MCB 734 Immunology Exam 1

Functions of the immune system (5)

- identify foreign Ag vs self Ag

- designate foreign origin

- recruit effector cells

- eliminate pathogen/threat

- prevent recurrent infection

The immune system is broken down into

- innate immunity

- adaptive immunity

Innate immunity

- 1st line of defense/immune system response

- rapid detection and response to Ag/pathogen

The innate immune system tends to react/occur

within minutes to hours after identification of an Ag/pathogen (rapid)

Adaptive immunity (acquired immunity)

- 2nd line of defense/response

- development of specific cells that can respond to subsequent infection more efficiently (faster and better)

The adaptive immune system tends to react/occur

days to weeks after Ag/pathogen recognition (slowly)

All immune cells in the body are derived/originate from

bone marrow (BM)

The immune cells that originate from BM are called

pluripotent hematopoietic stem cells (PHSC)

PHSCs differentiate into what two types of progenitor cells?

Common myeloid progenitors

Common lymphoid progenitors

Common myeloid progenitors

- immune cells derived from PHSCs

- give rise to granulocytes and monocytes, and immature dendritic cells

Common myeloid progenitors give rise to monocytes and immature dendritic cells, which will further differentiate primarily into

Monocytes >>>>>>>Macrophages and Mast cells

Immature DCs >>>>>>Dendritic cells (DCs)

Common myeloid progenitor cells will develop into cells that are primarily apart of the innate/adaptive immune system?

Innate

Common lymphoid progenitors

- immune cells derived from PHSCs

- give rise to B, T, and NK cells

Common lymphoid progenitors give rise to B, T, and NK cells, each which can further differentiate into

- B cells >>>> Plasma cells

- T and NK cells >>>>>> activated T and NK cells

Common lymphoid progenitors will develop into cells that are primarily apart of the innate/adaptive immune system?

adaptive immune system

Myeloid cells (innate cells)

- immune cells derived from common myeloid progenitors

- includes macrophages, dendritic cells, (granulocytes:) neutrophils, eosinophils, basophils, and mast cells

Macrophages

- myeloid cells/innate immune cells

- capable of phagocytosis, bactericide, and antigen presentation

Dendritic cells (DCs)

- myeloid cells/innate immune cells

- tissue resident cells

- primarily uptake Ag in periphery (tissue) and present Ag as well

DCs uptake Ag via

macropinocytosis

The granulocytes include

- neutrophils

- eosinophils

- basophils

- mast cells

Neutrophils

- myeloid cells/innate immune cells

- capable of phagocytosis

- primarily bactericidal (respond to bacterial pathogens)

Eosiniphils

- myeloid cells/innate immune cells

- primarily target parasites (respond and kill Ab coated parasites)

Basophils

- myeloid cells/innate immune cells

- primarily involved in allergic responses and anti-parasitic immunity

Mast cells

- myeloid cells/innate immune cells

- primarily release histamine granules

__________ cells link the innate and adaptive immune system by __________

- Dendritic cells

- uptaking Ag as an innate immune cell and presenting it to B and T cells

While NK cells are considered to be apart of the adaptive immune system, they function in innate immunity by

releasing granules that target virus-infected cells

Lymphocytes (adaptive immune cells)

- immune cells derived from common lymphoid progenitors

- included B, T, and NK cells

B cells

- a type of lymphocyte/adaptive immune cell

- primarily produce Abs in response to a specific Ag

T cells

- a type of lymphocyte/adaptive immune cell

- primarily bind to presented Ag, activate and proliferate into effector cells

Lymphocyte maturation

- cells 1st mature in either BM or thymus (primary lymphoid tissue)

- cells travel to finish maturation in 2ndary lymphoid tissue

Primary lymphoid tissue includes

The BM and thymus

B cells develop/mature in which primary lymphoid tissue?

Bone marrow

T cells develop/mature in which primary lymphoid tissue?

Thymus

The secondary lymphoid tissues include

- Lymph nodes (LN)

- tonsils

- spleen

- Peyer's Patch (small intestine)

To reach a secondary lymphoid tissue (ex. LN), lymphocytes circulate the body via

High endothelial venules (HEVs)

Circulating lymphocytes know to stop circulating once they reach a site of infection due to

- chemical signals being produced at the site of infection

- signals are either cytokines or chemokines

Cytokines

- chemicals secreted by cells @ infection site

- signal/signals used for cell to cell interaction and communication

Chemokines

- chemicals secreted by cells @ infection site

- signal/signals used to recruit/stimulate cells to migrate to the site

Pattern recognition receptors (PRRs)

receptors of innate immune system cells that detect and bind to Ag

PRRs binding to antigen is the initial discrimination between

self and non-self Ags

PRRs specifically recognize ________ on pathogens?

PAMPs (Pathogen Associated Molecular Patterns)

When innate immune cells bind to antigen, they converse with the adaptive immune response by

- traveling to secondary lymphoid tissue via LN

- presenting antigen to respective lymphocytes, which activates naive cells

Clonal Selection

the process of selecting lymphocytes for maturation based on their receptor binding to an Ag (specificity), which leads to proliferation of only lymphocytes with successful/proper specificity

Clonal selection starts with the

production of lymphocytes with different receptors for Ags (different specificity)

After lymphocytes are produced w/different specificities, they are tested

- for self reactivity

- lymphocytes that are reactive to self Ag are eliminated/removed

After self-reactive lymphocytes are removed, ___________ _____________ are produced/remain

naive lymphocytes

Naive lymphocytes essentially wait around and hang out until

they bind to their respective, specific Ag

Once naive lymphocytes bind to their Ag, they immediately

- activate (internal signaling)

- proliferate

Proliferating/activated naive lymphocytes will produce cells

that are exactly identical to itself, meaning all proliferating cells will have a receptor that can identify the Ag being reacted to

Ab receptors of lymphocytes

- BCR (B-cell receptor)

- TCR (T-cell receptor)

BCR

- B cell receptor

- a transmembrane Ab capable of binding to a specific Ag

The BCR Ab R is composed of

- a heavy chain

- a light chain

- variable region (@ the end of the Ab)

- constant region

The variable regions of an Ab is also called

the antigen binding site

TCR

- T cell receptor

- similar to BCR Ab; no top part of Ab (think just stem)

The TCR is composed of

- 1 heavy chain

- 1 light chain

- variable and constant regions

In order to bind and respond to specific Ag, BCRs and TCRs undergo

gene rearrangement, which produced specific and unique Abs/Rs

Epitope

the region on the Ag that specifically bind to the Ab

TCRs recognize specific foreign Ag by

recognizing Ag fragments bound to MHC molecules (typically on APCs)

Naive lymphocyte survival is determined by

receiving signals from Ag binding to their receptors

Naive lymphocytes that float around in the peripheral lymphoid organs/tissue can activate (binding to Ag), and become

effector cells

Naive lymphocyte activation typically requires what in addition to Ag binding?

additional signaling, either from DCs or other lymphocytes

Naive Lymphocytes requiring multiple signals before they can activate and become effector cells indicates

- activation is regulated

- acts as a checkpoint to ensure the proper rxn is occuring

In general, naive B cells becoming effector B cells will

secrete Ab that is specific to the Ag it is bound to

Abs secreted by effector B cells aid in

neutralizing the pathogen/Ag either via opsonization and/or activation of the complement system

In general, naive T cells becoming effector T cells will

- produce factors to activate other effector cells

- produce toxins for killing

- provide membrane-bound signals to induce cell death

Cytotoxic T cells

- an effector T cell

- recognizes viral peptides to kill infected cells

Cytotoxic T cells are specifically involved in

viral infections

cancer resistance

Helper T cells

- an effector T cell

- produce cytokines to activate other cells (ex. activating macrophages or giving additional signaling to activate naive B cells)

Professional Antigen Presenting Cells

- DCs

- Macrophages

- B lymphocytes

- all uptake Ag and present it to lymphocytes

APCs specifically present Ag via

MHC class I or II molecules

APC antigen uptake specificity from least to most specific

DCs

Macrophages

B lymphocytes

APCs specifically activate what cells?

B and T cells (APC activation question; repeat definition)

Immunological Memory

the ability of the immune system to respond to an Ag that has been recognized before, producing a response that is faster and more robust (in comparison to the 1st)

Identification of extracellular infection is typically responded to with/by

- Ab production

- anti-microbial ppep production

- phagocytosis

Identification of intracellular infection is typically responded to with/by

- NK cells

- Tcyto cells

- ^^^^^-cell dependent macrophage activation

The innate barriers to infection include

- epithelial barriers

- mechanical barriers

- chemical barriers

- normal microbiota

Epithelial barriers

- innate immune system barriers found in epithelia

- includes antimicrobial peptides, phagocytes, and activation of complement

Antimicrobial peptides (AMP) in the skin specifically function by

- forming pores in bacteria via charge disruption

- recruiting more cells (inducing chemotaxis)

Defensin

- an example of an AMP

- positively charged end of the AMP can insert itself into the membrane, physically opening a pore as more defensins insert

Mechanical barriers

- innate immune system barriers (usually in skin and mucosa)

- tight junctions of cells

- air/fluid flow

- cilia

Chemical barriers

- innate immune system barriers

- fatty acids

- peptides & enzymes

- pH changes

Lysozymes

- an example of an innate enzymatic barries

- digest gram +/- bacteria via cleaving peptidoglycan

- exposes the lipid bilayer of bacteria for destruction

Complement

soluble factors and cell surface proteins that aid in clearing pathogens via a cascade of different proteins and cleavage events

The main 3 key steps of complement are

1. recognition of an Ag

2. Cascade amplification of C3 convertase to produce C3

3. Pathogen clearance (inflammation, phagocytosis, membrane attack)

Complement pathways

Lectin

Classical

Alternative

Every complement pathway will always end up with

activation of C3 convertase to cleave C3 for deposition onto the pathogen surface

Lectin pathway of complement

- recognition of sugars not found on our cells (lectin)

The lectin pathways utilizes _________ receptors, more specifically ________________ and _________________

soluble

mannose-binding lectin (MBL)

ficolins

Once the MBL/ficolins bind to a pathogen, _________ are recruited and ____________

MASPs

bind to the MBL/ficolin complex (which is bound to the pathogen)

MASPs bound to MBL/ficolin become activated, leading to

- the recruitment of C4

- the start of the C4 complement cascade

MLB/ficolin cleaves C4 into ________ and ______

C4a

C4b

What happens next to C4a and C4b?

- C4a 'leaves’

- C4b is deposited on the pathogen's surface

After deposition on the pathogen's membrane, what happens to C4b and what does MASP do?

- C4b binds to C2

- MASP cleaves C2 into C2a and C2b

When C2 is cleaved by MASP, what happens?

- C2a stays bound to C4b (C4b2a)

- C2b 'leaves'

the C4b2a complex is now a functional

C3 convertase

Once C4b2a is formed, what happens?

- C3 can now bind to the complex and be cleaved

- C3 becomes C3a and C3b

Once C3 is cleaved, C3a and C3b

- C3a: 'leaves'

- C3b: stays bound/deposits on the pathogen's surface

The deposition of C3b onto a pathogen's surface allows for

- recognition of the pathogen by phagocytes

- phagocytes w/C3bRs will recognize C3b deposits and begin phagocytosis

C3a and C5a 'leaving' after being cleaved actually functions by

recruiting other phagocytic cells to travel to the site of infection

Membrane-attack complex

- a possible result of complement

- involves the insertion of other complement factors (C5b, C6-9)

- ^^^ factors will physically insert themselves into the membrane of the pathogen to induce lysis