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Which types of granulocytes phagocytize pathogens?
Neutrophils and Eosinophils
What type of cell in the bloodstream is the precursor to a macrophage?
monocyte
Increased eosinophils indicates the presence of…
allergies or parasitic worm infection
Increase in leukocytes (mostly neutrophils) indicates presence of…
bacterial diseases
Increase of lymphocytes indicates the presence of…
viral infection
Six stages of phagocytosis
chemotaxis, adherence, ingestion, fusion with lysosome, killing, elimination
How do eosinophils kills parasites?
attaching to surface then secreting toxins that kill or weaken the cell
Toll-like Receptors (TLRs)
integral membrane proteins produced by phagocytic cells
initiate defensive responses
What are TLRs function?
binds pathogen-associated molecular patterns (PAMPS) (PG, LPS, flagellin, viral RNA)
Interferons
protein molecule released by host cells to nonspecifically inhibit the spread of viral infections; cause symptoms of viral infections
Type I interferon
non-immune (alpha and beta)
Type II interferon
immune (gamma)
Complement
set of serum proteins designated numerically according to their order of discovery; activated by cleavage forming peptides
Complement pathways
all function the same way
1) alternate pathway
2) lectin pathway
3) classical pathway
alternate pathway (first)
activated by surface components of microbes directly
lectin pathway (second)
activated by microbial polysaccharides
classical pathway (third)
activated by antibody molecules coating the microbes
Membrane Attack Complex (MAC)
ring of C9 to create pore in pathogen; complex C5b678(9)
C5 Convertase is made up of…
C4a, C2b, C3b
C5a (inflammation)
chemotaxis agent for neutrophils and macrophages
C3a, C5a (inflammation)
anaphylatoxins; histamine release from mast cells
C3b (inflammation)
split product of this binds to cell membranes as opsonin which paints an x on cell as a bad guy
Two types of inflammation
acute (disease and virus) and chronic (long lasting)
local and systemic (throughout the body)
Acute Inflammation
short lived and usually beneficial, vascular and cellular, tissue repair
Vascular Events in Inflammation
dilation and increased permeability of blood vessels, histamine and anaphylotoxins
Cellular Events in Inflammation
migration of phagocytes to site of injury mediated by chemotactic factors, C5a, Interleukin, cytokine, C3b
What stimmulates inflammation?
C3a and C5a fragments of complement cascade cause mast cells to release inflammatory mediators
What triggers a fever?
pyrogens trigger the hypothalamus to increase body temp
antibody-anitgen complexes signal for production of interleukin-I (IL-1) by macrophages
First Line of Defense
skin and mucous membrane prevent the entrance of pathogens; chemicals like sweat enhance protection
Second line of Defense
Phagocytes, Extracellular killing, Complement, Interferons, Antimicrobial Peptides, Inflammation, Fever
B cell
leave bone marrow mature, recognizes antigens, production of antibodies, live in lymph nodes
T Cell
leave bone marrow immature, enter thymus for final development, recognizes pieces of antigen (only if presented by macrophage, dendritic cell, B cell), live in lymph nodes
Dendritic Cells
movement of antigens to nearest lymph node from site of infection;
antigen processing and presentation to T cells
Development of B cell repertoire
genetic rearrangements followed by antigen sampling in bone marrow
Development of T cell repertoire
have to recognize MHC molecule;
genetic rearrangements followed by “education” in the thymus
How does the adaptive immune system communicate?
between cells using receptors and cytokines
What are pathogens role in the lymphatic system?
transport to lymph nodes; activate immune response
what is the path of lymphatic circulation?
leave blood, enter lymph nodes, lymph, return to blood
Do B cells require MHC to recognize antigen?
no
How many binding sites do B cells have?
4
How many binding sites to T cells have?
2 (cannot be secreted & do not make antibodies)
What is an epitope? (antigenic determinants)
minimal 3D region of a non-self molecule that is recognized by an immunoglobulin
Antigens
molecules the immune system recognize as non self and worthy of attack
What are the four functions of antibodies?
Neutralization, Agglutination, Opsonization, Compliment Activation
Neutralization
antibody binds to antigen
Agglutination
formation of cluster
Opsonization
painting of bad guy; recognition
Complement Activation
pathway of the complement
5 Classes of Antibodies
IgM, IgG, IgA, IgE, IgD
IgM
first antibody produced (primary response)
10 binding sites, 5 molecules
IgG
most common and longest lasting (memory response)
IgA
dimeric form associated with mucosal secretions (gut)
4 binding sites, 2 molecules
IgE
involved in response to parasitic infections and allergies
IgD
not secreted
Do T cells need MHC on antigen?
yes
TCR recognizes…
processed antigens (those that have been presented by dendrites, macrophages, B cells); MHC I and II
TCRs only bind to…
epitopes associated with an MHC protein
Can TCR be secreted?
no
Can BCR be secreted?
yes
TCR acts primarily against…
cells that harbor intracellular pathogens
Naive T cells
don’t know the antigen that they are presented to, meaning they have no been activated
Two types of naive cells
CD8+ (MHC class I) and CD4+ (MHC class 2)
CD8+
can become cytotoxic T cells; directly kills other cells
CD4+
can become helper T cells; helps regulate the activities of B cells and cytotoxic T cells
Types of CD4+ cells
Th1, Th2, Tfl (activate adaptive immune response)
To be allowed in periphery, each T cell must….
1) recognize MHC
2) TCR cannot recognize self antigens
Cytokines
cells of immune system communicate by releasing soluble regulatory proteins that act on other cells
Cytokines are secreted by…
leukocytes
Types of Cytokines
interleukins, interferons, growth factors, tumor necrosis factor (TNF), chemokines
interleukins
signal among leukocytes and other tissues
interferons
antiviral proteins that may act as cytokines
Growth Factors
proteins that stimulate the stem cells to divide
Tumor necrosis factor
secreted by Macrophages and T cell to kill tumor cells
Chemokines
chemotactic cytokines that signal leukocytes to move
Exogenous Antigens
enter the body from the outside; inhaling & ingestion
Endogenous Antigens
generated within previously normal cells as a result of normal cell metabolism, or because of viral or intracellular bacterial infection
Non-peptide antigens
also known as T-independent antigens; cannot be loaded on MHC
Exogenous antigens are presented on…
MHC II (phagocytized)
Endogenous antigens are presented on…
MHC I (viral)
MHC I Proteins
expressed on all nucleated cells (not erythrocytes)
HL-A, HL-B, HL-C
MHC II Proteins
expressed on antigen presenting cells such as Macrophages and Dendritic cells
HLA-DR, HLA-DQ, HLA-DP
T cells are located where in the lymph node?
inner
B cells are located where in the lymph node?
outer
How do CD4 T cells become activate?
once associated with APC and antigen with MHC II then activated by TCR
TH1
activates macrophages
TH17
enhance neutrophil response
TH2
activate cellular and antibody response to parasites
TFH
activate B cells maturation of antibody response
Treg
suppress other effector T cells
Naive B cells can go 2 different options
1) straight to the plasma cell (IgM, low affinity)
2) germinal center, 2/3 die off, then death/memory B cell/plasma cell (high affinity)
There is no MHC involvement when..
non-peptide antigens/T-independent antigens
mostly IgM is produced
CTLs use two mechanisms
1) Perforin-Granzyme Pathway
2) CD95 cytotoxic pathway
Are Cytotoxic Lymphocytes tame or wild?
wild- once they start killing, they kill everything
Which becomes activated more efficiently? B or T cells
T cells since they already have an activated phenotype and will proliferate and resume function upon presentation of antigen
Active Immunization (vaccine)
administering antigens so patient can mount an immune response
Passive Immunization (antidote)
individual acquires immunity through transfer of antibodies formed by an immune individual
Who discovered vaccination?
Edward Jenner
Who created the first vaccine?
Louis Pasteur
Attenuated Vaccines
grown in culture so they lose some virulence factors
long term immunity, can cause mild infections but is a strong response
Inactivated vaccines
inject dead organsim
weaker immune response; antigenically weak