Chapter 6 part 1 Flashcards
Factors of Innate Immunity (5)
- Epithelial barriers
- Phagocytes
- Dendritic Cells
- Complement
- NK Cells
Adaptive Immunity (2)
- B-Lymphocytes => Antibodies
2. T-cells => Effector T-cells
Epithelial barriers (3)
- Produce antibicrobes - Defensins
- Lymphocytes found here
- Mechanical stuff
Phagocytes (2)
- Monocytes/Neutrophils in blood
2. Sense microbe presence and murder invaders
Dendritic Cells (3)
- Found in epithelium and lymphoid organs
- Capture Ags and present to T-cells
- Stim cytokine secretion (inflammation and Antiviral response)
Natural Killer cells (1)
- Early protection (viruses and INTRACELLULAR bacteria)
Mast Cells (1)
- Release inflammation mediators
Plasma Proteins types (3)
- Complement system
- Mannose binding lectin and C-Reactive protein
- Lung Surfactant
- Complement system
- Proteins activated by microbes
- Alternative and lectin pathways
- classic pathway activated via Abs (adaptive immunity)
Coat microbes and promote phagocytosis?
Mannose binding lectin and C-reactive protein
Protection against inhaled microbes?
Lung surfactant
How does Innate Rec Microbes?
Pattern Recognition patterns (infecting and cell damage activities)
Main Receptors? (2)
- TLRs
2. NOD-Like receptors (NLRs)
TLRs activate?
- NF-kB
2. Interferon Regulatory Factors (IRFs)
What does NF-kB do?
- Stimulates cytokine secretion and expression of adhesion molecules
- Results in the attraction of Leukocytes
Interferon Regulatory Factors (IRF
Increase Antiviral Cytokine secretion (type 1 interferons)
NLRs are found where?
in the cytosol
TLRs are found where?
Plasma membranes
How do NLRs signal?
Via the inlfammasome
What does the inlfammasome do?
- Activates Caspase 1
- Caspase 1 activates IL-1
- IL-1 induces fever
Gain of function mutation in NLR causes what?
Autoinflammatory syndrome
How do you treat Autoinflammatory syndrome?
IL-1 antagonist duh
NLR may also play a role in (3)
- Gout
- Type 2 Diabetes
- Atherosclerosis
Other Receptors? (4)
- C-Type Lectin
- RIG-like R
- G-protein coupled R
- Mannose R
This receptor is in the cytosol an activate cytokines when stimulated by the NA of viruses?
RIG-like R
C-type Lectin are found where?
Macrophages and dendritic cells
-In the plasma membrane
Receptor for Neutrophils, Macrophages and Leukocytes?
G Protein-Coupled R
Microbial sugars received by?
Mannose R
How Does Innate Respond? (3)
- Inflammation: Cytokines/complement
- Antiviral: Type 1 interferons
- Stim Adaptive Immunity
Adaptive immunity traits: 2 types
- Humoral Immunity
2. Cell Mediated Immunity
Extracellular and B-lymphocytes are examples of what type of immunity?
Humoral Immunity
T-cells and Intracellular microbes are involved in what type of immunity?
Cell-mediated Immunity
What allows Lymphocytes to respond to a wide array of AGs?
They have a highly diverse pool of receptors.
B and T cells: general facts (3)
- Circulate in blood
- Considered Naive prior to encountering Ag they are specific for
- Once activated they differentiate into Effector and Memory cells
These cells Neutralize Microbes, phagocytose and activate the complement system.
B-Cells!
These cells kill infected cells (2)
- Cytotoxic T Lymphocytes
2. Natural Killer Cells
Regulatory T-cells…
…suppress the immune system
Helper T-lymphocytes are activated by?
APC-Macrophages (they also activate macrophages themselves) and Dendritic cells
-remember multiples of 8. CD8 = class 1 and CD4 = Class 2 MHC
Helper T-lymphocyte functions?
- Activate Macrophages
- Inflammation
- Activate/proliferate T + B lymphocytes
Lymphocyte diversity
- 1 trillion in healthy adult
2. Not many for each Ag
What is clonal selection?
Once a lymphocyte is exposed to a specific Ag, it makes clones that are specific for that Ag.
How is diversity generated?
Somatic recombination of genes that encode R. Proteins
When and where does this somatic recombination occur?
Durring maturation
T-cells = thymus
B-Cells = Bone marrow
These genes mediate somatic recombination
RAG-1 and RAG-2
-Problems result in an inability to generate mature lymphocytes
Recombined T and B cells result in different…
TCRs and Igs
If lymphocyte proliferation is polyclonal…
…it is considered BENIGN and NON-NEOPLASTIC
If lymphocyte proliferation is neoplastic…
it is considered MONOCLONAL and Malignant
3 types of T-lymphocytes
- Helper T-lymphocytes
- Cytotoxic T-cells
- Regulatory T-cells
These cells stim activation of leukocytes
Helper T-cells
-stim B-cells and thus Ab formation/leukocytes
95% of TCRs are…
- Heterodimers w/alpha + Beta polypeptide chains
- A/B Rec Ags presented by MHC assure T-cells only see associated Ags
These T-cells don’t need MHCs for activation and where do they aggregate?
- Gamma-Delta TCR
2. Epithelial surfaces
These cells have TCR receptors for glycolipids presented by MHC-CD1 (MHC-like but not actually) cells
NK-t cells can express this TCR
More CD8 or CD4?
60% CD4 and 30% CD8
Assist macrophages and B-lymphocytes by secreting cytokines
CD4
CD8 cells are?
Cytotoxic T-lymphocytes => destroy host cells
MHC 1 bind __
MHC 2 bind ___
CD8
CD4
Where do you find B-lymphocytes? (3)
- Lymph nodes
- spleen
- mucosa associated lymphoid tissue
B-cell Ag receptor complex consists of?
- IgM and IgD (membrane bound)
- Found on surface of mature Naive cells
- After stim by Ag => plasma cells
- Igalpha/beta also involved
CR2 and CD21 are examples of?
Type 2 complement receptors
What disease uses Type 2 complement receptors to cause its effects?
Epstein-barr virus (EBV)
-Infects and enters B-cells through this mech
What receives Th signals?
CD40
Dendritic cells “coolest looking according to Dr. G”: Functions/facts
- APC for T-Cells
- Express TLRs and lectins
- Recruited by microbes to T-Cell zones
- Express high levels of MHC
Dendritic cells in the epithelium/skin are called?
Langerhans
Where do you find follicular dendritic cells?
In germ centers of lymph follikces
-Spleen and lymph nodes
What do follicular dendritic cells do?
- Trap Ags bound to Abs
2. Present Ags to B-cells.
Phagocytosis by macrophages is opsonized by? (2)
- IgG
2. C3b
How do T-cells activate Macrophages?
IFN-gamma
These cells need no previous exposure to destroy tumor and virus cells
Natural killer cells
NKCs are 5-10% of Lymphocytes and express what on their PM? (2)
- CD16
2. CD56
CD16 is a receptor for what and what does it cause?
- FC R for IgG
2. Lyse IgG coated cells
CD56 is used to do what?
Just ID NKCs
What TCRs and Igs do NKCs express?
None
What do NKCs secrete and what does this activate?
- IFN-gamma
2. Macrophages
How is NKC proliferation stimulated?
- IL-2
2. IL-15
What does IL-12 do?
activates NKC killing and IFN-gamma secretion
What do healthy cells express that stops NK cells from attacking them?
Class 1 MHCs
-Unhealthy cells will have reduced class 1 MHC and be attacked
How else are NKcells activated?
Viruses present activating ligands to NK cells
Innate Lymphoid cells (ILCs) are?
lymphocytes that lack TCRs but produce similar cytokines
What is an example of an ILc?
NK cells homes!
What do ILCs produce? (5)
- IFN-gamma
- IL-5
- IL-17
- IL-17
- IL-22
ILC functions? (3)
- Early defense against infection
- Rec + eliminate stressed cells
- Provide cytokines => influence T-cell differentiation
These molecules are involved in transplant rejection.
What is another name for them and what chromosome do you find them on?
- MHC
- Human Leukocyte antigens (HLA)
- Chromosome 6 (polymorphic = variable)
What HLAs are found in MHC class 1?
A, B, C
Where do you find MHC class 1?
All HEALTHY nucleated cells/platelets
-also display cytoplasmic peptides
What HLAs associated with MHC class 2?
- HLA-D (DP, DQ, DR)
Where do you find Class 2 MHC and what do they look for?
- Macrophages, B-cells and Dendrites
2. Internalize Extracellular microbes and soluble proteins into vesicles
Key Role of MHC?
Regulate T-cell immunity
Which cells of innate immunity release cytokines? (3)
- Macrophages
- Dendrites
- NK cells
Cytokines of innate immunity stimulate? (2)
- Inflammation
2. Viral attack
Cytokines released by innate immunity? (6)
- TNF
- IL-1 (fever)
- IL-12 (by NK cells)
- Type-1 IFNs
- INF-gamma (activate macrophages)
- Chemokines
Adaptive immunity cells that secrete cytokines?
- CD4+ T-cells
What does CD4 secrete? (5)
- IL-2
- IL-4
- IL-5
- IL-17
- IFN-gamma
What do these CD4 cytokines do?
- Lymphocyte proliferation
2. Differentiation into effector cells
These factors stimulate hematopoieses?
Colony stimulating factors (CSF)
What do CSF produce?
- GM-CSF
2. IL-7
TNF antagonists are given for what disease?
Rheumatoid arthritis
When would you give cytokines?
When you want to stimulate hematopoieses and viral protection
Where do Ag samples from lymph go?
Lymph nodes
Where do Ag samples from blood go?
Spleen
The lymphocytes in mucosa are mostly…
memory cells
ABCD acronym for hypersensitivity
Type 1: Allergies, Anaphalaxis, Atopy
Type 2: antiBody
Type 3: immune Complex
Type 4: Delayed
Hypersensitivity reactions require? (2)
- Previous exposure (sensitized
2. Imbalance btw effector mech and control
Type 1 is?
Immediate hypersensitivity
What stims type 1?
Allergens
What happens? (2)
- Rapid response
2. Ag bind to IgE on mast cells
What takes place in the immediate reaction/what is the time frame?
- min to Hrs
- Vasodilation and Vascular leakage
- Increased glandular secretions and SM spasms
When is the late phase, when does it happen and what are the major cell types? (4)
- Onset is 2-24 Hrs
- Eosinophils = major cells
(also, neutrophils, basophils, monocytes and CD4+ cells) - Lasts for days
- Asthma = example
These cells are found near blood vessels, have PM bound granules and crosslinking of IgE = activation
Mast cells
What receptors bind IgE
FCERi
When are Mast cells sensitized?
When they are covered by IgE
What triggers mast cells? (6)
- C5a and C3a
- Chemokines (IL-8)
- Drugs (Codeine and morphin)
- Adenosine
- Melittin (beeeeee venom!!)
- Phys stim
Steps after allergen binds
- CD4+ T cells bind to APC (dendrite) and release IL-4
- IL4 stims Th2 and class switches B-cells to produce IgE
- IL-5 stim eosinophils
- IL-13 stim IgE production and increase mucus secretion
- Th2 begets more Th2
First mediator released by Mast cells?
- Histamine
Histamine function? (3)
- SM contraction
- Vasc Permeability
- Increased Mucus Secretion
What types of enzymes are stim by Mast cells?
- Neutral proteases (chymase and tryptase)
- Hydrolases
- Enzymes cause tissue damage
Proteoglycans stimulated by Mast cells?
- Heparin (anticoagulant)
Lipid Mast Cell mediators activate?
Phospholipase A2
Phospholipase A2 stimulates production of? (3)
- Leukotrienes C4 and D4
- Prostaglandin D2
- Platelet activating factor (PAF)
These cause bronchospasms and increase mucus production.
Prostaglandin D2
What is the importance of Leukotrienes C4 and D4?
- The are the most potent vasoactive and spasmogenic agents (1000x Histamine)
PAF does what?
- Platelet aggregation
- Release of histamine
- Bronchospasms
- Increased vasc perm + vasc dilation
Cytokines produced by Mast cell? (4)
- TNF
- IL-1
- Chemokines
- IL-4
What cytokine(s) amplifies TH2 response?
IL-4
Cytokine(s) involved in late phase leukocyte recruitment and epithelial damage
TNF, IL-1 and Chemokines
Prominent cell in late phase reactions?
- Eosinophils
How do Eosinophils cause tissue damage?
- Proteolytic Enzyme
- Major Basic Protein
- Eosinophil Cationic Protein
What do you need for Lat-phase Tx?
Broad spectrum anti-inflammatory
Antihistamine is more acute
What is Atopy?
- Increased propensity for immediate hypersensitivity reaction
- Increased serum IgE and IL-4
- Chrome 5 + 6 linked to genetic propensity
Non-atopic allergies?
- temp/exercise
- No TH2 or IgE
- Mast cells are increasignly sensitive
Systemic anaphylaxis is “important to know about”
What does it result in?
- Vask shock w/in min
- Widespread Edema and itching rash
- Difficulty breathing with contracting airways
What is Type II?
- Ab-Mediated Hypersensitivity
2. AutoAbs specific for norm tissue
How do Ab mediate injury?
- Opsonization (C3b) + phagocytosis
- Complement (C3a + C5a) and Fc receptor Mediated inflammation
- Ab-mediated cell dysfunction (anti-receptor Abs disrupt function)
Specific Ab-mediated cell dysfunction for Myasthenia gravis
- AcH-R Abs => M. weakness + paralysis block N-M transmission
Ab-mediated dysfunction for Graves disease
TSH-R Abs => Hyperthyroidism
Autoimmune hemolytic anemia causes?
Opsonization of RBC and eventually anemia
Hemolytic disease of newborn
Erythroblastosis Fetalis
What causes Erythroblastosis Fetalis?
Maternal IgG, anti-erythrocyte Abs cross placenta and destroy RBC
Diseases with Abs to own blood cells? (3)
- Hemolytic anemia
- Agranulocytosis
- Thrombocytopenia
Ab can also cause tissue damage in what kidney disease?
Glomerulonephritis
Ab reactions/type 2 are also common in what type of reactions?
Transfusions
Type 3 is involved with…?
The Immune Complex
What is the immune complex?
Ag-Ab complex that causes tissue damage and inflammation
3 things associated with hypertension and the immune complex?
- Kidney (glomerulonephritis)
- Joints (arthritis)
- Small blood vessels (vasculitis)
1 more disease associated with Type 3
Lupus
What is the pathogenesis of the Immune complex?
- Complement fixing IgG and IgM
- Complement proteins at injury site
- Consumption of complement (reduce C3 levels)
What does IgG and IgM fixing do?
produces lesions
What are type 4 reactions?
Delayed/T-cell mediated
Inflammation is produced by…
CD4 and CD8
Diseases associated w/type 4 (5)
- Rheumatoid arthritis
- MS
- Type 1 diabetes
- Inflammatory bowl disease
- Psoriasis (scaly rash)
Stim Th-1 leads to production of?
IFN-gamma
Stim Th-17 leads to production of?
IL-17, IL-22 and chemokines
How does IFN-gamma stim macrophages?
- Increase ability to phagocytose
- Increase MHC class 2 expression
- Secrete TNF, IL-1 and chemokines (inflammation)
- Produce more IL-12 (stim TH-1 production)
Example of delayed th reaction?
Tuberculin Reaction (prev sensitized = reddening after 8-12 hrs)
TB infection quick facts (4)
- Non-degradable Ags
- Colonizes lungs
- Infiltrate dominated by macrophages
- Macrophages cause granulomas if sustained!!!
Cytokines characteristic of Granulomatous inflammation (2)
- Increased TH1
Increased IFN-gamma
What can be CD8 mediated? (2)
- Type 1 diabetes
2. Graft Rejections
Define Dysbiosis
Alteration in microbiom (less good and more bad)