with lysosomes to digest contents
Invasive pathogens that enter through endosomes must be able to
Disrupt normal cell vesicle trafficking, escape endosome in cytoplasm
How pathogens avoid being killed once in the cell
Modify endosome for survial
Escape endosome and replicate
Block endosome-lysosome fusion
How can a pathogen avoid phagocytosis by a macrophage and PMN
Capsule that interferes with complement deposition on bacteria
How a capsule aids in avoiding innate host defense
Binds factor H present in serum-degrades complement protein C3b preventing it’s deposition on bacterial cell surface
How a pathogen will avoid contact with phagocytes
Invade location not surveilled phagocytes
avoid inducing inflammation
Inhibit phagocyte chemotaxis
Bind host molecules to hide antigenic surface
How can a pathogen Inhibit phagocytosis
Polysaccharide Capsule M protein and fimbriae O Polysaccharide K Antigen Cell-bound Protein A
How Cell-bound Protein A inhibits phagocytosis
Binds to Fc region of IgG and blocks Ab binding(prevents opsonization)
How can a pathogen munipulat PAMPS and AMPS
Have poorly recognized Lipid A portion of LPS (TLR-4)
Lipid A modification-changes surface(prevent AMPS)
Alter cell wall with Teichoic acid(prevents TLR signalling
What does Varying surface antigens on pathogens do
Prevent PAMPS from being recognized
Why pathogens would kill host cells
Decrease number of defenders and prevent the alarm bells from sounding
Roll of strptolysin and Leukocidin
Target neutrophils to release lysozomal content into cytoplasm
Roll of Exotoxin A
Targets and kills Macrophages
Ways baceria can injur host
Exotoxin, endotoxin, hydrolytic enzymes, superantigen exotoxins
Inflammation
Bacterial secreted proteins
Exotoxins
Lipid A portion of LPS of Gram-negative bacteria that stimulates cytokine release(inflammation)
Endotoxin
Facilitate tissue invasion
Hydrolytic enzymes
Stimulate massive sytokine secretion (toxic shock)
superantigen exotoxins
Prolonged immune response to bacteria can damage host tissues
Inflammation
What can be exotins
Local or Systemic if in blood
What can exotoxins bind to
Host cell specific-bind to specific cell receptors
Effect of Exotoins
Depends on target but may inhibit, stimulate, or kill
A- B exotoxin parts
B=bind to host cell surface receptor glycoproteins or glycolipids
A=transported by direct fusion or endocytosis into host to act on target
Create pores in host cell membrane(DAMPS)
Membrane active exotoxins
Lipid A portion of LPS
Endotoxin
How endotoxin induces fever
macrophages release IL-1 and TNF
Useing antibiotics on Endotoxin
Makes it worse because Lipid A is released
Binds to MHC II, activating T cell non specifically, causing them to release Cytokines IL-1 and TNF to cause shock/inflammation
Superantigen
Chronic infection can cause
delayed type hypersensitivity reaction
