Immuno Exam 1

Inflammation

Inflammation

Increased vasodilation increases the permeability of the cell wall, allowing fluid, proteins, and cells to enter the tissue from the blood, and the infected tissue becomes inflamed with redness, heat, swelling and pain 

NK cell

kill virus infected cells, can recognize and kill infected cells that are displaying viral proteins on their surface.

Macrophage

phagocytize and kill microorganisms, are long-lived. Circulate for about a day before entering tissue and maturing into macrophages. Remove foreign substances and destroy old erythrocytes. Antigen-presenting cell.

Neutrophils

Phagocytize and kill microorganism but are short-lived and die after their purpose is fulfilled. Abundant in blood with reserves in the bone marrow. First cells to arrive at site of infection 

Dendritic cell

engulf pathogens and activate T cells to initiate the adaptive immune response

Mast cell

expel parasites from the body by releasing granules containing histamine and other active agents 

Basophils

control immune responses to parasites 

Eosinophils

kill antibody-coated parasites through release of toxic granule contents 

large fragment

The ____________ of convertase binds to bacteria

small fragment

The ____________ of convertase attracts effector cells.

Small lymphocyte

B cells make antibodies, T cells help B cells and kill infected cells 

Plasma cell

Terminally differentiated form of B cell that synthesizes and secretes antibodies

B cell

• Bind directly to toxins and pathogens 

• Secrete antibodies 

• Undergo somatic hypermutation to form better antibodies after each exposure 

T cells

• Recognize antigens 

• Two types:

• CD4 “helper” cell: cytokines activate B cells and orchestrate immune responses 

• CD8 “killer” cell: target tumor cells and virally-infected cells 

Clonal Expansion 

In development, progenitor cells give rise to a large number of lymphocytes, each with a different specificity, during an infection the lymphocytes with receptors that recognize the pathogen are activated and these lymphocytes proliferate and differentiate to give effector cells which terminate the infection. 

Innate immunity

Rapid response within hours, fixed, limited number of specificities. constant during the course of response. The body's first line of defense against infection. It is a nonspecific response that is present in all organisms. Includes physical barriers, such as the skin and mucous membranes, as well as cellular and humoral responses, such as phagocytosis and inflammation.

Adaptive immunity

Slow response (days to weeks), variable, numerous highly selective specificities, improves over the course of the response.

Primary lymphoid organs

• Where lymphocytes develop and mature  

• Bone marrow and thymus  

• B and T lymphocytes originate in the bone marrow  

• B cells originate and mature there, but T cells originate there and mature in the thymus. 

Secondary lymphoid organs

Lymph nodes (LNs), spleen, Peyer's patches (PPs) and mucosal tissues- the nasal associated lymphoid tissue (NALT), adenoids, and tonsils.

Where mature lymphocytes encounter pathogen-derived antigens and are activated to become effector cells that attack and eliminate the microbial invader. 

Lymphocytes

These cells are constantly recirculating regardless of infection, they leave the blood and enter the lymphatic system and will stay if activated by a pathogen, but if not, it will stay for some time and then leave, and return to the blood. 

Lymph nodes

• Packed with cells of the immune system (macrophages, lymphocytes) 

• Placed at the junctions of lymphatic vessels  

• Collect the plasma that leaks out of blood vessels and eventually return it to the blood. 

• Where B and T cells congregate. 

Germinal centers

Where somatic hypermutation of B cells takes place, in which B cells are mutated to make them have a higher affinity for the targeted antigens. 

Spleen

• Provides adaptive immunity to blood infections.  

• Filters the blood to remove damaged and senescent erythrocytes  

• Macrophages take up pathogens in the blood and stimulate B and T cells to arrive in the blood.  

Red pulp

Where red blood cells are monitored and damaged ones removed  

White pulp

• Works as a secondary lymphoid tissue 

• Aggregates of immune cells 

Hematopoiesis

Divide to give daughter cells that can differentiate into more mature stem cells which may commit to the erythroid, myeloid, or lymphoid lineages. 

Takes place in the bone marrow

Pluripotent hematopoietic stem cell

Leukocytes, erythrocytes, and megakaryocytes are all derived from the common ancestor called the ______________.

Self-renewal

Hematopoietic cells can also divide to give daughter cells which are also hematopoietic cells, this called ____________.

Physical barriers

Skin, mucosal surfaces

Chemical barriers

Complement, antimicrobial proteins, mucosal surfaces secreting antibacterial and antiviral substances (lysozyme, defensins, cathelicidins, surfactants)

Microbial barriers

The commensal microbiota

Natural Killer (NK) cells

• Kill virus infected cells and cancerous cells. 

• Short-lived 

• Killing requires cell-to-cell contact 

• Forms perforin in the membrane of the target cell 

• Granzymes induce apoptosis 

Complement

Coats the surface of bacteria and makes them more easily phagocytized. Many of these proteins are proteolytic enzymes or proteases that circulate as enzymatically inactive zymogens.

Acute inflammation

the initial response of the body to harmful stimuli involving the increased movement of leukocytes to the injured tissue

Chronic inflammation

prolonged inflammation, usually arthritis and cancer 

Alternative pathway

• Spontaneous hydrolysis and activation of C3 

• C3 convertase is C3bBb 

• Regulated by factor H

Lectin pathway

• Soluble PRRs bind to carbohydrate structures on pathogen surface 

• C3 convertase is C4b2a 

• Produces same effectors as the others plus MASPs 

• Regulated by MASP-2

Lectin pathway

• Soluble PRRs bind to carbohydrate structures on pathogen surface 

• C3 convertase is C4b2a 

• Produces same effectors as the others plus MASPs 

• Regulated by MASP-2

C3

made in the liver, enters ciculation, and slowly changes conformation to expose its thioester bond

iC3

C3 bonded to water

Factor B

iC3 bonds to _______ which is then cleaved by factor D and split into fragments.

Factor D

cleaves iC3b

Bb

fragment of factor B that remains bound to iC3

iC3b

the complex which cleaves C3 into C3a and C3b.

C3b

fragment of C3 which binds to the pathogen’s surface

C3a

fragment of C3 which recruits immune cells.

Factor P

Produced by neutrophils, increases complement activation by binding to C3bBb on pathogen surface and preventing its degradation by proteases. 

Factor H

A plasma protein which binds C3b and changes its conformation so it can be cleaved by Factor I 

Factor I

Cleaves C3b into iC3b, iC3b remains on microbial surface but cannot form a C3 convertase. Basically disables C3b, preventing it from activating the complement system. 

Factor B

binds to C3b and is cleaved by factor D to form C3bBb

Factor D

Cleaves factor B to form C3bBb 

DAF

Binds to the C3b component of C3 convertase causing its dissociation and inactivation 

MCP

Same function as DAF but the binding of MCP to C3b makes C3b also susceptible to cleavage and inactivation by factor I. 

C3b2Bb

C5 Convertase in MAC

C5b

Initiates the formation of the MAC

C6 and C7

Bind to C5b and exposes the hydrophobic site in C7

C7

inserts into the lipid bilayer after its hydrophobic site is exposed

C8

binds to C5b and inserts into the membrane, initiating polymerization of C9, 18 polymerized C9 molecules forms a transmembrane pore.

CD59 and CD55

Prevent the recruitment of C9 to the MAC on human cells

MCP

Same function as DAF but the binding of MCP to C3b makes C3b also susceptible to cleavage and inactivation by factor I. 

C3b

Opsonization, neutralization, B cell activation 

C5a

A ligand for receptors on phagocytes, endothelial cells, and mast cells. Increase inflammation at the site of complement activation. Can also induce anaphylactic shock. Also serves as a chemoattractant for neutrophils and monocytes.

C5b

initiates the formation of the MAC to make holes in the pathogen’s membrane 

Paroxysmal nocturnal hemoglobinuria

In _______________ lack of GPI-anchored proteins makes RBCs more susceptible to destruction by the complement system. This can lead to hemolytic anemia, a condition in which the body destroys its own RBCs. 

Lysozyme

Facilitates the hydrolysis of β-1-4 glycosidic bond between NAG and NAM in bacterial cell walls 

Α₂-macroglobulin

Trap microbial proteases

Defensins

HD6 and HD6 are a type of _________ made by Paneth cells which penetrate microbial membranes and disrupt their integrity and promote a localized unfolding of the structure to destabilize it.

Pentraxins

Multimeric proteins which bind to microbial surfaces and facilitate phagocytosis. Function as bridging molecules. 

Lectin

Carbohydrate-specific receptors which recognize human carbohydrates (self) from fungal and bacterial carbohydrates (non-self).

PRRs

Responsible for recognizing structural features common to many types of pathogen

PAMPs

structural features common to many types of pathogens

DAMPs

damage associated molecular pattern, recognized when damage to a cell is detected

Scavenger receptors

Trigger phagocytosis, cell adhesion, and intracellular signaling to identify microbes that may be harmful and cause their degradation. Also remove cells that have died by apoptosis. 

Mannose receptor (SR-E1)

A type of scavenger cell, a calcium ion coordinates the interaction of the carbohydrate ligand with the protein receptor. 

Dectin-1

A type of scavenger cell, a calcium ion coordinates the interaction of the carbohydrate ligand with the protein receptor. 

MARCO

Made of collagen-like triple helices, recognizes LPS. The triple helices are rigid rods which provide binding sites for microbial ligands and work to allow the receptor’s carbohydrate binding sites to stand out farther from the macrophage surface for better access to pathogens. 

Complement receptor

CR3 and CR4 are integrins which recognize PAMPs and also bind to iC3b. 

TLR4

The main macrophage for LPS in bacterial cell walls. The extracellular domain binds LPS.

MyD88

The bridging protein which brings the TIR domain of TLR4 in contact with interleukin-1 receptor-associated kinase 4 (IRAK4).

IRAK4

After being linked to the intracellular domain of TLR4 by MyD88, ____________ self-phosphorylates, dissociating from the complex and phosphorylating TRAF6.

IKK

activates NFkappaB

NFkappaB

initiates transcription of genes that induce cytokines, adhesion molecules, and other proteins that cause inflammation.

NOD-like receptors

recognizes bacterial degradation products in the cytoplasm. The CARD domain of this receptor dimerizes with the CARD receptor of kinase RIPK2

RIPK2

After being dimerized by the CARD domain of an NLR, ________________ phosphorylates the kinase TAK1 which activates IKK.

TAK1

activates IKK after being phosphorylated by RIPK2

IKK

When phosphorylated by TAK1, _________ mediates degradation of IkappaB

IkappaB

kappaB inhibitor, degraded by IKK

NFkappaB

When __________ is activated, it translocates to the nucleus of the cell and binds to DNA. This binding leads to the transcription of genes that encode proteins that are involved in inflammation, immunity, and cell growth.

NLRP3 Inflammasome

a multiprotein molecule that when triggered by DAMPs or NLRs, the ___________ releases IL-1beta and other cytokines to amplify the innate immune response.

Caspase-1

Pro-caspase-1 is activated after cleavage to become ____________, which cleaves pro-IL-1beta to become IL-1beta.

IL-1beta

The NLRP3 inflammsome increases production of the cytokine ___________ to amplify the immune response, overproduction of this cytokine can lead to autoinflammatory and autoimmune disorders.

Familial Mediterranean Fever

A mutation in the protein Pyrin causes disregulation of the inflammasome, which causes _________________.

Selectins

bind to carbohydrate ligands on the surface of other cells. This binding helps to slow down and tether leukocytes to the endothelium, which is a necessary step for them to migrate out of the blood vessels and into the tissues to fight infection.

Extravasation

the recruitment of innate cells from the circulation to the sites of infection and injury

ICAM-1, ICAM-2

Inflammation causes endothelial cells to increase expression of these selectins, which are ligands for CR3 and LFA-1

LFA-1, sialyl-Lewis

Neutrophils will express molecules corresponding to the adhesion molecules on endothelial cells. These include, ___________ and ___________.

Myeloperoxidase, defensin, lactoferrin, gelatinase

Neutrophils are loaded with four types of secretory granules…

Primary neutrophil granule

Contains myeloperxodiase, lysozyme, defensins, cathepsin G

Secondary neutrophil granules

Contains lactoferrin, lysozyme, NADPH oxidase