Immunology (EXAM 1- BIOMED)

Describe innate immunity

• First line of defense

• Killing invaders and activating adaptive immunity

• Rapidly mobilized

• NONSPECIFC

• Lacks immunological memory

Describe adaptive immunity

• Second line of defense

• SPECIFIC for individual agents

• prevents reinfection by creating antibodies

• Immunologic memory

Innate immunity arise from ___________ in the bone marrow

Myeloid progenitors

Adaptive immunity arise form _________ in the bone marrow

lymphoid progenitors

What are the cells involved in the innate immune system?

• Monocytes (macrophages and dendritic cells)

• Macrophages

• Polymorphonuclear cells (Granulocytes)

• NK cells

• Platelets

Describe monocytes in the innate immune system

• Arise from precursor cells within the bone marrow

• Migrate into peripheral circulation and then into tissue

• REACT TO INFLAMMATION

• differentiate into macrophages or dendritic cells on demand

Describe Macrophages in the innate immune system

• Derived from Monocytes

• Professional APCs (antigen presenting cells)

• Three main functions:

  • Phagocytosis

  • Antigen presentation

  • Cytokine production

Describe granulocytes (Polymorphonuclear cells)

• Type of WBC (leukocyte) w/ complexly lobed nucleus and granule-containing cytoplasm

  • Neutrophils

  • Eosinophils

  • Basophils

  • Mast cells

Describe neutrophils in the innate immune system

leukocyte that purses bacterial cells

• First WBC to arrive at site of infection

• phagocytosis and signaling inflammatory response

Describe eosinophils in the innate immune system

• Triggered by allergies and helminthic (worm) infections

• Release chemokines, cytokines, and lipid mediators

Describe Basophils and mast cells in the innate immune system

• contain immunoglobulin E (IgE) ( think of allergy)

• Secrete heparin and histamine in response to various antigens and allergens

• Basophils supplement the function of mast cells

______ circulate in the bloodstream, whereas ____ cells are fixed in tissue under skin and mucosa of GI and respiratory tract

• Basophils

• Mast cells

Describe NK cells in the innate immune system

• respond to virally infected and malignant cells

• kill virus-infected cells and tumor cells → secrete cytotoxins

  • perforins and granzymes

• produce gamma interferon (INF-y) → activate macrophages to kill bacteria

Explain the role Dendritic cells in linking innate and adaptive immune systems

• MAIN inducers of adaptive immunity

• Located in skin/mucosa

• Ingest foreign material and migrate → Process it → Present antigen with either I MHC or II MHC.

• produce cytokines to activate the adaptive response (T cells)

Explain the role of macrophages in linking innate and adaptive immune systems

• Collect antigens and migrate from barrier tissue

  • Through draining lymphatic vessels into lymph nodes

• Priming naive T cells

• Present endosomal antigen

What are the different types of cytokines that help link the innate and adaptive immune system

• IFN-Alpha

• IL-6

• IFN-Beta

• Granulocyte colony stimulating factor (G-CSG or CSF1) and Granulocyte-macrophage colony-stimulating factor (GM-CSG or CSF 2)

• Interferons

Describe IFN-alpha

• Produced by macrophages

• Increases synthesis of adhesion molecules

• Enhances killing power of phagocytosis

• Endogenous pyrogen

• Cachectin

Describe IFN-Beta

• Proinflammatory cytokine (inactive)

• Inflammasomes activate

• Primary function increase stickiness of blood vessel

• Increases production of chemokines

Describe IL-6

• Made by macrophages, mast cells, muscle, fat

• Signals liver to produce acute phase proteins

  • Cachexia and fever

• Trigger new neutrophils to be released from bone marrow

Describe Granulocyte colony stimulating factors

• stimulate leukocyte migration out of Bone marrow

• Boost leukocyte numbers

• Prevent infection

Describe Interferons

• innate

• virus detection and replication

• Type II (gamma interferon) activates macrophages

What are chemokines?

Attract leukocytes. produced by macrophages and endothelial cells to promote inflammation, then promote extravasation. Lymphatic tissue produces chemokines to guide dendritic cells.

Class I major histocompatibility complex (I MHC)

• All nucleated cells

• Intracellular or endogenous antigens

• Complexed with antigen peptides to signal cytotoxic T-cells

• presents antigens from within the cell

Class II major histocompatibility complex (II MHC)

• ONLY found in specialized APCs

  • Macrophages

  • Dendritic cells

• Endogenous or extracellular antigens

• Complexed with antigen peptides to signal helper T-cells

• presents antigens from outside of cell

Describe the function of the complement system

• Lysis of cells such as bacterial , allografts, and tumor cells

• Generation of mediators

  • participation in inflammation and attract neutrophils

• Opsonization: enhancement of phagocytes

Once recognition occurs, innate immunity is activated to increase production of proinflammatory signals that…

• Kill invaders and recruit other immune cells to the area

• Block infection through local inflammation

• Aid in repairing damaged barrier

Describe the activation of the complement system

• Initiated by antigen-antibody complexes or nonimmunologic molecules, such as endotoxins

• Occurs via 3 pathways:

  • Classical pathway

  • Lectin pathway

  • Alternative pathway

• ALL 3 PATHWAYS LEAD TO PRODUCTION OF C3b= creates membrane attack complex (MAC) to lyse cells

What is C3b?

makes c5 convertase, opsonizes bacteria

The alternative pathway of the complement system is activated by……

foreign cell surface substances (endotoxins, fungal cell walls, viral envelopes). Antibody independent and protective before an antibody is formed

The Lectin pathway of the complement system is activated when….

Mannan binding lectin binds to microbes, activates proteases that cleave C2 and C4, important prior to antibody formation

The classical pathway of the complement system is activated by …..

IgM or IgG, forms membrane attack complex (MAC) through antigen-antibody complex

Describe platelets in the innate immune system

• originate from common myeloid progenitor→ megakaryocytes

• Have Toll-like receptors that start immune response

Describe the cells involved in the adaptive immunity system and what are the two components of acquired immunity?

• B-cells

• T-cells

• Plasma cells

• components: Humoral immunity (B-cells) and Cellular immunity (T-cells)

Describe T cell Lymphocytes in the adaptive immune system

• Differentiate into CD4 (helper, MHCII) and CD8 (cytotoxic, MHCI), mature in thymus

• TCRs (T cell receptors) in thymus → mature naive T cell upon exiting

• derive from Common lymphoid progenitors

Primary Lymphoid organ

thymus

Secondary lymphoid organ

spleen, MALT, tonsils

Describe the activation of T cell lymphocytes

Primary Lymphoid organs

• T cells mature

• Develop TCRs

• Naive- have not yet encouraged foreign antigen

Secondary Lymphoid organs

• T cells travel via blood and lymphatics

• Concentrate and filter antigenic material

  • Sample material and remove it if necessary

• Priming of naive T cells

Describe CD4 positive T cells in adaptive immune system

• helper T cells

  • recognize antigens to make cytokines

  • Utilizes II MHC

Describe CD8 positive T cells in the adaptive immune system

• Cytotoxic T-cells

• detect and kill infected cells

• Utilizes I MHC

Describe B-cell Lymphocytes in the adaptive immune system

• Differentiate into plasma cells that produce antibodies (Igs/ immunoglobulins)

• PRVENT Reinfection

• Differentiate into long-lasting memory cells that respond robustly and rapidly to reinfection

• Stages of maturation:

  • T-cell independent response

  • T-cell dependent phase

Describe the activation of B cell lymphocytes

• Primary response (1st antigen encountered)

• Secondary response (Reinfection)

Describe the Primary response

First time antigen is encountered, T cell dependent activation, B-cells→ plasma cells→ IgM production

Describe the Secondary response

Reinfection. memory B cells. IgM and IgG are produced, IgG lasts longer. Rapid response to reinfection (3-5 days)

Describe the T-cell independent response in the adaptive immune system

• Allows B-cells to produce antibodies without requiring help from T-cells

• 2 signals needed for activation

• No memory cell production

Describe the T-cell dependent response in the adaptive immune system

• Strongest and most specific response

• CD4-positive T cells help elicit response

• Memory cell production

• 3 signals

Describe plasma cells in the adaptive immune system

Differentiated B cells that produce and secrete large amounts of immunoglobulin antibodies

Describe the basic structure of immunoglobulins

• Y shaped Glycoproteins consisting of 4 polypeptide chains

  • 2 Identical heavy (H) chains

  • 2 identical light (L) chain

List the 5 classes of immunoglobulins

Man Don’t Get Eaten Alive

• IgM

• IgD

• IgG

• IgE

• IgA

Describe the function of IgG in the adaptive immune system

Predominant antibody in the secondary response, the only antibody to cross the placenta, most abundant in newborns, and enhances phagocytosis (opsonizes)

Describe the function of IgA in the adaptive immune system

Main antibody in secretions (colostrum, saliva, tears, respiratory/intestinal tracts, genital tract) that prevents microorganisms from attaching to mucous membranes.

Describe the function of IgM in the adaptive immune system

Main antibody in the primary response, acts as an antigen-binding receptor on B cells, and is highly efficient in complement activation and agglutination. Important in defense against bacteria and viruses.

Describe the function of IgD in the adaptive immune system

Present on the surface of B cells and small amounts of serum with no known specific function, though it may be an antigen receptor

Describe the function of IgE in the adaptive immune system

• Mediates hypersensitivity (anaphylaxis) by binding to mast cells and basophils→ becomes receptor for allergens. Host defenses against parasites (helminths)

What are the four stages of antigen presentation?

1. Adhesion

2. Antigen Specific recognition

3. Co-stimulation

4. Cytokine signaling

Describe adhesion in reference to the stages of antigen presentation

This is part of the extravasation process where inflammatory cells adhere to endothelial surfaces in order to migrate into tissues.

Describe antigen specific recognition in reference to the stages of antigen presentation

Phagocytes ingest foreign material, process it, and present cleaved peptide antigens on Major Histocompatibility Complexes (Class I or II) so that T-cell receptors can uniquely recognize them.

Describe co-stimulation in reference to the stages of antigen presentation

This acts as a required secondary signal during antigen presentation to T-cells.

Describe cytokine signaling in reference to the stages of antigen presentation

serve as cell-cell communication to turn inflammation up or down and direct specific immune responses.

What are the specific mechanisms by which the immune system provides defense against intracellular pathogens such as viruses?

Natural Killer (NK) cells and CD8 Cytotoxic T cells target virally infected cells by inserting perforins to initiate apoptosis, or cell death. Interferons (Alpha and Beta) also aid in virus detection.

What are the specific mechanisms by which the immune system provides defense against intracellular pathogens such as bacteria?

Neutrophils and macrophages directly phagocytize bacterial cells. Additionally, the humoral immune system (antibodies) and the complement system are the major defenses against bacteria.

What are the specific mechanisms by which the immune system provides defense against intracellular pathogens such as parasites?

Eosinophils and IgE antibodies act specifically as host defenses against helminthic infections, or parasites.

What are the various factors that may affect the immune response?

Cytokines: They have the ability to "turn off" inflammation when it is no longer needed, or turn it up during an active response.

Immunological Memory: Reinfection leads to a secondary response where memory B cells produce a much more rapid and robust reaction with higher antibody affinity than the initial encounter.

Evaluate the features of immune responses specific to individual tissues (Localized reaction):

Inflammation happens directly at the site of infection and is characterized by pain, redness, warmth, and swelling due to vasodilation and vascular leak. Cytokines act over very short distances in local tissue and tissue-resident macrophages respond locally.

Evaluate the features of immune responses specific to individual tissues (systemic reaction):

This occurs when chemical signals reach widespread systems. For instance, the cytokine IL-6 signals the liver to produce acute phase proteins (causing fever and cachexia) and triggers the bone marrow to release new neutrophils globally.