The Immune System Flashcards
Innate immunity components:
Epithelial barriers Phagocytes Dendritic cells Complement NK cells
Adaptive immunity components:
B lymphocytes –> plasma cells –> antibodies
APCs –>T lymphocytes –> Effector T cells
Blood clotting:
- Platelets first respond and go to the injured site to decrease blood lost.
- Clotting cascade activate thrombin (enzyme)
- Thrombin cleave fibrinogen into monomers
- monomers assembling into fibrin
- Platelets + fibrin strands = Consolidation (Blood clot form.)
Non-Cellular Defense Systems:
- Coagulation cascade (blood clot)
- Complement system (Formation of the MAC, Opsonization, Chemotaxis, Functional complexes with Abs)
- Kinin System (Increase permeability, pain activators)
Macrophages wild range of activities:
- Antimicrobial actions (NO, ROS)
- Bone Resorption
- Phagocytosis
- Wound Healing (growth factors)
- Antigen Presentation (can present antigens to T cells)
- Antigen/Antibody uptake (IgG, have Fc gamma receptor)
Dendritics cells functions (steps)
- Catch antigens in the interstitial spaces
- Through Lymphatics, travel the lymph nodes.
- Antigens are absorbed via endocytosis and are processed through the ER and coupled with MHC proteins
- Present antigens to T cells via MHC Class II
Dendritics cells is the most efficient APC bc:
The only cell that can activate naive T cells.
MHC class I:
expressed on all nucleated cells
MHC class II:
specific to antigen presenting cells (APC) (ex. dendritic cells, macrophages, B cells)
How do Innate Immune Cells Recognize pathogens?
- Recognition pathogen-associated molecular patterns (PAMPs) (on the cell wall of bacteria)
- Receptors expressed on the host cell (where their is inflammation) called pattern recognition receptors (PRRs)
- DAMPs (from death cell)
PAMPs are produced by:
The microbes/virus
PPRs examples:
TLRs, MBL, RLRs, NLRs
PRRs are:
Receptors express on the host cells (where there is tissue inflammation), release nuclear and cytoplasmic content that can alert the Innate immune cell through their PPRs.
2 types of adaptive immune responses:
Humoral immunity
Cell-mediated (cellular) immunity
Humoral immunity are mediated by (which type of cell)?
B lymphocytes (B cells)
Cell-mediated immunity are mediated by (which type of cell)?
T lymphocytes (T cells)
Cytotoxic T lymphocytes (CD8+)
Killing directly infected cells
Helper T cells (CD4+)
-production of soluble protein mediators call cytokines who activating phagocytes to kill ingested microbes AND help B cells to produce antibodies.
Lymphocytes develop from precursors in the generative lymphoid organs, T lymphocytes and B lymphocytes mature in?
T lymphocytes mature in the Thymus
B lymphocytes mature in the bone marrow.
T cell do not detect free or circulating antigens. Instead, the vast majority (>95%) recognize by is T cell receptor:
only the peptide fragments of protein antigens bound to proteins of MHC (antigen fragment displayed by the MHC protein) are recognize by T cell receptor (TRC)
TRC (T cell receptor structure:
heterodimer composed of disulfide-linked alpha and beta protein chains (with a variable–> binding region and constant region)
CD4+ and CD8+ are expressed on distinct T cell subsets and serve as:
Coreceptors for T cells activation. (bind to MHC protein)
The variable region of TCR can recognize almost infinity types of antigens through the process called:
VDJ recombination (system allows for shuffling of DNA segments in the TRC genes)
CD4 molecule bind to:
MHC class II (to is invariable portion)
CD8 molecule bind to:
MHC class I (present on all nucleated cells–> virus-infected cells can be detected)
CD28 functions:
- Strengthen the bond between the T cells and APVs
- CD28 recognizes V7 on an antigen presenting cell
- This second signal is NEEDED to properly activated the T cell.
In human the MHC is called:
Human Leukocyte antigen complex (HLA) (encoded on chromosome 6)
During the time that T cell are naive (before reaching the thymus), they are considered:
Double-negative (do not express CD4 or CD8 co-receptor.
During the time that T cell are naive (before reaching the thymus), they pass through various stage of development:
- Are first Double-negative (do not express CD4 or CD8 co-receptor.
- Conversion from double-negative, to double positive.
- As double positive, they express both CD4 and CD 8.
- Interact with MHC class I molecules and become either CD4+ (T helper cells) or CD8 (cytotoxic T cell)
- Arriving in Thymus from bone marrow.
In the thymus, T cells are building a repertoire of T cell by passing through the selection process:
- T cells receptor able to interact with that self MHC proteins will be positively selected.
- Central tolerance: If react too high avidity will be deleted.
- During the Selection process, T cells leaving the thymus and go into periphery.
- Peripheral tolerance: If the T cell bind with the antigen being expressed be the APC with the right co-receptor, Proliferation and differentiation will take place. Or if not: Anergy, Delection or Suppression of the T cells.
Peripheral tolerance: Anergy
- Happen when the co-receptor of T cell is not present.
- T cell receive off signals and become functionally unresponsive.
Peripheral tolerance: Deletion
- Happen when recognition of T cell is too strong
- T cell undergo apoptosis (activation induced cell death)
Peripheral tolerance: Suppression
- Happen when T cell comes into contact with the antigen, but his surrounding of regulatory T cell.
- Regulatory T cells will release cytokines, blocking the activation.
Regulatory T cell function:
Suppress the immune response by secreting factors like TGF-beta
T cells is naive until:
it been in contact with the antigen.
Cytotoxic CD8+ T cells can attack the APC by:
- Expressing different types of receptors (eg. FAS ligand-FAS receptor) to induce apoptosis.
- Releasing perforins (poke holes in the membrane of the target cell. Granzymes enter and induce apoptosis.
B cell go through maturation process in:
the bone marrow.
Precursors of B cells:
Hemopoietic stem cells
B cells undergo the selection process, first step, they will come into contact with self-antigens displayed in the bone marrow. If they interact 2 things can happen:
- Receptor editing (go through another round of VDJ to modify their affinity)
- they can undergo apoptosis.
B cells undergo the selection process:
- Contact with the self-antigens displayed in the bone marrow.
- Move to the periphery (lymph nodes) to come in contact with antigen.
B cells role:
Produce antibodies and the effector cells of humoral immunity
B cells recognize antigen by:
the membrane-bound antibody of the immunoglobulin M (IgM) class, expressed on the surface together with signaling molecules to form B cell receptor( BCR) complex.
B cells become activated by 2 ways:
- T Cell Independent: Epitopes (multiple identical antigenic) that are able to engage several antigen receptor molecules on each B cell and initiate the process of B cell activation.
- T Cell Dependent: Requires the help from CD4+ T cells B cell also can act as APCs (ingest p+ antigens, degrade and display peptides bounb to class II MHC molecules for recognition by helper T cells) T cells express CD40L and secrete cytokines, which work together to activate the B cells.
B cell Activation, what’s next:
- Proliferation and differentiation into different types of cells (can produce plasma cells)
1. Antibody secretion from plasma cells
2. Class switching (usually IgM but can change to another type of antibodies - IgE or IgG..)
3. Affinity maturation (improve the affinity of an antibody for a specific antigen)
4. Memory cell
Who can generate memory cell?
B cell and T cell
Once the infection is cleared, many cells will die, but some survive. Those cells that survive will become:
memory cells (subsequent exposure to the pathogen)
NK cells role in missing-self (Cell who lost its expression of MHC proteins –> lacking self-antigen/self-protein)
- NK cells attack host cells that do not express MHC proteins by expressing both activating–> lysis and Inhibiting receptor–> no lysis.
- NK will attack infected cells or tumor cells who downregulate MHC class I molecules, so no longer detectable by T cells.
Antibody effector functions:
Neutralization of microbes and toxins Opsonization and phagocytosis Antibody-dependent cytotoxicity Complement activation: -Lysis of microbes -Phagocytosis of opsonized microbes -Inflammation
