INP midterm - IMMUNITY

Question 1

What is innate immunity?

Answer 1

initial protection against infection already present in a healthy individual

→ Block entry of intruders into host tissues

→ Rapid elimination of intruders that have succeeded in entering (not as specific as adaptive immunity)

Question 2

Innate immunity - inflammatory response. explain.

Answer 2

→ Chemical signaling mediates inflammatory response.

→ Injured cells produce histamine, inducing blood vessel dilation and capillary leakiness

→ Other molecules (various cytokines) stimulate release and attraction of leukoctyes to injury site

→ Small blood vessels dilate, allowing increased blood supply, redness, heat, swelling

→ Leakiness of capillaries allows movement of phagocytic cells to injury site

→ Cells engulf microorganisms and clean debris, including dying self cells

→ “Pus” (made up of dead cells and fluid from capillaries) accumulates at site of infection

→ Clotting proteins and platelets in blood begin repairing and sealing off infected area which prevents spread of infection to surrounding

Question 3

What are the five primary cell types used in the innate immune response?

Answer 3

1) PHAGOCTYES: neutrophils, macrophages and dendritic cells
2) natural killer cells
3) mast cells
4) eosinophils
5) basophils

Question 4

What are neutrophils?

Answer 4

→ 50-60% of leukocytes

→ they are the first cells to respond to most infections

→ their main target is bacteria and fungi

→ they self destruct as they destroy foreign invaders

→ they’re average life span is only a few hours-days

Question 5

What are macrophages?

Answer 5

→ 2-10% of leukocytes

→ they engulf and digest cellular debris and pathogens

→ they live much longer than neutrophils

Question 6

What are dendritic cells?

Answer 6

they’re involved in antigen presentation and link the innate and adaptive immune systems

Question 7

What are natural killer cells?

Answer 7

→ cells that attack cell membranes to cause lysis (production of perforin and granzyme)

→ they do NOT attack microorganisms directly

→ they are important in defense against viral infection and cancer

Question 8

What are mast cells?

Answer 8

→ cells involved in histamine release and in response to allergies

→ they reside in connective tissue and mucous membranes

→ they release granules containing histamine, heparin, and various cytokines when activated

→ they also release molecules to recruit neutrophils and macrophages

Question 9

What are eosinophils?

Answer 9

cells involved in allergic responses, asthma, immune response to helminths (parasitic worms/nematodes)

Question 10

What are basophils?

Answer 10

→ least common granuloctye

→ also involved in immune response to helminths (parasitic worms/nematodes)

Question 11

What is the complement system?

Answer 11

biochemical/enzymatic cascade that aids the ability of antibodies and phagoctyes to clear pathogens or mark them for destruction by other cells

Question 12

What are the important functions of the complement system?

Answer 12

→ Coats and promotes binding to antibodies and phagocytes

→ Chemotaxis in that it attracts macrophages and neutrophils

→ Clump foreign agents which makes it easier for antibodies and phagocytes to clear up the pathogens

→ Lysis of cells (MAC – membrane attack complex) by making pores on the surface of bacterial cells

Question 13

What are the three ways that the complement system can be activated?

Answer 13

1) Classical pathway
→ triggered by antibody binding, thus involves adaptive immunity)

2) Alternative pathway
→ more a part of innate response; involves direct binding of C3b to microbe)

3) Lectin pathway
→ triggered by binding of mannose binding lectin to mannose residues of microbial glycoproteins)

Question 14

What is adaptive immunity?

Answer 14

highly specific immune response that takes time to mount an attach against infection

Question 15

What are the two main types of lymphocytes involved in adaptive immunity?

Answer 15

B cells
→ for humoral (dealing with fluids in the humors) immunity
→ responsible for production of antibodies

T cells
→ for cell mediated immunity

Question 16

What are two main types of T cells?

Answer 16

1) helper T cells
→ help B cells in producing antibodies (have CD4)

2) cytotoxic T cells
→ can directly attack an intruder (have CD8)

Question 17

What are the antibodies (immunoglobulins) involved in adaptive immunity?

Answer 17

→ IgM

→ IgG

→ IgA

→ IgE

→ IgD

Question 18

IgM

Answer 18

→ early responder

→ only in bloodstream

Question 19

IgG

Answer 19

→ produced later in infection and is the most abundant in circulation

→ provides passive immunity for the fetus

Question 20

IgA

Answer 20

→ found in mucosal areas and the epithelial layer

→ it is the major antibody of breast milk

→ involved in autoimmunity

Question 21

IgE

Answer 21

→ associated with allergic exposure and binds to allergens

→ triggers histamine release from mast cells

Question 22

IgD

Answer 22

→ antigen receptor on B cells

→ involved in innate cell activation

Question 23

What are antibodies?

Answer 23

→ class of proteins called immunoglobulins (Ig)

→ each antibody has the ability to

1) bind to an antigen
2) assist in the elimination of that antigen

→ both functions are reflected in its structure

Question 24

How do antibodies work?

Answer 24

→ antibodies do not destroy antigen-bearing invaders directly - they “tag” foreign cells/molecules to mark them for destruction by phagocytic cells

Steps:

1) Neutralization.
2) Agglutination of cells/antigen
3) Activation of compliment system

Question 25

What is the difference between B and T cells?

Answer 25

B cells recognize intact antigens but T cells recognize antigens that are bound to cell-surface proteins called MHC

Question 26

What are MHC molecules?

Answer 26

→ MHC is Major Histocompatibility Complex/ Human Leukocyte Antigen (HLA)

→ they’re unique to every individual

→ two classes of MHC (I and II)

Question 27

MHC I. explain.

Answer 27

→ found on all nucleated cells

→ bind peptides derived from foreign antigens synthesized within the cell

→ any body cell that becomes infected or cancerous can display peptide antigens via MHC I

Question 28

MHC II. explain.

Answer 28

→ made by antigen presenting cells (dendritic, macrophages, B cells)

→ bind peptides derived from foreign materials that have been phagocytosed

Question 29

What is perforin?

Answer 29

molecule released by Tc cells that cause cells to lyse

Question 30

What are cytokines?

Answer 30

molecules released by Th cells that cause the destruction of antigens

Question 31

What do plasma cells do?

Answer 31

B cells that secrete antibodies

Question 32

What is the special function of the Fc region of an antibody?

Answer 32

it can bind to Fc receptors and activate other immune cells to kill pathogens or induce internalization of the Ig-pathogen immune complex by phagocytosis

Question 33

Why is the gut immune response so complicated?

Answer 33

Despite gut microbiota being essential to health by stimulating and developing the maturation process of the immune system, it is ALSO the primary site of entry of pathogenic agents

→ opportunistic invasions of host tissue can result in the breakdown of the symbiotic host-microorganism relationship and lead to chronic inflammation

→ it also has to avoid potentially harmful overreactions to microbiota and dietary antigens that can damage intestinal tissues or alter metabolic functions of the microbiota

Question 34

How does the gut cope with this challenge?

Answer 34

by minimizing the microbial-epithelial cell contact through:

1) MUCUS layer → produced by goblet cells that is resistant to bacterial penetration
2) Anti-microbial proteins → produced by Paneth cells-> Defensins,Lectins, Lysozymes
3) Antibodies/Immunoglobulins such as IgA

Question 35

What is an allergy?

Answer 35

→ most common disorder of the immune system characterized by exaggerated (hypersensitive) responses of the body’s immune system to certain antigens (allergens)

→ IgE- and mast-cell mediated

→ caused by an imbalance between Th1 (pro-inflammatory) and Th2 (anti-inflammatory) responses

Question 36

Describe the sequence of events of allergies.

Answer 36

1) Production of IgE by B cells in response to an allergen (in predisposed individuals/their first exposure)
2) Binding of IgE to mast cells (through the Fc region) called sensitization
3) Antigen re-encounter and cross-linking of bound IgE by re-introduced antigen
4) Release of mast cell mediators (degranulation) where these mediators are known as histamines and other inflammatory mediators which causes inflammation, including dilation and leakiness of blood capillaries and tissue damage → the release of these molecules leads to well-recognized symptoms

Question 37

What is anaphylaxis?

Answer 37

→ it is the most severe form of immediate hypersensitivity caused by widespread and sudden mast cell degranulation in response to an antigen.

→ abrupt dilation of peripheral blood vessels causes sharp drops in blood pressure

→ it can involve multiple organ systems where death can ensue from severe hypotension coupled with respiratory and cardiovascular complications

Question 38

What are the causes of food intolerance?

Answer 38

→ lack of specific enzymes seen in patients with lactose or alcohol intolerance

→ inability to absorb nutrients

→ biochemical/pharmacologic reaction to food

→ NOT IgE-mediated and do NOT involve abnormal immunologic mechanisms

→ non-IgE immune response to food like celiac disease (autoimmune disease)

Question 39

What are some common forms of food intolerance?

Answer 39

→ peanut
→ milk
→ shellfish
→ tree nuts
→ egg
→ fish
→ wheat
→ soy

Question 40

What is celiac disease?

Answer 40

→ an autoimmune disorder

→ defined as a T-cell mediated inflammatory disease of predominantly small bowel triggered by gluten in the diet from wheat, rye and barley in persons who are generally susceptible (defect in the mucosal processing of gliadinin celiac patients)

→ trigger is the consumption of gluten in wheat and related cereals (gluten is the storage protein of wheat)

→ leads to villous atrophy and decreased surface area for nutrient absorption → leads to down regulation of nutrient transport proteins in the intestinal epithelia

→ contains a genetic component which is linked to specific class II HLA genes (DQ2/DQ8)

Question 41

How is celiac disease diagnosed and treated?

Answer 41

Diagnosis
→ serum assay/immunoblot analysis to determine anti-gluten antibodies, anti-deamidated gluten antibody, or anti-transglutaminase 2 antibody

Treatment
→ Avoidance/lifelong diet free of gluten

Question 42

What is non-celiac wheat sensitivity?

Answer 42

→ it is gluten/wheat sensitivity that has negative celiac disease serologic markers, biopsy and IgE antibodies

→ lack of clear objective clinical findings/no biomarkers

→ condition associated with experiencing various symptoms in response to ingestion of wheat, rye and barley in individual in whom CD and wheat allergy have been ruled out

Question 43

What is the pathogenic mechanism of celiac disease?

Answer 43

1) Gluten peptides, due to increased intestinal permeability, are able to pass through the mucosal epithelial cells, into lamina propria – these gluten peptides contain toxic epitopes that cannot be digested by human pancreatic or intestinal proteases and thus renders it available to trigger an immune response
2) The peptides then become deamidated and negatively charged (makes the peptides more immunogenic) → native gliadin peptides or gliadin peptides rendered more negatively charged bind to positively charged pockets of HLA-DQ2/DQ8 molecules expressed on the outer membrane of APCs
3) Gluten-specific T cell contains a TCR and CD4 that recognizes the antigen of the APC and releases cytokines that recruit gluten-specific B cells that secrete anti-gluten antibodies and the Tg2-specific B cells that secrete anti-tG2 antibodies
4) Release of matrix metalloproteinases in response to cytokines causing cell death of the intestines and degradation of the mucosal matrix
5) Gliadin is also capable of activating the innate immune system by reprogramming intestinal epithelial cytotoxic T lymphocytes into NK-like cells → leads to release of cytokine IL-15 from the epithelium which participates in intestinal inflammation

Question 44

Describe the pathogenesis of Guillain-Barre Syndrome (autoimmune disease).

Answer 44

→ the primary target are the peripheral nerves triggered by a particular bacterium in contaminated raw meat

→ the humoral immune response is antibody to peripheral nerve glycolipids, not proteins, on the myelin of neurons

Question 45

What is molecular mimicry?

Answer 45

→ a foreign antigen shares a sequence of structural similarity with self-antigens

→ these sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides

→ upon activation of B or T cells, it is believed that these “peptide mimic” specific T or B cells can cross-react with self-epitopes thus leading to tissue pathology (autoimmunity)

→ there is a growing failure to recognize self-antigens as “self” (LOSS of the ability for an individual to discriminate between self and non-self

Question 46

How do macronutrient deficiencies affect immune function?

Answer 46

Macronutrient deficiencies such as protein is important because it is associated with:

a. altered T cell subsets
b. decreased cytokine response
c. decreased antibody function
d. increased risk of infection

Macronutrient deficiencies such as lipids is important because it is associated with:
a. lymphoid atrophy and depressed antibody responses

Question 47

How do micronutrient deficiencies affect immune function?

Answer 47

a. atrophy of lymph organs such as the thymus which is the primary origin of T cell development
b. T cell deficiency
c. decreased phagocyte and NK cell function
d. barrier defects of the mucous membranes

Question 48

How does overnutrition affect immune function?

Answer 48

Overnutrition of lipids leads to suppressed immune response particularly complement synthesis and cell-mediated immune function

Question 49

How does obesity affect immune function?

Answer 49

obesity has been associated with depressed immune response

Question 50

What are some considerations for the immune systems of infants?

Answer 50

undernutrition in infants and children leads to life-threatening infections

Question 51

What is the role of nutrition in postnatal immunity?

Answer 51

breast milk prevents infection and enhances immune function and may be beneficial against development of allergy and autoimmunity (breastmilk contains immunoprotective components like anti-microbial factors such as EGFs that decreases permeability to infectious agents, lactoferrin which contains protein for proper antibody production; one other interesting anti-microbial factor are oligosaccharides which act as soluble “decoys” to foil attempts of pathogens to attach and invade host intestine)