I&D Flashcards
What are the 4 main immune compartments? Which ones use cytokines and chemokines?
Innate: complement, phagocytes
Adaptive: B cells and T cells
Phagocytes and T cells use cytokines and chemokines.
What happens if the complement doest work?
Since complements creates opsonization, when it’s defective lots of encapsulated bacteria due to inefficient opsonization and phagocytosis. So we get lots of infection by encapsulated bacteria (like strep)
What is the end result of complement? How does it happen?
It’s the landmines of the innate system. After triggering several activation events –> end up in “explosion”. Major role is opsonization (coating of bacteria for phagocytosis) and formation of membrane attack complex (MAC)
What are some unique features of phagocytes? How are they related to T-cells?
- They move to the site of infection through tissue like marines and they are first deployed to the battle
- They eat, digest and present antigens to T-cells, T cells in turn required to have MHC to actually recognize peptides presented
What happens if phagocytes doesnt work? What disease can it cause?
Lots of infections by catalase + organisms, soft tissue abscesses, lymphadenitis and poor wound healing. Causes Chronic Granulomatous Disease ( defective NADPH oxidase -important for innate immunity) and unable to kill catalase + bacteria
What is the of of B cells?
B cells are like air force: the main role is to deploy a/b(immunoglobulins) that are like cruise missiles. Can deploy at or near site of inflammation or can be distant
What happens if B cells and A/B dont work?
Recurrent bacterial sinopulmonary infections
What is the role of T cells? What are the roles of three different types?
Known as generals, assassins and psychologists of the immune system
- CD4 - helper T cell: directs immune system where to go
- CD8 - cytotoxic T cells kill cells infected with intracellular pathogens like viruses, fungi, etc
- regulatory T cells control and modulate immune responses - modulates autoimmune and immune system, have to keep cells under control
What if T cells don’t work?
- cant generate effective a/b response
- severe viral infections (Herpes Simplex virus type 5(CMV) and type 4 (EBV))
- severe fungal infection
- autoimmunity
What do we mostly have issues with during one of the compartments absent?
Complement - encapsulated bacteria
Phagocytes - Bacteria, Fungi, Molds
B cells - bacteria
T cells - viruses, fungi, bacteria
What are the two goals of micro?
see
bacterial envelope: difference for G+ and G- bacteria? Why is this difference in cell wall assembly important?
One cell membrane surrounded by a thick cell wall: G+
Additional outer membrane: G-
Important because its an antibiotic target
What does cell envelope structure determine?
cell envelope structure Determines the gram stain
What are bacterial appendages and capsules important for?
colonization, attachment, movement. Its a part of pathogen factor
What are the 4 appendages in bacteria?
- flagella -colonize
- Pili/fimbriae - attachment are virulence factors
- specialized secretion systems-syringes to inject substances into the host
- capsules - external mucoid polysaccharide layer avoids immune recognition and phagocytosis
How does mucosal clearance happens? What are some barrier in mucosa?
tight junctions and mucus barrier forms a barrier
movement happens with cilia and peristalsis
What bactericidal compounds are present in mucus?
- Acid in stomach
- bile detergents in intestine
- antimicrobial peptides and enzymes
- IgA
What are the ways pathogens evade mucus clearance?
- Viruses have specialized molecules that attach to specific host-cell receptors (our body has receptors that help virus-ligand interaction, like sialic acid (for influenza) is a receptor our body has) Note! The physical barrier isn’t compromised. Its just a normal receptor
Whats is the other way other than receptors that pathogens can enter?
defective epithelia barrier!
skin defects, anatomic defect (Tracheoesophageal fistula), mucosal defects (chemotherapy causes mucositis)
how do pathogens cross the epithelial barrier?
Via target cells involved in immune surveillance
- dendritic cells - HIV (macrophages and DC on the surface of the membranes bind viruses and shuttle into lymph nodes
- Intestinal M cells - Salmonella
Does infection have to involve invasion?
NO. they can attach to cilia and use toxins to cause damage or they can attach and just steal nutrients
what are the 5 ways to avoid immune detection and
- intracellular invasion
- capsules to avoid phagocytosis
- antigenic variation
- immune modulation (go through)
- residence in immune privileged sites (VZV in sensory neurons in dorsal root ganglia and trigeminal ganglia)
How do bacteria and fungi steal nutrients? Whst do thry acquire?
using toxins. Micronutrients: iron (essential metal nutrient), sidephores (high-affinity iron chelating compounds), digestive enzymes
What are the three complement systems? What are they activated by?
- Classical pathway - activated by immune complexes (initiated by binding of an immune complex c1 to ab-ag complexes. Only IgM (mostly) and IgG can activate this complement. IgM>>>IgG3>IgG1>IgG2)
- Lectin pathway - activated by Pathogen Oligosaccharides -they recognize specific oligosaccharides (Mannose binding lectin (MBL) recognizes oligosaccharides associated with bacteria, yeast and parasites but DOESNT bind mammalian glycoproteins )
- Alternative pathway - activated by pathogen surfaces ( spontaneously activated by contact with various proteins, lipids, carbohydrates structures on pathogens)
What are the 5 major roles of complement?
Regardless of which one of the three pathways to take it forms MAC and attack bacteria. As a side arm it can attract Macrophages, Neutrophils, and activate Mast cells -→ HISTAMINE release
- Opsonization: Most important, binds to surface or encapsulated, slippery, slimy bacteria and provides handles for phagocytes to bind and ingest them
- Cytolysis: Forms MAC and directly destroyes bacteria
- Promotes AB production by B cells -enhances B cell AB response (Helping AB which are already made do their job)
- Chemotaxis - promotes movement of leukocytes into tissues. Draws innate immune cells to sites of inflammation
- Removal of immune complexes and apoptotic cells-by phagocytosis
What is the classical pathway? Which immoglobulins can activate it?
initiated by binding of an immune complex c1 to ab-ag complexes. Only IgM (mostly) and IgG can activate this complement. IgM>>>IgG3>IgG1>IgG2
How does Lectin pathway gets activated?
Mannose binding lectin (MBL) recognizes oligosaccharides associated with bacteria, yeast and parasites but DOESNT bind mammalian glycoproteins
How does the cell senses the non-self vs self? 2 things + examples
-
DAMPs: damage associated molecular patterns:
- HPS: heat, toxins, oxidants. Reduce denaturation/ enhance renaturation to regain correct tertiary structure
- HMGB1 released by necrotic cells can mediate inflammation in CNS & peripheral tissues
- MSU crystals precipitate within joints & soft tissues → inflammation → gout
- PAMPs (pathogen associated molecular patterns)
Whats the example of DAMP that we have seen in purine/pyrimidine metabolism?
Excess purine leads to monosodium urate (MSU-one of the examples of DAMPs) which leads to inflammation and Gout.
Whats the example of DAMP that we have seen in purine/pyrimidine metabolism?
Excess purine leads to monosodium urate (MSU-one of the examples of DAMPs) which leads to inflammation and Gout.
What are the 6 different cell-associated PRPs? And who do they target?
The ones she went over:
RIG-Like receptors (RLRs) - cytoplasmic on multiple cell types, sense viruses
C-Type Lectin receptors: targets microbial carbohydrates in bacterial, viral and fungal cell membranes
What receptors does our body have to sense pathogens in the cytosol? What do they sense? What do they signal through?
NOD-Like receptors (family of more than 20)
Sense cytoplasmic PAMPs and DAMPs (peptidoglycans, flagellin, viral RNA, Fungal hyphae)
Signal through “Inflammasomes” → activate caspases→ generate mature IL-1b
What are the local effects for TNFa, IL-1, IL-6. How does TNFa induce the inflammation?
TNFa induces inflamation through NFkB
Local effects:
- activates endothelial cells (to recruit leukocytes) to express selectin ligands, cell adhesion molecules, and chemokines
- activate resident immune cells
- stimulate phagocytosis, production of oxidants for microbe killing, and production of prostaglandins
What are the 5 systemic effects of TNFa?
- Act on the hypothalamus as endogenous pyrogens (increases fever)
- Induce hepatocytes to express acute-phase reactants (C-reactive P, fibrinogen, Complement)
- TNFa specific:inhibits myocardial contractility and vascular smooth muscle tone→ hypotension
- TNFa specific: causes intravascular thrombosis
- TNFa specific: causes wasting of muscle and fat cells -cachexia
What are the 2 systemic effects of IL-1 and IL-6?
- Act on the hypothalamus as endogenous pyrogens (increases fever)
- Induce hepatocytes to express acute-phase reactants (C-reactive P, fibrinogen, Complement)
What happens if too much cytokines are released (3 things)? Why does it happen (3 reasons)?
What? results in “cytokine storm” and causes systemic inflammatory response syndrome (SIRS): vascular collapse, disseminated intravascular coagulation, severe metabolic disturbances
Why? Cytokine storm is caused by bacterial sepsis, toxic shock, large scale lymphocyte activation
What are the two types of lipid inflammatory mediators pathways and the mediators? What do they cause? What are they derived from?
- Cyclooxyrgenase pathway→ Prostaglandins: cause vasodilation/vascular permeability, inflammatory pain, hyperalgesia, Fever
- Lipoxygenase pathway pathway →Leukotrienes: cause allergic reactions and inflammation
What are chemokines? What are their roles?
-large family of small secreted molecules, they are chemotactic cytokines.
Form chemotactic gradients and lead immune cells and WBC to an infection site
they can be presented on the surface if endothelium
stimulate leukocyte migration and leukocyte integrins
Tell WBC where to go!
What are the two types of inflammatory chemokines covered in lecture? What do they recruit?
- IL-8 (CXCL8) -recruits NEUTROPHILS
- Monocyte chemoattractant Protein (MCP-1, CCL2) - recruits monocytes
What happens after mast cell degranulate?
Activation: IgE binds and causes mast cells degranulation.
The effects of degranulation:
- biogenic amines → vasodilation and vascular leak
- Cytokines → Inflammation
- Enzymes → Tissue damage
Note: our body activates smth that causes tissue damage
What are the three steps of phagocytosis?
- recognition and attachment
- Engulfment and fusion of phagosome and lysosome
- Killing and degradation of ingested material (ROS and NO)
What is the main role of dendritic cells?
They are AG processing cells
They capture and process Antigens, converting proteins to peptides that are presented on MHC molecules recognized by T cells
Why is dendritic cells cells sometimes referred as to a bridge between innate and adaptive immunity?
They get activated by PRRs, and cytokines and in turn activate the T cells, B cells, NK cells, macrophages, Interstitial cells
What are the first cells to respond during an infection?
Innate like lymphocytes
Where are innate like lymphocytes found?
Intestinal mucosa, skin, lungs
What are the 5 recruited immune cells?
Neutrophils, Monocytes, NK, Eosinophils, basophils
What is the first recruited inflammatory cell to arrive?
Neutrophils. Fastest to arrive, but half life is only 6-8 hours. Most active in extra cellular bacterial infection
What are neutrophils mediated by?
Mediated by ROS and phagocytosis
What is the main job of neutrophils?
Production of anti microbial peptides- human neutrophil peptides (HNPs), alpha defensins
What are monocytes mostly effective against?
I travel lunar bacteria And viruses!
What are the 3 jobs of monocytes?
- Eat dead and dying cells -responsible for cleanup
- Produce large amounts of cytokines and chemokines to promote further inflammation
- When infection resolves they produce proteases and growth factors to meditate tissue repair
What is the job of NK cells and how do they accomplish it?
Kill infected cells and activate macrophages to destroy phagocytosed microbes
- Express perforin to make Holes in Cell membrane
- Express FasL and granzyme B to kill cells
- Express FcR to stimulate AB-dependent cellular cytotoxicity
what are Eosinophils 2 main jobs?
They are for parasitic infection and allergic reactions
What are Basophils important for? What are they similar to?
They infiltrate sites of allergic Reactions, release mediators and cytokines
they are least abundant. They are structurally and functionally similar to mast cells - activated by IgG like mast cells. And recruit cytokines
