tips for mclean's sections final

8/10/2019 Tips for McLean's Sections Final

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1. Diff between innate and adaptive immunity

Innate immunityis the fast responding, non specific, first line defense that we are born with and uses

recognition and recruitment to initiate phagocytosis and inflammation.

Adaptive immunityis the slow responding,specific defense we acquire.

2. Hematopoiesis (chart)

3. Immunogenicity vs antigenicity

Immunogenicityis the antigens ability to elicit this response

Antigenicity is the ability of an antigen to bind to the products that come from an immune response like

antibodies or surface receptors

4. Antibody structure

An epitope is the part of the antigen to which an antibody binds

Paratopes are the parts of the antibody that binds to the epitope

The variable regionof an antibody varies from one antibody to another and is where it binds to the pathogen

(this makes it the paratope)


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The constant regionof the antibody contains binding sites for phagocytes and compliment and is responsible for

recruiting cells for pathogen destruction

Antibodies/Igs are composed of 4 chains. 2 Heavy chains and 2 light chains linked by disulfide bonds. The light

chains are either 2 lamda L chains or 2 Kappa L chains.

There are 5 types (isotypes) of heavy chains. Different isotype=different function. IgG, IgM, IgD, IgA, IgE.The

constant regions of the heavy chain determines the Igs isotype

Subclasses of isotypes are designated by a number after the name to show its abundance. i.e; IgX1 is more

abundant than IgX2 is more abundant than IgX3 etc

The hinge region of the antibody is the flexible part of the y that allows the Ig to be flexible.When a normal antibody is digested by pepsin, the disulfide bonds break and you are left with a F(ab)2

fragment and the Fc fragments (the stem of the Y)

When the antibody is digested by papain, you are left with a Fab fragment and Fc fragments.

The Fab and the F(ab)2 fragments contain the antigen binding sites (paratope)

The paratope is composed of 3 regions of high variability, HV1, HV2 and HV3

Isotype=large difference in c regions of both chains. Allotypes=small diff. within one species in C regions of both

chains. Idiotypes=small differences in v regions of both chains within one individual

H chain V domains are encoded by 3 gene segments: Vh, Dh (diversity segment), Jh

Heavy chain=VDJ, light chain= VJ

5. MHc class 1 ad 2 CD8 and CD4.

MHC class-1CD8 cytotoxic T cells

MHC class-2CD4 helper T cells (TH1/TH2)


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6. B cell development chart (surrogate light chain) IgM and IgE on surface

B cell differentiation in the bone marrow involves the rearrangement ofimmunoglobulin genes. This leads to the expression in the cell surface membrane of a B cell

receptor (BCR) comprised of an immunoglobulin molecule with twoclosely associated transmembrane molecules known as Ig and Ig

7. Functions of diff immunoglobulins (IgA, etc.)

IgM antibodies are produced in large amounts and are important in protective immunity:

-Can form a pentamer


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- A soluble form is produced in a primary immune response

- When it is bound to B cells it forms the B cell receptor.

-It functions in complement activation with high activity

IgA:

-The dimeric form is most common. Dimers are joined by J chains and secretory component

- It has 2 subclasses: IgA1 (93%) and IgA2

-Predominant antibody in salivaand tears.the antibody passed through breast feeding

IgE:

-It has the shortest half life of 2 days

-It is present on surfaces of basophils and mast cells.

-It is involved in allergic reactions

IgD antibodies are produced only in small amounts and have no known effector function

IgG is the only antibody that Can pass through the placenta

8. Cytokines

Cytokines are soluble molecules that regulate the immune system and facilitate communication between cells othe immune system in order to maintain homeostasis.

Macrophages secrete:

- IL-1:inflamation

- IL-6:activates T cells and stimulates B cell Ig production

- TNF-a: inflammation and activates neutrophilsTH1 cells secrete:

- IL-2: T cells proliferation, NK activation/proliferation

- INFy: activates macrophages, inhibits TH2 cells

- TNFb:inflammation, stimulates CD8 T cells to kill target cells

TH2 cells secrete:

-IL-4:TH2 proliferation, B cell proliferation, IgE synthesis

-IL-5: eosinophil activation

-IL-10: inhibits TH1 production and macrophage production


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-IL-13: B cells proliferation

9. TH1/Th2 cells

TH1 produce cytokines that enhance cell mediated cytotoxicity

They activate macrophages, cytotoxic T cells, and participate in delayed type hypersensitivity.

Cytokines from TH1 cells aid Tccells development into cytotoxic T lymphocytes

TH2 produce cytokines that enhance humoral immune responses, allergic reactions and immune responseagainst parasites. These cytokines aid B cells development into antibody-producing plasma cells.

-Activated TH1 and TH2 cells produce cytokines which trigger the production of more

TH1 and TH2 cells.

-TH1 and TH2 also down-regulate each other:

TH2 secrete IL-10 which inhibit TH1 response.

TH1 secrete IFN-which inhibit TH2 response.

IL-3 IS THE ONLY CYTOKINE TO ACTIVATE BOTH TH1 AND TH2 CELLS

10.Compliment cascade:

Complement systema system of blood proteins that permanently marks a pathogen or antigen as foreign and targets itfor removal by the immune system. The complement components are soluble proteins that are produced by theliver.Many complement components are zymogensan inactive form of an enzyme. The initiation of the complementreaction starts a chain reactions that results in successive activation of zymogens by cleavage at specific sites. Cleavageusually produces two fragments: The larger fragment usually has enzymatic activity (activates the next component in thereaction.)The smaller fragment stimulates inflammation.

The most important and abundant complement molecule is C3. All 3 complement pathways produce enzymes that act as C3

convertase which cleaves C3 to C3a and C3b. C3b is what binds to the surface of the pathogen and does 3 things:

-recruitsinflammatory cells

-opsinization(coating) of the pathogen, marking it for phagocytosis

-activate a cascade that leads to the formation of C3-C9 which makes a ring in the pathogen cell membrane called the membrane

attack complex. This leads to the perforation f the membrane and lysis of the cell


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11.Classical, leptin, alternative pathways (compliment)

The complement system uses 3 different strategies to recognize pathogens, each of which activates the

complement pathway:

1. Classical pathwaytriggered by antibodies bound to the surface of the pathogen. Only

pathway in which antibodies are directly involved (adaptive immunity)

2. Alternative pathwaytriggered directly by components of bacterial cell surfaces.3. Lectin-mediated pathwaytriggered by mannose binding proteins that are bound to

molecules on the surface of pathogens.

(Mannose associated serine protease)

(Mannose binding lectin)


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12.Anaphilotoxins (c5a, C3a)

The smaller complement components 3a, C4a and C5a are known as anaphylatoxins. Anaphylatoxins induce

anaphylaxis, an acute systemic inflammatory response. Order of potency: C5a > C3a > C4a


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13.Know how each compliment cascade is triggered

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14.Hypersensativity reactions 1-4

The over reactions of the immune system to harmless environmental antigens (allergens) are called

hypersensitivity reactions:

Type 1 hypersensitivity rections:

- Immediate allergic reactions

-when Fc receptors on a mast cell are crossed linked by an antigen biding across IgEs on the surface, it signals

the release of preformed granules of histamine that lead to inflammation. And after activation granules ot

leukotrienes are released which cause vascular permeability

- In the skin, a wheal and flare inflammatory reaction will occur within minutes of exposure because of

histamine release-6-8 hours after, the late phase will occur due to the leukotrienes and will cause swelling due to the

recruitment of leukocytes.

Type 2 hypersensitivity reactions:are caused by antibodies that are specific for altered components of human

cells. Drug molecules can bind to the surfaces of platelets and RBCs and create new epitopes to which the

immune system is not tolerant. The new eopitopes stimulate the formation of IgM and IgG antibodies that are

specific for the drug markers on the surface.

Type 3 hypersensitivity reactions: are caused by immune complexes formed from IgG and soluble antigens in

circulation. These are produced in most immune responses and the larger complexes are taken up by

phagocytosis and removed form circulation, but small complexes are not easily removed and can deposit in

blood vessel walls. Once enough has accumulated they can cause an inflammatory response which is dangerous

Type 4 hypersensitivity reactions:are the delayed hypersensitivity reactionscaused by effector T cells that are

sensitive to the antigen. It occurs 1-3 days after infection. Ex; t.b. test. poison ivy/oak


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15.Leptin

-is a satiating hormone that inhibits hunger and the desire to eat.

-deficiency leads to obesity because of constant hunger. These people will have leptin levels that rise along with

BMI to try to diminish appetite, but it doesnt work because of leptin resistance.

16.Adiponectin

-inhibits inflammation and protects against insulin resistance and cardiovascular resistance.

-found in high levels in lean people.Researchers trying to find way to use in obese people to lower disease risks

17.How to calculate how many kcals are in a gram of fat.

1 kcal= 1 food Calorie= 4.2 Kilojoules

1lb. of fat=3500 kcal

1 gram of fat= 9 calories=9kcal.

e.g.; 5 grams of fat=45 kcal

18.Vitamin deficiencies

See excel chart

19.BMI calculations/rangesA healthy BMI is 18.5-24.9

BMI = weight (kg)

height (m)2

OTHER KEY POINTS1) Proteins are the best and most potent immunogens

2) Subcutaneous routes of antigen administration elicit the strongest of all immune responses

3) Pokeweed mitogens are the only mitogens to activate both B and T cells

4) IgG is the ONLY antibody that can pass through the placenta

5) IgA is the antibody passed through breast milk


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6) Bare lymphocyte syndrome is a rare disease characterized by defective TAP proteins and results in

retention of the MHC class-1 in the ER because it never receives the peptide antigen. It also results

in poor CD8 Tcell response

7) Know the autocrine, paracrine, endocrine actions (#8)

8) IL-3 is the ONLY cytokine that activates both TH1 and TH2 cells

9) 2 ways cytotoxic T cells induce apoptosis:

- Lytic granules: perforinforms holes in the target cell and granzymegoes through the hole and

initiates apoptosis

- Cell surface molecules: Fas-ligand on the membrane of the cytotoxic T cell binds to the Fas

receptor on the target cell and initiates apoptosis

10)A granuloma forms when other immune responses are unsuccessful. It is an area of chronic

inflammation composed of a giant cell of macrophages infected with resistant pathogens,

surrounded by a layer of activated T cells. The granuloma cuts the infected cells off from the blood

supply which leads to there death

11)C1INH (C1 esterase inhibitor) is used to inactivate the classical compliment pathway at key steps to

prevent if from getting out of control. Hereditary angioedemais a deficiency of C1 esterase which

leads to the classical complement pathway getting out of control and causing uncontrolled swelling

(face)

12)Disaccharides

Maltose = glucose + glucose

Sucrose = glucose + fructose

Lactose = glucose + galactose

13)Type 1 diabetes= no insulin produced

Type 2 diabetes= insulin resistance

14)Glycemic response= how high glucose rises after eating and how quickly it returns to normal

15)Glycemic index=classification of foods by their potential to raise blood glucose

16)Lipid density= protein content. So , VLDL (very low density lipoprotein) has a very low protein

content and a high fat content.

LDL=bad cholesterol, causes deposits

HDL=good cholesterol, cleans cholesterol form blood


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17)elevated LDL=increased risk of chronic heart disease (CHD)

18) statin drugs decrease cholesterol by inhibiting conversion form acetyl CoA

19) linoleic acid is an essential omega-6 fatty acid

a-linoleic acid is an essential omega-3 fatty acid

20)

21) Nitrogen balance occurs when the amount of nitrogen consumed equals that of the nitrogen

excreted in the urine, sweat, and feces. In children or in individuals undergoing healing, there is a netincrease in the amount of nitrogen in the body. Positive Nitrogen Balance. In wasting or degeneration

there is a Negative Nitrogen Balance

22) When excess protein is eliminated from the body as urinary nitrogen, it is often accompanied by

increased urinary calcium, increasing the risk of nephrolithiasis (kidney stones)and osteoporosis

23)When carbohydrate intake is low, amino acids are deaminated to provide carbon skeletons for the

synthesis of glucose. If carbohydrate intake is less than 130g/day, substantial amounts of protein are

metabolized to provide precursors for gluconeogenesis. Usually from muscle

24)2 forms of PEM (protein energy malnutrition)

HMG-CoA

reductase


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-kwashiorkor: caused from sudden food deprivation (acute)due to protein deficiency or illness. Main

symptom=edema(belly)

-marasmus: caused by severe food deprivation of a long period (chronic). Symptoms: stunted growth

muscle wasting, anemia

25)visceral fat is associated with increasedrisk of heart disease, stroke, diabetes, hypertension

26)LPL (lipoprotein lipase) removes triglycerides from blood for storage in adipose tissue and muscle

cells

27)after large weight loss,the body tries to restore the weight lost, so LPL activity increases, making

regain of weight easier.

28)the obesity gene is ob, and codes for leptin

29)Anorexia nervosa=refusal to maintain weight, fear of gaining weight.

Bulimia nervosa= binging and purging

Binge eating disorder= binge eating with little restraint

tips for mclean's sections final

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