Ch 6: Immunopathies (Part 1 - immunity)

Question 1

What is innate immunity? Cells and proteins involved?

Answer 1

Pre-existing defense against pathogens

Barrier defense = skin, epithelia
Cells = neutrophils, dendritic cells, NKs
Proteions = complement

Question 2

What is adaptive immunity? Cells involved?

Answer 2

Specific programmed defense in response to Ag presence

Cells = lymphocytes + antibodies

Question 3

Name some physical/chemical barriers of innate immunity.

Answer 3

Skin
Ciliated lining of tracheobronchial tree 
Saliva 
Tears 
pH of stomach

Question 4

What are Pattern Recognition Receptors? Types?

Answer 4

Recognize aspects of microbes

Types = TLRs, NOD-like receptors, C-type lectin receptors

Question 5

What is signaled when TLRs are activated?

Answer 5

Synthesis and secretion of NF-kB and interferon regulatory factors (IRF)

NF-kB stimulates synthesis and secretion of cytokines and adhesion molecules that are critical for recruitment of neutrophils

IRFs stim production of Type-1 IFN (antiviral cytokine)

Question 6

If TLRs are lost from germline mutation, what class of disease can you get?

Answer 6

Immunodeficiency diseases

Question 7

What do NOD-like receptors recognize?

Answer 7

Products of necrotic cells = uric acid, ATP

ion disturbances = loss of K

microbial products

Question 8

What is the pathway signaled by NLRs?

Answer 8

Signal via inflammasome –> activates caspase-1 (cleaves IL-1 precursor to active form

Question 9

If there is gain-of-function of NLRs, what class of disease can you get?

Answer 9

autoinflammatory disease (will respond well to IL-1 antagonists)

autoimmune diseases (gout, atherosclerosis)

Question 10

What are characteristic of CLRs, RIG-lie, GPCRs, and Mannose receptors?

Answer 10

CLRs = fungal glycan recognition

RIG-like = intracellular nucleic acids (viral RNA) recognition

GPCRs = N-formylmethionyl recognition (prokaryotes, mitochondria)

Mannose = recognize mannose - bacterial cell wall constituent

Question 11

What are the generative organs involved in adaptive immunity? What occurs there?

Answer 11

Bone marrow

Thymus

Question 12

What are peripheral organs involved in adaptive immunity? What occurs there?

Answer 12

Lymph nodes = can interact with APCs and Ags in circulating lymph

Spleen = Lymphocytes can interact with blood-borne Ags

MALT (tonsils, adenoids, peyers patches) = allow lymphocytes and plasma cells to be in vicinity of Ags within mouth and intestinal tract

Question 13

What is occurring in the bone marrow in regards to immunity?

Answer 13

Primary site of hematopoiesis

Generation of lymphocyte stem cells

B-lymphocyte maturation

Question 14

What is occurring in the thymus in regards to immunity?

Answer 14

Maturation of T-lymphocytes (naive cells migrate from cortex to medulla)

Medulla contains:
maturing T-cells
dendritic APCs with high levels of MHC 1 and 2
Hassall corpuscles = squamous cell nests

Question 15

What mediates gene recombination involved in receptor encoding? What happens if it is mutated?

Answer 15

RAG-1 and RAG-2

No mature lymphocytes is RAG mutated

Question 16

How can a molecular assay using PCR determine if lymphocyte proliferation is polyclonal or monoclonal?

Answer 16

B/c T and B cells and their clonal progeny have unique DNA rearrangements and receptors

Analysis of Ag receptor gene rearrangements is valuable assay to erect tumors derived from lymphocytes (lymphoma)

Question 17

What are the types of T-lymphocytes?

Answer 17

Helper T-cells (CD4+) = stimulates B-cells to make Ab and activate other leukocytes to kill microbes

CTLs (CD8+) = kill infected cells

Regulatory (tregs) = limit immune response and prevent reaction against self-ag

Question 18

Describe MHC class 1.

Answer 18

All nucleated cells
+ platelets

Typically recognize intracell Ags (viral, tumor)

Ags processed into peptides by proteosome –> transport to ER, load into groove of MHC –> complex travels to surface

Presentation to CTLs

Question 19

Describe MHC class 2.

Answer 19

Ag presenting cells

Typically recognize extracellular Ags (bacterial, allergens)

Ags process into peptides by endolysosomal enzymes –> vesicles form MHC complex

Presentation to Helper Ts

Question 20

What chromosome encodes HLA molecular structure?

Answer 20

Chromosome 6

Thousands of alleles

Question 21

What type of immunity are B-lymphocytes responsible for?

Answer 21

Humoral immunity - Ab production

Question 22

Describe the characteristics of Ab classes.

Answer 22

IgM - first Ig produced, pentamer

IgG - long half life, fetal protection

IgA - mucosal defense, colostrum

IgE - short half life, regulate hypersensitivity reactions

Question 23

What activated and inhibits NK cells?

Answer 23

Activated by damaged cells - recognized by NKG2D receptors

Inhibited by self MHC and class 1 MHC

Question 24

What is clonal selection? clonal deletion?

Answer 24

When an Ag is introduced, particular lymphocyte targeted against Ag is preferentially activated and produces identical cells

Clonal deletion is when lymphocytes are killed if they recognize self-ag

Question 25

Describe TH1 cells. What cytokines? Stimulated by? Triggers what? Implicated in?

Answer 25

Cytokines produced: IFN-Y
Stim by: IFN-y, IL-12

Triggers macrophage activation, IgG production
Good for killing intracellular microbes

Implicated in: autoimmune diseases, chronic inflammatory disease, granulomatous inflammation

Question 26

Describe TH2 cells. What cytokines? Stimulated by? Triggers what? Implicated in?

Answer 26

Major cytokines produced: IL-4, IL-5, IL-13
Stim by: IL-4

Triggers stim of IgE production, activation of mast cells and eosinophils

Implicated in: allergies

Question 27

Describe TH17 What cytokines? Stimulated by? Triggers what? Implicated in?

Answer 27

Major cytokines produced: IL-17, IL-22
Stim by: TGF-B, IL-6, IL-1, IL-23

Triggers recruitment of neutrophils and monocytes
Good for killing extra cell bacteria and fungi

Implicated in: autoimmune, chronic inflammation dz, psoriasis, MS