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Question 1

Allogenic vs. Autogenic

Answer 1

Allogenic: two members of the same species who are genetically different

Transplant will be rejected unless therapeutic intervention

Autogenic: cells or tissues that are derived from the same individual, twins count as autogenic

Question 2

Major Histocompatibility Complex

Answer 2

Cluster of genes on Chromosome 6, also called human leukocyte antigens

Present on WBCs but not RBCs, allows adaptive immune cells to distinguish self from non-self

Question 3

MHC Class I

Answer 3

HLA-A to HLA-G but no HLA-D

HLA-A,B,C are highly polymorphic and present antigens to T cells, heavy chains with monomorphic beta2-microglobulin

Expressed on almost all cells but not RBCs

Question 4

MHC Class II

Answer 4

HLA-DM,DO,DP,DQ,DR

HLA-DP,DQ,DR are polymorphic and present antigens to T cells

Expressed on professional antigen presenting cells like APCs, dendritic cells, macrophages, and B cells

Question 5

Antigen Processing and Presentation

Answer 5

MHC Class I: intracellular proteins degraded by proteasomes into peptide antigens, transported to ER by transporter associated with antigen processing (TAP), loaded onto peptide-binding glove of MHC Class I molecules

Present to CD8 T cell (Cytotoxic T cell) to kill/lyse

MHC Class II: same but professional APCs engulf proteins in extracellular environment and degrade via phagolysosome

Present to CD4 T cell (helper T cell) to release cytokines

Question 6

Antigen Presentation by B cell

Answer 6

B cell is triggered when it encounters its antigen binds, engulfs antigen and degrades in phagosome, displays antigen fragments on its MHC Class II receptor, helper T cell looks at MHC Class II receptor and releases cytokines to help the B cell multiply and mature into plasma cells that release antibodies

B Cell Activation: Helper T cells (TH1 or TH2) provide signals to B cells via CD40L/CD40 and cytokines that activate B cells and induce isotope switching, CD4 T cells become reactivated by antigen presentation and produce more cytokines

Question 7

Killing of Pathogens by B Cells

Answer 7

Classical Complement Pathway

Opsonization: Fc receptors on phagocytes and NK cells bind to the Fc end of antibodies to mediate endocytosis and lysis

Question 8

Thymic Education

Answer 8

Primary purpose of T cell development is to generate diverse repertoire of T cells that distinguish between self and nonself

Question 9

T Cell Development Pathway

Answer 9

T cell precursors originating from the bone marrow to the thymus in the blood

Mature naive T cells leave the thymus and travel to the secondary lymphoid tissues like lymph node, spleen, gut associated lymphoid tissue (GALT)

Question 10

DiGeorge’s Syndrome

Answer 10

Fail to develop a thymus, severely immunocompromised

Deletion in Chromosome 22

Question 11

Cell Surface Markers Associated with T Cell Development

Answer 11

1. CD34+ proginetor cells enter thymus via blood vessels
2. Interact with stromatolites epithelial cells and the immature T cells divide and differentiate
3. Stem cell markers (CD34 and CD44) are downregulated and T cell-specific markers are upregulated
4. IL-7 produced by stromatolites cells is a critical initial step in thymocyte differentiation

Mutations in IL-7 receptors result in no T Cell Development and Severe Combined Immunodeficiency Syndrome

Question 12

Double Negative T Cell Proginetor

Answer 12

Happens in sub-capsular region of thymic cortex

Beta, gamma, and delta rearrangement occur first

1-5% have gamma and delta chains rearrange first, no MHC presentation on surface, like innate immune cells since traffic to Inflammation site due to specific chemokine receptor expression
Un-committed double-positive thymocyte has beta chain with CD8 and CD4

Alpha, gamma, and delta rearrangement, gamma/delta rarely happen and lose CD4/8

Question 13

Positive Selection

Answer 13

Retina Cells that recognize self MHC

Occurs only for alpha/beta T cells, happens in cortex of at cells

Only 2% of double positive thymocytes hav T cell receptors that can recognize self, positive selection retains those that can recognize self, destroy others

Cortical epithelial cells express self peptides, if a T cell receptor (alpha/beta chain receptor) binds effectively to MHC/peptide complex a survival signal is sent to the T cell, weak binding leads to T cell apoptosis

If TCR binds to MHC Class I then the CD8 receptor will also bind to MHC Class I Receptor, the CD8 receptor is upregulated and CD4 is downregulated, opposite for MHC Class II

Question 14

Bare Lymphocyte Syndrome

Answer 14

No surface expression of MHC Class I or II molecules, due to transport defect

Severely immunocompromised

Question 15

Negative Selection

Answer 15

Deletes self-reactive T cells

Occurs in the cortico-medullary junction of thymus

Involves dendritic cells and macrophages

Tight binding to MHC/peptide complex results in cell death

Autoimmune regulator (aire): TF expressed in thymus that promotes expression of different tissue genes in thymus at low levels

Autoimmune Polyendicrinolathy-Candidiasis-Ectodermal Dystrophy: die from increased susceptibility yeast infections, autoimmune problems

Question 16

TCR Gene Rearrangement

Answer 16

Beta Chain Rearrangement: has V, D, J, and C regions (Alpha chain doesn’t have D region)

D region combines with J and excise DNA between, V region combines with DJ region and excise DNA in between

Alpha Chain a Rearrangement: V region combines with J region

How get vast heterogeneity:
1. Multiple V, D, and J segments

2. Addition or deletion of bases during gene Rearrangement
3. Different isotypes of alpha and beta for pairing

Question 17

Naive T Cell Adhesion to Lymph Nodes

Answer 17

Lymph nodes express chemokines CCL19,21 from stromal and dendritic cells

Naive T cells express CCR7, a receptor for those chemokines

Get tighter binding and then do diapedesis

Question 18

Activation of Naive T Cells

Answer 18

Dendritic Cells and Macrophages are APCs, express small amount of MHC receptors normally but have others like scavenger and TLR, activation increases expression of MHC and B7

Signal 1: TCR of T Cell binds to MHC/peptide Complex on APC

Signal 2: costimulation, CD28 of T Cell binds to B7 (CD80/CD86) on APC

Immunological synapse: region of contact/comm. between T cell and APC

Question 19

T Cell Receptor Signaling

Answer 19

TCR is associated with the CD3 complex, cytosolic tails of the CD3 complex have immunoreceptor tyrosine-based activation motifs (ITAMS) which associate with protein tyrosine kinases (PTK)

PTKs (like Zap70) activated by TCR binding to MHC receptors, phosphorylated tyrosines in ITAMs

Signaling molecules bind to ITAMs and become activated, lead to changes in gene transcription

NkB induces expression of IL-2 and the alpha chain of IL-2 to make high affinity receptors, proliferation to get clinal expansion

Question 20

CTLA-4

Answer 20

Unregulated on activated T cells, dampens T cell proliferation and cytokine production

Deficiency causes lymphoproliferative disease

Question 21

CD4 T Cell Types

Answer 21

TH1: make IFN-gamma and IL-2
Activate macrophages/B cells, make opsonizing antibodies like IgG1

TH2: make IL-4 and IL-5
General activation of B cells to make antibodies

IFN-gamma and IL-4 suppress the differentiation of the other cell type, infections become biased towards one type of TH cell like Mycobacterium leprae

Question 22

Macrophage Activation

Answer 22

Need two signals from CD4 TH1 Cells-

1. IFNgamma
2. CD40

Activation produces microcidal substances

Question 23

B Cell Activation

Answer 23

Signal 1: antigen binds to B cell receptor

Signal 2: CD40 ligand on T Cells binds to CD40R, most potent activating signal for B cells, needed for isotype class switching

Triggers NF-kB mediated transcription of Adhesion molecules, strengthens cognate interaction between B and T cell

TH2 cell releases IL-4 to cause B cell proliferation/differentiation

Question 24

CD8+ T Cells (Cytotoxic T Cells)

Answer 24

Cytotoxic T cells collide with infected cells, Adhesion molecules allow close contact for TCR to bind to MHC Class I

If infected: lytic granules in cytotoxic T cells will localize in area of cell contact, have perforin to make hole and granzyme to degrade proteins that can start apoptosis

Infected cell dies from apoptosis, cytotoxic T Cell can go to next cell

Question 25

Immunological Memory

Answer 25

Most effector T cells die after responding to an infection, memory T cells live though

Memory T cells do immune surveillance in spleen, blood, and tissues

Do not depend on costimulation the second time so can use lower levels of antigen

Secondary T cell response is rapid, reason for vaccines

Question 26

Integumentary System Components and Functions

Answer 26

Components-

1. Skin
2. Accessory structures and epidermal derivatives: oil/sweat glands, hair, nails

Functions-
1. Protection: physical, chemical, pathogenic, water loss/uptake, UV radiation

2. Sensation
3. Temperature regulation: sweat glands and dense vasculature do this
4. Metabolic: make Vitamin D
5. Waste elimination: ammonia, urea, water, salt

Question 27

Layers of the Dermis

Answer 27

1. Papillary Layer: superficial, loose connective tissue, ridges increase surface area of contact
2. Reticular Layer: deep, dense irregular connective tissue, type III collagen and some elastic fibers

Question 28

Skin Thickness

Answer 28

Gross Anatomy: epidermis and dermis

Upper back thickest at 5 mm, thinnest is scalp at 1 mm

Histology: epidermis only

Thickest is on soles of hands/feet at 400-1400 um, thinnest is 75-150 um

Question 29

Fascia

Answer 29

Sheet of connective tissue that separates, supports, and/or interconnects different structures

Provide route for blood vessels, nerves, and lymphatics to travel

Question 30

Superficial facia
Subcutaneous Layer
Hypodermis

Answer 30

Below dermis and above deep fascia, made of white adipose tissue and loose connective tissue, varies in thickness

Has an extensive vascular network

Binds skin to underlying tissue but allows skin movement, energy reserve and insulator

Question 31

Deep Fascia

Answer 31

Below hypodermis and above muscle, made of dense connective tissue

Intermuscular septa form muscular compartments and permit travel of neurovascular structures to the muscles, retinacula to hold tendons in place, elastic stocking around muscles to help compress veins better

Different names based on body location