Immunology Flashcards

1
Q

What are granulocytes?

A

Leukocytes with a granular appearance, include the neutrophils, eosinophils, and basophils and are myeloid derived.

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2
Q

What is the function of leukocytes?

A

Rapid and potent immune defense against infectious agents

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3
Q

How does leukocyte movement occur during infection?

A

WBCs enter blood circulation from bone marrow or lymphoid tissue and travel to the tissues where they are needed via selectin mediated diapedesis that deforms cells to allow them to pass through pores. Selectins are present in veins not arteries. JUST VEINS. The presence of chemotactic factors causes the movement of leukocytes to slow and allows diapedesis to occur.

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4
Q

Which leukocyte type has the longest lifespan? Which has the least?

A

Lymphocytes live the longest, months or years, and granulocytes live the shortest for 4-5 days. Monocytes become macrophages in the affected tissues and exist for months.

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5
Q

Define the two forms of immunity.

A

The Innate immune system which is a non-specific response and acts as the first line of defense against infection. It is functioning 24/7.

The adaptive/acquired immune system which is improved by repeated infection and involves specific response. Basis for vaccination, active only during infection.

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6
Q

What is the role of neutrophils?

A

They’re the first defensive cell type and the most abundant leukocyte in blood. They can neutralize bacteria or fungi by phagocytosis.

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7
Q

What is the role of eosinophils?

A

They are mobilized for parasitic infections and release substances to kill or weaken them like hydrolytic enzymes. They also detoxify inflammatory systems with the release of H2O2.

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8
Q

What is the role of basophils?

A

They’re the circulating counterpart to tissue Mast cells which produce heparin to prevent coagulation and facilitate fat particle removal. They produce histamines, bradykinin and serotonin. Important in allergic reactions mediated by IgE (recognized allergen)

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9
Q

How are phagocytic cells attracted by chemotaxis to infectious agents?

A
  1. Bacterial toxins
  2. Degenerative products of inflamed cells
  3. Complement complex
  4. Cytokines and other specific factors secreted by the host or invaders
  5. Foreign membrane proteins which trigger leukocytes
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10
Q

What leukocytes are capable of phagocytosis?

A

Neutrophils and macrophages matured from monocytes

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11
Q

What are the compounds of the innate immune system?

A

Physical barriers and factors
Soluble compounds
Cellular component

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12
Q

What is the role of physical barriers in innate immunity?

A

The innate immune system has intact skin as the most important physical barrier blocking most infectious agents.

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13
Q

What is the role of physiological factors in innate immunity?

A

pH, temp, and oxygen tension limit microbial growth. Ingested organisms destroyed by acids, digestive enzymes, and body temperature.

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14
Q

What are the main routes of infection?

A

The epithelial surface of the nasopharynx, gut, lungs, and genito-urinary tract. A network of macrophages are present (the reticuloendothelial system) and ready in these tissues to combat infection.

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15
Q

What are the important soluble compounds in the innate and adaptive immune systems?

A

Lysozymes, the complement complex system, C-reactive proteins and cytokines.

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16
Q

What is the role of lysozymes in the innate immune system?

A

They are produced by neutrophils and split bacterial cell walls made by proteoglycan. Specific for bacterial cell wall.

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17
Q

What is the role of C-reactive proteins in the innate immune system?

A

C-reactive proteins bind C-proteins of pneumococci, bind to the surface of damaged cells and bacteria to promote complement complex activation, and facilitate opsonization for more efficient phagocytosis. They are produced in response to inflammation.

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18
Q

What is the complement complex system?

A

A system of serum proteins that interact in a cascade and activate each other. There are three pathways of activation.

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19
Q

What are the three pathways of complement complex activation?

A
  1. Classical pathway - activated by Ab-Ag complexes. MOST COMMON.
  2. Alternative pathway - complements bind to surface molecules of pathogens
  3. pathway involving Mannose Binding Lectin on pathogen surface. These are adhesion proteins on some pathogens.

All three pathways activate C3 CONVERTASE which activates the cascade.

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20
Q

Describe the pathway of the complement complex system in the classical pathway

A

The Ag-Ab complex activates C1, C4 and C2 are C3 convertase and combine via C1 to activate C3 which creates C3b and C3a, C3b is an opsonin and both of these activate mast cells and basophils leading to an inflammatory response.
C3b then converts C5 to C5b and C5a and C5a attracts other leukocytes via chemotaxis. C5b then combines with C6 and C7 and then C8 and C9 to form the membrane attach complex which bind to and penetrate the membrane and create a donut hole causing lysis.

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21
Q

What is the role of cytokines/lymphokines in the innate immune system?

A

There are 5 classes and they act as biochemical messengers to stimulate leukocyte activity following infections.

22
Q

What is the pathway of cytokine release in the innate immune system?

A

Infection -> activation of macrophages which secrete cytokines (though neutrophils can also secrete it -> Interleukin-1 (IL-1) and tumor necrosis factor (TNF) secreted (cause inflammatory responses and stimulate progenitors to be produced and divide) and granulocyte-monocyte colony stimulating factor (GM-CSF) and derivatives produced (also pro inflammatory)-> increase production of leukocytes

23
Q

What is the role of IL-1?

A

It is a cytokine which is pro-inflammatory and produced by macrophages and neutrophils. It also stimulates hematopoiesis.

24
Q

What are the cellular components of the innate immune system?

A

NK Cells: lymphoid derived, no memory, certain functions
Phagocytic cells: can recognize and ingest and destroy foreign cells particles and components, myeloid derived. Includes macrophages and neutrophils (aka polymorphonuclear leukocytes)

25
Q

How do NK cells work?

A

They kill cancer cells via surface recognition of irregular gene expression. Lysis occurs via the formation of holes. They also recognize cell surface changes on virally infected and foreign cells. They bind, form an immunological synapse where compounds are released, and destroy the cells.

They are activated by interferons.

26
Q

How do interferons work?

A

They are cytokines produced early on in infection that prevent proliferation of virally infected cells and act as the first line of defense. They act on cells through membrane receptors and influence viral proteins and block some protein synthesis and proliferation.

27
Q

What enhances phagocytic activity?

A

Opsonization by C3b in the complement complex or Ab-Ag complex

28
Q

How does opsonization work?

A

It can occur via the complement C3b or an Ab-Ag complex or both. It enhances binding of the phagocyte to the foreign body so it can be more easily engulfed as macrophages and neutrophils both have receptors for C3b and antibodies.

29
Q

What is the reticuloendothelial system?

A

A network of phagocytic tissues in parts of the body that are prone to infection because they have an increased concentration of specialized resident macrophages. These include the skin and subcutaneous tissue, the liver sinuses (Kupffer cells b/c filtration), spleen, bone marrow, lymph nodes, and alveola.

30
Q

What is the adaptive immune system?

A

Mechanisms that provide specific immunity against invading agents and have memory of antigens for specific recognition of antibodies. It works in concert with the innate immune system.

31
Q

What are antibodies?

A

Gamma globulins called immunoglobulins composed of two heavy and two light chains bound by disulfide bridges and with an antigen binding site at the tips of the heavy and light chains (Fab for fragment antigen binding) which varies in antibodies and Fragment crystalline (Fc) which is similar in most antibodies and binds to host tissue. Leukocytes have Fc binding sites.

32
Q

How do Fabs bind?

A

They bind to an antigenic determinant domain/epitope and have specificity similar to enzymes. There is some level of cross-reactivity that just has lower sensitivity. Since one antigen has multiple epitopes, this increases the likelihood of recognition.

33
Q

What are the classes of immunoglobulins and their functions?

A

IgG: the major Ig. Major antibody of secondary immune response, anti toxin class, activates complement system.
IgA: major Ig in sero-mucous secretion
IgM: pentameric Ig in vascular pool, early antibody against complex organismms via agglutination
IgD: on B-lymphocyte membranes. Antigen recognition. Triggers lymphocyte differentiation.
IgE: on basophils and mast cells, parasitic immunity and pro inflammatory response. Allergic reactions.

34
Q

What cells does the adaptive immune response involve?

A

B-lymphocytes and T-lymphocytes.

35
Q

What is the role of B-lymphocytes in the adaptive immune system?

A

The production of specific antibodies against invading agents, mature in bone marrow. Humoral immunity.

36
Q

What is the role of T-lymphocytes in the adaptive immune system?

A

They destroy invading agents similarly to NK cells (another lymphocyte in the innate immune response) and develop in the thymus gland.

37
Q

How does clonal selection work?

A

There are many preformed B and T cells with distinct Fabs. Each B cell can only produce and recognize one type of antigen/antibody. Dormant until Fab bound. Identical binding domain to the antibodies they produce. The antigen binds to a preformed B-cells Fab domain and leads to its proliferation, this is clonal selection (mitotic).

Some B cells further differentiate after activation and enlargement and form plasma cells which produce gammaglobulin antibodies at a rapid rate.

Some B cells instead form memory cells with the membrane components to recognize the antigen which increases the amount of activatable B cells available if infection by the same antigen occurs again.

They can be activated directly by antigens or by antigen presenting cells, similar to Helper t cells

38
Q

What is the basis of secondary immune response?

A

Clonal selection leading to the production of more memory B-cells available to recognize the antigen during the first immune response which are triggered during subsequent reinfections. It’s the basic for vaccinations via antigen RNA or dead cells.

39
Q

What are some of the ways antibodies act?

A
  1. Agglutination/precipitation: clump around antigen. IgM
  2. Neutralization (mainly for toxins): Antibody binds to active molecule and alters structure or covers active site to inactivate. IgG
  3. Opsonization
  4. Complement activation (the classical pathway)
40
Q

What are the three major T-cell types?

A

Helper T-cells
Cytotoxic T-cells (act like NK cells BUT have memory)
Suppressor T-cells

41
Q

How do Helper T-cells work?

A

They can only be stimulated by histocompatibility complex proteins or antigen presenting cells, not directly by antigens, and secrete cytokines including interleukins, GM-CSF, and Interferon-gamma once activated. They sensitize other parts of the immune system.

42
Q

How do Cytotoxic/Killer T-cells work?

A

They bind to antigenic sites on the cell surface and secrete perforin (hole formation compound) in the immunological synapse through which cytotoxic compounds are released and cause apoptosis in viral and cancer cells. Very lethal for viral cells, important for organ transplant rejection. Mediated by histocompatibility complex proteins.

43
Q

How do Major Histocompatibility Complex genes contribute to immune function?

A

The membrane of all cells are marked by proteins (HLA/human leukocyte antigens in us) coded by these MHC genes that are specific to the individual. A difference in these proteins mark the cells as antigens. Each individual has genes to produce 3-6 types, very important in organ transplants (histocompatibility)

44
Q

How are T-cells activated?

A

T cells cannot be activated without the mediation of MHC, antigens must be presented by macrophages or cells bound to MHC receptors. Some T cells divide after activation to form memory T cells for a secondary response.

45
Q

What are the classes of MHC molecules recognized by and why does this matter?

A

Class 1: expressed by all cells But RBCs and recognized only by Cytotoxic T cells (because destroy all cell types)
Class 2: expressed by macrophages and B cells and dendritic cells and recognized only by Helper T cells (because enhance activities ofthese immune cells)

46
Q

Why are there restrictions in what cells recognize the classes of MHC?

A

Because of coreceptor CD4 on Helper T cells activated by Class 2 MHC bound Ags and coreceptor CD8 on Killer T cells activated by Class 1 MHC bound Ags. They are associated with the T cell’s MHC receptors.

47
Q

How are B cells activated?

A

By direct antigen binding to the Fab site or by having an antigen presented by other leukocytes (macrophages) and secretion by Helper T cells

48
Q

What are suppressor T cells?

A

They’re regulatory T cells that reduce helper T cell activity and are important in self immune tolerance. A lack of these causes immunodeficiency.W

49
Q

What are the mechanisms of Immune tolerance?

A

Clonal deletion: the destruction of lymphocytes with receptors for the self during developmental and fetal stages. This does not remove all threats.
Clonal anergy: lymphocytes directed against self antigens present but do not attack because of suppressor T cells.

50
Q

What causes allergy?

A

Hypersensitivity to an antigen which can result in pathological reactions upon subsequent exposure to that specific antigen. It is mediated by mast cells with IgE.

51
Q

How does inflammation work?

A

Tissue damage caused by invaders cause inflammation proportional to the damage. It is marked by the migration of macrophages and granulocytes into the tissue. Vasodilation of the local blood vessels occurs, there’s increased capillary permeability and thus interstitial fluid, this fluid clots because of more fibrinogen leaking which created a barrier in the tissue to wall off the infectious organisms and toxins and this leads to swelling of tissue cells with leukocytes and macrophages in the center.

52
Q

What tissue products cause inflammation and how?

A

Histamines, bradykinin, serotonin, prostaglandins, reaction products of complement system, reaction products of blood-clotting systems, lymphokines (from sensitized T-cells). Leads to itching, white, red, swollen, pain (secretion of leukocytes), exudate (pus). Attraction of tissue macrophages, increase neutrophils, attraction of monocytes from blood, and increased granulocyte and monocyte production in marrow.